WorldWideScience

Sample records for ancestry allelic variation

  1. Fast individual ancestry inference from DNA sequence data leveraging allele frequencies for multiple populations

    OpenAIRE

    Bansal, Vikas; Libiger, Ondrej

    2015-01-01

    Background Estimation of individual ancestry from genetic data is useful for the analysis of disease association studies, understanding human population history and interpreting personal genomic variation. New, computationally efficient methods are needed for ancestry inference that can effectively utilize existing information about allele frequencies associated with different human populations and can work directly with DNA sequence reads. Results We describe a fast method for estimating the...

  2. Comparison of genome-wide variation between Malawians and African ancestry HapMap populations.

    Science.gov (United States)

    Joubert, Bonnie R; North, Kari E; Wang, Yunfei; Mwapasa, Victor; Franceschini, Nora; Meshnick, Steven R; Lange, Ethan M

    2010-06-01

    Understanding genetic variation between populations is important because it affects the portability of human genome-wide analytical methods. We compared genetic variation and substructure between Malawians and other African and non-African HapMap populations. Allele frequencies and adjacent linkage disequilibrium (LD) were measured for 617 715 single nucleotide polymorphisms (SNPs) across subject genomes. Allele frequencies in the Malawian population (N=226) were highly correlated with allele frequencies in HapMap populations of African ancestry (AFA, N=376), namely Yoruban in Ibadan, Nigeria (Spearman's r(2)=0.97), Luhya in Webuye, Kenya (r(2)=0.97), African Americans in the southwest United States (r(2)=0.94) and Maasai in Kinyawa, Kenya (r(2)=0.91). This correlation was much lower between Malawians and other ancestry populations (r(2)0.82, other ancestries r(2)Maasai in Kenyawa, Kenya (rs3769013, rs730005, rs3769012, rs2304370; P-values <1 x 10(-33)). PMID:20485449

  3. Detection of ancestry informative HLA alleles confirms the admixed origins of Japanese population.

    Science.gov (United States)

    Nakaoka, Hirofumi; Mitsunaga, Shigeki; Hosomichi, Kazuyoshi; Shyh-Yuh, Liou; Sawamoto, Taiji; Fujiwara, Tsutomu; Tsutsui, Naohisa; Suematsu, Koji; Shinagawa, Akira; Inoko, Hidetoshi; Inoue, Ituro

    2013-01-01

    The polymorphisms in the human leukocyte antigen (HLA) region are powerful tool for studying human evolutionary processes. We investigated genetic structure of Japanese by using five-locus HLA genotypes (HLA-A, -B, -C, -DRB1, and -DPB1) of 2,005 individuals from 10 regions of Japan. We found a significant level of population substructure in Japanese; particularly the differentiation between Okinawa Island and mainland Japanese. By using a plot of the principal component scores, we identified ancestry informative alleles associated with the underlying population substructure. We examined extent of linkage disequilibrium (LD) between pairs of HLA alleles on the haplotypes that were differentiated among regions. The LDs were strong and weak for pairs of HLA alleles characterized by low and high frequencies in Okinawa Island, respectively. The five-locus haplotypes whose alleles exhibit strong LD were unique to Japanese and South Korean, suggesting that these haplotypes had been recently derived from the Korean Peninsula. The alleles characterized by high frequency in Japanese compared to South Korean formed segmented three-locus haplotype that was commonly found in Aleuts, Eskimos, and North- and Meso-Americans but not observed in Korean and Chinese. The serologically equivalent haplotype was found in Orchid Island in Taiwan, Mongol, Siberia, and Arctic regions. It suggests that early Japanese who existed prior to the migration wave from the Korean Peninsula shared ancestry with northern Asian who moved to the New World via the Bering Strait land bridge. These results may support the admixture model for peopling of Japanese Archipelago. PMID:23577161

  4. Detection of ancestry informative HLA alleles confirms the admixed origins of Japanese population.

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    Hirofumi Nakaoka

    Full Text Available The polymorphisms in the human leukocyte antigen (HLA region are powerful tool for studying human evolutionary processes. We investigated genetic structure of Japanese by using five-locus HLA genotypes (HLA-A, -B, -C, -DRB1, and -DPB1 of 2,005 individuals from 10 regions of Japan. We found a significant level of population substructure in Japanese; particularly the differentiation between Okinawa Island and mainland Japanese. By using a plot of the principal component scores, we identified ancestry informative alleles associated with the underlying population substructure. We examined extent of linkage disequilibrium (LD between pairs of HLA alleles on the haplotypes that were differentiated among regions. The LDs were strong and weak for pairs of HLA alleles characterized by low and high frequencies in Okinawa Island, respectively. The five-locus haplotypes whose alleles exhibit strong LD were unique to Japanese and South Korean, suggesting that these haplotypes had been recently derived from the Korean Peninsula. The alleles characterized by high frequency in Japanese compared to South Korean formed segmented three-locus haplotype that was commonly found in Aleuts, Eskimos, and North- and Meso-Americans but not observed in Korean and Chinese. The serologically equivalent haplotype was found in Orchid Island in Taiwan, Mongol, Siberia, and Arctic regions. It suggests that early Japanese who existed prior to the migration wave from the Korean Peninsula shared ancestry with northern Asian who moved to the New World via the Bering Strait land bridge. These results may support the admixture model for peopling of Japanese Archipelago.

  5. Lactase persistence alleles reveal partial East African ancestry of southern African Khoe pastoralists.

    Science.gov (United States)

    Breton, Gwenna; Schlebusch, Carina M; Lombard, Marlize; Sjödin, Per; Soodyall, Himla; Jakobsson, Mattias

    2014-04-14

    The ability to digest milk into adulthood, lactase persistence (LP), as well as specific genetic variants associated with LP, is heterogeneously distributed in global populations. These variants were most likely targets of selection when some populations converted from hunter-gatherer to pastoralist or farming lifestyles. Specific LP polymorphisms are associated with particular geographic regions and populations; however, they have not been extensively studied in southern Africa. We investigate the LP-regulatory region in 267 individuals from 13 southern African populations (including descendants of hunter-gatherers, pastoralists, and agropastoralists), providing the first comprehensive study of the LP-regulatory region in a large group of southern Africans. The "East African" LP single-nucleotide polymorphism (SNP) (14010G>C) was found at high frequency (>20%) in a strict pastoralist Khoe population, the Nama of Namibia, suggesting a connection to East Africa, whereas the "European" LP SNP (13910C>T) was found in populations of mixed ancestry. Using genome-wide data from various African populations, we identify admixture (13%) in the Nama, from an Afro-Asiatic group dating to >1,300 years ago, with the remaining fraction of their genomes being from San hunter-gatherers. We also find evidence of selection around the LCT gene among Khoe-speaking groups, and the substantial frequency of the 14010C variant among the Nama is best explained by adaptation to digesting milk. These genome-local and genome-wide results support a model in which an East African group brought pastoralist practices to southern Africa and admixed with local hunter-gatherers to form the ancestors of Khoe people. PMID:24704072

  6. Comparison of Genome Wide Variation between Malawians and African Ancestry HapMap Populations

    OpenAIRE

    Joubert, Bonnie R.; North, Kari E.; Wang, Yunfei; Mwapasa, Victor; Franceschini, Nora; Meshnick, Steven R; Lange, Ethan M.

    2010-01-01

    Understanding genetic variation between populations is important because it affects the portability of human genome wide analytical methods. We compared genetic variation and substructure between Malawians and other African and non-African HapMap populations. Allele frequencies and adjacent linkage disequilibrium (LD) were measured for 617,715 single nucleotide polymorphisms (SNPs) across subject genomes. Allele frequencies in the Malawian population (N = 226) were highly correlated with alle...

  7. The influence of genetic ancestry and ethnicity on breast cancer survival associated with genetic variation in the TGF-β-signaling pathway: The Breast Cancer Health Disparities Study

    OpenAIRE

    Slattery, Martha L.; Lundgreen, Abbie; Stern, Marianna C.; Hines, Lisa; Wolff, Roger K.; Giuliano, Anna R.; Baumgartner, Kathy B.; John, Esther M.

    2013-01-01

    The TGF-β signaling pathway regulates cellular proliferation and differentiation. We evaluated genetic variation in this pathway, its association with breast cancer survival, and survival differences by genetic ancestry and self-reported ethnicity.

  8. Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association

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    Amy Rebecca Bentley

    2012-01-01

    Full Text Available Low levels of high-density cholesterol (HDLc accompany chronic kidney disease, but the association between HDLc and the estimated glomerular filtration rate (eGFR in the general population is unclear. We investigated the HDLc-eGFR association in nondiabetic Han Chinese (HC, n=1100, West Africans (WA, n=1497, and African Americans (AA, n=1539. There were significant differences by ancestry: HDLc was positively associated with eGFR in HC (β=0.13, P<0.0001, but negatively associated among African ancestry populations (WA: −0.19, P<0.0001; AA: −0.09, P=0.02. These differences were also seen in nationally-representative NHANES data (among European Americans: 0.09, P=0.005; among African Americans −0.14, P=0.03. To further explore the findings in African ancestry populations, we investigated the role of an African ancestry-specific nephropathy risk variant, rs73885319, in the gene encoding HDL-associated APOL1. Among AA, an inverse HDLc-eGFR association was observed only with the risk genotype (−0.38 versus 0.001; P=0.03. This interaction was not seen in WA. In summary, counter to expectation, an inverse HDLc-eGFR association was observed among those of African ancestry. Given the APOL1 × HDLc interaction among AA, genetic factors may contribute to this paradoxical association. Notably, these findings suggest that the unexplained mechanism by which APOL1 affects kidney-disease risk may involve HDLc.

  9. Revealing the Genetic Variation and Allele Heterozygote Javanese and Arab Families in Malang East Java Indonesia

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    Nila Kartika Sari

    2014-02-01

    Results: Our result showed that the genetic variability and heterozygote allele increasing by using the 13 CODIS markers from the first generation to the next generation with paternity testing from each family were matched. Conclusion: We can conclude that in a Javanese-Arab family ethnic seems stimulate the increasing genetic variation and allele heterozygote.

  10. Generating Novel Allelic Variation Through Activator Insertional Mutagenesis in Maize

    OpenAIRE

    Bai, Ling; Singh, Manjit; Pitt, Lauren; Sweeney, Meredith; Brutnell, Thomas P.

    2007-01-01

    The maize transposable element Activator (Ac) has been exploited as an insertional mutagen to disrupt, clone, and characterize genes in a number of plant species. To develop an Ac-based mutagenesis platform for maize, a large-scale mutagenesis was conducted targeting the pink scutellum1 locus. We selected 1092 Ac transposition events from a closely linked donor Ac, resulting in the recovery of 17 novel ps1 alleles. Multiple phenotypic classes were identified corresponding to Ac insertions in ...

  11. Effects of sequence variation on differential allelic transcription factor occupancy and gene expression.

    Science.gov (United States)

    Reddy, Timothy E; Gertz, Jason; Pauli, Florencia; Kucera, Katerina S; Varley, Katherine E; Newberry, Kimberly M; Marinov, Georgi K; Mortazavi, Ali; Williams, Brian A; Song, Lingyun; Crawford, Gregory E; Wold, Barbara; Willard, Huntington F; Myers, Richard M

    2012-05-01

    A complex interplay between transcription factors (TFs) and the genome regulates transcription. However, connecting variation in genome sequence with variation in TF binding and gene expression is challenging due to environmental differences between individuals and cell types. To address this problem, we measured genome-wide differential allelic occupancy of 24 TFs and EP300 in a human lymphoblastoid cell line GM12878. Overall, 5% of human TF binding sites have an allelic imbalance in occupancy. At many sites, TFs clustered in TF-binding hubs on the same homolog in especially open chromatin. While genetic variation in core TF binding motifs generally resulted in large allelic differences in TF occupancy, most allelic differences in occupancy were subtle and associated with disruption of weak or noncanonical motifs. We also measured genome-wide differential allelic expression of genes with and without heterozygous exonic variants in the same cells. We found that genes with differential allelic expression were overall less expressed both in GM12878 cells and in unrelated human cell lines. Comparing TF occupancy with expression, we found strong association between allelic occupancy and expression within 100 bp of transcription start sites (TSSs), and weak association up to 100 kb from TSSs. Sites of differential allelic occupancy were significantly enriched for variants associated with disease, particularly autoimmune disease, suggesting that allelic differences in TF occupancy give functional insights into intergenic variants associated with disease. Our results have the potential to increase the power and interpretability of association studies by targeting functional intergenic variants in addition to protein coding sequences. PMID:22300769

  12. Allelic variation of bile salt hydrolase genes in Lactobacillus salivarius does not determine bile resistance levels.

    LENUS (Irish Health Repository)

    Fang, Fang

    2009-09-01

    Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius strains from different sources all harbored a bsh1 allele on their respective megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of two strains that had higher bile resistance levels. Four Bsh1-encoding allele groups were identified, defined by truncations or deletions involving a conserved residue. In vitro analyses showed that this allelic variation was correlated with widely varying bile deconjugation phenotypes. Despite very low activity of the UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile resistance, both in vitro and during intestinal transit in mice. However, the overall bile resistance phenotype of this and other strains was independent of the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure to bile and cholate identified a multiplicity of stress response proteins and putative efflux proteins that appear to broadly compensate for, or mask, the effects of allelic variation of bsh genes. Bsh enzymes with different bile-degrading kinetics, though apparently not the primary determinants of bile resistance in L. salivarius, may have additional biological importance because of varying effects upon bile as a signaling molecule in the host.

  13. Allelic variation in the squirrel monkey x-linked color vision gene: biogeographical and behavioral correlates.

    Science.gov (United States)

    Cropp, Susan; Boinski, Sue; Li, Wen-Hsiung

    2002-06-01

    Most Neotropical primate species possess a polymorphic X-linked and a monomorphic autosomal color vision gene. Consequently, populations are composed of both dichromatics and trichromatics. Most theories on the maintenance of this genetic system revolve around possible advantages for foraging ecology. To examine the issue from a different angle, we compared the numbers and relative frequencies of alleles at the X-linked locus among three species of Saimiri representing a wide range of geographical and behavioral variation in the genus. Exons 3, 4, and 5 of the X-linked opsin gene were sequenced for a large number of X chromosomes for all three species. Several synonymous mutations were detected in exons 4 and 5 for the originally reported alleles but only a single nonsynonymous change was detected. Two alleles were found that appeared to be the result of recombination events. The low occurrence of recombinant alleles and absence of mutations in the amino acids critical for spectral tuning indicates that stabilizing selection acts to maintain the combinations of critical sites specific to each allele. Allele frequencies were approximately the same for all Saimiri species, with a slight but significant difference between S. boliviensis and S. oerstedii. No apparent correlation exists between allele frequencies and behavioral or biogeographical differences between species, casting doubt on the speculation that the spectral sensitivities of the alleles have been maintained because they are specifically well-tuned to Saimiri visual ecology. Rather, the spectral tuning peaks might have been maintained because they are as widely spaced as possible within the limited range of middlewave to longwave spectra useful to all primates. This arrangement creates a balance between maximizing the distance between spectral tuning peaks (allowing the color opponency of the visual system to distinguish between peaks) and maximizing the number of alleles within a limited range (yielding

  14. The effect of subdivision on variation at multi-allelic loci under balancing selection

    DEFF Research Database (Denmark)

    Schierup, M H; Vekemans, X; Charlesworth, D

    2000-01-01

    Simulations are used to investigate the expected pattern of variation at loci under different forms of multi-allelic balancing selection in a finite island model of a subdivided population. The objective is to evaluate the effect of restricted migration among demes on the distribution of polymorp...

  15. Recent admixture in an Indian population of African ancestry.

    Science.gov (United States)

    Narang, Ankita; Jha, Pankaj; Rawat, Vimal; Mukhopadhyay, Arijit; Mukhopadhayay, Arijit; Dash, Debasis; Basu, Analabha; Mukerji, Mitali

    2011-07-15

    Identification and study of genetic variation in recently admixed populations not only provides insight into historical population events but also is a powerful approach for mapping disease loci. We studied a population (OG-W-IP) that is of African-Indian origin and has resided in the western part of India for 500 years; members of this population are believed to be descendants of the Bantu-speaking population of Africa. We have carried out this study by using a set of 18,534 autosomal markers common between Indian, CEPH-HGDP, and HapMap populations. Principal-components analysis clearly revealed that the African-Indian population derives its ancestry from Bantu-speaking west-African as well as Indo-European-speaking north and northwest Indian population(s). STRUCTURE and ADMIXTURE analyses show that, overall, the OG-W-IPs derive 58.7% of their genomic ancestry from their African past and have very little inter-individual ancestry variation (8.4%). The extent of linkage disequilibrium also reveals that the admixture event has been recent. Functional annotation of genes encompassing the ancestry-informative markers that are closer in allele frequency to the Indian ancestral population revealed significant enrichment of biological processes, such as ion-channel activity, and cadherins. We briefly examine the implications of determining the genetic diversity of this population, which could provide opportunities for studies involving admixture mapping. PMID:21737057

  16. Novel Natural Allelic Variations at the Rht-1 Loci in Wheat

    Institute of Scientific and Technical Information of China (English)

    Aixia Li; HongQing Ling; Aimin Zhang; Wenlong Yang; Xueyuan Lou; Dongcheng Liu; Jiazhu Sun; Xiaoli Guo; Jing Wang; Yiwen Li; Kehui Zhan

    2013-01-01

    Plant height is an important agronomic trait. Dramatic increase in wheat yield during the“green revolution”is mainly due to the widespread utilization of the Reduced height (Rht)-1 gene. We analyzed the natural allelic variations of three homoeologous loci Rht-A1, Rht-B1, and Rht-D1 in Chinese wheat (Triticum aestivum L.) micro-core collections and the Rht-B1/D1 genotypes in over 1,500 bred cultivars and germplasms using a modified EcoTILLING. We identified six new Rht-A1 allelic variations (Rht-A1b-g), eight new Rht-B1 allelic variations (Rht-B1h-o), and six new Rht-D1 allelic variations (Rht-D1e-j). These allelic variations contain single nucleotide polymorphisms (SNPs) or small insertions and deletions in the coding or uncoding regions, involving two frame-shift mutations and 15 missenses. Of which, Rht-D1e and Rht-D1h resulted in the loss of interactions of GID1-DELLA-GID2, Rht-B1i could increase plant height. We found that the Rht-B1h contains the same SNPs and 197 bp fragment insertion as reported in Rht-B1c. Further detection of Rht-B1h in Tibet wheat germplasms and wheat relatives indicated that Rht-B1c may originate from Rht-B1h. These results suggest rich genetic diversity at the Rht-1 loci and provide new resources for wheat breeding.

  17. Variation within the vat(E) Allele of Enterococcus faecium Isolates from Retail Poultry Samples

    OpenAIRE

    Simjee, S.; McDermott, P. F.; Wagner, D D; White, D. G.

    2001-01-01

    In a survey of retail meat samples, twelve quinupristin-dalfopristin-resistant (MICs, ≥4 mg/liter) Enterococcus faecium isolates that carried a vat(E) gene were recovered. DNA sequence comparison revealed five new variations in the vat(E) allele among 12 isolates, which were designated vat(E-4) through vat(E-8); two isolates had vat(E-1). There was no correlation between the number of base changes and the quinupristin-dalfopristin MIC.

  18. Interactions Between SNP Alleles at Multiple Loci and Variation in Skin Pigmentation in 122 Caucasians

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    Sumiko Anno

    2007-01-01

    Full Text Available This study was undertaken to clarify the molecular basis for human skin color variation and the environmental adaptability to ultraviolet irradiation, with the ultimate goal of predicting the impact of changes in future environments on human health risk. One hundred twenty-two Caucasians living in Toledo, Ohio participated. Back and cheek skin were assayed for melanin as a quantitative trait marker. Buccal cell samples were collected and used for DNA extraction. DNA was used for SNP genotyping using the Masscode™ system, which entails two-step PCR amplification and a platform chemistry which allows cleavable mass spectrometry tags. The results show gene-gene interaction between SNP alleles at multiple loci (not necessarily on the same chromosome contributes to inter-individual skin color variation while suggesting a high probability of linkage disequilibrium. Confirmation of these findings requires further study with other ethic groups to analyze the associations between SNP alleles at multiple loci and human skin color variation. Our overarching goal is to use remote sensing data to clarify the interaction between atmospheric environments and SNP allelic frequency and investigate human adaptability to ultraviolet irradiation. Such information should greatly assist in the prediction of the health effects of future environmental changes such as ozone depletion and increased ultraviolet exposure. If such health effects are to some extent predictable, it might be possible to prepare for such changes in advance and thus reduce the extent of their impact.

  19. Allelic Variation at the Rht8 Locus in a 19th Century Wheat Collection

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    Linnéa Asplund

    2012-01-01

    Full Text Available Wheat breeding during the 20th century has put large efforts into reducing straw length and increasing harvest index. In the 1920s an allele of Rht8 with dwarfing effects, found in the Japanese cultivar “Akakomugi,” was bred into European cultivars and subsequently spread over the world. Rht8 has not been cloned, but the microsatellite marker WMS261 has been shown to be closely linked to it and is commonly used for genotyping Rht8. The “Akakomugi” allele is strongly associated with WMS261-192bp. Numerous screens of wheat cultivars with different geographical origin have been performed to study the spread and influence of the WMS261-192bp during 20th century plant breeding. However, the allelic diversity of WMS261 in wheat cultivars before modern plant breeding and introduction of the Japanese dwarfing genes is largely unknown. Here, we report a study of WMS261 allelic diversity in a historical wheat collection from 1865 representing worldwide major wheats at the time. The majority carried the previously reported 164 bp or 174 bp allele, but with little geographical correlation. In a few lines, a rare 182 bp fragment was found. Although straw length was recognized as an important character already in the 19th century, Rht8 probably played a minor role for height variation. The use of WMS261 and other functional markers for analyses of historical specimens and characterization of historic crop traits is discussed.

  20. Allelic heterogeneity and trade-off shape natural variation for response to soil micronutrient.

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    Seifollah Poormohammad Kiani

    Full Text Available As sessile organisms, plants have to cope with diverse environmental constraints that may vary through time and space, eventually leading to changes in the phenotype of populations through fixation of adaptive genetic variation. To fully comprehend the mechanisms of evolution and make sense of the extensive genotypic diversity currently revealed by new sequencing technologies, we are challenged with identifying the molecular basis of such adaptive variation. Here, we have identified a new variant of a molybdenum (Mo transporter, MOT1, which is causal for fitness changes under artificial conditions of both Mo-deficiency and Mo-toxicity and in which allelic variation among West-Asian populations is strictly correlated with the concentration of available Mo in native soils. In addition, this association is accompanied at different scales with patterns of polymorphisms that are not consistent with neutral evolution and show signs of diversifying selection. Resolving such a case of allelic heterogeneity helps explain species-wide phenotypic variation for Mo homeostasis and potentially reveals trade-off effects, a finding still rarely linked to fitness.

  1. Hardy-Weinberg equilibrium revisited for inferences on genotypes featuring allele and copy-number variations.

    Science.gov (United States)

    Recke, Andreas; Recke, Klaus-Günther; Ibrahim, Saleh; Möller, Steffen; Vonthein, Reinhard

    2015-01-01

    Copy number variations represent a substantial source of genetic variation and are associated with a plethora of physiological and pathophysiological conditions. Joint copy number and allelic variations (CNAVs) are difficult to analyze and require new strategies to unravel the properties of genotype distributions. We developed a Bayesian hidden Markov model (HMM) approach that allows dissecting intrinsic properties and metastructures of the distribution of CNAVs within populations, in particular haplotype phases of genes with varying copy numbers. As a key feature, this approach incorporates an extension of the Hardy-Weinberg equilibrium, allowing both a comprehensive and parsimonious model design. We demonstrate the quality of performance and applicability of the HMM approach with a real data set describing the Fcγ receptor (FcγR) gene region. Our concept, using a dynamic process to analyze a static distribution, establishes the basis for a novel understanding of complex genomic data sets. PMID:25765626

  2. Allelic variations in Glu-1 and Glu-3 loci of historical and modern Iranian bread wheat (Triticum aestivum L.) cultivars

    Indian Academy of Sciences (India)

    Ali Izadi-Darbandi; Bahman Yazdi-Samadi; Ali-Akbar Su-Boushehri; Mohsen Mohammadi

    2010-08-01

    Proline and glutamine-rich wheat seed endosperm proteins are collectively referred to as prolamins. They are comprised of HMW-GSs, LMW-GSs and gliadins. HMW-GSs are major determinants of gluten elasticity and LMW-GSs considerably affect dough extensibility and maximum dough resistance. The inheritance of glutenin subunits follows Mendelian genetics with multiple alleles in each locus. Identification of the banding patterns of glutenin subunits could be used as an estimate for screening high quality wheat germplasm. Here, by means of a two-step 1D-SDS-PAGE procedure, we identified the allelic variations in high and low-molecular-weight glutenin subunits in 65 hexaploid wheat (Triticum aestivum L.) cultivars representing a historical trend in the cultivars introduced or released in Iran from the years 1940 to 1990. Distinct alleles 17 and 19 were detected for Glu-1 and Glu-3 loci, respectively. The allelic frequencies at the Glu-1 loci demonstrated unimodal distributions. At Glu-A1, Glu-B1 and Glu-D1, we found that the most frequent alleles were the null, 7 + 8, 2 + 12 alleles, respectively, in Iranian wheat cultivars. In contrast, Glu-3 loci showed bimodal or trimodal distributions. At Glu-A3, the most frequent alleles were c and e. At Glu-B3 the most frequent alleles were a, b and c. At Glu-D3 locus, the alleles b and a, were the most and the second most frequent alleles in Iranian wheat cultivars. This led to a significantly higher Nei coefficient of genetic variations in Glu-3 loci (0.756) as compared to Glu-1 loci (0.547). At Glu-3 loci, we observed relatively high quality alleles in Glu-A3 and Glu-D3 loci and low quality alleles at Glu-B3 locus.

  3. Genotyping of infectious laryngotracheitis virus using allelic variations from multiple genomic regions.

    Science.gov (United States)

    Choi, Eun-Jung; La, Tae-Min; Choi, In-Soo; Song, Chang-Seon; Park, Seung-Yong; Lee, Joong-Bok; Lee, Sang-Won

    2016-08-01

    Live attenuated vaccines are extensively used worldwide to control the outbreak of infectious laryngotracheitis. Virulent field strains showing close genetic relationship with the infectious laryngotracheitis virus (ILTV) vaccines of chicken embryo origin have been detected in the poultry industry. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, a reliable molecular epidemiological method, of multiple genomic regions was performed. The PCR-RFLP is a time-consuming method that requires considerable amount of intact viral genomic DNA to amplify genomic regions greater than 4 kb. In this study, six variable genomic regions were selected and amplified for sequencing. The multi-allelic PCR-sequence genotyping showed better discrimination power than that of previous PCR-sequencing schemes using single or two target regions. The allelic variation patterns yielded 16 strains of ILTV classified into 14 different genotypes. Three Korean field strains, 550/05/Ko, 0010/05/Ko and 40032/08/Ko, were found to have the same genotype as the commercial vaccine strain, Laryngo Vac (Zoetis, Florham Park, NJ, USA). Three other Korean field strains, 40798/10/Ko, 12/07/Ko, and 30678/14/Ko, showed recombined allelic patterns. The multi-allelic PCR-sequencing method was proved to be an efficient and practical procedure to classify the different strains of ILTV. The method could serve as an alternate diagnostic and differentiating tool for the classification of ILTV, and contribute to understanding of the epidemiology of the disease at a global level. PMID:26956802

  4. Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis.

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    Jill K Terra

    2011-12-01

    Full Text Available Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (LT, as well as by genetic variation within the host. To identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the LT-responsive CAST/Ei strain introgressed on a LT-resistant C57BL/6 (B6 background was screened for response to LT. Three congenic strains containing CAST/Ei regions of chromosome 11 were identified that displayed a rapid inflammatory response to LT similar to, but more severe than that driven by a LT-responsive allele of the inflammasome constituent NRLP1B. Importantly, increased response to LT in congenic mice correlated with greater resistance to infection by the Sterne strain of B. anthracis. The genomic region controlling the inflammatory response to LT was mapped to 66.36-74.67 Mb on chromosome 11, a region that encodes the LT-responsive CAST/Ei allele of Nlrp1b. However, known downstream effects of NLRP1B activation, including macrophage pyroptosis, cytokine release, and leukocyte infiltration could not fully explain the response to LT or the resistance to B. anthracis Sterne in congenic mice. Further, the exacerbated response in congenic mice is inherited in a recessive manner while the Nlrp1b-mediated response to LT is dominant. Finally, congenic mice displayed increased responsiveness in a model of sepsis compared with B6 mice. In total, these data suggest that allelic variation of one or more chromosome 11 genes in addition to Nlrp1b controls the severity of host response to multiple inflammatory stimuli and contributes to resistance to B. anthracis Sterne. Expression quantitative trait locus analysis revealed 25 genes within this region as high priority candidates for contributing to the host response to LT.

  5. Evaluation of Pakistani wheat germplasm for bread quality based on allelic variation in HMW glutenin subunits

    International Nuclear Information System (INIS)

    Seventy six Pakistani wheat genotypes including land races were investigated for Bread quality (BQ) based on allelic variation in HMW glutenin subunits at the Glu-1 loci through SDS- polyacrylamide gel electropherosis. Twenty five different allelic combinations were detected with a total of 14 Glu-1 loci. Highest polymorphism was revealed by Glu-B locus and some single/ rare sub units were also screened out. The frequencies of dominant subunits were 50% for 2*, 42.11% for subunit pair 17+18 and 48.68% for 5+10 and 2+12 respectively. The quality scores displayed a range from 4 to 10, however generally good quality score of eight was more frequent (39. 47%). The highest quality scores of 10 and 9 were observed in 22.36% and 19.74% of genotypes respectively. The UPGMA analysis grouped genotypes into three major with two additional sub clusters for each. The cluster 'a' 'b' and 'C' were separated at 73% genetic distance which was further differentiated at a genetic distance of 50% into their sub clusters. Pakistani wheat varieties/land races exhibited large variation in term of HMW-GS. The generated information will lead to the pyrimiding of sub units for high BQ through mission oriented marker assisted breeding programmes for quality improvement of wheat. (author)

  6. Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector.

    Directory of Open Access Journals (Sweden)

    Sulaiman S Ibrahim

    2015-10-01

    Full Text Available Scale up of Long Lasting Insecticide Nets (LLINs has massively contributed to reduce malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Deciphering the detailed molecular basis of such resistance and designing diagnostic tools is critical to implement suitable resistance management strategies. Here, we demonstrated that allelic variation in two cytochrome P450 genes is the most important driver of pyrethroid resistance in the major African malaria vector Anopheles funestus and detected key mutations controlling this resistance. An Africa-wide polymorphism analysis of the duplicated genes CYP6P9a and CYP6P9b revealed that both genes are directionally selected with alleles segregating according to resistance phenotypes. Modelling and docking simulations predicted that resistant alleles were better metabolizers of pyrethroids than susceptible alleles. Metabolism assays performed with recombinant enzymes of various alleles confirmed that alleles from resistant mosquitoes had significantly higher activities toward pyrethroids. Additionally, transgenic expression in Drosophila showed that flies expressing resistant alleles of both genes were significantly more resistant to pyrethroids compared with those expressing the susceptible alleles, indicating that allelic variation is the key resistance mechanism. Furthermore, site-directed mutagenesis and functional analyses demonstrated that three amino acid changes (Val109Ile, Asp335Glu and Asn384Ser from the resistant allele of CYP6P9b were key pyrethroid resistance mutations inducing high metabolic efficiency. The detection of these first DNA markers of metabolic resistance to pyrethroids allows the design of DNA-based diagnostic tools to detect and track resistance associated with bednets scale up, which will improve the design of evidence-based resistance management strategies.

  7. Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector.

    Science.gov (United States)

    Ibrahim, Sulaiman S; Riveron, Jacob M; Bibby, Jaclyn; Irving, Helen; Yunta, Cristina; Paine, Mark J I; Wondji, Charles S

    2015-10-01

    Scale up of Long Lasting Insecticide Nets (LLINs) has massively contributed to reduce malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Deciphering the detailed molecular basis of such resistance and designing diagnostic tools is critical to implement suitable resistance management strategies. Here, we demonstrated that allelic variation in two cytochrome P450 genes is the most important driver of pyrethroid resistance in the major African malaria vector Anopheles funestus and detected key mutations controlling this resistance. An Africa-wide polymorphism analysis of the duplicated genes CYP6P9a and CYP6P9b revealed that both genes are directionally selected with alleles segregating according to resistance phenotypes. Modelling and docking simulations predicted that resistant alleles were better metabolizers of pyrethroids than susceptible alleles. Metabolism assays performed with recombinant enzymes of various alleles confirmed that alleles from resistant mosquitoes had significantly higher activities toward pyrethroids. Additionally, transgenic expression in Drosophila showed that flies expressing resistant alleles of both genes were significantly more resistant to pyrethroids compared with those expressing the susceptible alleles, indicating that allelic variation is the key resistance mechanism. Furthermore, site-directed mutagenesis and functional analyses demonstrated that three amino acid changes (Val109Ile, Asp335Glu and Asn384Ser) from the resistant allele of CYP6P9b were key pyrethroid resistance mutations inducing high metabolic efficiency. The detection of these first DNA markers of metabolic resistance to pyrethroids allows the design of DNA-based diagnostic tools to detect and track resistance associated with bednets scale up, which will improve the design of evidence-based resistance management strategies. PMID:26517127

  8. SSR allelic variation of rice variety Hangxiangnuo bred by space mutation

    International Nuclear Information System (INIS)

    Hangxiangnuo, an indica fragrant glutinous rice mutant, was induced by space environment. Comparing with its wild type Nanfengnuo, the yield and blast resistance of Hangxiangnuo are improved significantly and the grain shape became slender and with fragrance. To understand the mechanisms of space mutation and identify the changes at molecular level associated with phenotypic variations, SSR allelic variation analysis were performed on Hangxiangnuo and Nanfengnuo in this study. The results showed that 45 loci were polymorphic among the 156 SSR loci tested throughout the genome, the frequency of variation was 28.85%. Among the polymorphic loci, 42 loci only showed variations in the molecular weight of the amplified bands, only on locus increased the number of amplification bands in Hangxiangnuo and two loci were differed by heterozygous loci (with two amplification bands at one locus) detected in Nanfengnuo and homozygous loci in Hangxiangnuo. It suggests that the change of some loci in mutants was due to the normal segregation and recombination of heterozygous loci of the wild type. The variation frequencies among different chromosomes were quite different, with the highest one at 50.00% detected on chromosomes 7, 8 and 12, and the lowest at 6.25% on chromosome 6. The polymorphic loci were clustered on chromosomes throughout the genome indicating that large DNA segments mutation is one of the major variation patterns induced by space environment. Some of reported QTLs involved in grain shape, yield, fragrance and blast resistance were found to be located exactly in the mutated regions. Therefore, further study is needed to confirm that these QTLs are responsible for the trait variations. (authors)

  9. Detection of Allelic Variation in Chinese Wheat (Triticum aestivum L.) Germplasm with Drought Tolerance Using SSR Markers

    Institute of Scientific and Technical Information of China (English)

    JING Rui-lian; CHANG Xiao-ping; Marcello Broggio; JIA Ji-zeng

    2002-01-01

    Allelic variation in two domestic wheat landraces, Pingyaobaimai and Mazhamai, two cornerstone breeding materials and their derived cultivars with drought tolerance was detected by SSR (simple sequence repeat) markers. The clustering of 25 accessions showed that the similarity between Pingyaobaimai and Yanda1817, the latter was developed from the former, was 0.71, the highest one of all accessions, but the similarities were very low between these two accessions and other accessions including their derived cultivars. A similar situation was revealed between Mazhamai and its derived cultivars. Pingyaobaimai and its three derived cultivars shared three alleles at loci Xgwm526, Xgwm538 and Xgwm126 on chromosome arms 2BL, 4BL and 5AL, respectively. There were six shared alleles in Mazhamai and its derived cultivars, in order of Xgwm157,Xgwm126, Xgwm212, Xgwm626, Xgwm471 and Xgwm44 on chromosome arms 2DL, 5AL, 5DL, 6BL, 7AS and 7DC, respectively. Only one shared allele was detected between the pedigrees of Pingyaobaimai and Mazhamai. The difference of shared alleles in two cornerstone breeding materials and their derived cultivars revealed the diversity in Chinese wheat germplasm with drought tolerance and the complication in genetic basis of drought tolerance in wheat.

  10. Allelic Variation in Developmental Genes and Effects on Winter Wheat Heading Date in the U.S. Great Plains.

    Science.gov (United States)

    Grogan, Sarah M; Brown-Guedira, Gina; Haley, Scott D; McMaster, Gregory S; Reid, Scott D; Smith, Jared; Byrne, Patrick F

    2016-01-01

    Heading date in wheat (Triticum aestivum L.) and other small grain cereals is affected by the vernalization and photoperiod pathways. The reduced-height loci also have an effect on growth and development. Heading date, which occurs just prior to anthesis, was evaluated in a population of 299 hard winter wheat entries representative of the U.S. Great Plains region, grown in nine environments during 2011-2012 and 2012-2013. The germplasm was evaluated for candidate genes at vernalization (Vrn-A1, Vrn-B1, and Vrn-D1), photoperiod (Ppd-A1, Ppd-B1 and Ppd-D1), and reduced-height (Rht-B1 and Rht-D1) loci using polymerase chain reaction (PCR) and Kompetitive Allele Specific PCR (KASP) assays. Our objectives were to determine allelic variants known to affect flowering time, assess the effect of allelic variants on heading date, and investigate changes in the geographic and temporal distribution of alleles and haplotypes. Our analyses enhanced understanding of the roles developmental genes have on the timing of heading date in wheat under varying environmental conditions, which could be used by breeding programs to improve breeding strategies under current and future climate scenarios. The significant main effects and two-way interactions between the candidate genes explained an average of 44% of variability in heading date at each environment. Among the loci we evaluated, most of the variation in heading date was explained by Ppd-D1, Ppd-B1, and their interaction. The prevalence of the photoperiod sensitive alleles Ppd-A1b, Ppd-B1b, and Ppd-D1b has gradually decreased in U.S. Great Plains germplasm over the past century. There is also geographic variation for photoperiod sensitive and reduced-height alleles, with germplasm from breeding programs in the northern Great Plains having greater incidences of the photoperiod sensitive alleles and lower incidence of the semi-dwarf alleles than germplasm from breeding programs in the central or southern plains. PMID:27058239

  11. Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector

    OpenAIRE

    Sulaiman S Ibrahim; Riveron, Jacob M.; Bibby, Jaclyn; Irving, Helen; Yunta, Cristina; Paine, Mark J. I.; Wondji, Charles S.

    2015-01-01

    Scale up of Long Lasting Insecticide Nets (LLINs) has massively contributed to reduce malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Deciphering the detailed molecular basis of such resistance and designing diagnostic tools is critical to implement suitable resistance management strategies. Here, we demonstrated that allelic variation in two cytochrome P450 genes is the most important driver of pyrethro...

  12. Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector.

    OpenAIRE

    Sulaiman S Ibrahim; Riveron, Jacob M.; Jaclyn Bibby; Helen Irving; Cristina Yunta; Paine, Mark J. I.; Wondji, Charles S.

    2015-01-01

    Scale up of Long Lasting Insecticide Nets (LLINs) has massively contributed to reduce malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Deciphering the detailed molecular basis of such resistance and designing diagnostic tools is critical to implement suitable resistance management strategies. Here, we demonstrated that allelic variation in two cytochrome P450 genes is the most important driver of pyrethro...

  13. Allelic distributions of CYP2D6 gene copy number variation in the Eastern Han Chinese population

    Institute of Scientific and Technical Information of China (English)

    Hai-hui SHENG; Yun-lan DU; Jian SUN; Hua-sheng XIAO; Ai-ping ZENG; Wen-xiang ZHU; Ren-fang ZHU; Hong-mei LI; Zhi-dong ZHU; Ying QIN; Wei JIN; Yan LIU

    2007-01-01

    Aim: The human cytochrome P450 2D6 (CYP2D6) gene copy number variation, involving CYP2D6 gene deletion (CYP2D6*5) and duplication or multiduplication (CYP2D6*×N), can result in reduced or increased metabolism of many clinically used drugs. The identification of CYP2D6*5 and CYP2D6*×N and the investigation of their allelic distributions in ethnic populations can be important in deter-mining the right drug and dosage for each patient. Methods: The CYP2D6*5 andCYP2D6 genes, and CYP2D6 gene duplication were identified by 2 modified long PCR, respectively. To determine duplicated alleles, a novel long PCR was developed to amplify the entire duplicated CYP2D6 gene which was used as template for subsequent PCR amplification. A total of 363 unrelated Eastern Han Chinese individuals were analyzed for CYP2D6 gene copy number variation. Results: The frequency of CYP2D6*5 and CYP2D6*×N were 4.82% (n=35) and 0.69% (n=5) in the Eastern Han Chinese population, respectively. Of the 5 duplicated alleles, 3were CYP2D6*1×N and 2 were CYP2D6*10×N. One individual was a carrier of both CYP2D6*5 and CYP2D6*1×N. Taken together, the CYP2D6 gene rear-rangements were present in 10.74% of subjects. Conclusion: Allelic distributions of the CYP2D6 gene copy number variation differ among Chinese from different regions, indicating ethnic variety in Chinese. Long PCR are convenient, cost effective, specific and semiquantitative for the detection of the CYP2D6 gene copy number variation, and amplification of the entire duplicated CYP2D6 gene is necessary for the accurate identification of duplicated alleles.

  14. Allelic variation at a single gene increases food value in a drought-tolerant staple cereal.

    Science.gov (United States)

    Gilding, Edward K; Frère, Celine H; Cruickshank, Alan; Rada, Anna K; Prentis, Peter J; Mudge, Agnieszka M; Mace, Emma S; Jordan, David R; Godwin, Ian D

    2013-01-01

    The production of adequate agricultural outputs to support the growing human population places great demands on agriculture, especially in light of ever-greater restrictions on input resources. Sorghum is a drought-adapted cereal capable of reliable production where other cereals fail, and thus represents a good candidate to address food security as agricultural inputs of water and arable land grow scarce. A long-standing issue with sorghum grain is that it has an inherently lower digestibility. Here we show that a low-frequency allele type in the starch metabolic gene, pullulanase, is associated with increased digestibility, regardless of genotypic background. We also provide evidence that the beneficial allele type is not associated with deleterious pleiotropic effects in the modern field environment. We argue that increasing the digestibility of an adapted crop is a viable way forward towards addressing food security while maximizing water and land-use efficiency. PMID:23403584

  15. Allelic variation in human mitochondrial genes based on patterns of restriction site polymorphism.

    OpenAIRE

    Whittam, T S; Clark, A. G.; Stoneking, M; Cann, R. L.; Wilson, A. C.

    1986-01-01

    Restriction maps of 145 human mtDNAs representing samples from five geographic regions were used to construct multilocus genotypes for 28 genetic loci of the mitochondrial genome. Alleles were defined as distinct combinations of the presence or absence of polymorphic restriction sites within each locus. The 28 loci included 13 genes encoding proteins, 10 genes specifying tRNAs, 2 genes specifying rRNAs, and 3 noncoding regions consisting of the D loop, the light strand origin of replication, ...

  16. Associations of PON1 and genetic ancestry with obesity in early childhood.

    Directory of Open Access Journals (Sweden)

    Karen Huen

    Full Text Available Obesity in children has become an epidemic in the U.S. and is particularly prominent in minority populations such as Mexican-Americans. In addition to physical activity and diet, genetics also plays a role in obesity etiology. A few studies in adults and adolescents suggest a link between obesity and paraoxonase 1 (PON1, a multifunctional enzyme that can metabolize organophosphate pesticides and also has antioxidant properties. We determined PON1192 genotype and arylesterase levels (ARYase, measure of PON1 enzyme quantity, to characterize the relationship between PON1 and obesity in young Mexican-American children (n = 373 living in an agricultural community in California. Since PON1 polymorphisms and obesity both vary between ethnic groups, we estimated proportional genetic ancestry using 106 ancestral informative markers (AIMs. Among children, PON1192 allele frequencies were 0.5 for both alleles, and the prevalence of obesity was high (15% and 33% at ages two and five, respectively. The average proportion of European, African, and Native American ancestry was 0.40, 0.09, and 0.51, yet there was wide inter-individual variation. We found a significantly higher odds of obesity (9.3 and 2.5- fold in PON1192QQ children compared to PON1192RR children at ages two and five, respectively. Similar relationships were seen with BMI Z-scores at age two and waist circumference at age five. After adjusting for genetic ancestry in models of PON1 and BMI Z-score, effect estimates for PON1192 genotype changed 15% and 9% among two and five year old children, respectively, providing evidence of genetic confounding by population stratification. However even after adjustment for genetic ancestry, the trend of increased BMI Z-scores with increased number of PON1192 Q alleles remained. Our findings suggest that PON1 may play a role in obesity independent of genetic ancestry and that studies of PON1 and health outcomes, especially in admixed populations, should

  17. Age-related cognitive decline : the role of allelic variations in two genes (COMT and APOE)

    OpenAIRE

    2011-01-01

    The catechol-O-methyltransferase (COMT) gene codes for the COMT enzyme, which has a role in the degradation of dopamine in the prefrontal cortex. The dopaminergic system declines with age, and aging might increase the effects of COMT on cognition. It is in particular the COMT Val158Met single nucleotide polymorphism (SNP) that has been investigated in association with cognition, but other COMT SNPs have also been studied. The ε4 allele of the Apolipoprotein E (APOE) gene is a known risk facto...

  18. Allelic sequence variation of the HLA-DQ loci: relationship to serology and to insulin-dependent diabetes susceptibility.

    Science.gov (United States)

    Horn, G T; Bugawan, T L; Long, C M; Erlich, H A

    1988-01-01

    Analysis of sequence variation in the polymorphic second exon of the major histocompatibility complex genes HLA-DQ alpha and -DQ beta has revealed 8 allelic variants at the alpha locus and 13 variants at the beta locus. Correlation of sequence variation with serologic typing suggests that the DQw2, DQw3, and DQ(blank) types are determined by the DQ beta subunit, while the DQw1 specificity is determined by DQ alpha. The nature of the amino acid at position 57 in the DQ beta subunit is correlated with susceptibility to insulin-dependent diabetes mellitus. This region of the DQ beta chain contains shared peptides with Epstein-Barr virus and rubella virus. PMID:2842756

  19. Distribution of CYP2D6 alleles and phenotypes in the Brazilian population.

    Directory of Open Access Journals (Sweden)

    Deise C Friedrich

    Full Text Available The CYP2D6 enzyme is one of the most important members of the cytochrome P450 superfamily. This enzyme metabolizes approximately 25% of currently prescribed medications. The CYP2D6 gene presents a high allele heterogeneity that determines great inter-individual variation. The aim of this study was to evaluate the variability of CYP2D6 alleles, genotypes and predicted phenotypes in Brazilians. Eleven single nucleotide polymorphisms and CYP2D6 duplications/multiplications were genotyped by TaqMan assays in 1020 individuals from North, Northeast, South, and Southeast Brazil. Eighteen CYP2D6 alleles were identified in the Brazilian population. The CYP2D6*1 and CYP2D6*2 alleles were the most frequent and widely distributed in different geographical regions of Brazil. The highest number of CYPD6 alleles observed was six and the frequency of individuals with more than two copies ranged from 6.3% (in Southern Brazil to 10.2% (Northern Brazil. The analysis of molecular variance showed that CYP2D6 is homogeneously distributed across different Brazilian regions and most of the differences can be attributed to inter-individual differences. The most frequent predicted metabolic status was EM (83.5%. Overall 2.5% and 3.7% of Brazilians were PMs and UMs respectively. Genomic ancestry proportions differ only in the prevalence of intermediate metabolizers. The IM predicted phenotype is associated with a higher proportion of African ancestry and a lower proportion of European ancestry in Brazilians. PM and UM classes did not vary among regions and/or ancestry proportions therefore unique CYP2D6 testing guidelines for Brazilians are possible and could potentially avoid ineffective or adverse events outcomes due to drug prescriptions.

  20. Allelic and copy-number variations of FcγRs affect granulocyte function and susceptibility for autoimmune blistering diseases.

    Science.gov (United States)

    Recke, Andreas; Vidarsson, Gestur; Ludwig, Ralf J; Freitag, Miriam; Möller, Steffen; Vonthein, Reinhard; Schellenberger, Julia; Haase, Ozan; Görg, Siegfried; Nebel, Almut; Flachsbart, Friederike; Schreiber, Stefan; Lieb, Wolfgang; Gläser, Regine; Benoit, Sandrine; Sárdy, Miklós; Eming, Rüdiger; Hertl, Michael; Zillikens, Detlef; König, Inke R; Schmidt, Enno; Ibrahim, Saleh

    2015-07-01

    Low-affinity Fcγ receptors (FcγR) bridge innate and adaptive immune responses. In many autoimmune diseases, these receptors act as key mediators of the pathogenic effects of autoantibodies. Genes encoding FcγR exhibit frequent variations in sequence and gene copy number that influence their functional properties. FcγR variations also affect the susceptibility to systemic autoimmunity, e.g. systemic lupus erythematosus and rheumatoid arthritis. This raises the question whether FcγR variations are also associated with organ-specific autoimmunity, particularly autoantibody-mediated diseases, such as subepidermal autoimmune blistering diseases (AIBD). A multitude of evidence suggests a pathogenic role of neutrophil granulocyte interaction with autoantibodies via FcγR. In a two-stage study, we analyzed whether the FcγR genotype affects neutrophil function and mRNA expression, and consequently, bullous pemphigoid (BP) disease risk. We compared this to findings in pemphigus vulgaris/foliaceus (PV/PF), two Fc-independent AIBDs. Our results indicate that both allele and copy number variation of FcγR genes affect FcγR mRNA expression and reactive oxygen species (ROS) release by granulocytes. Susceptibility of BP was associated with FcγR genotypes that led to a decreased ROS release by neutrophils, indicating an unexpected protective role for these cells. BP and PV/PF differed substantially regarding the FcγR genotype association patterns, pointing towards different disease etiologies. PMID:26032265

  1. Allelic variation, aneuploidy, and nongenetic mechanisms suppress a monogenic trait in yeast.

    Science.gov (United States)

    Sirr, Amy; Cromie, Gareth A; Jeffery, Eric W; Gilbert, Teresa L; Ludlow, Catherine L; Scott, Adrian C; Dudley, Aimée M

    2015-01-01

    Clinically relevant features of monogenic diseases, including severity of symptoms and age of onset, can vary widely in response to environmental differences as well as to the presence of genetic modifiers affecting the trait's penetrance and expressivity. While a better understanding of modifier loci could lead to treatments for Mendelian diseases, the rarity of individuals harboring both a disease-causing allele and a modifying genotype hinders their study in human populations. We examined the genetic architecture of monogenic trait modifiers using a well-characterized yeast model of the human Mendelian disease classic galactosemia. Yeast strains with loss-of-function mutations in the yeast ortholog (GAL7) of the human disease gene (GALT) fail to grow in the presence of even small amounts of galactose due to accumulation of the same toxic intermediates that poison human cells. To isolate and individually genotype large numbers of the very rare (∼0.1%) galactose-tolerant recombinant progeny from a cross between two gal7Δ parents, we developed a new method, called "FACS-QTL." FACS-QTL improves upon the currently used approaches of bulk segregant analysis and extreme QTL mapping by requiring less genome engineering and strain manipulation as well as maintaining individual genotype information. Our results identified multiple distinct solutions by which the monogenic trait could be suppressed, including genetic and nongenetic mechanisms as well as frequent aneuploidy. Taken together, our results imply that the modifiers of monogenic traits are likely to be genetically complex and heterogeneous. PMID:25398792

  2. Microsatellite Variation in Honey Bee (Apis Mellifera L.) Populations: Hierarchical Genetic Structure and Test of the Infinite Allele and Stepwise Mutation Models

    OpenAIRE

    Estoup, A.; Garnery, L.; Solignac, M.; Cornuet, J. M.

    1995-01-01

    Samples from nine populations belonging to three African (intermissa, scutellata and capensis) and four European (mellifera, ligustica, carnica and cecropia) Apis mellifera subspecies were scored for seven microsatellite loci. A large amount of genetic variation (between seven and 30 alleles per locus) was detected. Average heterozygosity and average number of alleles were significantly higher in African than in European subspecies, in agreement with larger effective population sizes in Afric...

  3. Preliminary evidence that allelic variation in the LMX1A gene influences training-related working memory improvement.

    Science.gov (United States)

    Bellander, Martin; Brehmer, Yvonne; Westerberg, Helena; Karlsson, Sari; Fürth, Daniel; Bergman, Olle; Eriksson, Elias; Bäckman, Lars

    2011-06-01

    LMX1A is a transcription factor involved in the development of dopamine (DA)-producing neurons in midbrain. Previous research has shown that allelic variations in three LMX1A single nucleotide polymorphisms (SNPs) were related to risk of Parkinson's disease (PD), suggesting that these SNPs may influence the number of mesencephalic DA neurons. Prompted by the established link between striatal DA functions and working memory (WM) performance, we examined two of these SNPs in relation to the ability to benefit from 4 weeks of WM training. One SNP (rs4657412) was strongly associated with the magnitude of training-related gains in verbal WM. The allele linked to larger gains has previously been suggested to be associated with higher dopaminergic nerve cell density. No differential gains of either SNP were observed for spatial WM, and the genotype groups were also indistinguishable in tests of attention, interference control, episodic memory, perceptual speed, and reasoning for both SNPs. This pattern of data is in agreement with previous findings from our group, suggesting that cognitive effects of DA-related genes may be more easily detected in a training context than for single-assessment performance scores. PMID:21435346

  4. Variation of DAT1 VNTR alleles and genotypes among old ethnic groups in Mesopotamia to the Oxus region.

    Science.gov (United States)

    Banoei, Mohammad Mehdi; Chaleshtori, Morteza Hashemzadeh; Sanati, Mohammad Hossein; Shariati, Parvin; Houshmand, Massoud; Majidizadeh, Tayebeh; Soltani, Niloofar Jahangir; Golalipour, Massoud

    2008-02-01

    Variation of a VNTR in the DAT1 gene in seven ethnic groups of the Middle East was used to infer the history and affinities of these groups. The populations consisted of Assyrian, Jewish, Zoroastrian, Armenian, Turkmen, and Arab peoples of Iran, Iraq, and Kuwait. Three hundred forty subjects from these seven ethnic groups were screened for DAT1. DAT1 VNTR genotyping showed 3, 6, 7, 8, 9, 10, 11, and 12 alleles in the samples. Analysis of these data revealed differentiation and relationship among the populations. In this region, which covers an area of 2-2.5 million km2, the influence of geography and especially of linguistic characteristics has had potentially major effects on differentiation. Religion also has played a major role in imposing restrictions on some ethnic groups, who as a consequence have maintained their community. Overall, these ethnic groups showed greater heterogeneity compared to other populations. PMID:18505046

  5. What Ancestry Can Tell Us About the Genetic Origins of Inter-Ethnic Differences in Asthma Expression.

    Science.gov (United States)

    Hernandez-Pacheco, Natalia; Flores, Carlos; Oh, Sam S; Burchard, Esteban G; Pino-Yanes, Maria

    2016-07-01

    Differences in asthma prevalence have been described across different populations, suggesting that genetic ancestry can play an important role in this disease. In fact, several studies have demonstrated an association between African ancestry with increased asthma susceptibility and severity, higher immunoglobulin E levels, and lower lung function. In contrast, Native American ancestry has been shown to have a protective role for this disease. Genome-wide association studies have allowed the identification of population-specific genetic variants with varying allele frequency among populations. Additionally, the correlation of genetic ancestry at the chromosomal level with asthma and related traits by means of admixture mapping has revealed regions of the genome where ancestry is correlated with the disease. In this review, we discuss the evidence supporting the association of genetic ancestry with asthma susceptibility and asthma-related traits, and highlight the regions of the genome harboring ancestry-specific genetic risk factors. PMID:27393700

  6. Allelic Variation and Genetic Diversity at HMW Glutenin Subunits Loci in Yunnan,Tibetan and Xinjiang Wheat

    Institute of Scientific and Technical Information of China (English)

    WANG Hai-yan; WANG Xiu-e; CHEN Pei-du; LIU Da-jun

    2004-01-01

    Allelic variation and genetic diversity at HMW glutenin subunits loci, Glu-A1, Glu-B1and Glu-D1 were investigated in 64 accessions of three unique wheats of western China using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Two HMW glutenin patterns (i.e., "null, 7+8, 2+12" and "null, 7, 2+12") in 34 Yunnan wheat accessions, 3 HMW glutenin patterns (i.e., "null, 7+8, 2+12"; "null, 6+8, 2+12" and "null, 7+8, 2") in 24 Tibetan accessions and 1 HMW glutenin pattern ("null, 7, 2+12") in 6 Xinjiang wheat accessions were found. The Tibetan accession TB18 was found to be with a rare subunit 2 encoded by Glu-D1. A total of 4 (i.e., Glu-A1c, Glu-B1a, Glu-B1b and Glu-D1a), 5 (i.e., Glu-A1c, Glu-B1d, Glu-B1b, Glu-D1a and Glu-D1) and 3 alleles (i.e.,Glu-A1c, Glu-B1a and Glu-D1a) at Glu-1 locus were identified among Yunnan, Tibetan and Xinjiang unique wheat accessions, respectively. For Yunnan wheat, Tibetan wheat and Xinjiang wheat, the Nei′s mean genetic variation indexes were 0.1574, 0.1366 and 0,respectively, which might indicate the higher genetic diversity at HMW glutenin subunits loci of Yunnan and Tibetan wheat accessions as compared to that of Xinjiang wheat accessions. Among the three genomes of hexaploid wheats of western China, the highest Nei′s genetic variation index was appeared in B genome with the mean value of 0.2674,while the indexes for genomes A and D were 0 and 0.0270, respectively. It might be reasonable to indicate that Glu-B1 showed the highest, Glu-D1 the intermediate and GluA1 always the lowest genetic diversity.

  7. Variations and transmission of QTL alleles for yield and fiber qualities in upland cotton cultivars developed in China.

    Directory of Open Access Journals (Sweden)

    Tianzhen Zhang

    Full Text Available Cotton is the world's leading cash crop, and genetic improvement of fiber yield and quality is the primary objective of cotton breeding program. In this study, we used various approaches to identify QTLs related to fiber yield and quality. Firstly, we constructed a four-way cross (4WC mapping population with four base core cultivars, Stoneville 2B, Foster 6, Deltapine 15 and Zhongmiansuo No.7 (CRI 7, as parents in Chinese cotton breeding history and identified 83 QTLs for 11 agronomic and fiber quality traits. Secondly, association mapping of agronomical and fiber quality traits was based on 121 simple sequence repeat (SSR markers using a general linear model (GLM. For this, 81 Gossypium hirsutum L. accessions including the four core parents and their derived cultivars were grown in seven diverse environments. Using these approaches, we successfully identified 180 QTLs significantly associated with agronomic and fiber quality traits. Among them were 66 QTLs that were identified via linkage disequilibrium (LD and 4WC family-based linkage (FBL mapping and by previously published family-based linkage (FBL mapping in modern Chinese cotton cultivars. Twenty eight and 44 consistent QTLs were identified by 4WC and LD mapping, and by FBL and LD mapping methods, respectively. Furthermore, transmission and variation of QTL-alleles mapped by LD association in the three breeding periods revealed that some could be detected in almost all Chinese cotton cultivars, suggesting their stable transmission and some identified only in the four base cultivars and not in the modern cultivars, suggesting they were missed in conventional breeding. These results will be useful to conduct genomics-assisted breeding effectively using these existing and novel QTL alleles to improve yield and fiber qualities in cotton.

  8. Variations and Transmission of QTL Alleles for Yield and Fiber Qualities in Upland Cotton Cultivars Developed in China

    Science.gov (United States)

    Zhang, Tianzhen; Qian, Neng; Zhu, Xiefei; Chen, Hong; Wang, Sen; Mei, Hongxian; Zhang, Yuanming

    2013-01-01

    Cotton is the world’s leading cash crop, and genetic improvement of fiber yield and quality is the primary objective of cotton breeding program. In this study, we used various approaches to identify QTLs related to fiber yield and quality. Firstly, we constructed a four-way cross (4WC) mapping population with four base core cultivars, Stoneville 2B, Foster 6, Deltapine 15 and Zhongmiansuo No.7 (CRI 7), as parents in Chinese cotton breeding history and identified 83 QTLs for 11 agronomic and fiber quality traits. Secondly, association mapping of agronomical and fiber quality traits was based on 121 simple sequence repeat (SSR) markers using a general linear model (GLM). For this, 81 Gossypium hirsutum L. accessions including the four core parents and their derived cultivars were grown in seven diverse environments. Using these approaches, we successfully identified 180 QTLs significantly associated with agronomic and fiber quality traits. Among them were 66 QTLs that were identified via linkage disequilibrium (LD) and 4WC family-based linkage (FBL) mapping and by previously published family-based linkage (FBL) mapping in modern Chinese cotton cultivars. Twenty eight and 44 consistent QTLs were identified by 4WC and LD mapping, and by FBL and LD mapping methods, respectively. Furthermore, transmission and variation of QTL-alleles mapped by LD association in the three breeding periods revealed that some could be detected in almost all Chinese cotton cultivars, suggesting their stable transmission and some identified only in the four base cultivars and not in the modern cultivars, suggesting they were missed in conventional breeding. These results will be useful to conduct genomics-assisted breeding effectively using these existing and novel QTL alleles to improve yield and fiber qualities in cotton. PMID:23468939

  9. Natural variation in rosette size under salt stress conditions corresponds to developmental differences between Arabidopsis accessions and allelic variation in the LRR-KISS gene

    KAUST Repository

    Julkowska, Magdalena M.

    2016-02-11

    Natural variation among Arabidopsis accessions is an important genetic resource to identify mechanisms underlying plant development and stress tolerance. To evaluate the natural variation in salinity stress tolerance, two large-scale experiments were performed on two populations consisting of 160 Arabidopsis accessions each. Multiple traits, including projected rosette area, and fresh and dry weight were collected as an estimate for salinity tolerance. Our results reveal a correlation between rosette size under salt stress conditions and developmental differences between the accessions grown in control conditions, suggesting that in general larger plants were more salt tolerant. This correlation was less pronounced when plants were grown under severe salt stress conditions. Subsequent genome wide association study (GWAS) revealed associations with novel candidate genes for salinity tolerance such as LRR-KISS (At4g08850), flowering locus KH-domain containing protein and a DUF1639-containing protein. Accessions with high LRR-KISS expression developed larger rosettes under salt stress conditions. Further characterization of allelic variation in candidate genes identified in this study will provide more insight into mechanisms of salt stress tolerance due to enhanced shoot growth.

  10. Determination of cis/trans phase of variations in the MC1R gene with allele-specific PCR and single base extension

    DEFF Research Database (Denmark)

    Mengel-From, Jonas; Børsting, Claus; Sanchez, Juan J;

    2008-01-01

    The MC1R gene encodes a protein with key regulatory functions in the melanin synthesis. A multiplex PCR and a multiplex single base extension protocol were established for genotyping six exonic MC1R variations highly penetrant for red hair (R), four exonic MC1R variations weakly penetrant for red...... hair (r), two frameshift variations highly penetrant for red hair (R) and three variations in the promoter region. We genotyped 600 individuals from Denmark using either CE or MALDI-TOF MS as the detection platform. A total of 62 individuals were genotyped R/R and among the 62 individuals, 57 had red...... hair and five had blond hair colour. Two different R alleles may be located in cis (RR/-) position or trans (R/R) position, and the phenotype associated with RR/- and R/R may be different. Two allele-specific PCRs were established with primers targeting the -G445A variation in the MC1R promoter and the...

  11. What Is Genetic Ancestry Testing?

    Science.gov (United States)

    ... type of test because Y chromosome and mitochondrial DNA test results, which represent only single ancestral lines, do ... relationships. On a larger scale, combined genetic ancestry test results from many people can be used ... promotes the use of DNA testing in genealogy. The American Society of Human ...

  12. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

    OpenAIRE

    Mahajan, Anubha; Go, Min Jin; Zhang, Weihua; Below, Jennifer E.; Gaulton, Kyle J.; Ferreira, Teresa; Horikoshi, Momoko; Johnson, Andrew D.; Ng, Maggie C. Y.; Prokopenko, Inga; Saleheen, Danish; Wang, Xu; Zeggini, Eleftheria; Goncalo R. Abecasis; Adair, Linda S

    2014-01-01

    To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signal...

  13. Dominance variation across six herbicides of the Arabidopsis thaliana csr1-1 and csr1-2 resistance alleles.

    Science.gov (United States)

    Roux, Fabrice; Matéjicek, Annick; Gasquez, Jacques; Reboud, Xavier

    2005-11-01

    Dominance of a resistance trait can be defined as a measure of the relative position of the phenotype of the heterozygote RS compared with the phenotype of the two corresponding homozygotes, SS and RR. This parameter has been shown to have primary importance in the dynamics of pesticide resistance evolution. Literature on insecticide resistance suggests that dominance levels in the presence of insecticide vary greatly from completely recessive to completely dominant. With insecticides, both the chemical applied and the dosages used have been demonstrated to affect the dominance. By contrast, almost all herbicide resistances have been found to be inherited as partially to totally dominant traits. This discrepancy between weeds and insects may partly result from the methodologies applied to measure the dominance, ie a single dose for herbicide versus several doses for insecticide. Using two well-known resistances (csr1-1 and csr1-2) to acetolactate synthase (ALS) inhibitors in Arabidopsis thaliana (L) Heynh (mouse-ear cress), we used several herbicide doses to determine the dominance level to six ALS-inhibiting herbicides. The dominance level in the presence of herbicide varied from completely dominant to completely recessive, depending on the resistance allele and the herbicide tested. The dominance of the csr1-1 and csr1-2 resistance alleles ranged from 0 (completely recessive) to 1.1 (dominant) and from 0 to 0.3 (partially dominant), respectively. The recessivity of some resistance alleles in the presence of herbicide could lead to the development of improved resistance management in order to delay or avoid herbicide resistance evolution, especially in the control of outcrossing weed species. PMID:16007690

  14. Allelic variations in the CYBA gene of NADPH oxidase and risk of kidney complications in patients with type 1 diabetes.

    Science.gov (United States)

    Patente, Thiago A; Mohammedi, Kamel; Bellili-Muñoz, Naïma; Driss, Fathi; Sanchez, Manuel; Fumeron, Frédéric; Roussel, Ronan; Hadjadj, Samy; Corrêa-Giannella, Maria Lúcia; Marre, Michel; Velho, Gilberto

    2015-09-01

    Oxidative stress plays a pivotal role in the pathophysiology of diabetic nephropathy, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system is an important source of reactive oxygen species in hyperglycemic conditions in the kidney. Plasma concentration of advanced oxidation protein products (AOPP), a marker of oxidative stress, is increased in patients with diabetic nephropathy. We investigated associations of variants in the CYBA gene, encoding the regulatory subunit p22(phox) of NADPH oxidase, with diabetic nephropathy and plasma AOPP and myeloperoxidase (MPO) concentrations in type 1 diabetic patients. Seven SNPs in the CYBA region were analyzed in 1357 Caucasian subjects with type 1 diabetes from the SURGENE (n=340), GENEDIAB (n=444), and GENESIS (n=573) cohorts. Duration of follow-up was 10, 9, and 6 years, respectively. Cox proportional hazards and logistic regression analyses were used to estimate hazard ratios (HR) or odds ratios (OR) for incidence and prevalence of diabetic nephropathy. The major G-allele of rs9932581 was associated with the incidence of renal events defined as new cases of microalbuminuria or the progression to a more severe stage of nephropathy during follow-up (HR 1.59, 95% CI 1.17-2.18, P=0.003) in SURGENE. The same allele was associated with established/advanced nephropathy (OR 1.52, 95% CI 1.22-1.92, P=0.0001) and with the incidence of end-stage renal disease (ESRD) (HR 2.01, 95% CI 1.30-3.24, P=0.001) in GENEDIAB/GENESIS pooled studies. The risk allele was also associated with higher plasma AOPP concentration in subsets of SURGENE and GENEDIAB, with higher plasma MPO concentration in a subset of GENEDIAB, and with lower estimated glomerular filtration rate (eGFR) in the three cohorts. In conclusion, a functional variant in the promoter of the CYBA gene was associated with lower eGFR and with prevalence and incidence of diabetic nephropathy and ESRD in type 1 diabetic patients. These results are consistent with

  15. A panel of 74 AISNPs: Improved ancestry inference within Eastern Asia.

    Science.gov (United States)

    Li, Cai-Xia; Pakstis, Andrew J; Jiang, Li; Wei, Yi-Liang; Sun, Qi-Fan; Wu, Hong; Bulbul, Ozlem; Wang, Ping; Kang, Long-Li; Kidd, Judith R; Kidd, Kenneth K

    2016-07-01

    Many ancestry informative SNP (AISNP) panels have been published. Ancestry resolution in them varies from three to eight continental clusters of populations depending on the panel used. However, none of these panels differentiates well among East Asian populations. To meet this need, we have developed a 74 AISNP panel after analyzing a much larger number of SNPs for Fst and allele frequency differences between two geographically close population groups within East Asia. The 74 AISNP panel can now distinguish at least 10 biogeographic groups of populations globally: Sub-Saharan Africa, North Africa, Europe, Southwest Asia, South Asia, North Asia, East Asia, Southeast Asia, Pacific and Americas. Compared with our previous 55-AISNP panel, Southeast Asia and North Asia are two newly assignable clusters. For individual ancestry assignment, the likelihood ratio and ancestry components were analyzed on a different set of 500 test individuals from 11 populations. All individuals from five of the test populations - Yoruba (YRI), European (CEU), Han Chinese in Henan (CHNH), Rondonian Surui (SUR) and Ticuna (TIC) - were assigned to their appropriate geographical regions unambiguously. For the other test populations, most of the individuals were assigned to their self-identified geographical regions with a certain degree of overlap with adjacent populations. These alternative ancestry components for each individual thus help give a clearer picture of the possible group origins of the individual. We have demonstrated that the new AISNP panel can achieve a deeper resolution of global ancestry. PMID:27077960

  16. Interethnic variation of CYP2C19 alleles, 'predicted' phenotypes and 'measured' metabolic phenotypes across world populations.

    Science.gov (United States)

    Fricke-Galindo, I; Céspedes-Garro, C; Rodrigues-Soares, F; Naranjo, M E G; Delgado, Á; de Andrés, F; López-López, M; Peñas-Lledó, E; LLerena, A

    2016-04-01

    The present study evaluates the worldwide frequency distribution of CYP2C19 alleles and CYP2C19 metabolic phenotypes ('predicted' from genotypes and 'measured' with a probe drug) among healthy volunteers from different ethnic groups and geographic regions, as well as the relationship between the 'predicted' and 'measured' CYP2C19 metabolic phenotypes. A total of 52 181 healthy volunteers were studied within 138 selected original research papers. CYP2C19*17 was 42- and 24-fold more frequent in Mediterranean-South Europeans and Middle Easterns than in East Asians (PIslands. Regarding CYP2C19 metabolic phenotype, poor metabolizers (PMs) were more frequent among Asians than in Europeans, contrarily to the phenomenon reported for CYP2D6. A correlation has been found between the frequencies of CYP2C19 poor metabolism 'predicted' from CYP2C19 genotypes (gPMs) and the poor metabolic phenotype 'measured' with a probe drug (mPMs) when subjects are either classified by ethnicity (r=0.94, P<0.001) or geographic region (r=0.99, P=0.002). Nevertheless, further research is needed in African and Asian populations, which are under-represented, and additional CYP2C19 variants and the 'measured' phenotype should be studied. PMID:26503820

  17. Variation in ion leakage parameters of two wheat genotypes with different Rht-B1 alleles in response to drought

    Indian Academy of Sciences (India)

    Konstantina V Kocheva; Svetlana P Landjeva; Georgi I Georgiev

    2014-12-01

    The reaction to soil drying was evaluated in two Triticum aestivum near-isogenic lines carrying different alleles of the height-reducing gene Rht-B1 based on an improved method for assessment of electrolyte leakage. The two lines were previously shown to differ in their physiological responses to induced water deficit stress. Drought was imposed for 6 days on 10-day-old seedlings. Ion efflux from leaves was measured conductometrically in multiple time points during the 24 h incubation period, and the obtained biphasic kinetics was interpreted according to a previously developed theoretical model proposing different leakage rates through the apoplast and the symplast. Most of the model parameters were able to properly differentiate the two closely related genotypes. The mutant Rht-B1c displayed lower and slower electrolyte leakage in comparison with the wild-type Rht-B1a. It was speculated that the Rht genes expressing defective DELLA proteins might be involved in water stress response through modulation of cell wall stiffness, which influences its capacity for ions retention, and also by their contribution to ROS detoxification, thus indirectly stabilizing cellular membranes. The presented analytical approach relating processes of ion and water flow in and out of the cell could be used for characterization of membrane and cell wall properties of different genotypes under normal and stress conditions.

  18. Multi-allelic major effect genes interact with minor effect QTLs to control adaptive color pattern variation in Heliconius erato.

    Directory of Open Access Journals (Sweden)

    Riccardo Papa

    Full Text Available Recent studies indicate that relatively few genomic regions are repeatedly involved in the evolution of Heliconius butterfly wing patterns. Although this work demonstrates a number of cases where homologous loci underlie both convergent and divergent wing pattern change among different Heliconius species, it is still unclear exactly how many loci underlie pattern variation across the genus. To address this question for Heliconius erato, we created fifteen independent crosses utilizing the four most distinct color pattern races and analyzed color pattern segregation across a total of 1271 F2 and backcross offspring. Additionally, we used the most variable brood, an F2 cross between H. himera and the east Ecuadorian H. erato notabilis, to perform a quantitative genetic analysis of color pattern variation and produce a detailed map of the loci likely involved in the H. erato color pattern radiation. Using AFLP and gene based markers, we show that fewer major genes than previously envisioned control the color pattern variation in H. erato. We describe for the first time the genetic architecture of H. erato wing color pattern by assessing quantitative variation in addition to traditional linkage mapping. In particular, our data suggest three genomic intervals modulate the bulk of the observed variation in color. Furthermore, we also identify several modifier loci of moderate effect size that contribute to the quantitative wing pattern variation. Our results are consistent with the two-step model for the evolution of mimetic wing patterns in Heliconius and support a growing body of empirical data demonstrating the importance of major effect loci in adaptive change.

  19. Allelic variation of the inducible costimulator (ICOS) gene: detection of polymorphisms, analysis of the promoter region, and extended haplotype estimation

    DEFF Research Database (Denmark)

    Andersen, A.D.H.; Lange, Marianne; Lillevang, S.T.

    2003-01-01

    which two resided in putative NF-kB and Sp1 sites In accordance with. previous studies we detected no variations in the coding regions except for a rare polymorphism that was found in one donor in the last codon of exon 5, which lead to a heterozygous genotype, but no amino acid change. This suggests...

  20. Allelic variation, alternative splicing and expression analysis of Psy1 gene in Hordeum chilense Roem. et Schult.

    Directory of Open Access Journals (Sweden)

    Cristina Rodríguez-Suárez

    Full Text Available BACKGROUND: The wild barley Hordeum chilense Roem. et Schult. is a valuable source of genes for increasing carotenoid content in wheat. Tritordeums, the amphiploids derived from durum or common wheat and H. chilense, systematically show higher values of yellow pigment colour and carotenoid content than durum wheat. Phytoene synthase 1 gene (Psy1 is considered a key step limiting the carotenoid biosynthesis, and the correlation of Psy1 transcripts accumulation and endosperm carotenoid content has been demonstrated in the main grass species. METHODOLOGY/PRINCIPAL FINDINGS: We analyze the variability of Psy1 alleles in three lines of H. chilense (H1, H7 and H16 representing the three ecotypes described in this species. Moreover, we analyze Psy1 expression in leaves and in two seed developing stages of H1 and H7, showing mRNA accumulation patterns similar to those of wheat. Finally, we identify thirty-six different transcripts forms originated by alternative splicing of the 5' UTR and/or exons 1 to 5 of Psy1 gene. Transcripts function is tested in a heterologous complementation assay, revealing that from the sixteen different predicted proteins only four types (those of 432, 370, 364 and 271 amino acids, are functional in the bacterial system. CONCLUSIONS/SIGNIFICANCE: The large number of transcripts originated by alternative splicing of Psy1, and the coexistence of functional and non functional forms, suggest a fine regulation of PSY activity in H. chilense. This work is the first analysis of H. chilense Psy1 gene and the results reported here are the bases for its potential use in carotenoid enhancement in durum wheat.

  1. Diurnal Expression Pattern, Allelic Variation, and Association Analysis Reveal Functional Features of the E1 Gene in Control of Photoperiodic Flowering in Soybean

    Science.gov (United States)

    Wu, Hongyan; Zhang, Yupeng; Zhang, Xingzheng; Yang, Jiayin; Wang, Yaying; Yang, Guang; Qiu, Hongmei; Cui, Tingting; Xia, Zhengjun

    2015-01-01

    Although four maturity genes, E1 to E4, in soybean have been successfully cloned, their functional mechanisms and the regulatory network of photoperiodic flowering remain to be elucidated. In this study, we investigated how the diurnal expression pattern of the E1 gene is related to photoperiodic length; and to what extent allelic variation in the B3-like domain of the E1 gene is associated with flowering time phenotype. The bimodal expression of the E1 gene peaked first at around 2 hours after dawn in long-day condition. The basal expression level of E1 was enhanced by the long light phase, and decreased by duration of dark. We identified a 5bp (3 SNP and 2-bp deletion) mutation, referred to an e1-b3a, which occurs in the middle of B3 domain of the E1 gene in the early flowering cultivar Yanhuang 3. Subcellular localization analysis showed that the putative truncated e1-b3a protein was predominately distributed in nuclei, indicating the distribution pattern of e1-b3a was similar to that of E1, but not to that of e1-as. Furthermore, genetic analysis demonstrated allelic variations at the E1 locus significantly underlay flowering time in three F2 populations. Taken together, we can conclude the legume specific E1 gene confers some special features in photoperiodic control of flowering in soybean. Further characterization of the E1 gene will extend our understanding of the soybean flowering pathway in soybean. PMID:26275311

  2. Whole Genome Re-Sequencing and Characterization of Powdery Mildew Disease-Associated Allelic Variation in Melon.

    Science.gov (United States)

    Natarajan, Sathishkumar; Kim, Hoy-Taek; Thamilarasan, Senthil Kumar; Veerappan, Karpagam; Park, Jong-In; Nou, Ill-Sup

    2016-01-01

    Powdery mildew is one of the most common fungal diseases in the world. This disease frequently affects melon (Cucumis melo L.) and other Cucurbitaceous family crops in both open field and greenhouse cultivation. One of the goals of genomics is to identify the polymorphic loci responsible for variation in phenotypic traits. In this study, powdery mildew disease assessment scores were calculated for four melon accessions, 'SCNU1154', 'Edisto47', 'MR-1', and 'PMR5'. To investigate the genetic variation of these accessions, whole genome re-sequencing using the Illumina HiSeq 2000 platform was performed. A total of 754,759,704 quality-filtered reads were generated, with an average of 82.64% coverage relative to the reference genome. Comparisons of the sequences for the melon accessions revealed around 7.4 million single nucleotide polymorphisms (SNPs), 1.9 million InDels, and 182,398 putative structural variations (SVs). Functional enrichment analysis of detected variations classified them into biological process, cellular component and molecular function categories. Further, a disease-associated QTL map was constructed for 390 SNPs and 45 InDels identified as related to defense-response genes. Among them 112 SNPs and 12 InDels were observed in powdery mildew responsive chromosomes. Accordingly, this whole genome re-sequencing study identified SNPs and InDels associated with defense genes that will serve as candidate polymorphisms in the search for sources of resistance against powdery mildew disease and could accelerate marker-assisted breeding in melon. PMID:27311063

  3. Whole Genome Re-Sequencing and Characterization of Powdery Mildew Disease-Associated Allelic Variation in Melon.

    Directory of Open Access Journals (Sweden)

    Sathishkumar Natarajan

    Full Text Available Powdery mildew is one of the most common fungal diseases in the world. This disease frequently affects melon (Cucumis melo L. and other Cucurbitaceous family crops in both open field and greenhouse cultivation. One of the goals of genomics is to identify the polymorphic loci responsible for variation in phenotypic traits. In this study, powdery mildew disease assessment scores were calculated for four melon accessions, 'SCNU1154', 'Edisto47', 'MR-1', and 'PMR5'. To investigate the genetic variation of these accessions, whole genome re-sequencing using the Illumina HiSeq 2000 platform was performed. A total of 754,759,704 quality-filtered reads were generated, with an average of 82.64% coverage relative to the reference genome. Comparisons of the sequences for the melon accessions revealed around 7.4 million single nucleotide polymorphisms (SNPs, 1.9 million InDels, and 182,398 putative structural variations (SVs. Functional enrichment analysis of detected variations classified them into biological process, cellular component and molecular function categories. Further, a disease-associated QTL map was constructed for 390 SNPs and 45 InDels identified as related to defense-response genes. Among them 112 SNPs and 12 InDels were observed in powdery mildew responsive chromosomes. Accordingly, this whole genome re-sequencing study identified SNPs and InDels associated with defense genes that will serve as candidate polymorphisms in the search for sources of resistance against powdery mildew disease and could accelerate marker-assisted breeding in melon.

  4. Whole Genome Re-Sequencing and Characterization of Powdery Mildew Disease-Associated Allelic Variation in Melon

    Science.gov (United States)

    Natarajan, Sathishkumar; Kim, Hoy-Taek; Thamilarasan, Senthil Kumar; Veerappan, Karpagam; Park, Jong-In; Nou, Ill-Sup

    2016-01-01

    Powdery mildew is one of the most common fungal diseases in the world. This disease frequently affects melon (Cucumis melo L.) and other Cucurbitaceous family crops in both open field and greenhouse cultivation. One of the goals of genomics is to identify the polymorphic loci responsible for variation in phenotypic traits. In this study, powdery mildew disease assessment scores were calculated for four melon accessions, ‘SCNU1154’, ‘Edisto47’, ‘MR-1’, and ‘PMR5’. To investigate the genetic variation of these accessions, whole genome re-sequencing using the Illumina HiSeq 2000 platform was performed. A total of 754,759,704 quality-filtered reads were generated, with an average of 82.64% coverage relative to the reference genome. Comparisons of the sequences for the melon accessions revealed around 7.4 million single nucleotide polymorphisms (SNPs), 1.9 million InDels, and 182,398 putative structural variations (SVs). Functional enrichment analysis of detected variations classified them into biological process, cellular component and molecular function categories. Further, a disease-associated QTL map was constructed for 390 SNPs and 45 InDels identified as related to defense-response genes. Among them 112 SNPs and 12 InDels were observed in powdery mildew responsive chromosomes. Accordingly, this whole genome re-sequencing study identified SNPs and InDels associated with defense genes that will serve as candidate polymorphisms in the search for sources of resistance against powdery mildew disease and could accelerate marker-assisted breeding in melon. PMID:27311063

  5. Effects of cis and trans genetic ancestry on gene expression in African Americans.

    Directory of Open Access Journals (Sweden)

    Alkes L Price

    2008-12-01

    Full Text Available Variation in gene expression is a fundamental aspect of human phenotypic variation. Several recent studies have analyzed gene expression levels in populations of different continental ancestry and reported population differences at a large number of genes. However, these differences could largely be due to non-genetic (e.g., environmental effects. Here, we analyze gene expression levels in African American cell lines, which differ from previously analyzed cell lines in that individuals from this population inherit variable proportions of two continental ancestries. We first relate gene expression levels in individual African Americans to their genome-wide proportion of European ancestry. The results provide strong evidence of a genetic contribution to expression differences between European and African populations, validating previous findings. Second, we infer local ancestry (0, 1, or 2 European chromosomes at each location in the genome and investigate the effects of ancestry proximal to the expressed gene (cis versus ancestry elsewhere in the genome (trans. Both effects are highly significant, and we estimate that 12+/-3% of all heritable variation in human gene expression is due to cis variants.

  6. Multiple post-domestication origins of kabuli chickpea through allelic variation in a diversification-associated transcription factor.

    Science.gov (United States)

    Varma Penmetsa, R; Carrasquilla-Garcia, Noelia; Bergmann, Emily M; Vance, Lisa; Castro, Brenna; Kassa, Mulualem T; Sarma, Birinchi K; Datta, Subhojit; Farmer, Andrew D; Baek, Jong-Min; Coyne, Clarice J; Varshney, Rajeev K; von Wettberg, Eric J B; Cook, Douglas R

    2016-09-01

    Chickpea (Cicer arietinum) is among the founder crops domesticated in the Fertile Crescent. One of two major forms of chickpea, the so-called kabuli type, has white flowers and light-colored seed coats, properties not known to exist in the wild progenitor. The origin of the kabuli form has been enigmatic. We genotyped a collection of wild and cultivated chickpea genotypes with 538 single nucleotide polymorphisms (SNPs) and examined patterns of molecular diversity relative to geographical sources and market types. In addition, we examined sequence and expression variation in candidate anthocyanin biosynthetic pathway genes. A reduction in genetic diversity and extensive genetic admixture distinguish cultivated chickpea from its wild progenitor species. Among germplasm, the kabuli form is polyphyletic. We identified a basic helix-loop-helix (bHLH) transcription factor at chickpea's B locus that conditions flower and seed colors, orthologous to Mendel's A gene of garden pea, whose loss of function is associated invariantly with the kabuli type of chickpea. From the polyphyletic distribution of the kabuli form in germplasm, an absence of nested variation within the bHLH gene and invariant association of loss of function of bHLH among the kabuli type, we conclude that the kabuli form arose multiple times during the phase of phenotypic diversification after initial domestication of cultivated chickpea. PMID:27193699

  7. HLA-DRB1*14 is a protective allele for multiple sclerosis in an admixed Colombian population

    OpenAIRE

    Toro, Jaime; Cuellar-Giraldo, David; Díaz-Cruz, Camilo; Burbano, Lisseth-Estefania; Guío, Claudia-Marcela; Reyes, Saúl; Cortes, Fabián; Cárdenas-Robledo, Simón; Diana M. Narváez; Cárdenas, Wilmer; Porras, Alexandra; Lattig, María-Claudia; Groot de Restrepo, Helena

    2015-01-01

    Objective: The aim of this study was to determine ancestry informative markers, mitochondrial DNA haplogroups, and the association between HLA-DRB1 alleles and multiple sclerosis (MS) in a group of patients from Bogotá, Colombia. Methods: In this case-control study, genomic DNA was isolated and purified from blood samples. HLA-DRB1 allele genotyping was done using PCR. Mitochondrial hypervariable region 1 was amplified and haplogroups were determined using HaploGrep software. Genomic ancestry...

  8. Neither self-reported ethnicity nor declared family origin are reliable indicators of genomic ancestry.

    Science.gov (United States)

    Ramos, Bruna Ribeiro de Andrade; D'Elia, Maria Paula Barbieri; Amador, Marcos Antônio Trindade; Santos, Ney Pereira Carneiro; Santos, Sidney Emanuel Batista; da Cruz Castelli, Erick; Witkin, Steven S; Miot, Hélio Amante; Miot, Luciane Donida Bartoli; da Silva, Márcia Guimarães

    2016-06-01

    Ancestry information can be useful in investigations of diseases with a genetic or infectious background. As the Brazilian population is highly admixed physical traits tend to be poor indicators of ancestry. The assessment of ancestry by ancestry informative markers (AIMs) can exclude the subjectivity of self-declared ethnicity and reported family origin. We aimed to evaluate the reliability of self-reported ethnicity or reported family origin as indicators of genomic ancestry in a female population from the Southeast of Brazil. Two cohorts were included: 404 women asked to self-report their ethnicity (Pop1) and 234 women asked to report their family's origin (Pop2). Identification of AIMs was performed using a panel of 61 markers and results were plotted against parental populations-Amerindian, Western European and Sub-Saharan African-using Structure v2.3.4. In Pop1 57.4 % of women self-reported as white, 34.6 % as brown and 8.0 % as black. Median global European, Amerindian and African contributions were 66.8, 12.6 and 16.6 %. In Pop2, 66.4 % of women declared European origin, 23.9 % African origin and 26.9 % Amerindian. Median global European, Amerindian and African contributions were 80.8, 7.3 and 7.6 %, respectively. Only 31.0 and 21.0 % of the global variation in African and European contributions, respectively, could be explained by self-reported ethnicity and reported family origin only accounted for 20.0 and 5.0 % of the variations observed in African and European ancestries, respectively. Amerindian ancestry did not influence self-reported ethnicity or declared family origin. Neither self-reported ethnicity nor declared family origin are reliable indicators of genomic ancestry in these Brazilian populations. PMID:26984822

  9. Ancestry informative markers and complete blood count parameters in Brazilian blood donors

    OpenAIRE

    Gabriela E. S. Felix; Kiyoko Abe-Sandes; Taísa M. Bonfim; Maria T. Bendicho; Patrícia Cisneiros; Rosalina Guedes; Cláudio J. F. Brandão; Alex J. L. Torres; Carlos Brites; Eduardo M. Netto; Roberto Meyer; Songeli M. Freire

    2010-01-01

    A complete blood count is very useful in clinical diagnoses when reference ranges are well established for the population. Complete blood counts and allele frequencies of Ancestry Informative Markers (AIMs) were analyzed in Brazilians with the aim of characterizing the hematological values of an admixed population. Positive associations were observed between gender and neutrophils, monocytes, eosinophils, erythrocytes, hemoglobin, hematocrit, MCV, MCHC and platelet counts. No significant diff...

  10. Clines of nuclear DNA markers suggest a largely Neolithic ancestry of the European gene pool

    OpenAIRE

    Chikhi, Lounès; Destro-Bisol, Giovanni; Bertorelle, Giorgio; Pascali, Vincenzo; Barbujani, Guido

    1998-01-01

    Comparisons between archaeological findings and allele frequencies at protein loci suggest that most genes of current Europeans descend from populations that have been expanding in Europe in the last 10,000 years, in the Neolithic period. Recent mitochondrial data have been interpreted as indicating a much older, Paleolithic ancestry. In a spatial autocorrelation study at seven hypervariable loci in Europe (four microsatellites, two larger, tandem-repeat loci, and a sequence polymorphism) bro...

  11. Gm and Km alleles in two Spanish Pyrenean populations (Andorra and Pallars Sobirà): a review of Gm variation in the Western Mediterranean basin.

    Science.gov (United States)

    Giraldo, M P; Esteban, E; Aluja, M P; Nogués, R M; Backés-Duró, C; Dugoujon, J M; Moral, P

    2001-11-01

    Two Spanish eastern Pyrenean populations, Andorra and Pallars Sobirà, have been tested for G1m(1,2,3,17), G2m(23), G3m(5,6,10,11,13,14,15,16,21,24,28) and Km(1) immunoglobulin allotypes. Km allele and Gm haplotype frequencies in both samples fit well into the Western Mediterranean and, more strictly, Pyrenean ranges with some peculiarities: Andorra showed an elevated frequency (14.7%) of the typical Asian and European Gm21,28;1,2,17;. haplotype, while Pallars Sobirà was characterized by high values (3.7%) of Gm5*;1,17;., a typical sub-Saharan Gm haplotype. Gm diversity assessed through genetic distance and variance analyses revealed a significant geographic partition (4.3%) of Mediterraneans among south, north-east, and north-west groups. It is interesting to note the relatively low genetic variance (2.1%) found between south and north-western Mediterraneans that could reflect ancient population relationships. More locally, genetic boundaries and diversity analyses failed to indicate any geographic pattern and/or genetic differentiation related with the political border in the Pyrenees. The present pattern of variation in this area is probably the result of genetic isolation processes, in addition to some specific demographic phenomena, in the Pyrenean valleys. PMID:11851984

  12. Allelic variation of the Tas1r3 taste receptor gene selectively affects taste responses to sweeteners: evidence from 129.B6-Tas1r3 congenic mice.

    Science.gov (United States)

    Inoue, Masashi; Glendinning, John I; Theodorides, Maria L; Harkness, Sarah; Li, Xia; Bosak, Natalia; Beauchamp, Gary K; Bachmanov, Alexander A

    2007-12-19

    The Tas1r3 gene encodes the T1R3 receptor protein, which is involved in sweet taste transduction. To characterize ligand specificity of the T1R3 receptor and the genetic architecture of sweet taste responsiveness, we analyzed taste responses of 129.B6-Tas1r3 congenic mice to a variety of chemically diverse sweeteners and glucose polymers with three different measures: consumption in 48-h two-bottle preference tests, initial licking responses, and responses of the chorda tympani nerve. The results were generally consistent across the three measures. Allelic variation of the Tas1r3 gene influenced taste responsiveness to nonnutritive sweeteners (saccharin, acesulfame-K, sucralose, SC-45647), sugars (sucrose, maltose, glucose, fructose), sugar alcohols (erythritol, sorbitol), and some amino acids (D-tryptophan, D-phenylalanine, L-proline). Tas1r3 genotype did not affect taste responses to several sweet-tasting amino acids (L-glutamine, L-threonine, L-alanine, glycine), glucose polymers (Polycose, maltooligosaccharide), and nonsweet NaCl, HCl, quinine, monosodium glutamate, and inosine 5'-monophosphate. Thus Tas1r3 polymorphisms affect taste responses to many nutritive and nonnutritive sweeteners (all of which must interact with a taste receptor involving T1R3), but not to all carbohydrates and amino acids. In addition, we found that the genetic architecture of sweet taste responsiveness changes depending on the measure of taste response and the intensity of the sweet taste stimulus. Variation in the T1R3 receptor influenced peripheral taste responsiveness over a wide range of sweetener concentrations, but behavioral responses to higher concentrations of some sweeteners increasingly depended on mechanisms that could override input from the peripheral taste system. PMID:17911381

  13. Blood group genotyping in a population of highly diverse ancestry.

    Science.gov (United States)

    Pellegrino, J; Castilho, L; Rios, M; De Souza, C A

    2001-01-01

    Accurate phenotyping of red blood cells (RBCs) can be difficult in transfusion-dependent patients such as those with thalassemia and sickle cell anemia because of the presence of previously transfused RBCs in the patient's circulation. Recently, the molecular basis associated with the expression of many blood group antigens was established. This allowed the development of a plethora of polymerase chain reaction (PCR)-based tests for identification of the blood group antigens by testing DNA. The new technologies complement phenotyping and overcome some of the limitations of hemagglutination assays. These molecular assays were developed on the basis of DNA sequences of individuals of Caucasian ancestry. The present study addresses the concern that these genotyping assays may not be applicable to populations of highly diverse ancestry because of variability in intronic regions or because of unrecognized alleles. We determined both phenotype and genotype for RH D, K 1/K 2, JK A/JK B, FY A/ FY B-GATA in 250 normal blood donors using PCR. Phenotype and genotype results agreed in 100% of the cases, indicating that molecular genotyping protocols can be effectively applied to populations with a highly diverse genetic background. However, genotyping for Duffy antigens provided information that could not be obtained by phenotyping. Essentially, 30.5 % of the donors with the FY B gene typed as Fy(b-) because of mutations in the GATA box. This information is very useful for the management of transfusion dependent patients. PMID:11170227

  14. Variation in Effects of Non-Hodgkin Lymphoma Risk Factors According to the Human Leukocyte Antigen (HLA)-DRB1*01:01 Allele and Ancestral Haplotype 8.1

    OpenAIRE

    Wang, Sophia S.; Lu, Yani; Rothman, Nathaniel; Amr M Abdou; Cerhan, James R.; De Roos, Anneclaire; Davis, Scott; Richard K Severson; Cozen, Wendy; Chanock, Stephen J.; Bernstein, Leslie; Morton, Lindsay M.; Hartge, Patricia

    2011-01-01

    Genetic variations in human leukocyte antigens (HLA) are critical in host responses to infections, transplantation, and immunological diseases. We previously identified associations with non-Hodgkin lymphoma (NHL) and the HLA-DRB1*01:01 allele and extended ancestral haplotype (AH) 8.1 (HLA-A*01-B*08-DR*03-TNF-308A). To illuminate how HLA alleles and haplotypes may influence NHL etiology, we examined potential interactions between HLA-DRB1*01:01 and AH 8.1, and a wide range of NHL risk factors...

  15. Genetic ancestry analysis in non-alcoholic fatty liver diseasepatients from Brazil and Portuga

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    AIM To study the association between genetic ancestry,non-alcoholic fatty liver disease (NAFLD) metaboliccharacteristics in two cohorts of patients, from Brazil andPortugal.METHODS: We included 131 subjects from Brazil [(n =45 with simple steatosis (S. Steatosis) and n = 86 withnonalcoholic steatohepatitis (NASH)] and 90 patientsfrom Portugal (n = 66, S. Steatosis; n = 24, NASH).All patients had biopsy-proven NAFLD. In histologicevaluation NAFLD activity score was used to assesshistology and more than 5 points defined NASH in thisstudy. Patients were divided into two groups accordingto histology diagnosis: simple steatosis or non-alcoholicstatohepatitis. Genetic ancestry was assessed usingreal-time polymerase chain reaction. Seven ancestryinformative markers (AT3-I/D, LPL, Sb19.3, APO, FYNull,PV92, and CKMM) with the greatest ethnicgeographicaldifferential frequencies (≥ 48%) wereused to define genetic ancestry. Data were analyzedusing R PROJECTS software. Ancestry allele frequenciesbetween groups were analyzed by GENEPOP online and the estimation of genetic ancestry contribution wasevaluated by ADMIX-95 software. The 5% alpha-errorwas considered as significant (P 〈 0.05).RESULTS: In the Brazilian sample, NASH was significantlymore frequent among the elderly patients withdiabetes (NASH 56 ± 1.1 years old vs S. Steatosis 51± 1.5 years old, P = 3.7 x 10-9), dyslipidemia (NASH63% vs S. Steatosis 37%, P = 0.009), higher fastingglucose levels (NASH 124 ± 5.2 vs S. Steatosis 106 ±5.3, P = 0.001) and Homeostatic Model of Assessmentindex 〉 2.5 [NASH 5.3 (70.8%) vs S. Steatosis 4.6(29.2%) P = 0.04]. In the Portuguese study population,dyslipidemia was present in all patients with NASH(P = 0.03) and hypertension was present in a largerpercentage of subjects in the S. Steatosis group (P =0.003, respectively). The genetic ancestry contributionamong Brazilian and Portuguese individuals with NASHwas similar

  16. Genetic variation at selected SNPs in the leptin gene and association of alleles with markers of kidney disease in a Xhosa population of South Africa.

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    Ikechi G Okpechi

    Full Text Available BACKGROUND: Chronic kidney disease (CKD is a significant public health problem that leads to end-stage renal disease (ESRD with as many as 2 million people predicted to need therapy worldwide by 2010. Obesity is a risk factor for CKD and leptin, the obesity hormone, correlates with body fat mass and markers of renal function. A number of clinical and experimental studies have suggested a link between serum leptin and kidney disease. We hypothesised that variants in the leptin gene (LEP may be associated with markers of CKD in indigenous black Africans. METHODOLOGY/PRINCIPAL FINDINGS: Black South Africans of Xhosa (distinct cultural Bantu-speaking population descent were recruited for the study and four common polymorphisms of the LEP (rs7799039, rs791620, rs2167270 and STS-U43653 [ENSSNP5824596] were analysed for genotype and haplotype association with urine albumin-to-creatinine ratio (UACR, estimated glomerular filtration rate (eGFR, Serum creatinine (Scr and serum leptin level. In one of the four single nucleotide polymorphisms (SNPs we examined, an association with the renal phenotypes was observed. Hypertensive subjects with the T allele (CT genotype of the ENSSNP5824596 SNP had a significantly higher eGFR (p = 0.0141, and significantly lower Scr (p = 0.0137. This was confirmed by haplotype analysis. Also, the haplotype GAAC had a modest effect on urine albumin-to-creatinine ratio in normotensive subjects (p = 0.0482. CONCLUSIONS/SIGNIFICANCE: These results suggest that genetic variations of the LEP may be associated with phenotypes that are markers of CKD in black Africans.

  17. European Ancestry Predominates in Neuromyelitis Optica and Multiple Sclerosis Patients from Brazil

    Science.gov (United States)

    Santos, Antônio Carlos; Lana-Peixoto, Marco Aurélio; Rocha, Cristiane Franklin; Brito, Maria Lucia; de Oliveira, Enedina Maria Lobato; Bichuetti, Denis Bernardi; Gabbai, Alberto Alan; Diniz, Denise Sisterolli; Kaimen-Maciel, Damacio Ramon; Comini-Frota, Elizabeth Regina; Vieira Wiezel, Claudia E.; Muniz, Yara Costa Netto; da Silva Costa, Roberta Martins; Mendes-Junior, Celso Teixeira; Donadi, Eduardo Antônio; Barreira, Amilton Antunes; Simões, Aguinaldo Luiz

    2013-01-01

    Background Neuromyelitis optica (NMO) is considered relatively more common in non-Whites, whereas multiple sclerosis (MS) presents a high prevalence rate, particularly in Whites from Western countries populations. However, no study has used ancestry informative markers (AIMs) to estimate the genetic ancestry contribution to NMO patients. Methods Twelve AIMs were selected based on the large allele frequency differences among European, African, and Amerindian populations, in order to investigate the genetic contribution of each ancestral group in 236 patients with MS and NMO, diagnosed using the McDonald and Wingerchuck criteria, respectively. All 128 MS patients were recruited at the Faculty of Medicine of Ribeirão Preto (MS-RP), Southeastern Brazil, as well as 108 healthy bone marrow donors considered as healthy controls. A total of 108 NMO patients were recruited from five Neurology centers from different Brazilian regions, including Ribeirão Preto (NMO-RP). Principal Findings European ancestry contribution was higher in MS-RP than in NMO-RP (78.5% vs. 68.7%) patients. In contrast, African ancestry estimates were higher in NMO-RP than in MS-RP (20.5% vs. 12.5%) patients. Moreover, principal component analyses showed that groups of NMO patients from different Brazilian regions were clustered close to the European ancestral population. Conclusions Our findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil. PMID:23527051

  18. European ancestry predominates in neuromyelitis optica and multiple sclerosis patients from Brazil.

    Directory of Open Access Journals (Sweden)

    Doralina Guimarães Brum

    Full Text Available BACKGROUND: Neuromyelitis optica (NMO is considered relatively more common in non-Whites, whereas multiple sclerosis (MS presents a high prevalence rate, particularly in Whites from Western countries populations. However, no study has used ancestry informative markers (AIMs to estimate the genetic ancestry contribution to NMO patients. METHODS: Twelve AIMs were selected based on the large allele frequency differences among European, African, and Amerindian populations, in order to investigate the genetic contribution of each ancestral group in 236 patients with MS and NMO, diagnosed using the McDonald and Wingerchuck criteria, respectively. All 128 MS patients were recruited at the Faculty of Medicine of Ribeirão Preto (MS-RP, Southeastern Brazil, as well as 108 healthy bone marrow donors considered as healthy controls. A total of 108 NMO patients were recruited from five Neurology centers from different Brazilian regions, including Ribeirão Preto (NMO-RP. PRINCIPAL FINDINGS: European ancestry contribution was higher in MS-RP than in NMO-RP (78.5% vs. 68.7% patients. In contrast, African ancestry estimates were higher in NMO-RP than in MS-RP (20.5% vs. 12.5% patients. Moreover, principal component analyses showed that groups of NMO patients from different Brazilian regions were clustered close to the European ancestral population. CONCLUSIONS: Our findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil.

  19. Genomics assisted ancestry deconvolution in grape.

    Directory of Open Access Journals (Sweden)

    Jason Sawler

    Full Text Available The genus Vitis (the grapevine is a group of highly diverse, diploid woody perennial vines consisting of approximately 60 species from across the northern hemisphere. It is the world's most valuable horticultural crop with ~8 million hectares planted, most of which is processed into wine. To gain insights into the use of wild Vitis species during the past century of interspecific grape breeding and to provide a foundation for marker-assisted breeding programmes, we present a principal components analysis (PCA based ancestry estimation method to calculate admixture proportions of hybrid grapes in the United States Department of Agriculture grape germplasm collection using genome-wide polymorphism data. We find that grape breeders have backcrossed to both the domesticated V. vinifera and wild Vitis species and that reasonably accurate genome-wide ancestry estimation can be performed on interspecific Vitis hybrids using a panel of fewer than 50 ancestry informative markers (AIMs. We compare measures of ancestry informativeness used in selecting SNP panels for two-way admixture estimation, and verify the accuracy of our method on simulated populations of admixed offspring. Our method of ancestry deconvolution provides a first step towards selection at the seed or seedling stage for desirable admixture profiles, which will facilitate marker-assisted breeding that aims to introgress traits from wild Vitis species while retaining the desirable characteristics of elite V. vinifera cultivars.

  20. Co-evolution of the MHC class I and KIR gene families in rhesus macaques: ancestry and plasticity.

    Science.gov (United States)

    de Groot, Natasja G; Blokhuis, Jeroen H; Otting, Nel; Doxiadis, Gaby G M; Bontrop, Ronald E

    2015-09-01

    Researchers dealing with the human leukocyte antigen (HLA) class I and killer immunoglobulin receptor (KIR) multi-gene families in humans are often wary of the complex and seemingly different situation that is encountered regarding these gene families in Old World monkeys. For the sake of comparison, the well-defined and thoroughly studied situation in humans has been taken as a reference. In macaques, both the major histocompatibility complex class I and KIR gene families are plastic entities that have experienced various rounds of expansion, contraction, and subsequent recombination processes. As a consequence, haplotypes in macaques display substantial diversity with regard to gene copy number variation. Additionally, for both multi-gene families, differential levels of polymorphism (allelic variation), and expression are observed as well. A comparative genetic approach has allowed us to answer questions related to ancestry, to shed light on unique adaptations of the species' immune system, and to provide insights into the genetic events and selective pressures that have shaped the range of these gene families. PMID:26284481

  1. Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals.

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    Andrés Ruiz-Linares

    2014-09-01

    Full Text Available The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú. These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.

  2. Admixture in Latin America: Geographic Structure, Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals

    Science.gov (United States)

    Ruiz-Linares, Andrés; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Quinto-Sanchez, Mirsha; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Everardo, Paola; de Avila, Francisco; Gómez-Valdés, Jorge; León-Mimila, Paola; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C.; Burley, Mari-Wyn; Konca, Esra; de Oliveira, Marcelo Zagonel; Veronez, Mauricio Roberto; Rubio-Codina, Marta; Attanasio, Orazio; Gibbon, Sahra; Ray, Nicolas; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Schuler-Faccini, Lavinia; Salzano, Francisco M.; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Balding, David; Gonzalez-José, Rolando

    2014-01-01

    The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry. PMID:25254375

  3. Paraoxonase1 Genetic Polymorphisms in a Mixed Ancestry African Population

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    M. Macharia

    2014-01-01

    Full Text Available Paraoxonase 1 (PON1 activity is markedly influenced by coding polymorphisms, Q/R at position 192 and M/L at position 55 of the PON1 gene. We investigated the frequencies of these polymorphisms and their effects on PON1 and antioxidant activities in 844 South African mixed ancestry individuals. Genotyping was done using allele-specific TaqMan technology, PON1 activities were measured using paraoxon and phenylacetate, oxidative status was determined by measuring the antioxidant activities of ferric reducing antioxidant power and trolox equivalent antioxidant capacity, and lipid peroxidation markers included malondialdehyde and oxidized LDL. The frequencies of Q192R and L55M were 47.6% and 28.8%, respectively, and the most common corresponding alleles were 192R (60.4% and 55M (82.6%. The Q192 was significantly associated with 5.8 units’ increase in PON1 concentration and 15.4 units’ decrease in PONase activity after adjustment for age, sex, BMI, and diabetes, with suggestion of differential effects by diabetes status. The PON1 L55 variant was associated with none of the measured indices. In conclusion, we have shown that the Q192R polymorphism is a determinant of both PON1 concentration and activity and this association appeared to be enhanced in subjects with diabetes.

  4. Quantification of Maxillary Dental Arcade Curvature and the Estimation of Biological Ancestry in Forensic Anthropology.

    Science.gov (United States)

    Clark, Melissa A; Guatelli-Steinberg, Debbie; Hubbe, Mark; Stout, Sam

    2016-01-01

    Previous studies suggest that palate shape is a useful indicator of biological ancestry in human remains. This study evaluates interobserver error in ancestry estimation using palate shape and explores palate shape variation in Gullah (descendants of West Africans) and Seminole (Indigenous American) population samples using geometric morphometric analysis. Ten participants were asked to ascribe biological ancestry and shape to 28 dental casts based on a classification scheme employed in previous studies. The mean correct classification was 42.0%, indicating that the likelihood of assigning the correct ancestry is very poor and not significantly different from random assignment (p = 0.12). The accuracy analysis based on categorical classification of the casts was complemented by geometric morphometric analysis of nine 3D landmarks reflecting palate shape of 158 casts. Principal component analysis results show no difference between populations regarding palate shape, and cross-validated discriminant function analysis correctly classified only 62.0% of the specimens. Combined, these results show that previous methods to estimate ancestry are inaccurate and that this inaccuracy is probably due to a lack of palate shape differences between groups, rather than limitation of the analytical method per se. Therefore, we recommend caution should be used when choosing to apply the analysis of palate shape in forensically relevant contexts. PMID:26259114

  5. Local Ancestry Inference in a Large US-Based Hispanic/Latino Study: Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

    Science.gov (United States)

    Browning, Sharon R; Grinde, Kelsey; Plantinga, Anna; Gogarten, Stephanie M; Stilp, Adrienne M; Kaplan, Robert C; Avilés-Santa, M Larissa; Browning, Brian L; Laurie, Cathy C

    2016-01-01

    We estimated local ancestry on the autosomes and X chromosome in a large US-based study of 12,793 Hispanic/Latino individuals using the RFMix method, and we compared different reference panels and approaches to local ancestry estimation on the X chromosome by means of Mendelian inconsistency rates as a proxy for accuracy. We developed a novel and straightforward approach to performing ancestry-specific PCA after finding artifactual behavior in the results from an existing approach. Using the ancestry-specific PCA, we found significant population structure within African, European, and Amerindian ancestries in the Hispanic/Latino individuals in our study. In the African ancestral component of the admixed individuals, individuals whose grandparents were from Central America clustered separately from individuals whose grandparents were from the Caribbean, and also from reference Yoruba and Mandenka West African individuals. In the European component, individuals whose grandparents were from Puerto Rico diverged partially from other background groups. In the Amerindian ancestral component, individuals clustered into multiple different groups depending on the grandparental country of origin. Therefore, local ancestry estimation provides further insight into the complex genetic structure of US Hispanic/Latino populations, which must be properly accounted for in genotype-phenotype association studies. It also provides a basis for admixture mapping and ancestry-specific allele frequency estimation, which are useful in the identification of risk factors for disease. PMID:27172203

  6. Pacifiplex: an ancestry-informative SNP panel centred on Australia and the Pacific region.

    Science.gov (United States)

    Santos, Carla; Phillips, Christopher; Fondevila, Manuel; Daniel, Runa; van Oorschot, Roland A H; Burchard, Esteban G; Schanfield, Moses S; Souto, Luis; Uacyisrael, Jolame; Via, Marc; Carracedo, Ángel; Lareu, Maria V

    2016-01-01

    The analysis of human population variation is an area of considerable interest in the forensic, medical genetics and anthropological fields. Several forensic single nucleotide polymorphism (SNP) assays provide ancestry-informative genotypes in sensitive tests designed to work with limited DNA samples, including a 34-SNP multiplex differentiating African, European and East Asian ancestries. Although assays capable of differentiating Oceanian ancestry at a global scale have become available, this study describes markers compiled specifically for differentiation of Oceanian populations. A sensitive multiplex assay, termed Pacifiplex, was developed and optimized in a small-scale test applicable to forensic analyses. The Pacifiplex assay comprises 29 ancestry-informative marker SNPs (AIM-SNPs) selected to complement the 34-plex test, that in a combined set distinguish Africans, Europeans, East Asians and Oceanians. Nine Pacific region study populations were genotyped with both SNP assays, then compared to four reference population groups from the HGDP-CEPH human diversity panel. STRUCTURE analyses estimated population cluster membership proportions that aligned with the patterns of variation suggested for each study population's currently inferred demographic histories. Aboriginal Taiwanese and Philippine samples indicated high East Asian ancestry components, Papua New Guinean and Aboriginal Australians samples were predominantly Oceanian, while other populations displayed cluster patterns explained by the distribution of divergence amongst Melanesians, Polynesians and Micronesians. Genotype data from Pacifiplex and 34-plex tests is particularly well suited to analysis of Australian Aboriginal populations and when combined with Y and mitochondrial DNA variation will provide a powerful set of markers for ancestry inference applied to modern Australian demographic profiles. On a broader geographic scale, Pacifiplex adds highly informative data for inferring the ancestry

  7. Socioeconomic and nutritional factors account for the association of gastric cancer with Amerindian ancestry in a Latin American admixed population.

    Directory of Open Access Journals (Sweden)

    Latife Pereira

    Full Text Available Gastric cancer is one of the most lethal types of cancer and its incidence varies worldwide, with the Andean region of South America showing high incidence rates. We evaluated the genetic structure of the population from Lima (Peru and performed a case-control genetic association study to test the contribution of African, European, or Native American ancestry to risk for gastric cancer, controlling for the effect of non-genetic factors. A wide set of socioeconomic, dietary, and clinic information was collected for each participant in the study and ancestry was estimated based on 103 ancestry informative markers. Although the urban population from Lima is usually considered as mestizo (i.e., admixed from Africans, Europeans, and Native Americans, we observed a high fraction of Native American ancestry (78.4% for the cases and 74.6% for the controls and a very low African ancestry (<5%. We determined that higher Native American individual ancestry is associated with gastric cancer, but socioeconomic factors associated both with gastric cancer and Native American ethnicity account for this association. Therefore, the high incidence of gastric cancer in Peru does not seem to be related to susceptibility alleles common in this population. Instead, our result suggests a predominant role for ethnic-associated socioeconomic factors and disparities in access to health services. Since Native Americans are a neglected group in genomic studies, we suggest that the population from Lima and other large cities from Western South America with high Native American ancestry background may be convenient targets for epidemiological studies focused on this ethnic group.

  8. Chromosome Connections: Compelling Clues to Common Ancestry

    Science.gov (United States)

    Flammer, Larry

    2013-01-01

    Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…

  9. New World cattle show ancestry from multiple independent domestication events.

    Science.gov (United States)

    McTavish, Emily Jane; Decker, Jared E; Schnabel, Robert D; Taylor, Jeremy F; Hillis, David M

    2013-04-01

    Previous archeological and genetic research has shown that modern cattle breeds are descended from multiple independent domestication events of the wild aurochs (Bos primigenius) ∼10,000 y ago. Two primary areas of domestication in the Middle East/Europe and the Indian subcontinent resulted in taurine and indicine lines of cattle, respectively. American descendants of cattle brought by European explorers to the New World beginning in 1493 generally have been considered to belong to the taurine lineage. Our analyses of 47,506 single nucleotide polymorphisms show that these New World cattle breeds, as well as many related breeds of cattle in southern Europe, actually exhibit ancestry from both the taurine and indicine lineages. In this study, we show that, although European cattle are largely descended from the taurine lineage, gene flow from African cattle (partially of indicine origin) contributed substantial genomic components to both southern European cattle breeds and their New World descendants. New World cattle breeds, such as Texas Longhorns, provide an opportunity to study global population structure and domestication in cattle. Following their introduction into the Americas in the late 1400s, semiferal herds of cattle underwent between 80 and 200 generations of predominantly natural selection, as opposed to the human-mediated artificial selection of Old World breeding programs. Our analyses of global cattle breed population history show that the hybrid ancestry of New World breeds contributed genetic variation that likely facilitated the adaptation of these breeds to a novel environment. PMID:23530234

  10. Merozoite surface protein 2 allelic variation influences the specific antibody response during acute malaria in individuals from a Brazilian endemic area

    OpenAIRE

    Selma Sallenave-Sales; Clarissa Perez Faria; Mariano Gustavo Zalis; Cláudio Tadeu Daniel-Ribeiro; Maria de Fátima Ferreira-da-Cruz

    2007-01-01

    The antibody response to Plasmodium falciparum parasites of naturally infected population is critical to elucidate the role of polymorphic alleles in malaria. Thus, we evaluated the impact of antigenic diversity of repetitive and family dimorphic domains of the merozoite surface protein 2 (MSP-2) on immune response of 96 individuals living in Peixoto de Azevedo (MT-Brazil), by ELISA using recombinant MSP-2 proteins. The majority of these individuals were carrying FC27-type infections. IgG ant...

  11. Anatomy, Medical Education, and Human Ancestral Variation

    Science.gov (United States)

    Strkalj, Goran; Spocter, Muhammad A.; Wilkinson, A. Tracey

    2011-01-01

    It is argued in this article that the human body both in health and disease cannot be fully understood without adequately accounting for the different levels of human variation. The article focuses on variation due to ancestry, arguing that the inclusion of information pertaining to ancestry in human anatomy teaching materials and courses should…

  12. Limited evidence for adaptive evolution and functional effect of allelic variation at rs702424 in the promoter of the TAS2R16 bitter taste receptor gene in Africa.

    Science.gov (United States)

    Campbell, Michael C; Ranciaro, Alessia; Zinshteyn, Daniel; Rawlings-Goss, Renata; Hirbo, Jibril; Thompson, Simon; Woldemeskel, Dawit; Froment, Alain; Omar, Sabah A; Bodo, Jean-Marie; Nyambo, Thomas; Belay, Gurja; Drayna, Dennis; Breslin, Paul A S; Tishkoff, Sarah A

    2014-06-01

    Bitter taste perception, mediated by receptors encoded by the TAS2R loci, has important roles in human health and nutrition. Prior studies have demonstrated that nonsynonymous variation at site 516 in the coding exon of TAS2R16, a bitter taste receptor gene on chromosome 7, has been subject to positive selection and is strongly correlated with differences in sensitivity to salicin, a bitter anti-inflammatory compound, in human populations. However, a recent study suggested that the derived G-allele at rs702424 in the TAS2R16 promoter has also been the target of recent selection and may have an additional effect on the levels of salicin bitter taste perception. Here, we examined alleles at rs702424 for signatures of selection using Extended Haplotype Homozygosity (EHH) and FST statistics in diverse populations from West Central, Central and East Africa. We also performed a genotype-phenotype analysis of salicin sensitivity in a subset of 135 individuals from East Africa. Based on our data, we did not find evidence for positive selection at rs702424 in African populations, suggesting that nucleotide position 516 is likely the site under selection at TAS2R16. Moreover, we did not detect a significant association between rs702424 alleles and salicin bitter taste recognition, implying that this site does not contribute to salicin phenotypic variance. Overall, this study of African diversity provides further information regarding the genetic architecture and evolutionary history of a biologically-relevant trait in humans. PMID:24785689

  13. Limited Evidence for Adaptive Evolution and Functional Effect of Allelic Variation at rs702424 in the Promoter of the TAS2R16 Bitter Taste Receptor Gene in Africa

    Science.gov (United States)

    Campbell, Michael C.; Ranciaro, Alessia; Zinshteyn, Daniel; Rawlings-Goss, Renata; Hirbo, Jibril; Thompson, Simon; Woldemeskel, Dawit; Froment, Alain; Omar, Sabah A.; Bodo, Jean-Marie; Nyambo, Thomas; Belay, Gurja; Drayna, Dennis; Breslin, Paul A.S.; Tishkoff, Sarah A.

    2014-01-01

    Bitter taste perception, mediated by receptors encoded by the TAS2R loci, plays important roles in human health and nutrition. Prior studies have demonstrated that nonsynonymous variation at site 516 in the coding exon of TAS2R16, a bitter taste receptor gene on chromosome 7, has been subject to positive selection and is strongly correlated with differences in sensitivity to salicin, a bitter anti-inflammatory compound, in human populations. However, a recent study suggested that the derived G-allele at rs702424 in the TAS2R16 promoter has also been the target of recent selection and may have an additional effect on levels of salicin bitter taste perception. Here, we examined alleles at rs702424 for signatures of selection using Extended Haplotype Homozygosity (EHH) and FST statistics in 44 diverse populations from West Central, Central and East Africa. We also performed a genotype-phenotype analysis of salicin sensitivity in a subset of 135 individuals from East Africa. Based on our data, we did not find evidence for positive selection at rs702424 in African populations, suggesting that site 516 is likely the variant under selection at TAS2R16. Additionally, we did not detect a significant association between rs702424 alleles and salicin bitter taste recognition, implying that this site does not contribute to salicin phenotypic variance. Overall, this study of African diversity provides further information regarding the genetic architecture and evolutionary history of a biologically-relevant trait in humans. PMID:24785689

  14. Variation in effects of non-Hodgkin lymphoma risk factors according to the human leukocyte antigen (HLA-DRB1*01:01 allele and ancestral haplotype 8.1.

    Directory of Open Access Journals (Sweden)

    Sophia S Wang

    Full Text Available Genetic variations in human leukocyte antigens (HLA are critical in host responses to infections, transplantation, and immunological diseases. We previously identified associations with non-Hodgkin lymphoma (NHL and the HLA-DRB1*01:01 allele and extended ancestral haplotype (AH 8.1 (HLA-A*01-B*08-DR*03-TNF-308A. To illuminate how HLA alleles and haplotypes may influence NHL etiology, we examined potential interactions between HLA-DRB1*01:01 and AH 8.1, and a wide range of NHL risk factors among 685 NHL cases and 646 controls from a United States population-based case-control study. We calculated odds ratios and 95% confidence intervals by HLA allele or haplotype status, adjusted for sex, age, race and study center for NHL and two major subtypes using polychotomous unconditional logistic regression models. The previously reported elevation in NHL risk associated with exposures to termite treatment and polychlorinated biphenyls were restricted to individuals who did not possess HLA-DRB1*01:01. Previous associations for NHL and DLBCL with decreased sun exposure, higher BMI, and autoimmune conditions were statistically significant only among those with AH 8.1, and null among those without AH 8.1. Our results suggest that NHL risk factors vary in their association based on HLA-DRB1*01:01 and AH 8.1 status. Our results further suggest that certain NHL risk factors may act through a common mechanism to alter NHL risk. Finally, control participants with either HLA-DRB1*01:01 or AH 8.1 reported having a family history of NHL twice as likely as those who did not have either allele or haplotype, providing the first empirical evidence that HLA associations may explain some of the well-established relationship between family history and NHL risk.

  15. Starch phosphorylation in potato tubers is influenced by allelic variation in the genes encoding glucan water dikinase, starch branching enzymes I and II, and starch synthase III

    Directory of Open Access Journals (Sweden)

    Margaret Ann Carpenter

    2015-03-01

    Full Text Available Starch phosphorylation is an important aspect of plant metabolism due to its role in starch degradation. Moreover, the degree of phosphorylation of starch determines its physicochemical properties and is therefore relevant for industrial uses of starch. Currently, starch is chemically phosphorylated to increase viscosity and paste stability. Potato cultivars with elevated starch phosphorylation would make this process unnecessary, thereby bestowing economic and environmental benefits. Starch phosphorylation is a complex trait which has been previously shown by antisense gene repression to be influenced by a number of genes including those involved in starch synthesis and degradation. We have used an association mapping approach to discover genetic markers associated with the degree of starch phosphorylation. A diverse collection of 193 potato lines was grown in replicated field trials, and the levels of starch phosphorylation at the C6 and C3 positions of the glucosyl residues were determined by mass spectrometry of hydrolyzed starch from tubers. In addition, the potato lines were genotyped by amplicon sequencing and microsatellite analysis, focusing on candidate genes known to be involved in starch synthesis. As potato is an autotetraploid, genotyping included determination of allele dosage. Significant associations (p<0.001 were found with SNPs in the glucan water dikinase (GWD, starch branching enzyme I (SBEI and the starch synthase III (SSIII genes, and with a SSR allele in the SBEII gene. SNPs in the GWD gene were associated with C6 phosphorylation, whereas polymorphisms in the SBEI and SBEII genes were associated with both C6 and C3 phosphorylation and the SNP in the SSIII gene was associated with C3 phosphorylation. These allelic variants have potential as genetic markers for starch phosphorylation in potato.

  16. Information system agnostic ancestry for digital objects

    OpenAIRE

    Heuscher, S J B

    2010-01-01

    More and more information is becoming available in digital form, most of it derived from digital sources. Digital information is made available as digital objects composed of a sequence of bits and managed by information systems. To date, these digital objects have no independent identification which can be refered outside of a specific information system. However, they normally outlive these systems and can be copied to other systems. In order for the ancestry of digital information to span ...

  17. Ancestry informative markers and complete blood count parameters in Brazilian blood donors

    Directory of Open Access Journals (Sweden)

    Gabriela E. S. Felix

    2010-01-01

    Full Text Available A complete blood count is very useful in clinical diagnoses when reference ranges are well established for the population. Complete blood counts and allele frequencies of Ancestry Informative Markers (AIMs were analyzed in Brazilians with the aim of characterizing the hematological values of an admixed population. Positive associations were observed between gender and neutrophils, monocytes, eosinophils, erythrocytes, hemoglobin, hematocrit, MCV, MCHC and platelet counts. No significant differences were found for age, alcohol consumption, educational status, ethnicity, smoking in respect to the complete blood count values. In general, men had higher red blood cell values, while women had higher values for white blood cells and platelets. The study of the population was highly heterogeneous with mean proportions (± SE of African, European and Amerindian ancestry being 49.0 ± 3.0%, 44.0 ± 9.0% and 7.0 ± 9.0%, respectively. Amerindian ancestry showed limited contribution to the makeup of the population, but estimated ancestral proportions were statistically significant (r = 0.9838; P<0.001. These hematologic values are similar to Afro-Americans, another admixed population.

  18. Allelic variation in the Depressaria pastinacella CYP6AB3 protein enhances metabolism of plant allelochemicals by altering a proximal surface residue and potential interactions with cytochrome P450 reductase.

    Science.gov (United States)

    Mao, Wenfu; Rupasinghe, Sanjeewa G; Zangerl, Arthur R; Berenbaum, May R; Schuler, Mary A

    2007-04-01

    CYP6AB3v1, a cytochrome P450 monooxygenase in Depressaria pastinacella (parsnip webworm), is highly specialized for metabolizing imperatorin, a toxic furanocoumarin in the apiaceous host plants of this insect. Cloning and heterologous expression of CYP6AB3v2, an allelic variant identified in D. pastinacella, reveals that it metabolizes imperatorin at a rate (V(max) of 10.02 pmol/min/pmol of cytochrome P450 monooxygenase (P450)) significantly higher than CYP6AB3v1 (V(max) of 2.41 pmol/min/pmol) when supplemented with even low levels of cytochrome P450 reductase. Comparisons of the NADPH consumption rates for these variants indicate that CYP6AB3v2 utilizes this electron source at a faster rate than does CYP6AB3v1. Molecular modeling of the five amino acid differences between these variants and their potential interactions with P450 reductase suggests that replacement of Val(92) on the proximal face of CYP6AB3v1 with Ala(92) in CYP6AB3v2 affects interactions with P450 reductase so as to enhance its catalytic activity. Allelic variation at this locus potentially allows D. pastinacella to adapt to both intraspecific and interspecific variation in imperatorin concentrations in its host plants. PMID:17244619

  19. Merozoite surface protein 2 allelic variation influences the specific antibody response during acute malaria in individuals from a Brazilian endemic area

    Directory of Open Access Journals (Sweden)

    Selma Sallenave-Sales

    2007-06-01

    Full Text Available The antibody response to Plasmodium falciparum parasites of naturally infected population is critical to elucidate the role of polymorphic alleles in malaria. Thus, we evaluated the impact of antigenic diversity of repetitive and family dimorphic domains of the merozoite surface protein 2 (MSP-2 on immune response of 96 individuals living in Peixoto de Azevedo (MT-Brazil, by ELISA using recombinant MSP-2 proteins. The majority of these individuals were carrying FC27-type infections. IgG antibody responses were predominantly directed to FC27 parasites and were correlated to the extension of polymorphism presented by each MSP-2 region. This finding demonstrated the impact of the genetic polymorphism on antibody response and therefore, its importance on malaria vaccine efficacy.

  20. Maximum-likelihood estimation of recent shared ancestry (ERSA)

    OpenAIRE

    Huff, Chad D.; Witherspoon, David J.; Simonson, Tatum S.; Xing, Jinchuan; Watkins, W Scott; Zhang, Yuhua; Tuohy, Therese M; Neklason, Deborah W.; Burt, Randall W.; Guthery, Stephen L; Woodward, Scott R.; Jorde, Lynn B

    2011-01-01

    Accurate estimation of recent shared ancestry is important for genetics, evolution, medicine, conservation biology, and forensics. Established methods estimate kinship accurately for first-degree through third-degree relatives. We demonstrate that chromosomal segments shared by two individuals due to identity by descent (IBD) provide much additional information about shared ancestry. We developed a maximum-likelihood method for the estimation of recent shared ancestry (ERSA) from the number a...

  1. A Method to Exploit the Structure of Genetic Ancestry Space to Enhance Case-Control Studies.

    Science.gov (United States)

    Bodea, Corneliu A; Neale, Benjamin M; Ripke, Stephan; Daly, Mark J; Devlin, Bernie; Roeder, Kathryn

    2016-05-01

    One goal of human genetics is to understand the genetic basis of disease, a challenge for diseases of complex inheritance because risk alleles are few relative to the vast set of benign variants. Risk variants are often sought by association studies in which allele frequencies in case subjects are contrasted with those from population-based samples used as control subjects. In an ideal world we would know population-level allele frequencies, releasing researchers to focus on case subjects. We argue this ideal is possible, at least theoretically, and we outline a path to achieving it in reality. If such a resource were to exist, it would yield ample savings and would facilitate the effective use of data repositories by removing administrative and technical barriers. We call this concept the Universal Control Repository Network (UNICORN), a means to perform association analyses without necessitating direct access to individual-level control data. Our approach to UNICORN uses existing genetic resources and various statistical tools to analyze these data, including hierarchical clustering with spectral analysis of ancestry; and empirical Bayesian analysis along with Gaussian spatial processes to estimate ancestry-specific allele frequencies. We demonstrate our approach using tens of thousands of control subjects from studies of Crohn disease, showing how it controls false positives, provides power similar to that achieved when all control data are directly accessible, and enhances power when control data are limiting or even imperfectly matched ancestrally. These results highlight how UNICORN can enable reliable, powerful, and convenient genetic association analyses without access to the individual-level data. PMID:27087321

  2. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

    Science.gov (United States)

    Mahajan, Anubha; Go, Min Jin; Zhang, Weihua; Below, Jennifer E; Gaulton, Kyle J; Ferreira, Teresa; Horikoshi, Momoko; Johnson, Andrew D; Ng, Maggie C Y; Prokopenko, Inga; Saleheen, Danish; Wang, Xu; Zeggini, Eleftheria; Abecasis, Goncalo R; Adair, Linda S; Almgren, Peter; Atalay, Mustafa; Aung, Tin; Baldassarre, Damiano; Balkau, Beverley; Bao, Yuqian; Barnett, Anthony H; Barroso, Ines; Basit, Abdul; Been, Latonya F; Beilby, John; Bell, Graeme I; Benediktsson, Rafn; Bergman, Richard N; Boehm, Bernhard O; Boerwinkle, Eric; Bonnycastle, Lori L; Burtt, Noël; Cai, Qiuyin; Campbell, Harry; Carey, Jason; Cauchi, Stephane; Caulfield, Mark; Chan, Juliana C N; Chang, Li-Ching; Chang, Tien-Jyun; Chang, Yi-Cheng; Charpentier, Guillaume; Chen, Chien-Hsiun; Chen, Han; Chen, Yuan-Tsong; Chia, Kee-Seng; Chidambaram, Manickam; Chines, Peter S; Cho, Nam H; Cho, Young Min; Chuang, Lee-Ming; Collins, Francis S; Cornelis, Marylin C; Couper, David J; Crenshaw, Andrew T; van Dam, Rob M; Danesh, John; Das, Debashish; de Faire, Ulf; Dedoussis, George; Deloukas, Panos; Dimas, Antigone S; Dina, Christian; Doney, Alex S; Donnelly, Peter J; Dorkhan, Mozhgan; van Duijn, Cornelia; Dupuis, Josée; Edkins, Sarah; Elliott, Paul; Emilsson, Valur; Erbel, Raimund; Eriksson, Johan G; Escobedo, Jorge; Esko, Tonu; Eury, Elodie; Florez, Jose C; Fontanillas, Pierre; Forouhi, Nita G; Forsen, Tom; Fox, Caroline; Fraser, Ross M; Frayling, Timothy M; Froguel, Philippe; Frossard, Philippe; Gao, Yutang; Gertow, Karl; Gieger, Christian; Gigante, Bruna; Grallert, Harald; Grant, George B; Grrop, Leif C; Groves, Chrisropher J; Grundberg, Elin; Guiducci, Candace; Hamsten, Anders; Han, Bok-Ghee; Hara, Kazuo; Hassanali, Neelam; Hattersley, Andrew T; Hayward, Caroline; Hedman, Asa K; Herder, Christian; Hofman, Albert; Holmen, Oddgeir L; Hovingh, Kees; Hreidarsson, Astradur B; Hu, Cheng; Hu, Frank B; Hui, Jennie; Humphries, Steve E; Hunt, Sarah E; Hunter, David J; Hveem, Kristian; Hydrie, Zafar I; Ikegami, Hiroshi; Illig, Thomas; Ingelsson, Erik; Islam, Muhammed; Isomaa, Bo; Jackson, Anne U; Jafar, Tazeen; James, Alan; Jia, Weiping; Jöckel, Karl-Heinz; Jonsson, Anna; Jowett, Jeremy B M; Kadowaki, Takashi; Kang, Hyun Min; Kanoni, Stavroula; Kao, Wen Hong L; Kathiresan, Sekar; Kato, Norihiro; Katulanda, Prasad; Keinanen-Kiukaanniemi, Kirkka M; Kelly, Ann M; Khan, Hassan; Khaw, Kay-Tee; Khor, Chiea-Chuen; Kim, Hyung-Lae; Kim, Sangsoo; Kim, Young Jin; Kinnunen, Leena; Klopp, Norman; Kong, Augustine; Korpi-Hyövälti, Eeva; Kowlessur, Sudhir; Kraft, Peter; Kravic, Jasmina; Kristensen, Malene M; Krithika, S; Kumar, Ashish; Kumate, Jesus; Kuusisto, Johanna; Kwak, Soo Heon; Laakso, Markku; Lagou, Vasiliki; Lakka, Timo A; Langenberg, Claudia; Langford, Cordelia; Lawrence, Robert; Leander, Karin; Lee, Jen-Mai; Lee, Nanette R; Li, Man; Li, Xinzhong; Li, Yun; Liang, Junbin; Liju, Samuel; Lim, Wei-Yen; Lind, Lars; Lindgren, Cecilia M; Lindholm, Eero; Liu, Ching-Ti; Liu, Jian Jun; Lobbens, Stéphane; Long, Jirong; Loos, Ruth J F; Lu, Wei; Luan, Jian'an; Lyssenko, Valeriya; Ma, Ronald C W; Maeda, Shiro; Mägi, Reedik; Männisto, Satu; Matthews, David R; Meigs, James B; Melander, Olle; Metspalu, Andres; Meyer, Julia; Mirza, Ghazala; Mihailov, Evelin; Moebus, Susanne; Mohan, Viswanathan; Mohlke, Karen L; Morris, Andrew D; Mühleisen, Thomas W; Müller-Nurasyid, Martina; Musk, Bill; Nakamura, Jiro; Nakashima, Eitaro; Navarro, Pau; Ng, Peng-Keat; Nica, Alexandra C; Nilsson, Peter M; Njølstad, Inger; Nöthen, Markus M; Ohnaka, Keizo; Ong, Twee Hee; Owen, Katharine R; Palmer, Colin N A; Pankow, James S; Park, Kyong Soo; Parkin, Melissa; Pechlivanis, Sonali; Pedersen, Nancy L; Peltonen, Leena; Perry, John R B; Peters, Annette; Pinidiyapathirage, Janini M; Platou, Carl G; Potter, Simon; Price, Jackie F; Qi, Lu; Radha, Venkatesan; Rallidis, Loukianos; Rasheed, Asif; Rathman, Wolfgang; Rauramaa, Rainer; Raychaudhuri, Soumya; Rayner, N William; Rees, Simon D; Rehnberg, Emil; Ripatti, Samuli; Robertson, Neil; Roden, Michael; Rossin, Elizabeth J; Rudan, Igor; Rybin, Denis; Saaristo, Timo E; Salomaa, Veikko; Saltevo, Juha; Samuel, Maria; Sanghera, Dharambir K; Saramies, Jouko; Scott, James; Scott, Laura J; Scott, Robert A; Segrè, Ayellet V; Sehmi, Joban; Sennblad, Bengt; Shah, Nabi; Shah, Sonia; Shera, A Samad; Shu, Xiao Ou; Shuldiner, Alan R; Sigurđsson, Gunnar; Sijbrands, Eric; Silveira, Angela; Sim, Xueling; Sivapalaratnam, Suthesh; Small, Kerrin S; So, Wing Yee; Stančáková, Alena; Stefansson, Kari; Steinbach, Gerald; Steinthorsdottir, Valgerdur; Stirrups, Kathleen; Strawbridge, Rona J; Stringham, Heather M; Sun, Qi; Suo, Chen; Syvänen, Ann-Christine; Takayanagi, Ryoichi; Takeuchi, Fumihiko; Tay, Wan Ting; Teslovich, Tanya M; Thorand, Barbara; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tikkanen, Emmi; Trakalo, Joseph; Tremoli, Elena; Trip, Mieke D; Tsai, Fuu Jen; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Uitterlinden, Andre G; Valladares-Salgado, Adan; Vedantam, Sailaja; Veglia, Fabrizio; Voight, Benjamin F; Wang, Congrong; Wareham, Nicholas J; Wennauer, Roman; Wickremasinghe, Ananda R; Wilsgaard, Tom; Wilson, James F; Wiltshire, Steven; Winckler, Wendy; Wong, Tien Yin; Wood, Andrew R; Wu, Jer-Yuarn; Wu, Ying; Yamamoto, Ken; Yamauchi, Toshimasa; Yang, Mingyu; Yengo, Loic; Yokota, Mitsuhiro; Young, Robin; Zabaneh, Delilah; Zhang, Fan; Zhang, Rong; Zheng, Wei; Zimmet, Paul Z; Altshuler, David; Bowden, Donald W; Cho, Yoon Shin; Cox, Nancy J; Cruz, Miguel; Hanis, Craig L; Kooner, Jaspal; Lee, Jong-Young; Seielstad, Mark; Teo, Yik Ying; Boehnke, Michael; Parra, Esteban J; Chambers, Jonh C; Tai, E Shyong; McCarthy, Mark I; Morris, Andrew P

    2014-03-01

    To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry. PMID:24509480

  3. Association of genetic ancestry with breast cancer in ethnically diverse women from Chicago.

    Directory of Open Access Journals (Sweden)

    Umaima Al-Alem

    Full Text Available INTRODUCTION: Non-Hispanic (nH Black and Hispanic women are disproportionately affected by early onset disease, later stage, and with more aggressive, higher grade and ER/PR negative breast cancers. The purpose of this analysis was to examine whether genetic ancestry could account for these variation in breast cancer characteristics, once data were stratified by self-reported race/ethnicity and adjusted for potential confounding by social and behavioral factors. METHODS: We used a panel of 100 ancestry informative markers (AIMs to estimate individual genetic ancestry in 656 women from the "Breast Cancer Care in Chicago" study, a multi-ethnic cohort of breast cancer patients to examine the association between individual genetic ancestry and breast cancer characteristics. In addition we examined the association of individual AIMs and breast cancer to identify genes/regions that may potentially play a role in breast cancer disease disparities. RESULTS: As expected, nH Black and Hispanic patients were more likely than nH White patients to be diagnosed at later stages, with higher grade, and with ER/PR negative tumors. Higher European genetic ancestry was protective against later stage at diagnosis (OR 0.7 95%CI: 0.54-0.92 among Hispanic patients, and higher grade (OR 0.73, 95%CI: 0.56-0.95 among nH Black patients. After adjustment for multiple social and behavioral risk factors, the association with later stage remained, while the association with grade was not significant. We also found that the AIM SNP rs10954631 on chromosome 7 was associated with later stage (p = 0.02 and higher grade (p = 0.012 in nH Whites and later stage (p = 0.03 in nH Blacks. CONCLUSION: Non-European genetic ancestry was associated with later stage at diagnosis in ethnic minorities. The relation between genetic ancestry and stage at diagnosis may be due to genetic factors and/or unmeasured environmental factors that are overrepresented within certain racial

  4. Polymorphisms of Estrogen Metabolism-Related Genes and Prostate Cancer Risk in Two Populations of African Ancestry

    Science.gov (United States)

    Emeville, Elise; Ferdinand, Séverine; Punga, Augustin; Lufuma, Simon; Blanchet, Pascal; Romana, Marc; Multigner, Luc

    2016-01-01

    Background Estrogens are thought to play a critical role in prostate carcinogenesis. It has been suggested that polymorphisms of genes encoding enzymes involved in estrogen metabolism are risk factors for prostate cancer. However, few studies have been performed on populations of African ancestry, which are known to have a high risk of prostate cancer. Objective We investigated whether functional polymorphisms of CYP17, CYP19, CYP1B1, COMT and UGT1A1 affected the risk of prostate cancer in two different populations of African ancestry. Methods In Guadeloupe (French West Indies), we compared 498 prostate cancer patients and 565 control subjects. In Kinshasa (Democratic Republic of Congo), 162 prostate cancer patients were compared with 144 controls. Gene polymorphisms were determined by the SNaPshot technique or short tandem repeat PCR analysis. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results The AA genotype and the A allele of rs4680 (COMT) appeared to be inversely associated with the risk of prostate cancer in adjusted models for both Afro-Caribbean and native African men. For the A allele, a significant inverse association was observed among cases with low-grade Gleason scores and localized clinical stage, in both populations. Conclusions These preliminary results support the hypothesis that polymorphisms of genes encoding enzymes involved in estrogen metabolism may modulate the risk of prostate cancer in populations of African ancestry. PMID:27074016

  5. Typing of 111 ancestry informative markers in an Albanian population

    DEFF Research Database (Denmark)

    Ribeiro, Joana; Pereira, V.; Kondili, A.; Miniati, P.; Børsting, C.; Morling, N.

    2015-01-01

    Genetically based prediction of ancestry has a great potential in forensic genetics and may be used as an investigative lead in crime case work or missing person identification.The EUROFORGEN-NoE consortium developed four PCR and SBE multiplexes for typing of 111 ancestry informative markers (AIM...

  6. Characterizing the admixed African ancestry of African Americans

    OpenAIRE

    Zakharia, Fouad; Basu, Analabha; Absher, Devin; Assimes, Themistocles L.; Go, Alan S.; Hlatky, Mark A.; Iribarren, Carlos; Knowles, Joshua W.; Li, Jun; Narasimhan, Balasubramanian; Sidney, Steven; Southwick, Audrey; Myers, Richard M.; Quertermous, Thomas; Risch, Neil

    2009-01-01

    Abstract Background Accurate, high-throughput genotyping allows the fine characterization of genetic ancestry. Here we applied recently developed statistical and computational techniques to the question of African ancestry in African Americans by using data on more than 450,000 single-nucleotide polymorphisms (SNPs) genotyped in 94 Africans of diverse geographic origins included in the...

  7. Building a forensic ancestry panel from the ground up

    DEFF Research Database (Denmark)

    Phillips, C; Parson, W; Lundsberg, Birgitte Møller;

    2014-01-01

    Emerging next-generation sequencing technologies will enable DNA analyses to add pigmentation predictive and ancestry informative (AIM) SNPs to the range of markers detectable from a single PCR test. This prompted us to re-appraise current forensic and genomics AIM-SNPs and from the best sets...... to minimize bias when estimating co-ancestry proportions in individuals with admixed ancestries. The differentiation of European from Middle East or South Asian ancestries was not chosen as a characteristic in order to concentrate on introducing Oceanian differentiation for the first time in a forensic AIM......-specific divergence in at least four groups. We describe subsets of 88, 55, 28, 20 and 12 AIMs, enabling both new and existing SNP genotyping technologies to exploit the best markers identified for forensic ancestry analysis....

  8. Allelic Variation in the Perennial Ryegrass FLOWERING LOCUS T Gene is Associated with Changes in Flowering Time across a Range of Populations

    DEFF Research Database (Denmark)

    Skøt, Leif; Sanderson, Ruth; Thomas, Ann;

    2011-01-01

    The Arabidopsis (Arabidopsis thaliana) FLOWERING LOCUS T (FT) gene and its orthologs in other plant species (e.g. rice [Oryza sativa] OsFTL2/Hd3a) have an established role in the photoperiodic induction of flowering response. The genomic and phenotypic variations associated with the perennial...... ryegrass (Lolium perenne) ortholog of FT, designated LpFT3, was assessed in a diverse collection of nine European germplasm populations, which together constituted an association panel of 864 plants. Sequencing and genotyping of a series of amplicons derived from the nine populations, containing the...... complete exon and intron sequences as well as 5' and 3' noncoding sequences of LpFT3, identified a total of seven haplotypes. Genotyping assays designed to detect the genomic variation showed that three haplotypes were present in approximately equal proportions and represented 84% of the total, with a...

  9. Disentangling the Roles of History and Local Selection in Shaping Clinal Variation of Allele Frequencies and Gene Expression in Norway Spruce (Picea abies)

    OpenAIRE

    J. Chen; Kallman, T.; Ma, X.; Gyllenstrand, N; Zaina, G.; M. Morgante; Bousquet, J; Eckert, A; Wegrzyn, J.; Neale, D.; Lagercrantz, U.; Lascoux, M

    2012-01-01

    Understanding the genetic basis of local adaptation is challenging due to the subtle balance among conflicting evolutionary forces that are involved in its establishment and maintenance. One system with which to tease apart these difficulties is clines in adaptive characters. Here we analyzed genetic and phenotypic variation in bud set, a highly heritable and adaptive trait, among 18 populations of Norway spruce (Picea abies), arrayed along a latitudinal gradient ranging from 47°N to 68°N. We...

  10. Allelic variations of a light harvesting chlorophyll a/b-binding protein gene (Lhcb1 associated with agronomic traits in barley.

    Directory of Open Access Journals (Sweden)

    Yanshi Xia

    Full Text Available Light-harvesting chlorophyll a/b-binding protein (LHCP is one of the most abundant chloroplast proteins in plants. Its main function is to collect and transfer light energy to photosynthetic reaction centers. However, the roles of different LHCPs in light-harvesting antenna systems remain obscure. Exploration of nucleotide variation in the genes encoding LHCP can facilitate a better understanding of the functions of LHCP. In this study, nucleotide variations in Lhcb1, a LHCP gene in barley, were investigated across 292 barley accessions collected from 35 different countries using EcoTILLING technology, a variation of the Targeting Induced Local Lesions In Genomes (TILLING. A total of 23 nucleotide variations were detected including three insert/deletions (indels and 20 single nucleotide polymorphisms (SNPs. Among them, 17 SNPs were in the coding region with nine missense changes. Two SNPs with missense changes are predicted to be deleterious to protein function. Seventeen SNP formed 31 distinguishable haplotypes in the barley collection. The levels of nucleotide diversity in the Lhcb1 locus differed markedly with geographic origins and species of accessions. The accessions from Middle East Asia exhibited the highest nucleotide and haplotype diversity. H. spontaneum showed greater nucleotide diversity than H. vulgare. Five SNPs in Lhcb1 were significantly associated with at least one of the six agronomic traits evaluated, namely plant height, spike length, number of grains per spike, thousand grain weight, flag leaf area and leaf color, and these SNPs may be used as potential markers for improvement of these barley traits.

  11. Allelic Variation of Glu-A1, Glu-B1 and Glu-D1 in Chinese Released Wheat Varieties in the Last 50 Years

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xue-yong; DONG Yu-chen; YOU Guang-xia; WANG Lan-fen; LI Pei; JIA Ji-zeng

    2002-01-01

    The high-molecular-weight glutenin subunit (HMW-GS) components from about 85 varieties were fractionated by SDS-PAGE, including 22 corner stone breeding parents, 45 varieties taking important role in Chinese wheat production and 18 varieties with good bread making quality. The 22 corner stone breeding lines carry either null (c) or 1 (a) subunits on Glu-A1 loci. Five types are detected on Glu-B1, which are 7+8(b), 7+9 (c), 14+15 (h), 17+18 (i), 6+8 (d). 7+8 and 7+9 are the two major types. Six types have been detected on Glu-D1, which are 2 + 12 (a), 2 + 10 (e), 5 + 10 (d), 4+ 10 (j), 4 + 12 (c), 2 + 11 (g). 2 + 12 and 2 + 11 are the two major types. In the corner stone breeding lines, early premium from American carries 5 + 10, St2422/464 from Italy carries the 14 + 15. In addition, two relatively essential varieties, Mara and Alondra carry 5 + 10. In the 45 commercialized varieties, sowed more than 666 000 ha (10 million mu) annually, only Yangmai 5 conveys the 5 + 10 on Glu-D1, and Xiaoyan 6 and Yumai 7 carry the 14 + 15 on Glu-B1. Four varieties, Funo, Nongda 139, Zhengzhou 683 and Fan 6 convey the 17 + 18 on Glu-B1. The 18 bread wheat varieties recommended by the Ministry of Agriculture in 1992 could be classified into two groups, 5 + 10 and 14 + 15. Zhongzuo 8131 and its selections are the typical genotype of 5 + 10. Genes coding the two subunits are from either Yecora F-70 or IRN68-181. Xiaoyan 6 and its derivative varieties are the typical genotype of 14 + 15. The genes coding 17 + 18 subunits in Chinese varieties were derived from Funo or its selections. These results basically reflect allelic changes on Glu-1 in Chinese wheatvarieties in the past 50 years. It is also proven that HMW-GS components may have great diversity betweenlines from the same cross, which causes great difference on baking quality.

  12. Forensic ancestry analysis with two capillary electrophoresis ancestry informative marker (AIM) panels

    DEFF Research Database (Denmark)

    Santos, C; Fondevila, M; Ballard, D;

    2015-01-01

    There is increasing interest in forensic ancestry tests, which are part of a growing number of DNA analyses that can enhance routine profiling by obtaining additional genetic information about unidentified DNA donors. Nearly all ancestry tests use single nucleotide polymorphisms (SNPs), but these...... relationship between input DNA and signal strength as each marker is detected with a single dye, so mixed DNA is more reliably detected. We report the results of a collaborative inter-laboratory exercise of 19 participants (15 from the EDNAP European DNA Profiling group) that assessed a 34-plex SNP test using...... DNA mixture as well as achieving complete and concordant profiles in nearly all cases. Lastly, two participants successfully ran parallel next-generation sequencing analyses (each using different systems) and achieved high levels of genotyping concordance using the exercise PCR primer mixes unmodified....

  13. Detection of Ancestry Informative HLA Alleles Confirms the Admixed Origins of Japanese Population

    OpenAIRE

    Hirofumi Nakaoka; Shigeki Mitsunaga; Kazuyoshi Hosomichi; Liou Shyh-Yuh; Taiji Sawamoto; Tsutomu Fujiwara; Naohisa Tsutsui; Koji Suematsu; Akira Shinagawa; Hidetoshi Inoko; Ituro Inoue

    2013-01-01

    The polymorphisms in the human leukocyte antigen (HLA) region are powerful tool for studying human evolutionary processes. We investigated genetic structure of Japanese by using five-locus HLA genotypes (HLA-A, -B, -C, -DRB1, and -DPB1) of 2,005 individuals from 10 regions of Japan. We found a significant level of population substructure in Japanese; particularly the differentiation between Okinawa Island and mainland Japanese. By using a plot of the principal component scores, we identified ...

  14. Analysis of Natural Allelic Variation Controlling Arabiciopsis thaliana Seed Germinability in Response to Cold and Dark: Identification of Three Major Quantitative Trait Loci

    Institute of Scientific and Technical Information of China (English)

    Ping-Hong Meng; Audrey Macquet; Olivier Loudet; Annie Marion-Poll; Helen M.North

    2008-01-01

    Light and temperature are key external factors in the control of Arabidopsis thaliana seed germination and dormancy mechanisms. Perception and response to these stimuli have to ensure that seedling emergence and growth occur at the most advantageous time for correct establishment. Analysis of over 300 Arabidopsis accessions identified 14, from 12 different geographical locations, that were able to germinate to greater than 20% at 6℃ in the dark. This natural variation was exploited to identify genetic loci responsible for cold-tolerant, dark germination. A quantitative trait loci approach was used on recombinant inbred line progeny of a cross between Bay-0 and Shahdara. Six distinct quantitative trait loci were identified, three of which were major loci, each responsible for 17-25% of the phenotypic variability in this trait. Parental phenotypes indicated that the majority of the cold-tolerant, dark-germination characteristics are related to light responses. Validation of the three major loci using heterogeneous inbred families confirmed the feasibility of fine mapping and cloning the genes at the quantitative trait loci responsible for cold-tolerant, dark germination.

  15. Allelic variation of the COMT gene in a despotic primate society: A haplotype is related to cortisol excretion in Macaca fuscata.

    Science.gov (United States)

    Pflüger, Lena S; Gutleb, Daria R; Hofer, Martin; Fieder, Martin; Wallner, Bernard; Steinborn, Ralf

    2016-02-01

    Sequence variations in genes of the monoamine neurotransmitter system and their common function in human and non-human primate species are an ongoing issue of investigation. However, the COMT gene, coding for the catechol-O-methyltransferase, has not yet attracted much scientific attention regarding its functional role in non-human primates. Considering that a polymorphism of the human COMT gene affects the enzyme activity and cortisol level in response to a social stressor, this study investigated the impact of COMT on endocrine stress and behavioural parameters in Japanese macaques (Macaca fuscata). The species exemplifies a despotic hierarchy in which males' social rank positions require an adaptation of behaviour strategies. During the mating period steroid secretion and the frequency of aggressive encounters between males increase. We addressed i) whether this species exhibits potential functional COMT variants, ii) whether these variants are associated with faecal cortisol excretion of males, iii) how they are distributed among different social rank positions and iv) whether they are associated with behavioural strategies during times of mate competition. By genotyping 26 males we identified three COMT haplotypes (HT), including a putative splice mutant (HT3). This variant was associated with increased cortisol excretion. Given the observed inverse correlation between cortisol and physical aggression, we assume that different COMT haplotypes may predispose individuals to pursue more or less aggressive strategies. How these gene-stress effects might favour a specific social role is discussed. Our study of non-invasive genotyping in combination with behavioural and endocrine parameters represents an important step towards the understanding of gene-stress effects in a hierarchically organised primate society. PMID:26657779

  16. Tetra-allelic SNPs: Informative forensic markers compiled from public whole-genome sequence data.

    Science.gov (United States)

    Phillips, C; Amigo, J; Carracedo, Á; Lareu, M V

    2015-11-01

    Multiple-allele single nucleotide polymorphisms (SNPs) are potentially useful for forensic DNA analysis as they can provide more discrimination power than normal binary SNPs. In addition, the presence in a profile of more than two alleles per marker provides a clearer indication of mixed DNA than assessments of imbalanced signals in the peak pairs of binary SNPs. Using the 1000 Genomes Phase III human variant data release of 2014 as the starting point, this study collated 961 tetra-allelic SNPs that pass minimum sequence quality thresholds and where four separate nucleotide substitution alleles were detected. Although most of these loci had three of the four alleles in combined frequencies of 2% or less, 160 had high heterozygosities with 50 exceeding those of 'ideal' 0.5:0.5 binary SNPs. From this set of most polymorphic tetra-allelic SNPs, we identified markers most informative for forensic purposes and explored these loci in detail. Subsets of the most polymorphic tetra-allelic SNPs will make useful additions to current panels of forensic identification SNPs and ancestry-informative SNPs. The 24 most discriminatory tetra-allelic SNPs were estimated to detect more than two alleles in at least one marker per profile in 99.9% of mixtures of African contributors. In European contributor mixtures 99.4% of profiles would show multiple allele patterns, but this drops to 92.6% of East Asian contributor mixtures due to reduced levels of polymorphism for the 24 SNPs in this population group. PMID:26209763

  17. Inferring geographic coordinates of origin for Europeans using small panels of ancestry informative markers.

    Directory of Open Access Journals (Sweden)

    Petros Drineas

    Full Text Available Recent large-scale studies of European populations have demonstrated the existence of population genetic structure within Europe and the potential to accurately infer individual ancestry when information from hundreds of thousands of genetic markers is used. In fact, when genomewide genetic variation of European populations is projected down to a two-dimensional Principal Components Analysis plot, a surprising correlation with actual geographic coordinates of self-reported ancestry has been reported. This substructure can hamper the search of susceptibility genes for common complex disorders leading to spurious correlations. The identification of genetic markers that can correct for population stratification becomes therefore of paramount importance. Analyzing 1,200 individuals from 11 populations genotyped for more than 500,000 SNPs (Population Reference Sample, we present a systematic exploration of the extent to which geographic coordinates of origin within Europe can be predicted, with small panels of SNPs. Markers are selected to correlate with the top principal components of the dataset, as we have previously demonstrated. Performing thorough cross-validation experiments we show that it is indeed possible to predict individual ancestry within Europe down to a few hundred kilometers from actual individual origin, using information from carefully selected panels of 500 or 1,000 SNPs. Furthermore, we show that these panels can be used to correctly assign the HapMap Phase 3 European populations to their geographic origin. The SNPs that we propose can prove extremely useful in a variety of different settings, such as stratification correction or genetic ancestry testing, and the study of the history of European populations.

  18. The contribution of ancestry, chance, and past and ongoing selection to adaptive evolution

    Indian Academy of Sciences (India)

    Amitabh Joshi; Robinson B. Castillo; Laurence D. Mueller

    2003-12-01

    The relative contributions of ancestry, chance, and past and ongoing selection to variation in one adaptive (larval feeding rate) and one seemingly nonadaptive (pupation height) trait were determined in populations of Drosophila melanogaster adapting to either low or high larval densities in the laboratory. Larval feeding rates increased rapidly in response to high density, and the effects of ancestry, past selection and chance were ameliorated by ongoing selection within 15–20 generations. Similarly, in populations previously kept at high larval density, and then switched to low larval density, the decline of larval feeding rate to ancestral levels was rapid (15–20 generations) and complete, providing support for a previously stated hypothesis regarding the costs of faster feeding in Drosophila larvae. Variation among individuals was the major contributor to variation in pupation height, a trait that would superficially appear to be nonadaptive in the environmental context of the populations used in this study because it did not diverge between sets of populations kept at low versus high larval density for many generations. However, the degree of divergence among populations ($F_{\\text{ST}}$) for pupation height was significantly less than expected for a selectively neutral trait, and we integrate results from previous studies to suggest that the variation for pupation height among populations is constrained by stabilizing selection, with a flat, plateau-like fitness function that, consequently, allows for substantial phenotypic variation within populations. Our results support the view that the genetic imprints of history (ancestry and past selection) in outbreeding sexual populations are typically likely to be transient in the face of ongoing selection and recombination. The results also illustrate the heuristic point that different forms of selection—for example directional versus stabilizing selection—acting on a trait in different populations may

  19. Forensic ancestry analysis with two capillary electrophoresis ancestry informative marker (AIM) panels:Results of a collaborative EDNAP exercise

    OpenAIRE

    Santos, C.; Fondevila, M; Ballard, D; Banemann, R; Bento, A. M.; Børsting, C; Branicki, W.; Brisighelli, F.; Burrington, M.; Capal, T.; Chaitanya, L; Daniel, R; Decroyer, V.; R. England; Gettings, K. B.

    2015-01-01

    There is increasing interest in forensic ancestry tests, which are part of a growing number of DNA analyses that can enhance routine profiling by obtaining additional genetic information about unidentified DNA donors. Nearly all ancestry tests use single nucleotide polymorphisms (SNPs), but these currently rely on SNaPshot single base extension chemistry that can fail to detect mixed DNA. Insertion-deletion polymorphism (Indel) tests have been developed using dye-labeled primers that allow di...

  20. Genetic ancestry, self-reported race and ethnicity in African Americans and European Americans in the PCaP cohort.

    Directory of Open Access Journals (Sweden)

    Lara E Sucheston

    Full Text Available BACKGROUND: Family history and African-American race are important risk factors for both prostate cancer (CaP incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP. METHODS: Individual ancestry (IA was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP, a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information comprising roughly equal numbers of research subjects reporting as Black/African American (AA or European American/Caucasian/Caucasian American/White (EA from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino using multivariate analysis of variance models. Principal components (PC were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states. RESULTS: Mean individual ancestries differed by state for self-reporting AA (p = 0.03 and EA (p = 0.001. This geographic difference attenuated for AAs who answered "no" to all ethnicity membership questions (non-ethnic research subjects; p = 0.78 but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA. CONCLUSIONS: Mean IA differed by race between states, elucidating a potential contributing factor to these differences in AA

  1. Global genetic variation at nine short tandem repeat loci and implications on forensic genetics.

    Science.gov (United States)

    Sun, Guangyun; McGarvey, Stephen T; Bayoumi, Riad; Mulligan, Connie J; Barrantes, Ramiro; Raskin, Salmo; Zhong, Yixi; Akey, Joshua; Chakraborty, Ranajit; Deka, Ranjan

    2003-01-01

    We have studied genetic variation at nine autosomal short tandem repeat loci in 20 globally distributed human populations defined by geographic and ethnic origins, viz., African, Caucasian, Asian, Native American and Oceanic. The purpose of this study is to evaluate the utility and applicability of these nine loci in forensic analysis in worldwide populations. The levels of genetic variation measured by number of alleles, allele size variance and heterozygosity are high in all populations irrespective of their effective sizes. Single- as well as multi-locus genotype frequencies are in conformity with the assumptions of Hardy-Weinberg equilibrium. Further, alleles across the entire set of nine loci are mutually independent in all populations. Gene diversity analysis shows that pooling of population data by major geographic groupings does not introduce substructure effects beyond the levels recommended by the National Research Council, validating the establishment of population databases based on major geographic and ethnic groupings. A network tree based on genetic distances further supports this assertion, in which populations of common ancestry cluster together. With respect to the power of discrimination and exclusion probabilities, even the relatively reduced levels of genetic variation at these nine STR loci in smaller and isolated populations provide an exclusionary power over 99%. However, in paternity testing with unknown genotype of the mother, the power of exclusion could fall below 80% in some isolated populations, and in such cases use of additional loci supplementing the battery of the nine loci is recommended. PMID:12529704

  2. What phylogeny and gene genealogy analyses reveal about homoplasy in citrus microsatellite alleles

    OpenAIRE

    Barkley, Noelle A.; Krueger, Robert R.; Federici, Claire T.; Roose, Mikeal L

    2009-01-01

    Sixty-five microsatellite alleles amplified from ancestral citrus accessions classified in three separate genera were evaluated for sequence polymorphism to establish the basis of inter- and intra-allelic genetic variation, evaluate the extent of size homoplasy, and determine an appropriate model (stepwise or infinite allele) for analysis of citrus microsatellite alleles. Sequences for each locus were aligned and subsequently used to determine relationships between alleles of different taxa v...

  3. Adaptive variation regulates the expression of the human SGK1 gene in response to stress.

    Directory of Open Access Journals (Sweden)

    Francesca Luca

    2009-05-01

    Full Text Available The Serum and Glucocorticoid-regulated Kinase1 (SGK1 gene is a target of the glucocorticoid receptor (GR and is central to the stress response in many human tissues. Because environmental stress varies across habitats, we hypothesized that natural selection shaped the geographic distribution of genetic variants regulating the level of SGK1 expression following GR activation. By combining population genetics and molecular biology methods, we identified a variant (rs9493857 with marked allele frequency differences between populations of African and European ancestry and with a strong correlation between allele frequency and latitude in worldwide population samples. This SNP is located in a GR-binding region upstream of SGK1 that was identified using a GR ChIP-chip. SNP rs9493857 also lies within a predicted binding site for Oct1, a transcription factor known to cooperate with the GR in the transactivation of target genes. Using ChIP assays, we show that both GR and Oct1 bind to this region and that the ancestral allele at rs9493857 binds the GR-Oct1 complex more efficiently than the derived allele. Finally, using a reporter gene assay, we demonstrate that the ancestral allele is associated with increased glucocorticoid-dependent gene expression when compared to the derived allele. Our results suggest a novel paradigm in which hormonal responsiveness is modulated by sequence variation in the regulatory regions of nuclear receptor target genes. Identifying such functional variants may shed light on the mechanisms underlying inter-individual variation in response to environmental stressors and to hormonal therapy, as well as in the susceptibility to hormone-dependent diseases.

  4. Exploring the Y Chromosomal Ancestry of Modern Panamanians.

    Directory of Open Access Journals (Sweden)

    Viola Grugni

    Full Text Available Geologically, Panama belongs to the Central American land-bridge between North and South America crossed by Homo sapiens >14 ka ago. Archaeologically, it belongs to a wider Isthmo-Colombian Area. Today, seven indigenous ethnic groups account for 12.3% of Panama's population. Five speak Chibchan languages and are characterized by low genetic diversity and a high level of differentiation. In addition, no evidence of differential structuring between maternally and paternally inherited genes has been reported in isthmian Chibchan cultural groups. Recent data have shown that 83% of the Panamanian general population harbour mitochondrial DNAs (mtDNAs of Native American ancestry. Considering differential male/female mortality at European contact and multiple degrees of geographical and genetic isolation over the subsequent five centuries, the Y-chromosome Native American component is expected to vary across different geographic regions and communities in Panama. To address this issue, we investigated Y-chromosome variation in 408 modern males from the nine provinces of Panama and one indigenous territory (the comarca of Kuna Yala. In contrast to mtDNA data, the Y-chromosome Native American component (haplogroup Q exceeds 50% only in three populations facing the Caribbean Sea: the comarca of Kuna Yala and Bocas del Toro province where Chibchan languages are spoken by the majority, and the province of Colón where many Kuna and people of mixed indigenous-African-and-European descent live. Elsewhere the Old World component is dominant and mostly represented by western Eurasian haplogroups, which signal the strong male genetic impact of invaders. Sub-Saharan African input accounts for 5.9% of male haplotypes. This reflects the consequences of the colonial Atlantic slave trade and more recent influxes of West Indians of African heritage. Overall, our findings reveal a local evolution of the male Native American ancestral gene pool, and a strong but

  5. Exploring the Y Chromosomal Ancestry of Modern Panamanians.

    Science.gov (United States)

    Grugni, Viola; Battaglia, Vincenza; Perego, Ugo Alessandro; Raveane, Alessandro; Lancioni, Hovirag; Olivieri, Anna; Ferretti, Luca; Woodward, Scott R; Pascale, Juan Miguel; Cooke, Richard; Myres, Natalie; Motta, Jorge; Torroni, Antonio; Achilli, Alessandro; Semino, Ornella

    2015-01-01

    Geologically, Panama belongs to the Central American land-bridge between North and South America crossed by Homo sapiens >14 ka ago. Archaeologically, it belongs to a wider Isthmo-Colombian Area. Today, seven indigenous ethnic groups account for 12.3% of Panama's population. Five speak Chibchan languages and are characterized by low genetic diversity and a high level of differentiation. In addition, no evidence of differential structuring between maternally and paternally inherited genes has been reported in isthmian Chibchan cultural groups. Recent data have shown that 83% of the Panamanian general population harbour mitochondrial DNAs (mtDNAs) of Native American ancestry. Considering differential male/female mortality at European contact and multiple degrees of geographical and genetic isolation over the subsequent five centuries, the Y-chromosome Native American component is expected to vary across different geographic regions and communities in Panama. To address this issue, we investigated Y-chromosome variation in 408 modern males from the nine provinces of Panama and one indigenous territory (the comarca of Kuna Yala). In contrast to mtDNA data, the Y-chromosome Native American component (haplogroup Q) exceeds 50% only in three populations facing the Caribbean Sea: the comarca of Kuna Yala and Bocas del Toro province where Chibchan languages are spoken by the majority, and the province of Colón where many Kuna and people of mixed indigenous-African-and-European descent live. Elsewhere the Old World component is dominant and mostly represented by western Eurasian haplogroups, which signal the strong male genetic impact of invaders. Sub-Saharan African input accounts for 5.9% of male haplotypes. This reflects the consequences of the colonial Atlantic slave trade and more recent influxes of West Indians of African heritage. Overall, our findings reveal a local evolution of the male Native American ancestral gene pool, and a strong but geographically

  6. Ancestry of the Iban is predominantly Southeast Asian: genetic evidence from autosomal, mitochondrial, and Y chromosomes.

    Directory of Open Access Journals (Sweden)

    Tatum S Simonson

    Full Text Available Humans reached present-day Island Southeast Asia (ISEA in one of the first major human migrations out of Africa. Population movements in the millennia following this initial settlement are thought to have greatly influenced the genetic makeup of current inhabitants, yet the extent attributed to different events is not clear. Recent studies suggest that south-to-north gene flow largely influenced present-day patterns of genetic variation in Southeast Asian populations and that late Pleistocene and early Holocene migrations from Southeast Asia are responsible for a substantial proportion of ISEA ancestry. Archaeological and linguistic evidence suggests that the ancestors of present-day inhabitants came mainly from north-to-south migrations from Taiwan and throughout ISEA approximately 4,000 years ago. We report a large-scale genetic analysis of human variation in the Iban population from the Malaysian state of Sarawak in northwestern Borneo, located in the center of ISEA. Genome-wide single-nucleotide polymorphism (SNP markers analyzed here suggest that the Iban exhibit greatest genetic similarity to Indonesian and mainland Southeast Asian populations. The most common non-recombining Y (NRY and mitochondrial (mt DNA haplogroups present in the Iban are associated with populations of Southeast Asia. We conclude that migrations from Southeast Asia made a large contribution to Iban ancestry, although evidence of potential gene flow from Taiwan is also seen in uniparentally inherited marker data.

  7. Ancestry of the Iban is predominantly Southeast Asian: genetic evidence from autosomal, mitochondrial, and Y chromosomes.

    Science.gov (United States)

    Simonson, Tatum S; Xing, Jinchuan; Barrett, Robert; Jerah, Edward; Loa, Peter; Zhang, Yuhua; Watkins, W Scott; Witherspoon, David J; Huff, Chad D; Woodward, Scott; Mowry, Bryan; Jorde, Lynn B

    2011-01-01

    Humans reached present-day Island Southeast Asia (ISEA) in one of the first major human migrations out of Africa. Population movements in the millennia following this initial settlement are thought to have greatly influenced the genetic makeup of current inhabitants, yet the extent attributed to different events is not clear. Recent studies suggest that south-to-north gene flow largely influenced present-day patterns of genetic variation in Southeast Asian populations and that late Pleistocene and early Holocene migrations from Southeast Asia are responsible for a substantial proportion of ISEA ancestry. Archaeological and linguistic evidence suggests that the ancestors of present-day inhabitants came mainly from north-to-south migrations from Taiwan and throughout ISEA approximately 4,000 years ago. We report a large-scale genetic analysis of human variation in the Iban population from the Malaysian state of Sarawak in northwestern Borneo, located in the center of ISEA. Genome-wide single-nucleotide polymorphism (SNP) markers analyzed here suggest that the Iban exhibit greatest genetic similarity to Indonesian and mainland Southeast Asian populations. The most common non-recombining Y (NRY) and mitochondrial (mt) DNA haplogroups present in the Iban are associated with populations of Southeast Asia. We conclude that migrations from Southeast Asia made a large contribution to Iban ancestry, although evidence of potential gene flow from Taiwan is also seen in uniparentally inherited marker data. PMID:21305013

  8. Forensic ancestry analysis with two capillary electrophoresis ancestry informative marker (AIM) panels: Results of a collaborative EDNAP exercise.

    Science.gov (United States)

    Santos, C; Fondevila, M; Ballard, D; Banemann, R; Bento, A M; Børsting, C; Branicki, W; Brisighelli, F; Burrington, M; Capal, T; Chaitanya, L; Daniel, R; Decroyer, V; England, R; Gettings, K B; Gross, T E; Haas, C; Harteveld, J; Hoff-Olsen, P; Hoffmann, A; Kayser, M; Kohler, P; Linacre, A; Mayr-Eduardoff, M; McGovern, C; Morling, N; O'Donnell, G; Parson, W; Pascali, V L; Porto, M J; Roseth, A; Schneider, P M; Sijen, T; Stenzl, V; Court, D Syndercombe; Templeton, J E; Turanska, M; Vallone, P M; van Oorschot, R A H; Zatkalikova, L; Carracedo, Á; Phillips, C

    2015-11-01

    There is increasing interest in forensic ancestry tests, which are part of a growing number of DNA analyses that can enhance routine profiling by obtaining additional genetic information about unidentified DNA donors. Nearly all ancestry tests use single nucleotide polymorphisms (SNPs), but these currently rely on SNaPshot single base extension chemistry that can fail to detect mixed DNA. Insertion-deletion polymorphism (Indel) tests have been developed using dye-labeled primers that allow direct capillary electrophoresis detection of PCR products (PCR-to-CE). PCR-to-CE maintains the direct relationship between input DNA and signal strength as each marker is detected with a single dye, so mixed DNA is more reliably detected. We report the results of a collaborative inter-laboratory exercise of 19 participants (15 from the EDNAP European DNA Profiling group) that assessed a 34-plex SNP test using SNaPshot and a 46-plex Indel test using PCR-to-CE. Laboratories were asked to type five samples with different ancestries and detect an additional mixed DNA sample. Statistical inference of ancestry was made by participants using the Snipper online Bayes analysis portal plus an optional PCA module that analyzes the genotype data alongside calculation of Bayes likelihood ratios. Exercise results indicated consistent genotyping performance from both tests, reaching a particularly high level of reliability for the Indel test. SNP genotyping gave 93.5% concordance (compared to the organizing laboratory's data) that rose to 97.3% excluding one laboratory with a large number of miscalled genotypes. Indel genotyping gave a higher concordance rate of 99.8% and a reduced no-call rate compared to SNP analysis. All participants detected the mixture from their Indel peak height data and successfully assigned the correct ancestry to the other samples using Snipper, with the exception of one laboratory with SNP miscalls that incorrectly assigned ancestry of two samples and did not obtain

  9. The Genetics of Bene Israel from India Reveals Both Substantial Jewish and Indian Ancestry

    Science.gov (United States)

    Davidson, Natalie R.; Billing-Ross, Paul; Dubrovsky, Maya; Campbell, Christopher L.; Oddoux, Carole; Friedman, Eitan; Atzmon, Gil; Halperin, Eran; Ostrer, Harry; Keinan, Alon

    2016-01-01

    The Bene Israel Jewish community from West India is a unique population whose history before the 18th century remains largely unknown. Bene Israel members consider themselves as descendants of Jews, yet the identity of Jewish ancestors and their arrival time to India are unknown, with speculations on arrival time varying between the 8th century BCE and the 6th century CE. Here, we characterize the genetic history of Bene Israel by collecting and genotyping 18 Bene Israel individuals. Combining with 486 individuals from 41 other Jewish, Indian and Pakistani populations, and additional individuals from worldwide populations, we conducted comprehensive genome-wide analyses based on FST, principal component analysis, ADMIXTURE, identity-by-descent sharing, admixture linkage disequilibrium decay, haplotype sharing and allele sharing autocorrelation decay, as well as contrasted patterns between the X chromosome and the autosomes. The genetics of Bene Israel individuals resemble local Indian populations, while at the same time constituting a clearly separated and unique population in India. They are unique among Indian and Pakistani populations we analyzed in sharing considerable genetic ancestry with other Jewish populations. Putting together the results from all analyses point to Bene Israel being an admixed population with both Jewish and Indian ancestry, with the genetic contribution of each of these ancestral populations being substantial. The admixture took place in the last millennium, about 19–33 generations ago. It involved Middle-Eastern Jews and was sex-biased, with more male Jewish and local female contribution. It was followed by a population bottleneck and high endogamy, which can lead to increased prevalence of recessive diseases in this population. This study provides an example of how genetic analysis advances our knowledge of human history in cases where other disciplines lack the relevant data to do so. PMID:27010569

  10. Phylogenomic evidence of adaptive evolution in the ancestry of humans

    OpenAIRE

    Goodman, Morris; Sterner, Kirstin N.

    2010-01-01

    In Charles Darwin’s tree model for life’s evolution, natural selection adaptively modifies newly arisen species as they branch apart from their common ancestor. In accord with this Darwinian concept, the phylogenomic approach to elucidating adaptive evolution in genes and genomes in the ancestry of modern humans requires a well supported and well sampled phylogeny that accurately places humans and other primates and mammals with respect to one another. For more than a century, first from the ...

  11. Infinitely long branches and an informal test of common ancestry

    OpenAIRE

    de Oliveira Martins, Leonardo; Posada, David

    2016-01-01

    Background The evidence for universal common ancestry (UCA) is vast and persuasive. A phylogenetic test has been proposed for quantifying its odds against independently originated sequences based on the comparison between one versus several trees. This test was successfully applied to a well-supported homologous sequence alignment, which was however criticized on the basis of simulations showing that alignments without any phylogenetic structure could mislead its conclusions. Results Here we ...

  12. Ancestry Analysis in the 11-M Madrid Bomb Attack Investigation

    OpenAIRE

    Christopher Phillips; Lourdes Prieto; Manuel Fondevila; Antonio Salas; Antonio Gómez-Tato; José Alvarez-Dios; Antonio Alonso; Alejandro Blanco-Verea; María Brión; Marta Montesino; Angel Carracedo; María Victoria Lareu

    2009-01-01

    The 11-M Madrid commuter train bombings of 2004 constituted the second biggest terrorist attack to occur in Europe after Lockerbie, while the subsequent investigation became the most complex and wide-ranging forensic case in Spain. Standard short tandem repeat (STR) profiling of 600 exhibits left certain key incriminatory samples unmatched to any of the apprehended suspects. A judicial order to perform analyses of unmatched samples to differentiate European and North African ancestry became a...

  13. MHC-DAB allele polymorphism in Japanese flounders Paralichthys olivaceus

    OpenAIRE

    XU Tian-Jun; Chen, Song-Lin; Tian, Yong-Sheng

    2008-01-01

    Polymorphism of the major histocompatibility complex DAB gene in Japanese flounder (Paralichthys olivaceus) was investigated using sequences analysis. In this study, 24 individuals were selected to amplify partial exon1 and intron2, complete intron1 and exon2 of DAB gene. 131 sequences were subsequently used to analyze genetic variation and revealed 31 different sequences, which presented 31 novel alleles belonging to 19 allele major types according to accepted nomenclature rules. Frequency o...

  14. Genome-Wide Association of the Laboratory-Based Nicotine Metabolite Ratio in Three Ancestries

    Science.gov (United States)

    Baurley, James W.; Edlund, Christopher K.; Pardamean, Carissa I.; Conti, David V.; Krasnow, Ruth; Javitz, Harold S.; Hops, Hyman; Swan, Gary E.; Benowitz, Neal L.

    2016-01-01

    Introduction: Metabolic enzyme variation and other patient and environmental characteristics influence smoking behaviors, treatment success, and risk of related disease. Population-specific variation in metabolic genes contributes to challenges in developing and optimizing pharmacogenetic interventions. We applied a custom genome-wide genotyping array for addiction research (Smokescreen), to three laboratory-based studies of nicotine metabolism with oral or venous administration of labeled nicotine and cotinine, to model nicotine metabolism in multiple populations. The trans-3′-hydroxycotinine/cotinine ratio, the nicotine metabolite ratio (NMR), was the nicotine metabolism measure analyzed. Methods: Three hundred twelve individuals of self-identified European, African, and Asian American ancestry were genotyped and included in ancestry-specific genome-wide association scans (GWAS) and a meta-GWAS analysis of the NMR. We modeled natural-log transformed NMR with covariates: principal components of genetic ancestry, age, sex, body mass index, and smoking status. Results: African and Asian American NMRs were statistically significantly (P values ≤ 5E-5) lower than European American NMRs. Meta-GWAS analysis identified 36 genome-wide significant variants over a 43 kilobase pair region at CYP2A6 with minimum P = 2.46E-18 at rs12459249, proximal to CYP2A6. Additional minima were located in intron 4 (rs56113850, P = 6.61E-18) and in the CYP2A6-CYP2A7 intergenic region (rs34226463, P = 1.45E-12). Most (34/36) genome-wide significant variants suggested reduced CYP2A6 activity; functional mechanisms were identified and tested in knowledge-bases. Conditional analysis resulted in intergenic variants of possible interest (P values genome-wide association of CYP2A6 single nucleotide and insertion–deletion polymorphisms. We identify three regions of genome-wide significance: proximal, intronic, and distal to CYP2A6. We replicate the top-ranking single nucleotide polymorphism

  15. Allele coding in genomic evaluation

    Directory of Open Access Journals (Sweden)

    Christensen Ole F

    2011-06-01

    Full Text Available Abstract Background Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call this centered allele coding. This study considered effects of different allele coding methods on inference. Both marker-based and equivalent models were considered, and restricted maximum likelihood and Bayesian methods were used in inference. Results Theoretical derivations showed that parameter estimates and estimated marker effects in marker-based models are the same irrespective of the allele coding, provided that the model has a fixed general mean. For the equivalent models, the same results hold, even though different allele coding methods lead to different genomic relationship matrices. Calculated genomic breeding values are independent of allele coding when the estimate of the general mean is included into the values. Reliabilities of estimated genomic breeding values calculated using elements of the inverse of the coefficient matrix depend on the allele coding because different allele coding methods imply different models. Finally, allele coding affects the mixing of Markov chain Monte Carlo algorithms, with the centered coding being

  16. Ancestry analysis in the 11-M Madrid bomb attack investigation.

    Directory of Open Access Journals (Sweden)

    Christopher Phillips

    Full Text Available The 11-M Madrid commuter train bombings of 2004 constituted the second biggest terrorist attack to occur in Europe after Lockerbie, while the subsequent investigation became the most complex and wide-ranging forensic case in Spain. Standard short tandem repeat (STR profiling of 600 exhibits left certain key incriminatory samples unmatched to any of the apprehended suspects. A judicial order to perform analyses of unmatched samples to differentiate European and North African ancestry became a critical part of the investigation and was instigated to help refine the search for further suspects. Although mitochondrial DNA (mtDNA and Y-chromosome markers routinely demonstrate informative geographic differentiation, the populations compared in this analysis were known to show a proportion of shared mtDNA and Y haplotypes as a result of recent gene-flow across the western Mediterranean, while any two loci can be unrepresentative of the ancestry of an individual as a whole. We based our principal analysis on a validated 34plex autosomal ancestry-informative-marker single nucleotide polymorphism (AIM-SNP assay to make an assignment of ancestry for DNA from seven unmatched case samples including a handprint from a bag containing undetonated explosives together with personal items recovered from various locations in Madrid associated with the suspects. To assess marker informativeness before genotyping, we predicted the probable classification success for the 34plex assay with standard error estimators for a naïve Bayesian classifier using Moroccan and Spanish training sets (each n = 48. Once misclassification error was found to be sufficiently low, genotyping yielded seven near-complete profiles (33 of 34 AIM-SNPs that in four cases gave probabilities providing a clear assignment of ancestry. One of the suspects predicted to be North African by AIM-SNP analysis of DNA from a toothbrush was identified late in the investigation as Algerian in origin. The

  17. Optimum contribution selection combined with weighting rare favourable alleles increases long-term genetic gain

    DEFF Research Database (Denmark)

    Liu, Huiming; Sørensen, Anders Christian; Berg, Peer

    the selection strategy where optimum contribution selection (OCS) are combined with genomic estimated breeding values with additional weights on rare favorable alleles (wGEBV) will boost long-term genetic gain, while at the same time effectively controlling inbreeding. Six breeding schemes were...... simulated by combining GEBV or wGEBV and truncation selection (TS) or OCS. Optimum contribution selection was further categorized into OCSA and OCSG depending on whether pedigree (A) or genomic data (G) was used for penalizing average co-ancestry. The selection was performed for 40 generations. It was shown...

  18. Heterozygosity for Tay-Sachs and Sandhoff diseases in non-Jewish Americans with ancestry from Ireland, Great Britain, or Italy.

    Science.gov (United States)

    Branda, Kelly Johnston; Tomczak, Jerzy; Natowicz, Marvin R

    2004-01-01

    Previous reports have found that non-Jewish Americans with ancestry from Ireland have an increased frequency of heterozygosity for Tay-Sachs disease (TSD), although frequency estimates are substantially different. Our goal in this study was to determine the frequency of heterozygosity for TSD and Sandhoff diseases (SD) among Irish Americans, as well as in persons of English, Scottish, and/or Welsh ancestry and in individuals with Italian heritage, who were referred for determination of their heterozygosity status and who had no known family history of TSD or SD or of heterozygosity for these conditions. Of 610 nonpregnant subjects with Irish background, 24 TSD heterozygotes were identified by biochemical testing, corresponding to a heterozygote frequency of 1 in 25 (4%; 95% CI, 1/39-1/17). In comparison, of 322 nonpregnant individuals with ancestry from England, Scotland, or Wales, two TSD heterozygotes were identified (1 in 161 or 0.62%; 95% CI, 1/328-1/45), and three TSD heterozygotes were ascertained from 436 nonpregnant individuals with Italian heritage (1 in 145 or 0.69%; 95% CI, 1/714-1/50). Samples from 21 Irish heterozygotes were analyzed for HEXA gene mutations. Two (9.5%) Irish heterozygotes had the lethal + 1 IVS-9 G --> A mutation, whereas 9 (42.8%) had a benign pseudodeficiency mutation. No mutation was found in 10 (47.6%) heterozygotes. These data allow for a frequency estimate of deleterious alleles for TSD among Irish Americans of 1 in 305 (95% CI, 1/2517-1/85) to 1 in 41 (95% CI, 1/72-1/35), depending on whether one, respectively, excludes or includes enzyme-defined heterozygotes lacking a defined deleterious mutation. Pseudodeficiency mutations were identified in both of the heterozygotes with ancestry from other countries in the British Isles, suggesting that individuals with ancestry from these countries do not have an increased rate of TSD heterozygosity. Four SD heterozygotes were found among individuals of Italian descent, a frequency of 1 in

  19. Phylogeography and Genetic Ancestry of Tigers (Panthera tigris

    Directory of Open Access Journals (Sweden)

    Luo Shu-Jin

    2004-01-01

    Full Text Available Eight traditional subspecies of tiger (Panthera tigris, of which three recently became extinct, are commonly recognized on the basis of geographic isolation and morphological characteristics. To investigate the species' evolutionary history and to establish objective methods for subspecies recognition, voucher specimens of blood, skin, hair, and/or skin biopsies from 134 tigers with verified geographic origins or heritage across the whole distribution range were examined for three molecular markers: (1 4.0 kb of mitochondrial DNA (mtDNA sequence; (2 allele variation in the nuclear major histocompatibility complex class II DRB gene; and (3 composite nuclear microsatellite genotypes based on 30 loci. Relatively low genetic variation with mtDNA, DRB, and microsatellite loci was found, but significant population subdivision was nonetheless apparent among five living subspecies. In addition, a distinct partition of the Indochinese subspecies P. t. corbetti into northern Indochinese and Malayan Peninsula populations was discovered. Population genetic structure would suggest recognition of six taxonomic units or subspecies: (1 Amur tiger P. t. altaica; (2 northern Indochinese tiger P. t. corbetti; (3 South China tiger P. t. amoyensis; (4 Malayan tiger P. t. jacksoni, named for the tiger conservationist Peter Jackson; (5 Sumatran tiger P. t. sumatrae; and (6 Bengal tiger P. t. tigris. The proposed South China tiger lineage is tentative due to limited sampling. The age of the most recent common ancestor for tiger mtDNA was estimated to be 72,000-108,000 y, relatively younger than some other Panthera species. A combination of population expansions, reduced gene flow, and genetic drift following the last genetic diminution, and the recent anthropogenic range contraction, have led to the distinct genetic partitions. These results provide an explicit basis for subspecies recognition and will lead to the improved management and conservation of these recently

  20. Analysis of the distribution of HLA-A alleles in populations from five continents.

    Science.gov (United States)

    Middleton, D; Williams, F; Meenagh, A; Daar, A S; Gorodezky, C; Hammond, M; Nascimento, E; Briceno, I; Perez, M P

    2000-10-01

    The variation and frequency of HLA-A genotypes were established by PCR-SSOP typing in diverse geographically distributed populations: Brazilian, Colombian Kogui, Cuban, Mexican, Omani, Singapore Chinese, and South African Zulu. HLA-A allelic families with only one allele were identified for HLA-A*01, -A*23, -A*25, -A*31, -A*32, -A*36, -A*43, -A*69, -A*80; and with two alleles for HLA-A*03, -A*11, -A*26, -A*29, -A*33, -A*34, and -A*66. Greater variation was detected for HLA-A*02, -A*24, and -A*68 allele families. Colombian Kogui and Mexican Seris showed the least diversity with respect to HLA-A alleles, albeit with small numbers tested, with only four and five HLA-A alleles identified, respectively. It would appear by their presence in all populations studied, either rural or indigenous, that certain alleles are very important in pathogen peptide presentation. PMID:11082518

  1. A recurrent homozygous nonsense mutation within the LAMA3 gene as a cause of Herlitz junctional epidermolysis bullosa in patients of Pakistani ancestry: evidence for a founder effect.

    Science.gov (United States)

    McGrath, J A; Kivirikko, S; Ciatti, S; Moss, C; Christiano, A M; Uitto, J

    1996-04-01

    The anchoring filament protein laminin 5 is abnormally expressed in the skin of patients with Herlitz junctional epidermolysis bullosa (H-JEB). In this study, we performed mutational analysis on genomic DNA from a H-JEB child of first-cousin Pakistani parents, and identified a homozygous C-to-T transition in the LAMA3 gene of laminin 5 resulting in a premature termination codon (CGA-TGA) on both alleles. This mutation, R650X, has been previously reported in two other seemingly unrelated H-JEB individuals of Pakistani ancestry. Although this mutation may represent a mutational hotspot within the LAMA3 gene, haplotype analysis based on a silent intragenic polymorphism (GCC/GCG, alanine 429; GenBank no. L34155), and on three flanking microsatellite polymorphism (D18S45, D18S478, and D18S480), suggests that a common ancestral allele may be present in all three cases. PMID:8618022

  2. From Bows to Sound-Chests: Tracing the Ancestry of the Violin

    Directory of Open Access Journals (Sweden)

    Janelle R. Finley

    2016-04-01

    Full Text Available The ancestry of the violin is a subject that has been studied, researched, debated, and written about in great detail. However, despite all of the research and study, the ancestry of the violin is still not certain. This paper presents two schools of thought that propose different theories as to how the ancestry of the violin should be determined and what instruments should be included in the ancestry of the violin. The first school of thought proposes that the violin’s ancestry should be traced through the bow. The second theory proposes that the violin’s ancestry should be traced through the sound-chest of the violin. This paper also presents the different arguments for and against each theory, the importance of this topic, and the paper’s position on this topic. Research for this paper was accomplished through the use of scholarly books on the subject of the history of the violin.

  3. Habitual Diets Rich in Dark-Green Vegetables Are Associated with an Increased Response to ω-3 Fatty Acid Supplementation in Americans of African Ancestry123

    OpenAIRE

    O’Sullivan, Aifric; Armstrong, Patrice; Schuster, Gertrud U.; Pedersen, Theresa L.; Allayee, Hooman; Stephensen, Charles B.; Newman, John W.

    2013-01-01

    Although substantial variation exists in individual responses to omega-3 (ω-3) (n–3) fatty acid supplementation, the causes for differences in response are largely unknown. Here we investigated the associations between the efficacy of ω-3 fatty acid supplementation and a broad range of nutritional and clinical factors collected during a double-blind, placebo-controlled trial in participants of African ancestry, randomly assigned to receive either 2 g eicosapentaenoic acid (EPA) + 1 g docosahe...

  4. Common alleles contribute to schizophrenia in CNV carriers

    Science.gov (United States)

    Tansey, K E; Rees, E; Linden, D E; Ripke, S; Chambert, K D; Moran, J L; McCarroll, S A; Holmans, P; Kirov, G; Walters, J; Owen, M J; O'Donovan, M C

    2016-01-01

    The genetic architecture of schizophrenia is complex, involving risk alleles ranging from common alleles of weak effect to rare alleles of large effect, the best exemplar of the latter being large copy number variants (CNVs). It is currently unknown whether pathophysiology in those with defined rare mutations overlaps with that in other individuals with the disorder who do not share the same rare mutation. Under an extreme heterogeneity model, carriers of specific high-penetrance mutations form distinct subgroups. In contrast, under a polygenic threshold model, high-penetrance rare allele carriers possess many risk factors, of which the rare allele is the only one, albeit an important, factor. Under the latter model, cases with rare mutations can be expected to share some common risk alleles, and therefore pathophysiological mechanisms, with cases without the same mutation. Here we show that, compared with controls, individuals with schizophrenia who have known pathogenic CNVs carry an excess burden of common risk alleles (P=2.25 × 10−17) defined from a genome-wide association study largely based on individuals without known CNVs. Our finding is not consistent with an extreme heterogeneity model for CNV carriers, but does offer support for the polygenic threshold model of schizophrenia. That this is so provides support for the notion that studies aiming to model the effects of rare variation may uncover pathophysiological mechanisms of relevance to those with the disorder more widely. PMID:26390827

  5. New Evidence on the Common Ancestry of Tetrapods and Lungfish

    Institute of Scientific and Technical Information of China (English)

    Zhao Baohua

    2002-01-01

    @@ As reported in a recent issue of Nature (Aug. 15, 2002),two Chinese scientists pinpoint their newly discovered fossil fish as the most direct piece of evi dence on the common ancestry shared by tetrapods (all land verte brates including human beings) and lungfish. This latest advance in studying the origin and evolution of early fishes was jointly made by Professor Zhu Min from the CAS Institute of Vertebrate Paleontology & Paleoanthropology and his colleague Yu Xiaobo, now a Professor at the Biology Department of Kean University (New Jersey, USA).

  6. Higher levels of neanderthal ancestry in East Asians than in Europeans.

    Science.gov (United States)

    Wall, Jeffrey D; Yang, Melinda A; Jay, Flora; Kim, Sung K; Durand, Eric Y; Stevison, Laurie S; Gignoux, Christopher; Woerner, August; Hammer, Michael F; Slatkin, Montgomery

    2013-05-01

    Neanderthals were a group of archaic hominins that occupied most of Europe and parts of Western Asia from ∼30,000 to 300,000 years ago (KYA). They coexisted with modern humans during part of this time. Previous genetic analyses that compared a draft sequence of the Neanderthal genome with genomes of several modern humans concluded that Neanderthals made a small (1-4%) contribution to the gene pools of all non-African populations. This observation was consistent with a single episode of admixture from Neanderthals into the ancestors of all non-Africans when the two groups coexisted in the Middle East 50-80 KYA. We examined the relationship between Neanderthals and modern humans in greater detail by applying two complementary methods to the published draft Neanderthal genome and an expanded set of high-coverage modern human genome sequences. We find that, consistent with the recent finding of Meyer et al. (2012), Neanderthals contributed more DNA to modern East Asians than to modern Europeans. Furthermore we find that the Maasai of East Africa have a small but significant fraction of Neanderthal DNA. Because our analysis is of several genomic samples from each modern human population considered, we are able to document the extent of variation in Neanderthal ancestry within and among populations. Our results combined with those previously published show that a more complex model of admixture between Neanderthals and modern humans is necessary to account for the different levels of Neanderthal ancestry among human populations. In particular, at least some Neanderthal-modern human admixture must postdate the separation of the ancestors of modern European and modern East Asian populations. PMID:23410836

  7. Allele coding in genomic evaluation

    DEFF Research Database (Denmark)

    Standen, Ismo; Christensen, Ole Fredslund

    2011-01-01

    Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker...... effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous...... estimates and estimated marker effects in marker-based models are the same irrespective of the allele coding, provided that the model has a fixed general mean. For the equivalent models, the same results hold, even though different allele coding methods lead to different genomic relationship matrices...

  8. Genome-wide Ancestry Patterns in Rapanui Suggest Pre-European Admixture with Native Americans

    DEFF Research Database (Denmark)

    Moreno-Mayar, J. Víctor; Rasmussen, Simon; Seguin-Orlando, Andaine;

    2014-01-01

    . We found a mostly Polynesian ancestry among Rapanui and detected genome-wide patterns consistent with Native American and European admixture. By considering the distribution of local ancestry tracts of eight unrelated Rapanui, we found statistical support for Native American admixture dating to AD...

  9. Frequencies of HID-ion ampliseq ancestry panel markers among greenlanders

    DEFF Research Database (Denmark)

    Espregueira Themudo, Gonçalo; Smidt Mogensen, Helle; Børsting, Claus;

    2016-01-01

    The HID-Ion AmpliSeq Ancestry Panel from Life Techologies includes 123 SNPs from the Seldin panel and 55 SNPs from Kidd panel in a single multiplex assay that helps to determine the continental biogeographic ancestry of individuals. We tested the panel on 104 Greenlanders, divided into a training...

  10. Ethnic variation in inflammatory profile in tuberculosis.

    Directory of Open Access Journals (Sweden)

    Anna K Coussens

    Full Text Available Distinct phylogenetic lineages of Mycobacterium tuberculosis (MTB cause disease in patients of particular genetic ancestry, and elicit different patterns of cytokine and chemokine secretion when cultured with human macrophages in vitro. Circulating and antigen-stimulated concentrations of these inflammatory mediators might therefore be expected to vary significantly between tuberculosis patients of different ethnic origin. Studies to characterise such variation, and to determine whether it relates to host or bacillary factors, have not been conducted. We therefore compared circulating and antigen-stimulated concentrations of 43 inflammatory mediators and 14 haematological parameters (inflammatory profile in 45 pulmonary tuberculosis patients of African ancestry vs. 83 patients of Eurasian ancestry in London, UK, and investigated the influence of bacillary and host genotype on these profiles. Despite having similar demographic and clinical characteristics, patients of differing ancestry exhibited distinct inflammatory profiles at presentation: those of African ancestry had lower neutrophil counts, lower serum concentrations of CCL2, CCL11 and vitamin D binding protein (DBP but higher serum CCL5 concentrations and higher antigen-stimulated IL-1 receptor antagonist and IL-12 secretion. These differences associated with ethnic variation in host DBP genotype, but not with ethnic variation in MTB strain. Ethnic differences in inflammatory profile became more marked following initiation of antimicrobial therapy, and immunological correlates of speed of elimination of MTB from the sputum differed between patients of African vs. Eurasian ancestry. Our study demonstrates a hitherto unappreciated degree of ethnic heterogeneity in inflammatory profile in tuberculosis patients that associates primarily with ethnic variation in host, rather than bacillary, genotype. Candidate immunodiagnostics and immunological biomarkers of response to antimicrobial therapy

  11. Ethnic background and genetic variation in the evaluation of cancer risk: a systematic review.

    Directory of Open Access Journals (Sweden)

    Lijun Jing

    Full Text Available The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort's ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be

  12. An assessment of the portability of ancestry informative markers between human populations

    Directory of Open Access Journals (Sweden)

    Stoneking Mark

    2009-07-01

    Full Text Available Abstract Background Recent work has shown that population stratification can have confounding effects on genetic association studies and statistical methods have been developed to correct for these effects. Subsets of markers that are highly-differentiated between populations, ancestry-informative markers (AIMs, have been used to correct for population stratification. Often AIMs are discovered in one set of populations and then employed in a different set of populations. The underlying assumption in these cases is that the population under study has the same substructure as the population in which the AIMs were discovered. The present study assesses this assumption and evaluates the portability between worldwide populations of 10 SNPs found to be highly-differentiated within Britain (BritAIMs. Methods We genotyped 10 BritAIMs in ~1000 individuals from 53 populations worldwide. We assessed the degree to which these 10 BritAIMs capture population stratification in other groups of populations by use of the Fst statistic. We used Fst values from 2750 random markers typed in the same set of individuals as an empirical distribution to which the Fst values of the 10 BritAIMs were compared. Results Allele frequency differences between continental groups for the BritAIMs are not unusually high. This is also the case for comparisons within continental groups distantly related to Britain. However, two BritAIMs show high Fst between European populations and two BritAIMs show high Fst between populations from the Middle East. Overall the median Fst across all BritAIMs is not unusually high compared to the empirical distribution. Conclusion We find that BritAIMs are generally not useful to distinguish between continental groups or within continental groups distantly related to Britain. Moreover, our analyses suggest that the portability of AIMs across geographical scales (e.g. between Europe and Britain can be limited and should therefore be taken into

  13. DRD4 dopamine receptor allelic diversity in various primate species

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, M.; Higley, D. [NIAAA, Rockville, MD (United States); O`Brien, S. [NCI, Frederick, MD (United States)] [and others

    1994-09-01

    The DRD4 dopamine receptor is uniquely characterized by a 48 bp repeating segment within the coding region, located in exon III. Different DRD4 alleles are produced by the presence of additional 48 bp repeats, each of which adds 16 amino acids to the length of the 3rd intracytoplasmic loop of the receptor. The DRD4 receptor is therefore an intriguing candidate gene for behaviors which are influenced by dopamine function. In several human populations, DRD4 alleles with 2-8 and 10 repeats have previously been identified, and the 4 and 7 repeat alleles are the most abundant. We have determined DRD4 genotypes in the following nonhuman primate species: chimpanzee N=2, pygmy chimpanzee N=2, gorilla N=4, siamang N=2, Gelada baboon N=1, gibbon N=1, orangutan (Bornean and Sumatran) N=62, spider monkey N=4, owl monkey N=1, Colobus monkey N=1, Patas monkey N=1, ruffed lemur N=1, rhesus macaque N=8, and vervet monkey N=28. The degree of DRD4 polymorphism and which DRD4 alleles were present both showed considerable variation across primate species. In contrast to the human, rhesus macaque monkeys were monomorphic. The 4 and 7 repeat allels, highly abundant in the human, may not be present in certain other primates. For example, the four spider monkeys we studied showed the 7, 8 and 9 repeat length alleles and the only gibbon we analyzed was homozygous for the 9 repeat allele (thus far not observed in the human). Genotyping of other primate species and sequencing of the individual DRD4 repeat alleles in different species may help us determine the ancestral DRD4 repeat length and identify connections between DRD4 genotype and phenotype.

  14. Spread of pedigree versus genetic ancestry in spatially distributed populations.

    Science.gov (United States)

    Kelleher, J; Etheridge, A M; Véber, A; Barton, N H

    2016-04-01

    Ancestral processes are fundamental to modern population genetics and spatial structure has been the subject of intense interest for many years. Despite this interest, almost nothing is known about the distribution of the locations of pedigree or genetic ancestors. Using both spatially continuous and stepping-stone models, we show that the distribution of pedigree ancestors approaches a travelling wave, for which we develop two alternative approximations. The speed and width of the wave are sensitive to the local details of the model. After a short time, genetic ancestors spread far more slowly than pedigree ancestors, ultimately diffusing out with radius ∼t rather than spreading at constant speed. In contrast to the wave of pedigree ancestors, the spread of genetic ancestry is insensitive to the local details of the models. PMID:26546979

  15. Disparities in allele frequencies and population differentiation for 101 disease-associated single nucleotide polymorphisms between Puerto Ricans and non-Hispanic whites

    Science.gov (United States)

    Background: Variations in gene allele frequencies can contribute to differences in the prevalence of some common complex diseases among populations. Natural selection modulates the balance in allele frequencies across populations. Population differentiation (FST) can evidence environmental selection...

  16. The role of inflammatory pathway genetic variation on maternal metabolic phenotypes during pregnancy.

    Directory of Open Access Journals (Sweden)

    Margrit Urbanek

    Full Text Available BACKGROUND: Since mediators of inflammation are associated with insulin resistance, and the risk of developing diabetes mellitus and gestational diabetes, we hypothesized that genetic variation in members of the inflammatory gene pathway impact glucose levels and related phenotypes in pregnancy. We evaluated this hypothesis by testing for association between genetic variants in 31 inflammatory pathway genes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO cohort, a large multiethnic multicenter study designed to address the impact of glycemia less than overt diabetes on pregnancy outcome. RESULTS: Fasting, 1-hour, and 2-hour glucose, fasting and 1-hour C-peptide, and HbA1c levels were measured in blood samples obtained from HAPO participants during an oral glucose tolerance test at 24-32 weeks gestation. We tested for association between 458 SNPs mapping to 31 genes in the inflammatory pathway and metabolic phenotypes in 3836 European ancestry and 1713 Thai pregnant women. The strongest evidence for association was observed with TNF alpha and HbA1c (rs1052248; 0.04% increase per allele C; p-value = 4.4×10(-5, RETN and fasting plasma glucose (rs1423096; 0.7 mg/dl decrease per allele A; p-value = 1.1×10(-4, IL8 and 1 hr plasma glucose (rs2886920; 2.6 mg/dl decrease per allele T; p-value = 1.3×10(-4, ADIPOR2 and fasting C-peptide (rs2041139; 0.55 ug/L decrease per allele A; p-value = 1.4×10(-4, LEPR and 1-hour C-peptide (rs1171278; 0.62 ug/L decrease per allele T; p-value = 2.4×10(-4, and IL6 and 1-hour plasma glucose (rs6954897; -2.29 mg/dl decrease per allele G, p-value = 4.3×10(-4. CONCLUSIONS: Based on the genes surveyed in this study the inflammatory pathway is unlikely to have a strong impact on maternal metabolic phenotypes in pregnancy although variation in individual members of the pathway (e.g. RETN, IL8, ADIPOR2, LEPR, IL6, and TNF alpha, may contribute to metabolic phenotypes in pregnant women.

  17. Influence of admixture components on CYP2C9*2 allele frequency in eight indigenous populations from Northwest Mexico.

    Science.gov (United States)

    Sosa-Macías, M; Lazalde-Ramos, B P; Galaviz-Hernández, C; Rangel-Villalobos, H; Salazar-Flores, J; Martínez-Sevilla, V M; Martínez-Fierro, M L; Dorado, P; Wong, M L; Licinio, J; LLerena, A

    2013-12-01

    We previously documented the lowest frequency of CYP2C9*2 in Mexican indigenous Tepehuanos followed by Mestizos and Mexican-Americans populations, suggesting a negative correlation between the CYP2C9*2 frequency and the degree of Asian ancestry in indigenous Americans. We determined the influence of ethnic admixture components on the CYP2C9 allele distribution in 505 Amerindian from eight indigenous populations through genotyping CYP2C9*2, *3 and *6 alleles by real-time PCR and molecular evaluation of ancestry. The frequencies for CYP2C9*2 were 0.026 in Seris and 0.057 in Mayos, being higher than in Asians (P<0.001). CYP2C9*3 was found in Tarahumaras (0.104), Mayos (0.091), Tepehuanos (0.075), Guarijíos (0.067), Huicholes (0.033) and Coras (0.037), with East Asians having lower frequencies than the former three groups (P<0.001). CYP2C9*6 was not found. The frequency of CYP2C9*2 was lower in Amerindians than in European populations, and higher than their Asian ancestors. The presence of this allele in ethnic groups in Mexico can be explained by European admixture. PMID:23358499

  18. Estimating allele age and selection coefficient from Time-serial data

    DEFF Research Database (Denmark)

    Malaspinas, Anna Sapfo; Malaspinas, Orestis; Evans, Steven N.;

    2012-01-01

    age of an allele from time-serial data. Our method can be used for allele frequencies sampled from a single diallelic locus. The transition probabilities are calculated by approximating the standard diffusion equation of the Wright–Fisher model with a one-step process. We show that our method...... the age of the allele, it is possible to gain traction on the important problem of distinguishing selection on new mutations from selection on standing variation. In this coat color example for instance, we estimate the age of this allele, which is found to predate domestication....

  19. Impact of ancestry and body size on sonographic ulnar nerve dimensions

    International Nuclear Information System (INIS)

    Introduction: The purpose of this study was to investigate the impact that geographic ancestry and body size have on ultrasonographic measurements of the ulnar nerve size measured at the elbow. Materials and methods: We performed anthropometric measurements of body size and ultrasonographic measurements of the ulnar nerve at the elbow on 13 Vietnamese and 24 European participants. Regression analysis was used to determine the effect of body size and geographic ancestry on ulnar nerve size. Results: BMI had the greatest impact on ulnar nerve size. The short axis diameter was least resilient, and the long axis diameter was the most resilient to the effects of body size and geographic ancestry. Discussion: The long axis diameter has an apparent immunity to the influences of overall body size, arm size, or geographic ancestry and has the most potential as a sensitive discriminator between normal nerves and nerves affected by ulnar neuropathy at the elbow.

  20. Multilocus Inherited Neoplasia Alleles Syndrome

    DEFF Research Database (Denmark)

    Whitworth, James; Skytte, Anne-Bine; Sunde, Lone; Lim, Derek H; Arends, Mark J; Happerfield, Lisa; Frayling, Ian M; van Minkelen, Rick; Woodward, Emma R; Tischkowitz, Marc D; Maher, Eamonn R

    Mendelian causes of inherited cancer susceptibility are mostly rare and characterized by variable expression and incomplete penetrance. Phenotypic variability may result from a range of causes including locus heterogeneity, allelic heterogeneity, genetic and environmental modifier effects, or...... chance. Another potential cause is the presence of 2 or more inherited cancer predisposition alleles in the same individual. Although the frequency of such occurrences might be predicted to be low, such cases have probably been underascertained because standard clinical practice has been to test...... candidate inherited cancer genes sequentially until a pathogenic mutation is detected. However, recent advances in next-generation sequencing technologies now provide the opportunity to perform simultaneous parallel testing of large numbers of inherited cancer genes. Herein we provide examples of patients...

  1. Genetic identification of Theobroma cacao L. trees with high Criollo ancestry in Soconusco, Chiapas, Mexico.

    Science.gov (United States)

    Vázquez-Ovando, J A; Molina-Freaner, F; Nuñez-Farfán, J; Ovando-Medina, I; Salvador-Figueroa, M

    2014-01-01

    Criollo-type cacao trees are an important pool of genes with potential to be used in cacao breeding and selection programs. For that reason, we assessed the diversity and population structure of Criollo-type trees (108 cultivars with Criollo phenotypic characteristics and 10 Criollo references) using 12 simple sequence repeat (SSR) markers. Cultivars were selected from 7 demes in the Soconusco region of southern Mexico. SSRs amplified 74 alleles with an average of 3.6 alleles per population. The overall populations showed an average observed heterozygosity of 0.28, indicating heterozygote deficiency (average fixation index F = 0.50). However, moderate allelic diversity was found within populations (Shannon index for all populations I = 0.97). Bayesian method analysis determined 2 genetic clusters (K = 2) within individuals. In concordance, an assignment test grouped 37 multilocus genotypes (including 10 references) into a first cluster (Criollo), 54 into a second (presumably Amelonado), and 27 admixed individuals unassigned at the 90% threshold likely corresponding to the Trinitario genotype. This classification was supported by the principal coordinate analysis and analysis of molecular variance, which showed 12% of variation among populations (FST = 0.123, P cocoa. PMID:25511024

  2. Genetic Ancestry-Smoking Interactions and Lung Function in African Americans: A Cohort Study

    OpenAIRE

    Aldrich, Melinda C.; Kumar, Rajesh; Colangelo, Laura A.; Williams, L. Keoki; Sen, Saunak; Kritchevsky, Stephen B.; Meibohm, Bernd; Galanter, Joshua; Hu, Donglei; Gignoux, Christopher R.; Liu, Yongmei; Harris, Tamara B.; Ziv, Elad; Zmuda, Joseph; Garcia, Melissa

    2012-01-01

    Background Smoking tobacco reduces lung function. African Americans have both lower lung function and decreased metabolism of tobacco smoke compared to European Americans. African ancestry is also associated with lower pulmonary function in African Americans. We aimed to determine whether African ancestry modifies the association between smoking and lung function and its rate of decline in African Americans. Methodology/Principal Findings We evaluated a prospective ongoing cohort of 1,281 Afr...

  3. Amerind ancestry, socioeconomic status and the genetics of type 2 diabetes in a Colombian population.

    Directory of Open Access Journals (Sweden)

    Desmond D Campbell

    Full Text Available The "thrifty genotype" hypothesis proposes that the high prevalence of type 2 diabetes (T2D in Native Americans and admixed Latin Americans has a genetic basis and reflects an evolutionary adaptation to a past low calorie/high exercise lifestyle. However, identification of the gene variants underpinning this hypothesis remains elusive. Here we assessed the role of Native American ancestry, socioeconomic status (SES and 21 candidate gene loci in susceptibility to T2D in a sample of 876 T2D cases and 399 controls from Antioquia (Colombia. Although mean Native American ancestry is significantly higher in T2D cases than in controls (32% v 29%, this difference is confounded by the correlation of ancestry with SES, which is a stronger predictor of disease status. Nominally significant association (P1 was observed for markers selected from previous T2D genome-wide association studies, consistent with a role for Old World variants in susceptibility to T2D in Latin Americans. No association was found to the only known Native American-specific gene variant previously associated with T2D in a Mexican sample (rs9282541 in ABCA1. An admixture mapping scan with 1,536 ancestry informative markers (AIMs did not identify genome regions with significant deviation of ancestry in Antioquia. Exclusion analysis indicates that this scan rules out ~95% of the genome as harboring loci with ancestry risk ratios >1.22 (at P < 0.05.

  4. Regional differences in awareness and attitudes regarding genetic testing for disease risk and ancestry.

    Science.gov (United States)

    Jonassaint, Charles R; Santos, Eunice R; Glover, Crystal M; Payne, Perry W; Fasaye, Grace-Ann; Oji-Njideka, Nefertiti; Hooker, Stanley; Hernandez, Wenndy; Foster, Morris W; Kittles, Rick A; Royal, Charmaine D

    2010-09-01

    Little is known about the lay public's awareness and attitudes concerning genetic testing and what factors influence their perspectives. The existing literature focuses mainly on ethnic and socioeconomic differences; however, here we focus on how awareness and attitudes regarding genetic testing differ by geographical regions in the US. We compared awareness and attitudes concerning genetic testing for disease risk and ancestry among 452 adults (41% Black and 67% female) in four major US cities, Norman, OK; Cincinnati, OH; Harlem, NY; and Washington, DC; prior to their participation in genetic ancestry testing. The OK participants reported more detail about their personal ancestries (p = 0.02) and valued ancestry testing over disease testing more than all other sites (p < 0.01). The NY participants were more likely than other sites to seek genetic testing for disease (p = 0.01) and to see benefit in finding out more about one's ancestry (p = 0.02), while the DC participants reported reading and hearing more about genetic testing for African ancestry than all other sites (p < 0.01). These site differences were not better accounted for by sex, age, education, self-reported ethnicity, religion, or previous experience with genetic testing/counseling. Regional differences in awareness and attitudes transcend traditional demographic predictors, such as ethnicity, age and education. Local sociocultural factors, more than ethnicity and socioeconomic status, may influence the public's awareness and belief systems, particularly with respect to genetics. PMID:20549517

  5. Tissue-specific patterns of allelically-skewed DNA methylation

    Science.gov (United States)

    Marzi, Sarah J.; Meaburn, Emma L.; Dempster, Emma L.; Lunnon, Katie; Paya-Cano, Jose L.; Smith, Rebecca G.; Volta, Manuela; Troakes, Claire; Schalkwyk, Leonard C.; Mill, Jonathan

    2016-01-01

    ABSTRACT While DNA methylation is usually thought to be symmetrical across both alleles, there are some notable exceptions. Genomic imprinting and X chromosome inactivation are two well-studied sources of allele-specific methylation (ASM), but recent research has indicated a more complex pattern in which genotypic variation can be associated with allelically-skewed DNA methylation in cis. Given the known heterogeneity of DNA methylation across tissues and cell types we explored inter- and intra-individual variation in ASM across several regions of the human brain and whole blood from multiple individuals. Consistent with previous studies, we find widespread ASM with > 4% of the ∼220,000 loci interrogated showing evidence of allelically-skewed DNA methylation. We identify ASM flanking known imprinted regions, and show that ASM sites are enriched in DNase I hypersensitivity sites and often located in an extended genomic context of intermediate DNA methylation. We also detect examples of genotype-driven ASM, some of which are tissue-specific. These findings contribute to our understanding of the nature of differential DNA methylation across tissues and have important implications for genetic studies of complex disease. As a resource to the community, ASM patterns across each of the tissues studied are available in a searchable online database: http://epigenetics.essex.ac.uk/ASMBrainBlood. PMID:26786711

  6. Genetic ancestry of the extinct Javan and Bali tigers.

    Science.gov (United States)

    Xue, Hao-Ran; Yamaguchi, Nobuyuki; Driscoll, Carlos A; Han, Yu; Bar-Gal, Gila Kahila; Zhuang, Yan; Mazak, Ji H; Macdonald, David W; O'Brien, Stephen J; Luo, Shu-Jin

    2015-01-01

    The Bali (Panthera tigris balica) and Javan (P. t. sondaica) tigers are recognized as distinct tiger subspecies that went extinct in the 1940s and 1980s, respectively. Yet their genetic ancestry and taxonomic status remain controversial. Following ancient DNA procedures, we generated concatenated 1750bp mtDNA sequences from 23 museum samples including 11 voucher specimens from Java and Bali and compared these to diagnostic mtDNA sequences from 122 specimens of living tiger subspecies and the extinct Caspian tiger. The results revealed a close genetic affinity of the 3 groups from the Sunda Islands (Bali, Javan, and Sumatran tigers P. t. sumatrae). Bali and Javan mtDNA haplotypes differ from Sumatran haplotypes by 1-2 nucleotides, and the 3 island populations define a monophyletic assemblage distinctive and equidistant from other mainland subspecies. Despite this close phylogenetic relationship, no mtDNA haplotype was shared between Sumatran and Javan/Bali tigers, indicating little or no matrilineal gene flow among the islands after they were colonized. The close phylogenetic relationship among Sunda tiger subspecies suggests either recent colonization across the islands, or else a once continuous tiger population that had subsequently isolated into different island subspecies. This supports the hypothesis that the Sumatran tiger is the closest living relative to the extinct Javan and Bali tigers. PMID:25754539

  7. Resolving the ancestry of Austronesian-speaking populations.

    Science.gov (United States)

    Soares, Pedro A; Trejaut, Jean A; Rito, Teresa; Cavadas, Bruno; Hill, Catherine; Eng, Ken Khong; Mormina, Maru; Brandão, Andreia; Fraser, Ross M; Wang, Tse-Yi; Loo, Jun-Hun; Snell, Christopher; Ko, Tsang-Ming; Amorim, António; Pala, Maria; Macaulay, Vincent; Bulbeck, David; Wilson, James F; Gusmão, Leonor; Pereira, Luísa; Oppenheimer, Stephen; Lin, Marie; Richards, Martin B

    2016-03-01

    There are two very different interpretations of the prehistory of Island Southeast Asia (ISEA), with genetic evidence invoked in support of both. The "out-of-Taiwan" model proposes a major Late Holocene expansion of Neolithic Austronesian speakers from Taiwan. An alternative, proposing that Late Glacial/postglacial sea-level rises triggered largely autochthonous dispersals, accounts for some otherwise enigmatic genetic patterns, but fails to explain the Austronesian language dispersal. Combining mitochondrial DNA (mtDNA), Y-chromosome and genome-wide data, we performed the most comprehensive analysis of the region to date, obtaining highly consistent results across all three systems and allowing us to reconcile the models. We infer a primarily common ancestry for Taiwan/ISEA populations established before the Neolithic, but also detected clear signals of two minor Late Holocene migrations, probably representing Neolithic input from both Mainland Southeast Asia and South China, via Taiwan. This latter may therefore have mediated the Austronesian language dispersal, implying small-scale migration and language shift rather than large-scale expansion. PMID:26781090

  8. Invasive Allele Spread under Preemptive Competition

    OpenAIRE

    Yasi, J. A.; Korniss, G.; Caraco, T.

    2005-01-01

    We study a discrete spatial model for invasive allele spread in which two alleles compete preemptively, initially only the "residents" (weaker competitors) being present. We find that the spread of the advantageous mutation is well described by homogeneous nucleation; in particular, in large systems the time-dependent global density of the resident allele is well approximated by Avrami's law.

  9. Understanding the Y chromosome variation in Korea--relevance of combined haplogroup and haplotype analyses.

    Science.gov (United States)

    Park, Myung Jin; Lee, Hwan Young; Yang, Woo Ick; Shin, Kyoung-Jin

    2012-07-01

    We performed a molecular characterization of Korean Y-chromosomal haplogroups using a combination of Y-chromosomal single nucleotide polymorphisms (Y-SNPs) and Y-chromosomal short tandem repeats (Y-STRs). In a test using DNA samples from 706 Korean males, a total of 19 different haplogroups were identified by 26 Y-SNPs including the newly redefined markers (PK4, KL2, and P164) in haplogroup O. When genotyping the SNPs, phylogenetic nonequivalence was found between SNPs M117 and M133, which define haplogroup O3a3c1 (O3a2c1a according to the updated tree of haplogroup O by Yan et al. (European Journal of Human Genetics 19:1013-1015, 2011)), suggesting that the position of the M133 marker should be corrected. We have shown that the haplotypes consisted of DYS392, DYS393, DYS437, DYS438, DYS448, and DYS388 loci, which exhibit a relatively lower mutation rate, can preserve phylogenetic information and hence can be used to roughly distinguish Y-chromosome haplogroups, whereas more rapidly mutating Y-STRs such as DYS449 and DYS458 are useful for differentiating male lineages. However, at the relatively rapidly mutating DYS447, DYS449, DYS458, and DYS464 loci, unusually short alleles and intermediate alleles with common sequence structures are informative for elucidating the substructure within the context of a particular haplogroup. In addition, some deletion mutations in the DYS385 flanking region and the null allele at DYS448 were associated with a single haplogroup background. These high-resolution haplogroup and haplotype data will improve our understanding of regional Y-chromosome variation or recent migration routes and will also help to infer haplogroup background or common ancestry. PMID:22569803

  10. Inference of population splits and mixtures from genome-wide allele frequency data.

    Directory of Open Access Journals (Sweden)

    Joseph K Pickrell

    Full Text Available Many aspects of the historical relationships between populations in a species are reflected in genetic data. Inferring these relationships from genetic data, however, remains a challenging task. In this paper, we present a statistical model for inferring the patterns of population splits and mixtures in multiple populations. In our model, the sampled populations in a species are related to their common ancestor through a graph of ancestral populations. Using genome-wide allele frequency data and a Gaussian approximation to genetic drift, we infer the structure of this graph. We applied this method to a set of 55 human populations and a set of 82 dog breeds and wild canids. In both species, we show that a simple bifurcating tree does not fully describe the data; in contrast, we infer many migration events. While some of the migration events that we find have been detected previously, many have not. For example, in the human data, we infer that Cambodians trace approximately 16% of their ancestry to a population ancestral to other extant East Asian populations. In the dog data, we infer that both the boxer and basenji trace a considerable fraction of their ancestry (9% and 25%, respectively to wolves subsequent to domestication and that East Asian toy breeds (the Shih Tzu and the Pekingese result from admixture between modern toy breeds and "ancient" Asian breeds. Software implementing the model described here, called TreeMix, is available at http://treemix.googlecode.com.

  11. Demographic history and rare allele sharing among human populations

    OpenAIRE

    Henn, Brenna M.; Indap, Amit R.; Donnelly, Peter; Nickerson, Debbie A.; Peltonen, Leena; Deiros, David; Metzker, Mike; Li, Jingxiang; Jian, Min; Liang, Huiqing; Tian, Geng; Wang, Bo; Wang, Wei; Zhang, Xiuqing; Zheng, Huisong

    2011-01-01

    High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2–4× coverage data for 179 samples from HapMap European, As...

  12. Allele-specific enzymatic amplification of. beta. -globin genomic DNA for diagnosis of sickle cell anemia

    Energy Technology Data Exchange (ETDEWEB)

    Wu, D.Y.; Ugozzoli, L.; Pal, B.K.; Wallace, B. (Beckman Research Institute of the City of Hope, Duarte, CA (USA))

    1989-04-01

    A rapid nonradioactive approach to the diagnosis of sickle cell anemia is described based on an allele-specific polymerase chain reaction (ASPCR). This method allows direct detection of the normal or the sickle cell {beta}-globin allele in genomic DNA without additional steps of probe hybridization, ligation, or restriction enzyme cleavage. Two allele-specific oligonucleotide primers, one specific for the sickle cell allele and one specific for the normal allele, together with another primer complementary to both alleles were used in the polymerase chain reaction with genomic DNA templates. The allele-specific primers differed from each other in their terminal 3{prime} nucleotide. Under the proper annealing temperature and polymerase chain reaction conditions, these primers only directed amplification on their complementary allele. In a single blind study of DNA samples from 12 individuals, this method correctly and unambiguously allowed for the determination of the genotypes with no false negatives or positives. If ASPCR is able to discriminate all allelic variation (both transition and transversion mutations), this method has the potential to be a powerful approach for genetic disease diagnosis, carrier screening, HLA typing, human gene mapping, forensics, and paternity testing.

  13. Genetic Diversity Based on Allozyme Alleles of Chinese Cultivated Rice

    Institute of Scientific and Technical Information of China (English)

    TANG Sheng-xiang; WEI Xing-hua; JIANG Yun-zhu; D S Brar; G S Khush

    2007-01-01

    Genetic diversity was analyzed with 6 632 core rice cultivars selected from 60 282 Chinese rice accessions on the basis of 12 allozyme loci, Pgil, Pgi2, Ampl, Amp2, Amp3, Amp4, Sdh1, Adh1, Est1, Est2, Est5 and Est9, by starch gel electrophoresis. Among the materials examined, 52 alleles at 12 polymorphic loci were identified, which occupied 96.3% of 54 alleles found in cultivated germplasm of O.sativa L. The number of alleles per locus ranged from 2 to 7 with an average of 4.33. The gene diversity (He) each locus varied considerably from 0.017 for Amp4 to 0.583 for Est2 with an average gene diversity (Ht) 0.271, and Shannon-Wiener index from 0.055 to 0.946 with an average of 0.468. The degree of polymorphism (DP) was in a range from 0.9 to 46.9% with an average of 21.4%. It was found that the genetic diversity in japonica (Keng) subspecies was lower in terms of allele's number, Ht and S-W index, being 91.8, 66.2 and 75.7% of indica (Hsien) one, respectively. Significant genetic differentiation between indica and japonica rice has been appeared in the loci Pgil, Amp2, Pgi2, and Est2, with higher average coefficient of genetic differentiation (Gst) 0.635, 0.626, 0.322 and 0.282, respectively. Except less allele number per locus (3.33) for modern cultivars, being 76.9% of landraces, the Ht and S-W index showed in similar between the modern cultivars and the landraces detected. In terms of allozyme, the rice cultivars in the Southwest Plateau and Central China have richer genetic diversity. The present study reveals again that Chinese cultivated rice germplasm has rich genetic diversity, showed by the allozyme allele variation.

  14. Allele-specific DNA methylation reinforces PEAR1 enhancer activity.

    Science.gov (United States)

    Izzi, Benedetta; Pistoni, Mariaelena; Cludts, Katrien; Akkor, Pinar; Lambrechts, Diether; Verfaillie, Catherine; Verhamme, Peter; Freson, Kathleen; Hoylaerts, Marc F

    2016-08-18

    Genetic variation in the PEAR1 locus is linked to platelet reactivity and cardiovascular disease. The major G allele of rs12041331, an intronic cytosine guanine dinucleotide-single-nucleotide polymorphism (CpG-SNP), is associated with higher PEAR1 expression in platelets and endothelial cells than the minor A allele. The molecular mechanism underlying this difference remains elusive. We have characterized the histone modification profiles of the intronic region surrounding rs12041331 and identified H3K4Me1 enhancer-specific enrichment for the region that covers the CpG-SNP. Interestingly, methylation studies revealed that the CpG site is fully methylated in leukocytes of GG carriers. Nuclear protein extracts from megakaryocytes, endothelial cells, vs control HEK-293 cells show a 3-fold higher affinity for the methylated G allele compared with nonmethylated G or A alleles in a gel electrophoretic mobility shift assay. To understand the positive relationship between methylation and gene expression, we studied DNA methylation at 4 different loci of PEAR1 during in vitro megakaryopoiesis. During differentiation, the CpG-SNP remained fully methylated, while we observed rapid methylation increases at the CpG-island overlapping the first 5'-untranslated region exon, paralleling the increased PEAR1 expression. In the same region, A-allele carriers of rs12041331 showed significantly lower DNA methylation at CGI1 compared with GG homozygote. This CpG-island contains binding sites for the methylation-sensitive transcription factor CTCF, whose binding is known to play a role in enhancer activation and/or repression. In conclusion, we report the molecular characterization of the first platelet function-related CpG-SNP, a genetic predisposition that reinforces PEAR1 enhancer activity through allele-specific DNA methylation. PMID:27313330

  15. 春化、光周期和矮秆基因在不同国家小麦品种中的分布及其效应%Distribution of Allelic Variation for Vernalization, Photoperiod, and Dwarfing Genes and Their Effects on Growth Period and Plant Height among Cultivars from Major Wheat Producing Countries

    Institute of Scientific and Technical Information of China (English)

    杨芳萍; 李式昭; 何中虎; 夏先春; 张勇; 张晓科; 刘建军; 唐建卫; 杨学明; 张俊儒; 刘茜

    2012-01-01

    To efficiently use exotic resources in Chinese wheat breeding programs, we investigated the heading date, maturity date, and plant height of 100 representative cultivars collected from 14 countries at eight locations in China, and detected the allelic variations of vernalization loci VRN-1 and VRN-B3, photoperiod gene Ppd-Dla, and dwarfing genes Rht-Bib and Rht-Dib by means of molecular markers. The frequencies of vernalization loci were 8.0% for Vrn-Ala, 21.0% for Vrn-BI, 21.0% for Vrn-DI and 64.0% for vrn-AI+vm-BI+ vrn-Dl, except for the absence of dominant allele Vrn-B3 in all tested materials. Dominant vernalization alleles Vrn-Ala, Vm-BI, and Vm-DI were mainly observed in cultivars from Chinese spring wheat region, Italy, India, Canada, Mexico, and Australia; whereas, cultivars carrying all recessive alleles at the four vernalization loci and vm-AI+ vrn-DI+Vm-BI+vm-B3 genotype were mostly found in cultivars from Chinese winter wheat region, United States (US) winter wheat region, Russia winter wheat region, United Kingdom (UK), France, Germany, Romania, Turkey, and Hungary. All cultivars headed normally when sown in autumn. Cultivars with dominant alleles showed earlier heading date than those with recessive alleles, and genotypes with two or more dominant alleles showed additive effects. Some European and US cultivars with recessive genes at the four vernalization loci could not mature in Yangling and Chengdu. Under spring-sown condition, the cultivars with dominant vernalization alleles showed high heading frequency; in contrast, most cultivars with recessive alleles failed to head. Gene Ppd-Dla was distributed mainly in cultivars from China, France, Romania, Russia, Mexico, Australia, and India with the total frequency of 68%. Most cultivars with Ppd-Dlb were from high latitude regions, such as UK, Germany, Hungary, and Canada. The Ppd-Dla genotypes appeared to head earlier than the Ppd-Dlb genotypes. Daylight condition had no effect on maturity of most Ppd

  16. Genomic Insights into the Ancestry and Demographic History of South America.

    Directory of Open Access Journals (Sweden)

    Julian R Homburger

    2015-12-01

    Full Text Available South America has a complex demographic history shaped by multiple migration and admixture events in pre- and post-colonial times. Settled over 14,000 years ago by Native Americans, South America has experienced migrations of European and African individuals, similar to other regions in the Americas. However, the timing and magnitude of these events resulted in markedly different patterns of admixture throughout Latin America. We use genome-wide SNP data for 437 admixed individuals from 5 countries (Colombia, Ecuador, Peru, Chile, and Argentina to explore the population structure and demographic history of South American Latinos. We combined these data with population reference panels from Africa, Asia, Europe and the Americas to perform global ancestry analysis and infer the subcontinental origin of the European and Native American ancestry components of the admixed individuals. By applying ancestry-specific PCA analyses we find that most of the European ancestry in South American Latinos is from the Iberian Peninsula; however, many individuals trace their ancestry back to Italy, especially within Argentina. We find a strong gradient in the Native American ancestry component of South American Latinos associated with country of origin and the geography of local indigenous populations. For example, Native American genomic segments in Peruvians show greater affinities with Andean indigenous peoples like Quechua and Aymara, whereas Native American haplotypes from Colombians tend to cluster with Amazonian and coastal tribes from northern South America. Using ancestry tract length analysis we modeled post-colonial South American migration history as the youngest in Latin America during European colonization (9-14 generations ago, with an additional strong pulse of European migration occurring between 3 and 9 generations ago. These genetic footprints can impact our understanding of population-level differences in biomedical traits and, thus, inform

  17. Genomic Insights into the Ancestry and Demographic History of South America

    Science.gov (United States)

    Homburger, Julian R.; Moreno-Estrada, Andrés; Gignoux, Christopher R.; Nelson, Dominic; Sanchez, Elena; Ortiz-Tello, Patricia; Pons-Estel, Bernardo A.; Acevedo-Vasquez, Eduardo; Miranda, Pedro; Langefeld, Carl D.; Gravel, Simon; Alarcón-Riquelme, Marta E.; Bustamante, Carlos D.

    2015-01-01

    South America has a complex demographic history shaped by multiple migration and admixture events in pre- and post-colonial times. Settled over 14,000 years ago by Native Americans, South America has experienced migrations of European and African individuals, similar to other regions in the Americas. However, the timing and magnitude of these events resulted in markedly different patterns of admixture throughout Latin America. We use genome-wide SNP data for 437 admixed individuals from 5 countries (Colombia, Ecuador, Peru, Chile, and Argentina) to explore the population structure and demographic history of South American Latinos. We combined these data with population reference panels from Africa, Asia, Europe and the Americas to perform global ancestry analysis and infer the subcontinental origin of the European and Native American ancestry components of the admixed individuals. By applying ancestry-specific PCA analyses we find that most of the European ancestry in South American Latinos is from the Iberian Peninsula; however, many individuals trace their ancestry back to Italy, especially within Argentina. We find a strong gradient in the Native American ancestry component of South American Latinos associated with country of origin and the geography of local indigenous populations. For example, Native American genomic segments in Peruvians show greater affinities with Andean indigenous peoples like Quechua and Aymara, whereas Native American haplotypes from Colombians tend to cluster with Amazonian and coastal tribes from northern South America. Using ancestry tract length analysis we modeled post-colonial South American migration history as the youngest in Latin America during European colonization (9–14 generations ago), with an additional strong pulse of European migration occurring between 3 and 9 generations ago. These genetic footprints can impact our understanding of population-level differences in biomedical traits and, thus, inform future medical

  18. Genomic Insights into the Ancestry and Demographic History of South America.

    Science.gov (United States)

    Homburger, Julian R; Moreno-Estrada, Andrés; Gignoux, Christopher R; Nelson, Dominic; Sanchez, Elena; Ortiz-Tello, Patricia; Pons-Estel, Bernardo A; Acevedo-Vasquez, Eduardo; Miranda, Pedro; Langefeld, Carl D; Gravel, Simon; Alarcón-Riquelme, Marta E; Bustamante, Carlos D

    2015-12-01

    South America has a complex demographic history shaped by multiple migration and admixture events in pre- and post-colonial times. Settled over 14,000 years ago by Native Americans, South America has experienced migrations of European and African individuals, similar to other regions in the Americas. However, the timing and magnitude of these events resulted in markedly different patterns of admixture throughout Latin America. We use genome-wide SNP data for 437 admixed individuals from 5 countries (Colombia, Ecuador, Peru, Chile, and Argentina) to explore the population structure and demographic history of South American Latinos. We combined these data with population reference panels from Africa, Asia, Europe and the Americas to perform global ancestry analysis and infer the subcontinental origin of the European and Native American ancestry components of the admixed individuals. By applying ancestry-specific PCA analyses we find that most of the European ancestry in South American Latinos is from the Iberian Peninsula; however, many individuals trace their ancestry back to Italy, especially within Argentina. We find a strong gradient in the Native American ancestry component of South American Latinos associated with country of origin and the geography of local indigenous populations. For example, Native American genomic segments in Peruvians show greater affinities with Andean indigenous peoples like Quechua and Aymara, whereas Native American haplotypes from Colombians tend to cluster with Amazonian and coastal tribes from northern South America. Using ancestry tract length analysis we modeled post-colonial South American migration history as the youngest in Latin America during European colonization (9-14 generations ago), with an additional strong pulse of European migration occurring between 3 and 9 generations ago. These genetic footprints can impact our understanding of population-level differences in biomedical traits and, thus, inform future medical

  19. RHD allele distribution in Africans of Mali

    Directory of Open Access Journals (Sweden)

    Moulds Joann M

    2003-09-01

    Full Text Available Abstract Background Aberrant and non-functional RHD alleles are much more frequent in Africans than in Europeans. The DAU cluster of RHD alleles exemplifies that the alleles frequent in Africans have evaded recognition until recently. A comprehensive survey of RHD alleles in any African population was lacking. Results We surveyed the molecular structure and frequency of RHD alleles in Mali (West Africa by evaluating 116 haplotypes. Only 69% could be attributed to standard RHD (55% or the RHD deletion (14%. The aberrant RHD allele DAU-0 was predicted for 19%, RHDΨ for 7% and Ccdes for 4% of all haplotypes. DAU-3 and the new RHD allele RHD(L207F, dubbed DMA, were found in one haplotype each. A PCR-RFLP for the detection of the hybrid Rhesus box diagnostic for the RHD deletion in Europeans was false positive in 9 individuals, including all carriers of RHDΨ . Including two silent mutations and the RHD deletion, a total of 9 alleles could be differentiated. Conclusion Besides standard RHD and the RHD deletion, DAU-0, RHDΨ and Ccdes are major alleles in Mali. Our survey proved that the most frequent alleles of West Africans have been recognized allowing to devise reliable genotyping and phenotyping strategies.

  20. Admixture mapping of end stage kidney disease genetic susceptibility using estimated mutual information ancestry informative markers

    Directory of Open Access Journals (Sweden)

    Geiger Dan

    2010-10-01

    Full Text Available Abstract Background The question of a genetic contribution to the higher prevalence and incidence of end stage kidney disease (ESKD among African Americans (AA remained unresolved, until recent findings using admixture mapping pointed to the association of a genomic locus on chromosome 22 with this disease phenotype. In the current study we utilize this example to demonstrate the utility of applying a multi-step admixture mapping approach. Methods A multi-step case only admixture mapping study, consisted of the following steps was designed: 1 Assembly of the sample dataset (ESKD AA; 2 Design of the estimated mutual information ancestry informative markers (n = 2016 screening panel 3; Genotyping the sample set whose size was determined by a power analysis (n = 576 appropriate for the initial screening panel; 4 Inference of local ancestry for each individual and identification of regions with increased AA ancestry using two different ancestry inference statistical approaches; 5 Enrichment of the initial screening panel; 6 Power analysis of the enriched panel 7 Genotyping of additional samples. 8 Re-analysis of the genotyping results to identify a genetic risk locus. Results The initial screening phase yielded a significant peak using the ADMIXMAP ancestry inference program applying case only statistics. Subgroup analysis of 299 ESKD patients with no history of diabetes yielded peaks using both the ANCESTRYMAP and ADMIXMAP ancestry inference programs. The significant peak was found on chromosome 22. Genotyping of additional ancestry informative markers on chromosome 22 that took into account linkage disequilibrium in the ancestral populations, and the addition of samples increased the statistical significance of the finding. Conclusions A multi-step admixture mapping analysis of AA ESKD patients replicated the finding of a candidate risk locus on chromosome 22, contributing to the heightened susceptibility of African Americans to develop non

  1. Pedigree genotyping: a new pedigree-based approach of QTL identification and allele mining by exploiting breeding material

    OpenAIRE

    Weg, van de, H; Voorrips, R. E.; Finkers, H. J.; Kodde, L.P.; Meulenbroek, E.J.; Jansen, J; Bink, M.C.A.M.

    2005-01-01

    To date, molecular markers have been made available for many economically important traits. Unfortunately, lack of knowledge of their allelic variation hampers their full exploitation in commercial breeding programs. These markers have usually been identified in one single cross. Consequently, only one or two favourable alleles of the related QTL are identified and may be exploited for marker-assisted breeding (MAB), while a breeding program may include several alleles. Selection for only the...

  2. Estimating the age of alleles by use of intraallelic variability

    Energy Technology Data Exchange (ETDEWEB)

    Slatkin, M.; Rannala, B. [Univ of California, Berkeley, CA (United States)

    1997-02-01

    A method is presented for estimating the age of an allele by use of its frequency and the extent of variation among different copies. The method uses the joint distribution of the number of copies in a population sample and the coalescence times of the intraallelic gene genealogy conditioned on the number of copies. The linear birth-death process is used to approximate the dynamics of a rare allele in a finite population. A maximum-likelihood estimate of the age of the allele is obtained by Monte Carlo integration over the coalescence times. The method is applied to two alleles at the cystic fibrosis (CFTR) locus, {Delta}F508 and G542X, for which intraallelic variability at three intronic microsatellite loci has been examined. Our results indicate that G542X is somewhat older than {Delta}F508. Although absolute estimates depend on the mutation rates at the microsatellite loci, our results support the hypothesis that {Delta}F508 arose <500 generations ({approx}10,000 years) ago. 32 refs., 4 figs.

  3. Mosaic maternal ancestry in the Great Lakes region of East Africa.

    Science.gov (United States)

    Gomes, Verónica; Pala, Maria; Salas, Antonio; Álvarez-Iglesias, Vanesa; Amorim, António; Gómez-Carballa, Alberto; Carracedo, Ángel; Clarke, Douglas J; Hill, Catherine; Mormina, Maru; Shaw, Marie-Anne; Dunne, David W; Pereira, Rui; Pereira, Vânia; Prata, Maria João; Sánchez-Diz, Paula; Rito, Teresa; Soares, Pedro; Gusmão, Leonor; Richards, Martin B

    2015-09-01

    The Great Lakes lie within a region of East Africa with very high human genetic diversity, home of many ethno-linguistic groups usually assumed to be the product of a small number of major dispersals. However, our knowledge of these dispersals relies primarily on the inferences of historical, linguistics and oral traditions, with attempts to match up the archaeological evidence where possible. This is an obvious area to which archaeogenetics can contribute, yet Uganda, at the heart of these developments, has not been studied for mitochondrial DNA (mtDNA) variation. Here, we compare mtDNA lineages at this putative genetic crossroads across 409 representatives of the major language groups: Bantu speakers and Eastern and Western Nilotic speakers. We show that Uganda harbours one of the highest mtDNA diversities within and between linguistic groups, with the various groups significantly differentiated from each other. Despite an inferred linguistic origin in South Sudan, the data from the two Nilotic-speaking groups point to a much more complex history, involving not only possible dispersals from Sudan and the Horn but also large-scale assimilation of autochthonous lineages within East Africa and even Uganda itself. The Eastern Nilotic group also carries signals characteristic of West-Central Africa, primarily due to Bantu influence, whereas a much stronger signal in the Western Nilotic group suggests direct West-Central African ancestry. Bantu speakers share lineages with both Nilotic groups, and also harbour East African lineages not found in Western Nilotic speakers, likely due to assimilating indigenous populations since arriving in the region ~3000 years ago. PMID:26188410

  4. Allelic differences within and among sister spores of the arbuscular mycorrhizal fungus Glomus etunicatum suggest segregation at sporulation.

    Directory of Open Access Journals (Sweden)

    Eva Boon

    Full Text Available Arbuscular mycorrhizal fungi (AMF are root-inhabiting fungi that form mutualistic symbioses with their host plants. AMF are made up of coenocytic networks of hyphae through which nuclei and organelles can freely migrate. In this study, we investigated the possibility of a genetic bottleneck and segregation of allelic variation at sporulation for a low-copy Polymerase1-like gene, PLS. Specifically, our objectives were (1 to estimate what allelic diversity is passed on to a single spore (2 to determine whether this diversity is less than the total amount of variation found in all spores (3 to investigate whether there is any differential segregation of allelic variation. We inoculated three tomato plants with a single spore of Glomus etunicatum each and after six months sampled between two and three daughter spores per tomato plant. Pyrosequencing PLS amplicons in eight spores revealed high levels of allelic diversity; between 43 and 152 alleles per spore. We corroborated the spore pyrosequencing results with Sanger- and pyrosequenced allele distributions from the original parent isolate. Both sequencing methods retrieved the most abundant alleles from the offspring spore allele distributions. Our results indicate that individual spores contain only a subset of the total allelic variation from the pooled spores and parent isolate. Patterns of allele diversity between spores suggest the possibility for segregation of PLS alleles among spores. We conclude that a genetic bottleneck could potentially occur during sporulation in AMF, with resulting differences in genetic variation among sister spores. We suggest that the effects of this bottleneck may be countered by anastomosis (hyphal fusion between related hyphae.

  5. Ancestry Estimation in Forensic Anthropology: Geometric Morphometric versus Standard and Nonstandard Interlandmark Distances.

    Science.gov (United States)

    Katherine Spradley, M; Jantz, Richard L

    2016-07-01

    Standard cranial measurements are commonly used for ancestry estimation; however, 3D digitizers have made cranial landmark data collection and geometric morphometric (GM) analyses more popular within forensic anthropology. Yet there has been little focus on which data type works best. The goal of the present research is to test the discrimination ability of standard and nonstandard craniometric measurements and data derived from GM analysis. A total of 31 cranial landmarks were used to generate 465 interlandmark distances, including a subset of 20 commonly used measurements, and to generate principal component scores from procrustes coordinates. All were subjected to discriminant function analysis to ascertain which type of data performed best for ancestry estimation of American Black and White and Hispanic males and females. The nonstandard interlandmark distances generated the highest classification rates for females (90.5%) and males (88.2%). Using nonstandard interlandmark distances over more commonly used measurements leads to better ancestry estimates for our current population structure. PMID:27364267

  6. Allele frequency changes due to hitch-hiking in genomic selection programs

    DEFF Research Database (Denmark)

    Liu, Huiming; Sørensen, Anders Christian; Meuwissen, Theo H E;

    2014-01-01

    Background Genomic selection makes it possible to reduce pedigree-based inbreeding over best linear unbiased prediction (BLUP) by increasing emphasis on own rather than family information. However, pedigree inbreeding might not accurately reflect the loss of genetic variation and the true level of...... inbreeding due to changes in allele frequencies and hitch-hiking. This study aimed at understanding the impact of using long-term genomic selection on changes in allele frequencies, genetic variation and the level of inbreeding. Methods Selection was performed in simulated scenarios with a population of 400......-BLUP, Genomic BLUP and Bayesian Lasso. Changes in allele frequencies at QTL, markers and linked neutral loci were investigated for the different selection criteria and different scenarios, along with the loss of favourable alleles and the rate of inbreeding measured by pedigree and runs of homozygosity. Results...

  7. Enhancement of allele discrimination by introduction of nucleotide mismatches into siRNA in allele-specific gene silencing by RNAi.

    Directory of Open Access Journals (Sweden)

    Yusuke Ohnishi

    Full Text Available Allele-specific gene silencing by RNA interference (RNAi is therapeutically useful for specifically inhibiting the expression of disease-associated alleles without suppressing the expression of corresponding wild-type alleles. To realize such allele-specific RNAi (ASP-RNAi, the design and assessment of small interfering RNA (siRNA duplexes conferring ASP-RNAi is vital; however, it is also difficult. In a previous study, we developed an assay system to assess ASP-RNAi with mutant and wild-type reporter alleles encoding the Photinus and Renilla luciferase genes. In line with experiments using the system, we realized that it is necessary and important to enhance allele discrimination between mutant and corresponding wild-type alleles. Here, we describe the improvement of ASP-RNAi against mutant alleles carrying single nucleotide variations by introducing base substitutions into siRNA sequences, where original variations are present in the central position. Artificially mismatched siRNAs or short-hairpin RNAs (shRNAs against mutant alleles of the human Prion Protein (PRNP gene, which appear to be associated with susceptibility to prion diseases, were examined using this assessment system. The data indicates that introduction of a one-base mismatch into the siRNAs and shRNAs was able to enhance discrimination between the mutant and wild-type alleles. Interestingly, the introduced mismatches that conferred marked improvement in ASP-RNAi, appeared to be largely present in the guide siRNA elements, corresponding to the 'seed region' of microRNAs. Due to the essential role of the 'seed region' of microRNAs in their association with target RNAs, it is conceivable that disruption of the base-pairing interactions in the corresponding seed region, as well as the central position (involved in cleavage of target RNAs, of guide siRNA elements could influence allele discrimination. In addition, we also suggest that nucleotide mismatches at the 3'-ends of sense

  8. Allelic expression analysis of the osteoarthritis susceptibility locus that maps to MICAL3

    Directory of Open Access Journals (Sweden)

    Ratnayake Madhushika

    2012-03-01

    Full Text Available Abstract Background A genome-wide association scan with subsequent replication study that involved over 67,000 individuals of European ancestry has produced evidence of association of single nucleotide polymorphism rs2277831 to primary osteoarthritis (OA with a P-value of 2.9 × 10-5. rs2277831, an A/G transition, is located in an intron of MICAL3. This gene is located on chromosome 22q11.21 and the association signal encompasses two additional genes, BCL2L13 and BID. It is becoming increasingly apparent that many common complex traits are mediated by cis-acting regulatory polymorphisms that influence, in a tissue-specific manner, gene expression or transcript stability. Methods We used total and allelic expression analysis to assess whether the OA association to rs2277831 is mediated by an influence on MICAL3, BCL2L13 or BID expression. Using RNA extracted from joint tissues of 60 patients who had undergone elective joint replacement surgery, we assessed whether rs2277831 correlated with allelic expression of either of the three genes by: 1 measuring the expression of each gene by quantitative PCR and then stratifying the data by genotype at rs2277831 and 2 accurately discriminating and quantifying the mRNA synthesised from the alleles of OA patients using allelic-quantitative PCR. Results We found no evidence for a correlation between gene expression and genotype at rs2277831, with P-values of 0.09 for BCL2L13, 0.07 for BID and 0.33 for MICAL3. In the allelic expression analysis we observed several examples of significant (p BCL2L13 (P = 0.004, 2.09 at BID (P = 0.001 and the most extreme case being at MICAL3, with an allelic expression ratio of 5.47 (P = 0.001. However, there was no correlation observed between the pattern of allelic expression and the genotype at rs2277831. Conclusions In the tissues that we have studied, our data do not support our hypothesis that the association between rs2277831 and OA is due to the effect this SNP has on

  9. The multiethnic ancestry of Bolivians as revealed by the analysis of Y-chromosome markers.

    Science.gov (United States)

    Cárdenas, Jorge Mario; Heinz, Tanja; Pardo-Seco, Jacobo; Álvarez-Iglesias, Vanesa; Taboada-Echalar, Patricia; Sánchez-Diz, Paula; Carracedo, Ángel; Salas, Antonio

    2015-01-01

    We have analyzed the specific male genetic component of 226 Bolivians recruited in five different regions ("departments"), La Paz, Cochabamba, Pando, Beni, and Santa Cruz. To evaluate the effect of geography on the distribution of genetic variability, the samples were also grouped into three main eco-geographical regions, namely, Andean, Sub-Andean, and Llanos. All the individuals were genotyped for 17 Y-STR and 32 Y-SNP markers. The average Y-chromosome Native American component in Bolivians is 28%, and it is mainly represented by haplogroup Q1a3a, while the average Y-chromosome European ancestry is 65%, and it is mainly represented by haplogroup R1b1-P25. The data indicate that there exists significant population sub-division in the country in terms of continental ancestry. Thus, the partition of ancestries in Llanos, Sub-Andean, and Andean regions is as follows (respectively): (i) Native American ancestry: 47%, 7%, and 19%, (ii) European ancestry: 46%, 86%, and 75%, and (iii) African ancestry: 7%, 7%, and 6%. The population sub-structure in the country is also well mirrored when inferred from an AMOVA analysis, indicating that among-population variance in the country reaches 9.74-11.15%. This suggests the convenience of using regional datasets for forensic applications in Bolivia, instead of using a global and single country database. By comparing the Y-chromosome patterns with those previously reported on the same individuals on autosomal SNPs and mitochondrial DNA (mtDNA), it becomes clear that Bolivians show a strong gender-bias. PMID:25450796

  10. Genetic analysis of ancestry, admixture and selection in Bolivian and Totonac populations of the New World

    Directory of Open Access Journals (Sweden)

    Watkins W

    2012-05-01

    Full Text Available Abstract Background Populations of the Americas were founded by early migrants from Asia, and some have experienced recent genetic admixture. To better characterize the native and non-native ancestry components in populations from the Americas, we analyzed 815,377 autosomal SNPs, mitochondrial hypervariable segments I and II, and 36 Y-chromosome STRs from 24 Mesoamerican Totonacs and 23 South American Bolivians. Results and Conclusions We analyzed common genomic regions from native Bolivian and Totonac populations to identify 324 highly predictive Native American ancestry informative markers (AIMs. As few as 40–50 of these AIMs perform nearly as well as large panels of random genome-wide SNPs for predicting and estimating Native American ancestry and admixture levels. These AIMs have greater New World vs. Old World specificity than previous AIMs sets. We identify highly-divergent New World SNPs that coincide with high-frequency haplotypes found at similar frequencies in all populations examined, including the HGDP Pima, Maya, Colombian, Karitiana, and Surui American populations. Some of these regions are potential candidates for positive selection. European admixture in the Bolivian sample is approximately 12%, though individual estimates range from 0–48%. We estimate that the admixture occurred ~360–384 years ago. Little evidence of European or African admixture was found in Totonac individuals. Bolivians with pre-Columbian mtDNA and Y-chromosome haplogroups had 5–30% autosomal European ancestry, demonstrating the limitations of Y-chromosome and mtDNA haplogroups and the need for autosomal ancestry informative markers for assessing ancestry in admixed populations.

  11. No association between genetic ancestry and susceptibility to asthma or atopy in Canary Islanders.

    Science.gov (United States)

    Pino-Yanes, María; Corrales, Almudena; Cumplido, José; González, Ruperto; Torres-Galván, María José; Fernández, Orlando Acosta; Sánchez-Machín, Inmaculada; Figueroa, Javier; Sánchez-Palacios, Anselmo; Villar, Jesús; Hernández, Mariano; Carrillo, Teresa; Flores, Carlos

    2012-09-01

    Asthma is a complex respiratory disease characterized by chronic inflammation of airways and frequently associated with atopic symptoms. The population from the Canary Islands, which has resulted from a recent admixture of North African and Iberian populations, shows the highest prevalence of asthma and atopic symptoms among the Spanish populations. Although environmental particularities would account for the majority of such disparity, genetic ancestry might play a role in increasing the susceptibility of asthma or atopy, as have been demonstrated in other recently African-admixed populations. Here, we aimed to explore whether genetic ancestry was associated with asthma or related traits in the Canary Islanders. For that, a total of 734 DNA samples from unrelated individuals of the GOA study, self-reporting at least two generations of ancestors from the Canary Islands (391 asthmatics and 343 controls), were successfully genotyped for 83 ancestry informative markers (AIMs), which allowed to precisely distinguishing between North African and Iberian ancestries. No association was found between genetic ancestry and asthma or related traits after adjusting by demographic variables differing among compared groups. Similarly, none of the individual AIMs was associated with asthma when results were considered in the context of the multiple comparisons performed (0.005 ≤ p value ≤ 0.042; 0.221 ≤ q value ≤ 0.443). Our results suggest that if genetic ancestry were involved in the susceptibility to asthma or related traits among Canary Islanders, its effects would be modest. Larger studies, examining more genetic variants, would be needed to explore such possibility. PMID:22710824

  12. Variation in the gene coding for the M5 Muscarinic receptor (CHRM5 influences cigarette dose but is not associated with dependence to drugs of addiction: evidence from a prospective population based cohort study of young adults

    Directory of Open Access Journals (Sweden)

    Olsson Craig A

    2007-07-01

    Full Text Available Abstract Background The mesolimbic structures of the brain are important in the anticipation and perception of reward. Moreover, many drugs of addiction elicit their response in these structures. The M5 muscarinic receptor (M5R is expressed in dopamine-containing neurones of the substantia nigra pars compacta and ventral tegmental area, and regulates the release of mesolimbic dopamine. Mice lacking M5R show a substantial reduction in both reward and withdrawal responses to morphine and cocaine. The CHRM5, the gene that codes for the M5R, is a strong biological candidate for a role in human addiction. We screened the coding and core promoter sequences of CHRM5 using denaturing high performance liquid chromatography to identify common polymorphisms. Additional polymorphisms within the coding and core promoter regions that were identified through dbSNP were validated in the test population. We investigated whether these polymorphisms influence substance dependence and dose in a cohort of 1947 young Australians. Results Analysis was performed on 815 participants of European ancestry who were interviewed at wave 8 of the cohort study and provided DNA. We observed a 26.8% increase in cigarette consumption in carriers of the rs7162140 T-allele, equating to 20.1 cigarettes per week (p=0.01. Carriers of the rs7162140 T-allele were also found to have nearly a 3-fold increased risk of developing cannabis dependence (OR=2.9 (95%CI 1.1-7.4; p=0.03. Conclusion Our data suggest that variation within the CHRM5 locus may play an important role in tobacco and cannabis but not alcohol addiction in European ancestry populations. This is the first study to show an association between CHRM5 and substance use in humans. These data support the further investigation of this gene as a risk factor in substance use and dependence.

  13. Extensive Variation in Chromatin States Across Humans

    KAUST Repository

    Kasowski, M.

    2013-10-17

    The majority of disease-associated variants lie outside protein-coding regions, suggesting a link between variation in regulatory regions and disease predisposition. We studied differences in chromatin states using five histone modifications, cohesin, and CTCF in lymphoblastoid lines from 19 individuals of diverse ancestry. We found extensive signal variation in regulatory regions, which often switch between active and repressed states across individuals. Enhancer activity is particularly diverse among individuals, whereas gene expression remains relatively stable. Chromatin variability shows genetic inheritance in trios, correlates with genetic variation and population divergence, and is associated with disruptions of transcription factor binding motifs. Overall, our results provide insights into chromatin variation among humans.

  14. Estimates of Continental Ancestry Vary Widely among Individuals with the Same mtDNA Haplogroup

    OpenAIRE

    Emery, Leslie S.; Magnaye, Kevin M.; Bigham, Abigail W.; Akey, Joshua M.; Bamshad, Michael J.

    2015-01-01

    The association between a geographical region and an mtDNA haplogroup(s) has provided the basis for using mtDNA haplogroups to infer an individual’s place of origin and genetic ancestry. Although it is well known that ancestry inferences using mtDNA haplogroups and those using genome-wide markers are frequently discrepant, little empirical information exists on the magnitude and scope of such discrepancies between multiple mtDNA haplogroups and worldwide populations. We compared genetic-ances...

  15. A genome-wide association study of breast cancer in women of African ancestry

    OpenAIRE

    Chen, Fang; Chen, Gary K.; Stram, Daniel O.; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M; Bernstein, Leslie; Zheng, Wei; Palmer, Julie R.; Jennifer J Hu; Rebbeck, Tim R.; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Sue A Ingles

    2012-01-01

    Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of > 1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p < 0.05) in stage 2, wh...

  16. Genetic tests for alleles of complementary-sex-determiner to support honeybee breeding programmes

    OpenAIRE

    Hyink, Otto; Laas, Frans; Dearden, Peter

    2013-01-01

    International audience The honeybee haplodiploid sex determination system depends on genetic variation at the complementary sex-determiner (csd) locus. In closed populations of honeybees, especially those undergoing selective breeding, the number of csd alleles can drop such that brood viability is affected. Here we present two polymerase chain reaction tests that allow the discrimination of csd alleles. Such tests should find utility in bee breeding programmes allowing the tracking and ma...

  17. Allele frequencies and segregation of human polymorphic keratins K4 and K5.

    OpenAIRE

    Mischke, D; Wille, G; Wild, A G

    1990-01-01

    Two electrophoretic variants for each of the human keratins K4 and K5 that are expressed in squamous nonkeratinizing epithelia lining the upper digestive tract could be distinguished on SDS-PAGE. Based on a sampling size of 1,299 unrelated individuals, calculation of allele frequencies showed the alleles to be in Hardy-Weinberg equilibrium. The genetic basis of this variation was confirmed by both quantitative gene dosage dependence and the transmission of the variants as Mendelian traits in ...

  18. A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry

    NARCIS (Netherlands)

    Monda, Keri L.; Chen, Gary K.; Taylor, Kira C.; Palmer, Cameron; Edwards, Todd L.; Lange, Leslie A.; Ng, Maggie C. Y.; Adeyemo, Adebowale A.; Allison, Matthew A.; Bielak, Lawrence F.; Chen, Guanjie; Graff, Mariaelisa; Irvin, Marguerite R.; Rhie, Suhn K.; Li, Guo; Liu, Yongmei; Liu, Youfang; Lu, Yingchang; Nalls, Michael A.; Sun, Yan V.; Wojczynski, Mary K.; Yanek, Lisa R.; Aldrich, Melinda C.; Ademola, Adeyinka; Amos, Christopher I.; Bandera, Elisa V.; Bock, Cathryn H.; Britton, Angela; Broeckel, Ulrich; Cai, Quiyin; Caporaso, Neil E.; Carlson, Chris S.; Carpten, John; Casey, Graham; Chen, Wei-Min; Chen, Fang; Chen, Yii-Der I.; Chiang, Charleston W. K.; Coetzee, Gerhard A.; Demerath, Ellen; Deming-Halverson, Sandra L.; Driver, Ryan W.; Dubbert, Patricia; Feitosa, Mary F.; Feng, Ye; Freedman, Barry I.; Gillanders, Elizabeth M.; Gottesman, Omri; Guo, Xiuqing; Haritunians, Talin; Harris, Tamara; Harris, Curtis C.; Hennis, Anselm J. M.; Hernandez, Dena G.; McNeill, Lorna H.; Howard, Timothy D.; Howard, Barbara V.; Howard, Virginia J.; Johnson, Karen C.; Kang, Sun J.; Keating, Brendan J.; Kolb, Suzanne; Kuller, Lewis H.; Kutlar, Abdullah; Langefeld, Carl D.; Lettre, Guillaume; Lohman, Kurt; Lotay, Vaneet; Lyon, Helen; Manson, Joann E.; Maixner, William; Meng, Yan A.; Monroe, Kristine R.; Morhason-Bello, Imran; Murphy, Adam B.; Mychaleckyj, Josyf C.; Nadukuru, Rajiv; Nathanson, Katherine L.; Nayak, Uma; N'Diaye, Amidou; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina; Neslund-Dudas, Christine; Neuhouser, Marian; Nyante, Sarah; Ochs-Balcom, Heather; Ogunniyi, Adesola; Ogundiran, Temidayo O.; Ojengbede, Oladosu; Olopade, Olufunmilayo I.; Palmer, Julie R.; Ruiz-Narvaez, Edward A.; Palmer, Nicholette D.; Press, Michael F.; Rampersaud, Evandine; Rasmussen-Torvik, Laura J.; Rodriguez-Gil, Jorge L.; Salako, Babatunde; Schadt, Eric E.; Schwartz, Ann G.; Shriner, Daniel A.; Siscovick, David; Smith, Shad B.; Wassertheil-Smoller, Sylvia; Speliotes, Elizabeth K.; Spitz, Margaret R.; Sucheston, Lara; Taylor, Herman; Tayo, Bamidele O.; Tucker, Margaret A.; Van Den Berg, David J.; Edwards, Digna R. Velez; Wang, Zhaoming; Wiencke, John K.; Winkler, Thomas W.; Witte, John S.; Wrensch, Margaret; Wu, Xifeng; Yang, James J.; Levin, Albert M.; Young, Taylor R.; Zakai, Neil A.; Cushman, Mary; Zanetti, Krista A.; Zhao, Jing Hua; Zhao, Wei; Zheng, Yonglan; Zhou, Jie; Ziegler, Regina G.; Zmuda, Joseph M.; Fernandes, Jyotika K.; Gilkeson, Gary S.; Kamen, Diane L.; Hunt, Kelly J.; Spruill, Ida J.; Ambrosone, Christine B.; Ambs, Stefan; Arnett, Donna K.; Atwood, Larry; Becker, Diane M.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Borecki, Ingrid B.; Bottinger, Erwin P.; Bowden, Donald W.; Burke, Gregory; Chanock, Stephen J.; Cooper, Richard S.; Ding, Jingzhong; Duggan, David; Evans, Michele K.; Fox, Caroline; Garvey, W. Timothy; Bradfield, Jonathan P.; Hakonarson, Hakon; Grant, Struan F. A.; Hsing, Ann; Chu, Lisa; Hu, Jennifer J.; Huo, Dezheng; Ingles, Sue A.; John, Esther M.; Jordan, Joanne M.; Kabagambe, Edmond K.; Kardia, Sharon L. R.; Kittles, Rick A.; Goodman, Phyllis J.; Klein, Eric A.; Kolonel, Laurence N.; Le Marchand, Loic; Liu, Simin; McKnight, Barbara; Millikan, Robert C.; Mosley, Thomas H.; Padhukasahasram, Badri; Williams, L. Keoki; Patel, Sanjay R.; Peters, Ulrike; Pettaway, Curtis A.; Peyser, Patricia A.; Psaty, Bruce M.; Redline, Susan; Rotimi, Charles N.; Rybicki, Benjamin A.; Sale, Michele M.; Schreiner, Pamela J.; Signorello, Lisa B.; Singleton, Andrew B.; Stanford, Janet L.; Strom, Sara S.; Thun, Michael J.; Vitolins, Mara; Zheng, Wei; Moore, Jason H.; Williams, Scott M.; Ketkar, Shamika; Zhu, Xiaofeng; Zonderman, Alan B.; Kooperberg, Charles; Papanicolaou, George J.; Henderson, Brian E.; Reiner, Alex P.; Hirschhorn, Joel N.; Loos, Ruth J. F.; North, Kari E.; Haiman, Christopher A.

    2013-01-01

    Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up t

  19. Estimating the probability of allelic drop-out of STR alleles in forensic genetics

    DEFF Research Database (Denmark)

    Tvedebrink, Torben; Eriksen, Poul Svante; Mogensen, Helle Smidt;

    2009-01-01

    In crime cases with available DNA evidence, the amount of DNA is often sparse due to the setting of the crime. In such cases, allelic drop-out of one or more true alleles in STR typing is possible. We present a statistical model for estimating the per locus and overall probability of allelic drop...

  20. Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry.

    Directory of Open Access Journals (Sweden)

    Shafqat Ahmad

    Full Text Available Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2, sex, study center (for multicenter studies, and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS × physical activity interaction effect estimate (Pinteraction  = 0.015. However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, Pinteraction  = 0.014 vs. n = 71,611, Pinteraction  = 0.275 for Europeans. In secondary analyses, both the FTO rs1121980 (Pinteraction  = 0.003 and the SEC16B rs10913469 (Pinteraction  = 0.025 variants showed evidence of SNP × physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.

  1. Ancestry informative markers and complete blood count parameters in Brazilian blood donors Marcadores informativos de ancestralidade e parâmetros no hemograma de doadores de sangue brasileiros

    Directory of Open Access Journals (Sweden)

    Gabriela E. S. Felix

    2010-01-01

    Full Text Available A complete blood count is very useful in clinical diagnoses when reference ranges are well established for the population. Complete blood counts and allele frequencies of Ancestry Informative Markers (AIMs were analyzed in Brazilians with the aim of characterizing the hematological values of an admixed population. Positive associations were observed between gender and neutrophils, monocytes, eosinophils, erythrocytes, hemoglobin, hematocrit, MCV, MCHC and platelet counts. No significant differences were found for age, alcohol consumption, educational status, ethnicity, smoking in respect to the complete blood count values. In general, men had higher red blood cell values, while women had higher values for white blood cells and platelets. The study of the population was highly heterogeneous with mean proportions (± SE of African, European and Amerindian ancestry being 49.0 ± 3.0%, 44.0 ± 9.0% and 7.0 ± 9.0%, respectively. Amerindian ancestry showed limited contribution to the makeup of the population, but estimated ancestral proportions were statistically significant (r = 0.9838; PO hemograma é muito útil no diagnóstico quando o intervalo de referência é adequadamente estabelecido para população. Com o objetivo de verificar os valores hematológicos em população heterogênea foi analisado o hemograma e frequências alélica de marcadores informativos de ancestralidade de brasileiros. Foi observada associação positiva entre sexo e os valores de neutrófilos, monócitos, eosinófilos, eritrócitos, hemoglobina, hematócrito, MCV, MCHC e plaquetas (IC 95%; P0,05. Os homens apresentaram valores maiores no eritrograma, enquanto no leucograma e plaquetograma foram as mulheres. Foi observado também que a população é altamente heterogênea e as médias proporcionais (±DP de ancestralidade Africana, Europeia e Ameríndia estimada foram: 49,0 ± 3,0 %, 44,0 ± 9,0% e 7,0 ± 9,0%, respectivamente. A contribuição ancestral ameríndia se

  2. 75 FR 11940 - Office of the Chief Human Capital Officer; Information Collection; Ancestry and Ethnicity Data...

    Science.gov (United States)

    2010-03-12

    ... NATIONAL INTELLIGENCE Office of the Chief Human Capital Officer; Information Collection; Ancestry and... the Chief Human Capital Officer, ODNI, at Washington, DC 20511, or call 703-275-3369. Please cite... submitted on or before April 12, 2010. FOR FURTHER INFORMATION CONTACT: The Office of the Chief...

  3. Ethnic Variation in Inflammatory Profile in Tuberculosis

    OpenAIRE

    Coussens, Anna K.; Wilkinson, Robert J.; Nikolayevskyy, Vladyslav; Elkington, Paul T.; Hanifa, Yasmeen; Islam, Kamrul; Timms, Peter M.; Bothamley, Graham H; Claxton, Alleyna P.; Packe, Geoffrey E.; Darmalingam, Mathina; Davidson, Robert N.; Milburn, Heather J.; Baker, Lucy V.; Barker, Richard D

    2013-01-01

    Distinct phylogenetic lineages of Mycobacterium tuberculosis (MTB) cause disease in patients of particular genetic ancestry, and elicit different patterns of cytokine and chemokine secretion when cultured with human macrophages in vitro. Circulating and antigen-stimulated concentrations of these inflammatory mediators might therefore be expected to vary significantly between tuberculosis patients of different ethnic origin. Studies to characterise such variation, and to determine whether it r...

  4. Mitochondrial and Y chromosome haplotype motifs as diagnostic markers of Jewish ancestry: a reconsideration

    Science.gov (United States)

    Tofanelli, Sergio; Taglioli, Luca; Bertoncini, Stefania; Francalacci, Paolo; Klyosov, Anatole; Pagani, Luca

    2014-01-01

    Several authors have proposed haplotype motifs based on site variants at the mitochondrial genome (mtDNA) and the non-recombining portion of the Y chromosome (NRY) to trace the genealogies of Jewish people. Here, we analyzed their main approaches and test the feasibility of adopting motifs as ancestry markers through construction of a large database of mtDNA and NRY haplotypes from public genetic genealogical repositories. We verified the reliability of Jewish ancestry prediction based on the Cohen and Levite Modal Haplotypes in their “classical” 6 STR marker format or in the “extended” 12 STR format, as well as four founder mtDNA lineages (HVS-I segments) accounting for about 40% of the current population of Ashkenazi Jews. For this purpose we compared haplotype composition in individuals of self-reported Jewish ancestry with the rest of European, African or Middle Eastern samples, to test for non-random association of ethno-geographic groups and haplotypes. Overall, NRY and mtDNA based motifs, previously reported to differentiate between groups, were found to be more represented in Jewish compared to non-Jewish groups. However, this seems to stem from common ancestors of Jewish lineages being rather recent respect to ancestors of non-Jewish lineages with the same “haplotype signatures.” Moreover, the polyphyly of haplotypes which contain the proposed motifs and the misuse of constant mutation rates heavily affected previous attempts to correctly dating the origin of common ancestries. Accordingly, our results stress the limitations of using the above haplotype motifs as reliable Jewish ancestry predictors and show its inadequacy for forensic or genealogical purposes. PMID:25431579

  5. Multiplex genotyping system for efficient inference of matrilineal genetic ancestry with continental resolution

    Directory of Open Access Journals (Sweden)

    van Oven Mannis

    2011-03-01

    Full Text Available Abstract Background In recent years, phylogeographic studies have produced detailed knowledge on the worldwide distribution of mitochondrial DNA (mtDNA variants, linking specific clades of the mtDNA phylogeny with certain geographic areas. However, a multiplex genotyping system for the detection of the mtDNA haplogroups of major continental distribution that would be desirable for efficient DNA-based bio-geographic ancestry testing in various applications is still missing. Results Three multiplex genotyping assays, based on single-base primer extension technology, were developed targeting a total of 36 coding-region mtDNA variants that together differentiate 43 matrilineal haplo-/paragroups. These include the major diagnostic haplogroups for Africa, Western Eurasia, Eastern Eurasia and Native America. The assays show high sensitivity with respect to the amount of template DNA: successful amplification could still be obtained when using as little as 4 pg of genomic DNA and the technology is suitable for medium-throughput analyses. Conclusions We introduce an efficient and sensitive multiplex genotyping system for bio-geographic ancestry inference from mtDNA that provides resolution on the continental level. The method can be applied in forensics, to aid tracing unknown suspects, as well as in population studies, genealogy and personal ancestry testing. For more complete inferences of overall bio-geographic ancestry from DNA, the mtDNA system provided here can be combined with multiplex systems for suitable autosomal and, in the case of males, Y-chromosomal ancestry-sensitive DNA markers.

  6. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.

    Science.gov (United States)

    Kato, Norihiro; Loh, Marie; Takeuchi, Fumihiko; Verweij, Niek; Wang, Xu; Zhang, Weihua; Kelly, Tanika N; Saleheen, Danish; Lehne, Benjamin; Mateo Leach, Irene; Drong, Alexander W; Abbott, James; Wahl, Simone; Tan, Sian-Tsung; Scott, William R; Campanella, Gianluca; Chadeau-Hyam, Marc; Afzal, Uzma; Ahluwalia, Tarunveer S; Bonder, Marc Jan; Chen, Peng; Dehghan, Abbas; Edwards, Todd L; Esko, Tõnu; Go, Min Jin; Harris, Sarah E; Hartiala, Jaana; Kasela, Silva; Kasturiratne, Anuradhani; Khor, Chiea-Chuen; Kleber, Marcus E; Li, Huaixing; Mok, Zuan Yu; Nakatochi, Masahiro; Sapari, Nur Sabrina; Saxena, Richa; Stewart, Alexandre F R; Stolk, Lisette; Tabara, Yasuharu; Teh, Ai Ling; Wu, Ying; Wu, Jer-Yuarn; Zhang, Yi; Aits, Imke; Da Silva Couto Alves, Alexessander; Das, Shikta; Dorajoo, Rajkumar; Hopewell, Jemma C; Kim, Yun Kyoung; Koivula, Robert W; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Nguyen, Quang N; Pereira, Mark A; Postmus, Iris; Raitakari, Olli T; Bryan, Molly Scannell; Scott, Robert A; Sorice, Rossella; Tragante, Vinicius; Traglia, Michela; White, Jon; Yamamoto, Ken; Zhang, Yonghong; Adair, Linda S; Ahmed, Alauddin; Akiyama, Koichi; Asif, Rasheed; Aung, Tin; Barroso, Inês; Bjonnes, Andrew; Braun, Timothy R; Cai, Hui; Chang, Li-Ching; Chen, Chien-Hsiun; Cheng, Ching-Yu; Chong, Yap-Seng; Collins, Rory; Courtney, Regina; Davies, Gail; Delgado, Graciela; Do, Loi D; Doevendans, Pieter A; Gansevoort, Ron T; Gao, Yu-Tang; Grammer, Tanja B; Grarup, Niels; Grewal, Jagvir; Gu, Dongfeng; Wander, Gurpreet S; Hartikainen, Anna-Liisa; Hazen, Stanley L; He, Jing; Heng, Chew-Kiat; Hixson, James E; Hofman, Albert; Hsu, Chris; Huang, Wei; Husemoen, Lise L N; Hwang, Joo-Yeon; Ichihara, Sahoko; Igase, Michiya; Isono, Masato; Justesen, Johanne M; Katsuya, Tomohiro; Kibriya, Muhammad G; Kim, Young Jin; Kishimoto, Miyako; Koh, Woon-Puay; Kohara, Katsuhiko; Kumari, Meena; Kwek, Kenneth; Lee, Nanette R; Lee, Jeannette; Liao, Jiemin; Lieb, Wolfgang; Liewald, David C M; Matsubara, Tatsuaki; Matsushita, Yumi; Meitinger, Thomas; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Mononen, Nina; Müller-Nurasyid, Martina; Nabika, Toru; Nakashima, Eitaro; Ng, Hong Kiat; Nikus, Kjell; Nutile, Teresa; Ohkubo, Takayoshi; Ohnaka, Keizo; Parish, Sarah; Paternoster, Lavinia; Peng, Hao; Peters, Annette; Pham, Son T; Pinidiyapathirage, Mohitha J; Rahman, Mahfuzar; Rakugi, Hiromi; Rolandsson, Olov; Rozario, Michelle Ann; Ruggiero, Daniela; Sala, Cinzia F; Sarju, Ralhan; Shimokawa, Kazuro; Snieder, Harold; Sparsø, Thomas; Spiering, Wilko; Starr, John M; Stott, David J; Stram, Daniel O; Sugiyama, Takao; Szymczak, Silke; Tang, W H Wilson; Tong, Lin; Trompet, Stella; Turjanmaa, Väinö; Ueshima, Hirotsugu; Uitterlinden, André G; Umemura, Satoshi; Vaarasmaki, Marja; van Dam, Rob M; van Gilst, Wiek H; van Veldhuisen, Dirk J; Viikari, Jorma S; Waldenberger, Melanie; Wang, Yiqin; Wang, Aili; Wilson, Rory; Wong, Tien-Yin; Xiang, Yong-Bing; Yamaguchi, Shuhei; Ye, Xingwang; Young, Robin D; Young, Terri L; Yuan, Jian-Min; Zhou, Xueya; Asselbergs, Folkert W; Ciullo, Marina; Clarke, Robert; Deloukas, Panos; Franke, Andre; Franks, Paul W; Franks, Steve; Friedlander, Yechiel; Gross, Myron D; Guo, Zhirong; Hansen, Torben; Jarvelin, Marjo-Riitta; Jørgensen, Torben; Jukema, J Wouter; Kähönen, Mika; Kajio, Hiroshi; Kivimaki, Mika; Lee, Jong-Young; Lehtimäki, Terho; Linneberg, Allan; Miki, Tetsuro; Pedersen, Oluf; Samani, Nilesh J; Sørensen, Thorkild I A; Takayanagi, Ryoichi; Toniolo, Daniela; Ahsan, Habibul; Allayee, Hooman; Chen, Yuan-Tsong; Danesh, John; Deary, Ian J; Franco, Oscar H; Franke, Lude; Heijman, Bastiaan T; Holbrook, Joanna D; Isaacs, Aaron; Kim, Bong-Jo; Lin, Xu; Liu, Jianjun; März, Winfried; Metspalu, Andres; Mohlke, Karen L; Sanghera, Dharambir K; Shu, Xiao-Ou; van Meurs, Joyce B J; Vithana, Eranga; Wickremasinghe, Ananda R; Wijmenga, Cisca; Wolffenbuttel, Bruce H W; Yokota, Mitsuhiro; Zheng, Wei; Zhu, Dingliang; Vineis, Paolo; Kyrtopoulos, Soterios A; Kleinjans, Jos C S; McCarthy, Mark I; Soong, Richie; Gieger, Christian; Scott, James; Teo, Yik-Ying; He, Jiang; Elliott, Paul; Tai, E Shyong; van der Harst, Pim; Kooner, Jaspal S; Chambers, John C

    2015-11-01

    We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation. PMID:26390057

  7. Variation in regulator of G-protein signaling 17 gene (RGS17 is associated with multiple substance dependence diagnoses

    Directory of Open Access Journals (Sweden)

    Zhang Huiping

    2012-05-01

    Full Text Available Abstract Background RGS17 and RGS20 encode two members of the regulator of G-protein signaling RGS-Rz subfamily. Variation in these genes may alter their transcription and thereby influence the function of G protein-coupled receptors, including opioid receptors, and modify risk for substance dependence. Methods The association of 13 RGS17 and eight RGS20 tag single nucleotide polymorphisms (SNPs was examined with four substance dependence diagnoses (alcohol (AD, cocaine (CD, opioid (OD or marijuana (MjD] in 1,905 African Americans (AAs: 1,562 cases and 343 controls and 1,332 European Americans (EAs: 981 cases and 351 controls. Analyses were performed using both χ2 tests and logistic regression analyses that covaried sex, age, and ancestry proportion. Correlation of genotypes and mRNA expression levels was assessed by linear regression analyses. Results Seven RGS17 SNPs showed a significant association with at least one of the four dependence traits after a permutation-based correction for multiple testing (0.003≤Pempirical≤0.037. The G allele of SNP rs596359, in the RGS17 promoter region, was associated with AD, CD, OD, or MjD in both populations (0.005≤Pempirical≤0.019. This allele was also associated with significantly lower mRNA expression levels of RGS17 in YRI subjects (P = 0.002 and non-significantly lower mRNA expression levels of RGS17 in CEU subjects (P = 0.185. No RGS20 SNPs were associated with any of the four dependence traits in either population. Conclusions This study demonstrated that variation in RGS17 was associated with risk for substance dependence diagnoses in both AA and EA populations.

  8. Using multi-locus allelic sequence data to estimate genetic divergence among four Lilium (Liliaceae cultivars

    Directory of Open Access Journals (Sweden)

    Arwa eShahin

    2014-10-01

    Full Text Available Next Generation Sequencing (NGS may enable estimating relationships among genotypes using allelic variation of multiple nuclear genes simultaneously. We explored the potential and caveats of this strategy in four genetically distant Lilium cultivars to estimate their genetic divergence from transcriptome sequences using three approaches: POFAD (Phylogeny of Organisms from Allelic Data, uses allelic information of sequence data, RAxML (Randomized Accelerated Maximum Likelihood, tree building based on concatenated consensus sequences and Consensus Network (constructing a network summarizing among gene tree conflicts. Twenty six gene contigs were chosen based on the presence of orthologous sequences in all cultivars, seven of which also had an orthologous sequence in Tulipa, used as out-group. The three approaches generated the same topology. Although the resolution offered by these approaches is high, in this case there was no extra benefit in using allelic information. We conclude that these 26 genes can be widely applied to construct a species tree for the genus Lilium.

  9. Allele Re-sequencing Technologies

    DEFF Research Database (Denmark)

    Byrne, Stephen; Farrell, Jacqueline Danielle; Asp, Torben

    The development of next-generation sequencing technologies has made sequencing an affordable approach for detection of genetic variations associated with various traits. However, the cost of whole genome re-sequencing still remains too high to be feasible for many plant species with large and...... complex genomes. Recent developments in strategies for target-enrichment, transcriptome re-sequencing, and partial genome re-sequencing allows for enrichment for regions of interest at a scale that is matched to the throughput of next-generation sequencing platforms, and has emerged as a promising...

  10. Large-scale SNP analysis reveals clustered and continuous patterns of human genetic variation

    Directory of Open Access Journals (Sweden)

    Shriver Mark D

    2005-06-01

    Full Text Available Abstract Understanding the distribution of human genetic variation is an important foundation for research into the genetics of common diseases. Some of the alleles that modify common disease risk are themselves likely to be common and, thus, amenable to identification using gene-association methods. A problem with this approach is that the large sample sizes required for sufficient statistical power to detect alleles with moderate effect make gene-association studies susceptible to false-positive findings as the result of population stratification 12. Such type I errors can be eliminated by using either family-based association tests or methods that sufficiently adjust for population stratification 345. These methods require the availability of genetic markers that can detect and, thus, control for sources of genetic stratification among populations. In an effort to investigate population stratification and identify appropriate marker panels, we have analysed 11,555 single nucleotide polymorphisms in 203 individuals from 12 diverse human populations. Individuals in each population cluster to the exclusion of individuals from other populations using two clustering methods. Higher-order branching and clustering of the populations are consistent with the geographic origins of populations and with previously published genetic analyses. These data provide a valuable resource for the definition of marker panels to detect and control for population stratification in population-based gene identification studies. Using three US resident populations (European-American, African-American and Puerto Rican, we demonstrate how such studies can proceed, quantifying proportional ancestry levels and detecting significant admixture structure in each of these populations.

  11. Highly discrepant proportions of female and male Scandinavian and British Isles ancestry within the isolated population of the Faroe Islands

    DEFF Research Database (Denmark)

    Als, Thomas D; Jorgensen, Tove H; Børglum, Anders D;

    2006-01-01

    frequency-based admixture approach taking private haplotypes into account by the use of phylogenetic information. While previous studies have suggested an excess of Scandinavian ancestry among the male settlers of the Faroe Islands, the current study indicates an excess of British Isles ancestry among the...... female settlers of the Faroe Islands. Compared to other admixed populations of the North Atlantic region, the population of the Faroe Islands appears to have the highest level of asymmetry in Scandinavian vs British Isles ancestry proportions among female and male settlers of the archipelago....

  12. A Meta-Analysis Identifies New Loci Associated with Body Mass index in Individuals of African Ancestry

    OpenAIRE

    Keri L Monda; Chen, Gary K.; Taylor, Kira C.; Palmer, Cameron; Edwards, Todd L.; Lange, Leslie A.; Ng, Maggie C. Y.; Adeyemo, Adebowale A.; Allison, Matthew A.; Bielak, Lawrence F; Chen, Guanji; Graff, Mariaelisa; Irvin, Marguerite R.; Rhie, Suhn K.; Li, Guo

    2013-01-01

    Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry, and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one novel locus at 5q33 (GALNT10, rs7708584, p=3.4×10−11) and another at 7p15 when combined ...

  13. Allele Workbench: transcriptome pipeline and interactive graphics for allele-specific expression.

    Directory of Open Access Journals (Sweden)

    Carol A Soderlund

    Full Text Available Sequencing the transcriptome can answer various questions such as determining the transcripts expressed in a given species for a specific tissue or condition, evaluating differential expression, discovering variants, and evaluating allele-specific expression. Differential expression evaluates the expression differences between different strains, tissues, and conditions. Allele-specific expression evaluates expression differences between parental alleles. Both differential expression and allele-specific expression have been studied for heterosis (hybrid vigor, where the hybrid has improved performance over the parents for one or more traits. The Allele Workbench software was developed for a heterosis study that evaluated allele-specific expression for a mouse F1 hybrid using libraries from multiple tissues with biological replicates. This software has been made into a distributable package, which includes a pipeline, a Java interface to build the database, and a Java interface for query and display of the results. The required input is a reference genome, annotation file, and one or more RNA-Seq libraries with optional replicates. It evaluates allelic imbalance at the SNP and transcript level and flags transcripts with significant opposite directional allele-specific expression. The Java interface allows the user to view data from libraries, replicates, genes, transcripts, exons, and variants, including queries on allele imbalance for selected libraries. To determine the impact of allele-specific SNPs on protein folding, variants are annotated with their effect (e.g., missense, and the parental protein sequences may be exported for protein folding analysis. The Allele Workbench processing results in transcript files and read counts that can be used as input to the previously published Transcriptome Computational Workbench, which has a new algorithm for determining a trimmed set of gene ontology terms. The software with demo files is available

  14. Morpho morphometrics: Shared ancestry and selection drive the evolution of wing size and shape in Morpho butterflies.

    Science.gov (United States)

    Chazot, Nicolas; Panara, Stephen; Zilbermann, Nicolas; Blandin, Patrick; Le Poul, Yann; Cornette, Raphaël; Elias, Marianne; Debat, Vincent

    2016-01-01

    Butterfly wings harbor highly diverse phenotypes and are involved in many functions. Wing size and shape result from interactions between adaptive processes, phylogenetic history, and developmental constraints, which are complex to disentangle. Here, we focus on the genus Morpho (Nymphalidae: Satyrinae, 30 species), which presents a high diversity of sizes, shapes, and color patterns. First, we generate a comprehensive molecular phylogeny of these 30 species. Next, using 911 collection specimens, we quantify the variation of wing size and shape across species, to assess the importance of shared ancestry, microhabitat use, and sexual selection in the evolution of the wings. While accounting for phylogenetic and allometric effects, we detect a significant difference in wing shape but not size among microhabitats. Fore and hindwings covary at the individual and species levels, and the covariation differs among microhabitats. However, the microhabitat structure in covariation disappears when phylogenetic relationships are taken into account. Our results demonstrate that microhabitat has driven wing shape evolution, although it has not strongly affected forewing and hindwing integration. We also found that sexual dimorphism of forewing shape and color pattern are coupled, suggesting a common selective force. PMID:26688277

  15. Cytochrome allelic variants and clopidogrel metabolism in cardiovascular diseases therapy.

    Science.gov (United States)

    Jarrar, Mohammed; Behl, Shalini; Manyam, Ganiraju; Ganah, Hany; Nazir, Mohammed; Nasab, Reem; Moustafa, Khaled

    2016-06-01

    Clopidogrel and aspirin are among the most prescribed dual antiplatelet therapies to treat the acute coronary syndrome and heart attacks. However, their potential clinical impacts are a subject of intense debates. The therapeutic efficiency of clopidogrel is controlled by the actions of hepatic cytochrome P450 (CYPs) enzymes and impacted by individual genetic variations. Inter-individual polymorphisms in CYPs enzymes affect the metabolism of clopidogrel into its active metabolites and, therefore, modify its turnover and clinical outcome. So far, clinical trials fail to confirm higher or lower adverse cardiovascular effects in patients treated with combinations of clopidogrel and proton pump inhibitors, compared with clopidogrel alone. Such inconclusive findings may be due to genetic variations in the cytochromes CYP2C19 and CYP3A4/5. To investigate potential interactions/effects of these cytochromes and their allele variants on the treatment of acute coronary syndrome with clopidogrel alone or in combination with proton pump inhibitors, we analyze recent literature and discuss the potential impact of the cytochrome allelic variants on cardiovascular events and stent thrombosis treated with clopidogrel. The diversity of CYP2C19 polymorphisms and prevalence span within various ethnic groups, subpopulations and demographic areas are also debated. PMID:27072373

  16. Genetic evidence for the Mongolian ancestry of Kalmyks.

    Science.gov (United States)

    Nasidze, Ivan; Quinque, Dominique; Dupanloup, Isabelle; Cordaux, Richard; Kokshunova, Lyudmila; Stoneking, Mark

    2005-12-01

    The Kalmyks are an ethnic group along the lower Volga River in Russia who are thought to have migrated there from Mongolia about 300 years ago. To investigate their origins, we studied mtDNA and Y-chromosome variation in 99 Kalmyks. Both mtDNA HV1 sequences and Y-chromosome SNP haplogroups indicate a close relationship of Kalmyks with Mongolians. In addition, genetic diversity for both mtDNA and the Y chromosome are comparable in Kalmyks, Mongolians, and other Central Asian groups, indicating that the Kalmyk migration was not associated with a substantial bottleneck. The so-called "Genghis Khan" Y-chromosome short tandem repeat (STR) haplotype was found in high frequency (31.3%) among Kalmyks, further supporting a strong genetic connection between Kalmyks and Mongolians. Genetic analyses of even recent, relatively well-documented migrations such as of the Kalmyks can therefore lead to new insights concerning such migrations. PMID:16028228

  17. Common Ancestry of Borrelia burgdorferi Sensu Lato Strains from North America and Europe

    OpenAIRE

    Postic, D; Ras, N. Marti; Lane, R S; Humair, P.-F.; Wittenbrink, M. M.; Baranton, G

    1999-01-01

    Ten atypical European Borrelia burgdorferi sensu lato (Borrelia spp.) strains were genetically characterized, and the diversity was compared to that encountered among related Borrelia spp. from North America. Phylogenetic analyses of a limited region of the genome and of the whole genome extend existing knowledge about borrelial diversity reported earlier in Europe and the United States. Our results accord with the evidence that North American and European strains may have a common ancestry.

  18. Assessing the reliability of eBURST using simulated populations with known ancestry

    OpenAIRE

    Connor Thomas R; Fraser Christophe; Hanage William P; Turner Katherine ME; Spratt Brian G

    2007-01-01

    Abstract Background The program eBURST uses multilocus sequence typing data to divide bacterial populations into groups of closely related strains (clonal complexes), predicts the founding genotype of each group, and displays the patterns of recent evolutionary descent of all other strains in the group from the founder. The reliability of eBURST was evaluated using populations simulated with different levels of recombination in which the ancestry of all strains was known. Results For strictly...

  19. Biogeographic Ancestry, Self-Identified Race, and Admixture-Phenotype Associations in the Heart SCORE Study

    OpenAIRE

    Halder, Indrani; Kip, Kevin E.; Mulukutla, Suresh R.; Aiyer, Aryan N.; Marroquin, Oscar C; Huggins, Gordon S.; Reis, Steven E.

    2012-01-01

    Large epidemiologic studies examining differences in cardiovascular disease (CVD) risk factor profiles between European Americans and African Americans have exclusively used self-identified race (SIR) to classify individuals. Recent genetic epidemiology studies of some CVD risk factors have suggested that biogeographic ancestry (BGA) may be a better predictor of CVD risk than SIR. This hypothesis was investigated in 464 African Americans and 771 European Americans enrolled in the Heart Strate...

  20. Multiplex genotyping system for efficient inference of matrilineal genetic ancestry with continental resolution

    OpenAIRE

    van Oven Mannis; Vermeulen Mark; Kayser Manfred

    2011-01-01

    Abstract Background In recent years, phylogeographic studies have produced detailed knowledge on the worldwide distribution of mitochondrial DNA (mtDNA) variants, linking specific clades of the mtDNA phylogeny with certain geographic areas. However, a multiplex genotyping system for the detection of the mtDNA haplogroups of major continental distribution that would be desirable for efficient DNA-based bio-geographic ancestry testing in various applications is still missing. Results Three mult...

  1. Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci

    OpenAIRE

    Liu, Ching-Ti; Keri L Monda; Taylor, Kira C.; Lange, Leslie; Demerath, Ellen W; Palmas, Walter; Wojczynski, Mary K.; Jaclyn C Ellis; Mara Z Vitolins; Liu, Simin; Papanicolaou, George J.; Irvin, Marguerite R.; Xue, Luting; Griffin, Paula J.; Michael A Nalls

    2013-01-01

    Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in...

  2. Validation of two prediction models of undiagnosed chronic kidney disease in mixed-ancestry South Africans

    OpenAIRE

    Mogueo, Amelie; Echouffo-Tcheugui, Justin B; Matsha, Tandi E.; Erasmus, Rajiv T; Kengne, Andre P.

    2015-01-01

    Background Chronic kidney disease (CKD) is a global challenge. Risk models to predict prevalent undiagnosed CKD have been published. However, none was developed or validated in an African population. We validated the Korean and Thai CKD prediction model in mixed-ancestry South Africans. Methods Discrimination and calibration were assessed overall and by major subgroups. CKD was defined as ‘estimated glomerular filtration rate (eGFR)

  3. Disparities in Birth Weight and Gestational Age by Ethnic Ancestry in South American countries

    Science.gov (United States)

    Wehby, George L.; Gili, Juan A.; Pawluk, Mariela; Castilla, Eduardo E.; López-Camelo, Jorge S.

    2015-01-01

    Objective We examine disparities in birth weight and gestational age by ethnic ancestry in 2000–2011 in eight South American countries. Methods The sample included 60480 singleton live-births. Regression models were estimated to evaluate differences in birth outcomes by ethnic ancestry controlling for time trends. Results Significant disparities were found in seven countries. In four countries – Brazil, Ecuador, Uruguay, and Venezuela – we found significant disparities in both low birth weight and preterm birth. Disparities in preterm birth alone were observed in Argentina, Bolivia, and Colombia. Several differences in continuous birth weight, gestational age, and fetal growth rate were also observed. There were no systematic patterns of disparities between the evaluated ethnic ancestry groups across the study countries, in that no racial/ethnic group consistently had the best or worst outcomes in all countries. Conclusions Racial/ethnic disparities in infant health are common in several South American countries. Differences across countries suggest that racial/ethnic disparities are driven by social and economic mechanisms. Researchers and policymakers should acknowledge these disparities and develop research and policy programs to effectively target them. PMID:25542227

  4. Allelic associations of two polymorphic microsatellites in intron 40 of the human von Willebrand factor gene

    Energy Technology Data Exchange (ETDEWEB)

    Pena, S.D.J.; De Souza, K.T. (Nucleo de Genetica Medica de Minas Gerais, Belo Horizonte (Brazil)); De Andrade, M.; Chakraborty, R. (Univ. of Texas Graduate School of Biomedical Sciences, Houston, TX (United States))

    1994-01-18

    At intron 40 of the von Willebrand factor (vWF) gene, two GATA-repeat polymorphic sites exist that are physically separated by 212 bp. At the first site (vWF1 locus), seven segregating repeat alleles were observed in a Brazilian Caucasian population, and at the second (vWF2 locus) there were eight alleles, detected through PCR amplifications of this DNA region. Haplotype analysis of individuals revealed 36 different haplotypes in a sample of 338 chromosomes examined. Allele frequencies between generations and gender at each locus were not significantly different, and the genotype frequencies were consistent with their Hardy-Weinberg expectations. Linkage disequilibrium between loci is highly significant with positive allele size association; that is, large alleles at the loci tend to occur together, and so do the same alleles. Variability at each locus appeared to have arisen in a stepwise fashion, suggesting replication slippage as a possible mechanism of production of new alleles. However, the authors observed an increased number of haplotypes, in contrast with the predictions of a stepwise production of variation in the entire region, suggesting some form of cooperative changes between loci that could be due to either gene conversion, or a common control mechanism of production of new variation at these repeat polymorphism sites. The high degree of polymorphism (gene diversity values of 72% and 78% at vWF1 and vWF2, respectively, and of 93% at the haplotype level) makes these markers informative for paternity testing, genetic counseling, and individual-identification purposes.

  5. Always look on both sides: phylogenetic information conveyed by simple sequence repeat allele sequences.

    Directory of Open Access Journals (Sweden)

    Stéphanie Barthe

    Full Text Available Simple sequence repeat (SSR markers are widely used tools for inferences about genetic diversity, phylogeography and spatial genetic structure. Their applications assume that variation among alleles is essentially caused by an expansion or contraction of the number of repeats and that, accessorily, mutations in the target sequences follow the stepwise mutation model (SMM. Generally speaking, PCR amplicon sizes are used as direct indicators of the number of SSR repeats composing an allele with the data analysis either ignoring the extent of allele size differences or assuming that there is a direct correlation between differences in amplicon size and evolutionary distance. However, without precisely knowing the kind and distribution of polymorphism within an allele (SSR and the associated flanking region (FR sequences, it is hard to say what kind of evolutionary message is conveyed by such a synthetic descriptor of polymorphism as DNA amplicon size. In this study, we sequenced several SSR alleles in multiple populations of three divergent tree genera and disentangled the types of polymorphisms contained in each portion of the DNA amplicon containing an SSR. The patterns of diversity provided by amplicon size variation, SSR variation itself, insertions/deletions (indels, and single nucleotide polymorphisms (SNPs observed in the FRs were compared. Amplicon size variation largely reflected SSR repeat number. The amount of variation was as large in FRs as in the SSR itself. The former contributed significantly to the phylogenetic information and sometimes was the main source of differentiation among individuals and populations contained by FR and SSR regions of SSR markers. The presence of mutations occurring at different rates within a marker's sequence offers the opportunity to analyse evolutionary events occurring on various timescales, but at the same time calls for caution in the interpretation of SSR marker data when the distribution of within

  6. Characterization of new allele influencing flowering time in bread wheat introgressed from Triticum militinae.

    Science.gov (United States)

    Ivaničová, Zuzana; Jakobson, Irena; Reis, Diana; Šafář, Jan; Milec, Zbyněk; Abrouk, Michael; Doležel, Jaroslav; Järve, Kadri; Valárik, Miroslav

    2016-09-25

    Flowering time variation was identified within a mapping population of doubled haploid lines developed from a cross between the introgressive line 8.1 and spring bread wheat cv. Tähti. The line 8.1 carried introgressions from tetraploid Triticum militinae in the cv. Tähti genetic background on chromosomes 1A, 2A, 4A, 5A, 7A, 1B and 5B. The most significant QTL for the flowering time variation was identified within the introgressed region on chromosome 5A and its largest effect was associated with the VRN-A1 locus, accounting for up to 70% of phenotypic variance. The allele of T. militinae origin was designated as VRN-A1f-like. The effect of the VRN-A1f-like allele was verified in two other mapping populations. QTL analysis identified that in cv. Tähti and cv. Mooni genetic background, VRN-A1f-like allele incurred a delay of 1.9-18.6 days in flowering time, depending on growing conditions. Sequence comparison of the VRN-A1f-like and VRN-A1a alleles from the parental lines of the mapping populations revealed major mutations in the promoter region as well as in the first intron, including insertion of a MITE element and a large deletion. The sequence variation allowed construction of specific diagnostic PCR markers for VRN-A1f-like allele determination. Identification and quantification of the effect of the VRN-A1f-like allele offers a useful tool for wheat breeding and for studying fine-scale regulation of flowering pathways in wheat. PMID:26899284

  7. Variation in the maternal corticotrophin releasing hormone-binding protein (CRH-BP gene and birth weight in Blacks, Hispanics and Whites.

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    Pathik D Wadhwa

    Full Text Available BACKGROUND: Given the unique role of the corticotrophin-releasing hormone (CRH system in human fetal development, the aim of our study was to estimate the association of birth weight with DNA sequence variation in three maternal genes involved in regulating CRH production, bioavailability and action: CRH, CRH-Binding Protein (CRH-BP, and CRH type 1 receptor (CRH-R1, respectively, in three racial groups (African-Americans, Hispanics, and non-Hispanic Whites. METHODS: Our study was carried out on a population-based sample of 575 mother-child dyads. We resequenced the three genes in mouse-human hybrid somatic cell lines and selected SNPs for genotyping. RESULTS: A significant association was observed in each race between birth weight and maternal CRH-BP SNP genotypes. Estimates of linkage disequilibrium and haplotypes established three common haplotypes marked by the rs1053989 SNP in all three races. This SNP predicted significant birth weight variation after adjustment for gestational age, maternal BMI, parity, and smoking. African American and Hispanic mothers carrying the A allele had infants whose birth weight was on average 254 and 302 grams, respectively, less than infants having C/C mothers. Non-Hispanic White mothers homozygous for the A allele had infants who were on average 148 grams less than those infants having A/C and C/C mothers. CONCLUSIONS: The magnitudes of the estimates of the birth weight effects are comparable to the combined effects of multiple SNPs reported in a recent meta-analysis of 6 GWAS studies and is quantitatively larger than that associated with maternal cigarette smoking. This effect was persistent across subpopulations that vary with respect to ancestry and environment.

  8. Genomic African and Native American Ancestry and Chagas Disease: The Bambui (Brazil) Epigen Cohort Study of Aging

    Science.gov (United States)

    2016-01-01

    Background The influence of genetic ancestry on Trypanosoma cruzi infection and Chagas disease outcomes is unknown. Methodology/Principal Findings We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual proportions of African, European and Native American genomic ancestry with T. cruzi infection and related outcomes in 1,341 participants (aged ≥ 60 years) of the Bambui (Brazil) population-based cohort study of aging. Potential confounding variables included sociodemographic characteristics and an array of health measures. The prevalence of T. cruzi infection was 37.5% and 56.3% of those infected had a major ECG abnormality. Baseline T. cruzi infection was correlated with higher levels of African and Native American ancestry, which in turn were strongly associated with poor socioeconomic circumstances. Cardiomyopathy in infected persons was not significantly associated with African or Native American ancestry levels. Infected persons with a major ECG abnormality were at increased risk of 15-year mortality relative to their counterparts with no such abnormalities (adjusted hazard ratio = 1.80; 95% 1.41, 2.32). African and Native American ancestry levels had no significant effect modifying this association. Conclusions/Significance Our findings indicate that African and Native American ancestry have no influence on the presence of major ECG abnormalities and had no influence on the ability of an ECG abnormality to predict mortality in older people infected with T. cruzi. In contrast, our results revealed a strong and independent association between prevalent T. cruzi infection and higher levels of African and Native American ancestry. Whether this association is a consequence of genetic background or differential exposure to infection remains to be determined. PMID:27182885

  9. Diversity of Lactase Persistence Alleles in Ethiopia

    DEFF Research Database (Denmark)

    Jones, BL; Raga, TO; Liebert, Anke;

    2013-01-01

    The persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (−13910∗T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene ...

  10. RHD alleles in the Tunisian population

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    Mouna Ouchari

    2013-01-01

    Full Text Available Background: A comprehensive survey of RHD alleles in Tunisia population was lacking. The aim of this study was to use a multiplex RHD typing assay for simultaneous detection of partial D especially with RHD/RHCE deoxyribonucleic acid (DNA sequence exchange mechanism and some weak D alleles. Materials and Methods: Six RHD specific primer sets were designed to amplify RHD exons 3, 4, 5, 6, 7 and 9. DNA from 2000 blood donors (1777 D+ and 223 D- from several regions was selected for RHD genotyping using a PCR multiplex assay. Further molecular investigations were done to characterize the RHD variants that were identified by the PCR multiplex assay. Results: In the 1777 D+ samples, only 10 individuals showed the absence of amplification of exons 4 and 5 that were subsequently identified by PCR-SSP as weak D type 4 variants. No hybrid allele was detected. In the 223 D-, RHD amplification of some exons was observed only in 5 samples: 4 individuals expressed only RHD exon 9, and one subject lacking exons 4 and 5. These samples were then screened by PCR-SSPs on d(C ce s and weak D type 4, respectively. Conclusion: The weak D type 4 appears to be the most common D variant allele. We have not found any partial D variant. Findings also indicated that RHD gene deletion is the most prevalent cause of the D- phenotype in the Tunisian population.

  11. Local Ancestry Inference in a Large US-Based Hispanic/Latino Study: Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

    OpenAIRE

    Browning, Sharon R.; Kelsey Grinde; Anna Plantinga; Gogarten, Stephanie M.; Stilp, Adrienne M.; Kaplan, Robert C.; M. Larissa Avilés-Santa; Browning, Brian L; Laurie, Cathy C.

    2016-01-01

    We estimated local ancestry on the autosomes and X chromosome in a large US-based study of 12,793 Hispanic/Latino individuals using the RFMix method, and we compared different reference panels and approaches to local ancestry estimation on the X chromosome by means of Mendelian inconsistency rates as a proxy for accuracy. We developed a novel and straightforward approach to performing ancestry-specific PCA after finding artifactual behavior in the results from an existing approach. Using the ...

  12. Composition and functional analysis of low-molecular-weight glutenin alleles with Aroona near-isogenic lines of bread wheat

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    Zhang Xiaofei

    2012-12-01

    Full Text Available Abstract Background Low-molecular-weight glutenin subunits (LMW-GS strongly influence the bread-making quality of bread wheat. These proteins are encoded by a multi-gene family located at the Glu-A3, Glu-B3 and Glu-D3 loci on the short arms of homoeologous group 1 chromosomes, and show high allelic variation. To characterize the genetic and protein compositions of LMW-GS alleles, we investigated 16 Aroona near-isogenic lines (NILs using SDS-PAGE, 2D-PAGE and the LMW-GS gene marker system. Moreover, the composition of glutenin macro-polymers, dough properties and pan bread quality parameters were determined for functional analysis of LMW-GS alleles in the NILs. Results Using the LMW-GS gene marker system, 14–20 LMW-GS genes were identified in individual NILs. At the Glu-A3 locus, two m-type and 2–4 i-type genes were identified and their allelic variants showed high polymorphisms in length and nucleotide sequences. The Glu-A3d allele possessed three active genes, the highest number among Glu-A3 alleles. At the Glu-B3 locus, 2–3 m-type and 1–3 s-type genes were identified from individual NILs. Based on the different compositions of s-type genes, Glu-B3 alleles were divided into two groups, one containing Glu-B3a, B3b, B3f and B3g, and the other comprising Glu-B3c, B3d, B3h and B3i. Eight conserved genes were identified among Glu-D3 alleles, except for Glu-D3f. The protein products of the unique active genes in each NIL were detected using protein electrophoresis. Among Glu-3 alleles, the Glu-A3e genotype without i-type LMW-GS performed worst in almost all quality properties. Glu-B3b, B3g and B3i showed better quality parameters than the other Glu-B3 alleles, whereas the Glu-B3c allele containing s-type genes with low expression levels had an inferior effect on bread-making quality. Due to the conserved genes at Glu-D3 locus, Glu-D3 alleles showed no significant differences in effects on all quality parameters. Conclusions This work

  13. A novel simple method for determining CYP2D6 gene copy number and identifying allele(s with duplication/multiplication.

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    Taimour Langaee

    Full Text Available Cytochrome P450 2D6 (CYP2D6 gene duplication and multiplication can result in ultrarapid drug metabolism and therapeutic failure or excessive response in patients. Long range polymerase chain reaction (PCR, restriction fragment length polymorphism (RFLP and sequencing are usually used for genotyping CYP2D6 duplication/multiplications and identification, but are labor intensive, time consuming, and costly.We developed a simple allele quantification-based Pyrosequencing genotyping method that facilitates CYP2D6 copy number variation (CNV genotyping while also identifying allele-specific CYP2D6 CNV in heterozygous samples. Most routine assays do not identify the allele containing a CNV. A total of 237 clinical and Coriell DNA samples with different known CYP2D6 gene copy numbers were genotyped for CYP2D6 *2, *3, *4, *6, *10, *17, *41 polymorphisms and CNV determination.The CYP2D6 gene allele quantification/identification were determined simultaneously with CYP2D6*2, *3, *4, *6, *10, *17, *41 genotyping. We determined the exact CYP2D6 gene copy number, identified which allele had the duplication or multiplication, and assigned the correct phenotype and activity score for all samples.Our method can efficiently identify the duplicated CYP2D6 allele in heterozygous samples, determine its copy number in a fraction of time compared to conventional methods and prevent incorrect ultrarapid phenotype calls. It also greatly reduces the cost, effort and time associated with CYP2D6 CNV genotyping.

  14. Differences in the ability to suppress interferon β production between allele A and allele B NS1 proteins from H10 influenza A viruses

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    Zohari Siamak

    2010-12-01

    Full Text Available Abstract Background In our previous study concerning the genetic relationship among H10 avian influenza viruses with different pathogenicity in mink (Mustela vison, we found that these differences were related to amino acid variations in the NS1 protein. In this study, we extend our previous work to further investigate the effect of the NS1 from different gene pools on type I IFN promoter activity, the production of IFN-β, as well as the expression of the IFN-β mRNA in response to poly I:C. Results Using a model system, we first demonstrated that NS1 from A/mink/Sweden/84 (H10N4 (allele A could suppress an interferon-stimulated response element (ISRE reporter system to about 85%. The other NS1 (allele B, from A/chicken/Germany/N/49 (H10N7, was also able to suppress the reporter system, but only to about 20%. The differences in the abilities of the two NS1s from different alleles to suppress the ISRE reporter system were clearly reflected by the protein and mRNA expressions of IFN-β as shown by ELISA and RT-PCR assays. Conclusions These studies reveal that different non-structural protein 1 (NS1 of influenza viruses, one from allele A and another from allele B, show different abilities to suppress the type I interferon β expression. It has been hypothesised that some of the differences in the different abilities of the alleles to suppress ISRE were because of the interactions and inhibitions at later stages from the IFN receptor, such as the JAK/STAT pathway. This might reflect the additional effects of the immune evasion potential of different NS1s.

  15. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium.

    Science.gov (United States)

    Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B; Behrens, Sabine; Goode, Ellen L; Bolla, Manjeet K; Dennis, Joe; Dunning, Alison M; Easton, Douglas F; Wang, Qin; Benitez, Javier; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Fasching, Peter A; Haeberle, Lothar; Peto, Julian; Dos-Santos-Silva, Isabel; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marmé, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Nielsen, Sune F; Nordestgaard, Børge G; González-Neira, Anna; Menéndez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Fagerholm, Rainer; Dörk, Thilo; Bogdanova, Natalia V; Mannermaa, Arto; Hartikainen, Jaana M; Van Dijck, Laurien; Smeets, Ann; Flesch-Janys, Dieter; Eilber, Ursula; Radice, Paolo; Peterlongo, Paolo; Couch, Fergus J; Hallberg, Emily; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Schumacher, Fredrick; Simard, Jacques; Goldberg, Mark S; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Winqvist, Robert; Grip, Mervi; Andrulis, Irene L; Glendon, Gord; García-Closas, Montserrat; Figueroa, Jonine; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Eriksson, Mikael; Hall, Per; Li, Jingmei; Cox, Angela; Cross, Simon S; Pharoah, Paul D P; Shah, Mitul; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Ademuyiwa, Foluso; Ambrosone, Christine B; Swerdlow, Anthony; Jones, Michael; Chang-Claude, Jenny

    2016-01-01

    Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 × 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10(-3), 4.5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry. PMID:26621531

  16. Global divergence of the human follicle mite Demodex folliculorum: Persistent associations between host ancestry and mite lineages.

    Science.gov (United States)

    Palopoli, Michael F; Fergus, Daniel J; Minot, Samuel; Pei, Dorothy T; Simison, W Brian; Fernandez-Silva, Iria; Thoemmes, Megan S; Dunn, Robert R; Trautwein, Michelle

    2015-12-29

    Microscopic mites of the genus Demodex live within the hair follicles of mammals and are ubiquitous symbionts of humans, but little molecular work has been done to understand their genetic diversity or transmission. Here we sampled mite DNA from 70 human hosts of diverse geographic ancestries and analyzed 241 sequences from the mitochondrial genome of the species Demodex folliculorum. Phylogenetic analyses recovered multiple deep lineages including a globally distributed lineage common among hosts of European ancestry and three lineages that primarily include hosts of Asian, African, and Latin American ancestry. To a great extent, the ancestral geography of hosts predicted the lineages of mites found on them; 27% of the total molecular variance segregated according to the regional ancestries of hosts. We found that D. folliculorum populations are stable on an individual over the course of years and that some Asian and African American hosts maintain specific mite lineages over the course of years or generations outside their geographic region of birth or ancestry. D. folliculorum haplotypes were much more likely to be shared within families and between spouses than between unrelated individuals, indicating that transmission requires close contact. Dating analyses indicated that D. folliculorum origins may predate modern humans. Overall, D. folliculorum evolution reflects ancient human population divergences, is consistent with an out-of-Africa dispersal hypothesis, and presents an excellent model system for further understanding the history of human movement. PMID:26668374

  17. Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.

    Directory of Open Access Journals (Sweden)

    Amidou N'Diaye

    2011-10-01

    Full Text Available Adult height is a classic polygenic trait of high heritability (h(2 approximately 0.8. More than 180 single nucleotide polymorphisms (SNPs, identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain approximately10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10(-12 and 2p14-rs4315565, P = 1.2×10(-8. As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10(-4 for overall replication. Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P<0.01. Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits.

  18. Genetic association for renal traits among participants of African ancestry reveals new loci for renal function.

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    Ching-Ti Liu

    2011-09-01

    Full Text Available Chronic kidney disease (CKD is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA, and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR, CKD (eGFR 30 mg/g and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B. Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3. In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3×10(-7 and FNDC1 (p-value = 3.0×10(-7 for UACR, and KCNQ1 with eGFR (p = 3.6×10(-6. Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish.

  19. Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain

    OpenAIRE

    Richards, Alexander L.; Jones, Lesley; Moskvina, Valentina; Kirov, George; Gejman, Pablo V.; Levinson, Douglas F.; Sanders, Alan R; Purcell, Shaun; Visscher, Peter M.; Craddock, Nick; Owen, Michael J.; Holmans, Peter; O’Donovan, Michael C

    2011-01-01

    It is widely thought that alleles that influence susceptibility to common diseases, including schizophrenia, will frequently do so through effects on gene expression. Since only a small proportion of the genetic variance for schizophrenia has been attributed to specific loci, this remains an unproven hypothesis. The International Schizophrenia Consortium (ISC) recently reported a substantial polygenic contribution to that disorder, and that schizophrenia risk alleles are enriched among SNPs s...

  20. Cost-effective genome-wide estimation of allele frequencies from pooled DNA in Atlantic salmon (Salmo salar L.

    Directory of Open Access Journals (Sweden)

    Ozerov Mikhail

    2013-01-01

    Full Text Available Abstract Background New sequencing technologies have tremendously increased the number of known molecular markers (single nucleotide polymorphisms; SNPs in a variety of species. Concurrently, improvements to genotyping technology have now made it possible to efficiently genotype large numbers of genome-wide distributed SNPs enabling genome wide association studies (GWAS. However, genotyping significant numbers of individuals with large number of SNPs remains prohibitively expensive for many research groups. A possible solution to this problem is to determine allele frequencies from pooled DNA samples, such ‘allelotyping’ has been presented as a cost-effective alternative to individual genotyping and has become popular in human GWAS. In this article we have tested the effectiveness of DNA pooling to obtain accurate allele frequency estimates for Atlantic salmon (Salmo salar L. populations using an Illumina SNP-chip. Results In total, 56 Atlantic salmon DNA pools from 14 populations were analyzed on an Atlantic salmon SNP-chip containing probes for 5568 SNP markers, 3928 of which were bi-allelic. We developed an efficient quality control filter which enables exclusion of loci showing high error rate and minor allele frequency (MAF close to zero. After applying multiple quality control filters we obtained allele frequency estimates for 3631 bi-allelic loci. We observed high concordance (r > 0.99 between allele frequency estimates derived from individual genotyping and DNA pools. Our results also indicate that even relatively small DNA pools (35 individuals can provide accurate allele frequency estimates for a given sample. Conclusions Despite of higher level of variation associated with array replicates compared to pool construction, we suggest that both sources of variation should be taken into account. This study demonstrates that DNA pooling allows fast and high-throughput determination of allele frequencies in Atlantic salmon enabling cost

  1. Differential allelic expression of a fibrillin gene (FBNI) in patients with Marfan syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hewett, D.; Lynch, J.; Sykes, B. [Univ. of Oxford (United Kingdom); Firth, H. [Churchill Hospital, Oxford (United Kingdom); Child, A. [St. George`s Hospital Medical School, London (United Kingdom)

    1994-09-01

    Marfan syndrome is a connective-tissue disorder affecting cardiovascular, skeletal, and ocular systems. The major Marfan locus has been identified as the FBN1 gene on chromosome 15; this codes for the extracellular-matrix protein fibrillin, a 350-kD constituent of the 8-10-nm elastin-associated microfibrils. The authors identified five MFS patients who were heterozygous for an RsaI restriction-site dimorphism in the 3{prime} UTR of the FBN1 gene. This expressed variation was used to distinguish the mRNA output from each of the two FBN1 alleles in fibroblast cultures from these five patients. Three of the patients were shown to produce <5% of the normal level of FBN1 transcripts from one of their alleles. This null-allele phenotype was not observed in 10 nonmarfanoid fibroblast cell lines. 26 refs., 4 figs.

  2. Screening for the beta-thalassaemia trait: hazards among populations of West African Ancestry

    OpenAIRE

    Gibson, Felicea; Mason, Karlene; Serjeant, Beryl; Kulozik, Andreas; Happich, Margit; Tolle, Gabriele; Hambleton, Ian; Serjeant, Graham

    2011-01-01

    The aim of this study was to examine the accuracy and characteristics of detecting the beta-thalassaemia trait in populations of West African ancestry. School children, aged 16–19 years, in Manchester Parish, Jamaica were screened to detect the genes which could give rise to offspring with sickle cell disease. Haematological indices and HbA2 levels in subjects with an MCH ≤ 26 pg and an RDW G in 19 (25%), −90 C>T in 7 (9%), the IVS II-849 A>G in 5 (6%) with smaller contributions from five oth...

  3. Microsatellite allele frequencies in humans and chimpanzees, with implications for constraints on allele size.

    Science.gov (United States)

    Garza, J C; Slatkin, M; Freimer, N B

    1995-07-01

    The distributions of allele sizes at eight simple-sequence repeat (SSR) or microsatellite loci in chimpanzees are found and compared with the distributions previously obtained from several human populations. At several loci, the differences in average allele size between chimpanzees and humans are sufficiently small that there might be a constraint on the evolution of average allele size. Furthermore, a model that allows for a bias in the mutation process shows that for some loci a weak bias can account for the observations. Several alleles at one of the loci (Mfd 59) were sequenced. Differences between alleles of different lengths were found to be more complex than previously assumed. An 8-base-pair deletion was present in the nonvariable region of the chimpanzee locus. This locus contains a previously unrecognized repeated region, which is imperfect in humans and perfect in chimpanzees. The apparently greater opportunity for mutation conferred by the two perfect repeat regions in chimpanzees is reflected in the higher variance in repeat number at Mfd 59 in chimpanzees than in humans. These data indicate that interspecific differences in allele length are not always attributable to simple changes in the number of repeats. PMID:7659015

  4. Ancestry-informative markers on chromosomes 2, 8 and 15 are associated with insulin-related traits in a racially diverse sample of children

    Directory of Open Access Journals (Sweden)

    Klimentidis Yann C

    2011-01-01

    Full Text Available Abstract Type 2 diabetes represents an increasing health burden. Its prevalence is rising among younger age groups and differs among racial/ethnic groups. Little is known about its genetic basis, including whether there is a genetic basis for racial/ethnic disparities. We examined a multi-ethnic sample of 253 healthy children to evaluate associations between insulin-related phenotypes and 142 ancestry-informative markers (AIMs, while adjusting for sex, age, Tanner stage, genetic admixture, total body fat, height and socio-economic status. We also evaluated the effect of measurement errors in the estimation of the individual ancestry proportions on the regression results. We found that European genetic admixture is positively associated with insulin sensitivity (SI, and negatively associated with the acute insulin response to glucose, fasting insulin levels and the homeostasis model assessment of insulin resistance. Our analysis revealed associations between individual AIMs on chromosomes 2, 8 and 15 and these phenotypes. Most notably, marker rs3287 at chromosome 2p21 was found to be associated with SI (p = 5.8 × 10-5. This marker may be in admixture linkage disequilibrium with nearby loci (THADA and BCL11A that previously have been reported to be associated with diabetes and diabetes-related phenotypes in several genome-wide association and linkage studies. Our results provide further evidence that variation in the 2p21 region containing THADA and BCL11A is associated with type 2 diabetes. Importantly, we have implicated this region in the early development of diabetes-related phenotypes, and in the genetic aetiology of population differences in these phenotypes.

  5. Genome Destabilizing Mutator Alleles Drive Specific Mutational Trajectories in Saccharomyces cerevisiae

    Science.gov (United States)

    Stirling, Peter C.; Shen, Yaoqing; Corbett, Richard; Jones, Steven J. M.; Hieter, Philip

    2014-01-01

    In addition to environmental factors and intrinsic variations in base substitution rates, specific genome-destabilizing mutations can shape the mutational trajectory of genomes. How specific alleles influence the nature and position of accumulated mutations in a genomic context is largely unknown. Understanding the impact of genome-destabilizing alleles is particularly relevant to cancer genomes where biased mutational signatures are identifiable. We first created a more complete picture of cellular pathways that impact mutation rate using a primary screen to identify essential Saccharomyces cerevisiae gene mutations that cause mutator phenotypes. Drawing primarily on new alleles identified in this resource, we measure the impact of diverse mutator alleles on mutation patterns directly by whole-genome sequencing of 68 mutation-accumulation strains derived from wild-type and 11 parental mutator genotypes. The accumulated mutations differ across mutator strains, displaying base-substitution biases, allele-specific mutation hotspots, and break-associated mutation clustering. For example, in mutants of POLα and the Cdc13–Stn1–Ten1 complex, we find a distinct subtelomeric bias for mutations that we show is independent of the target sequence. Together our data suggest that specific genome-instability mutations are sufficient to drive discrete mutational signatures, some of which share properties with mutation patterns seen in tumors. Thus, in a population of cells, genome-instability mutations could influence clonal evolution by establishing discrete mutational trajectories for genomes. PMID:24336748

  6. Allele-specific copy-number discovery from whole-genome and whole-exome sequencing.

    Science.gov (United States)

    Wang, WeiBo; Wang, Wei; Sun, Wei; Crowley, James J; Szatkiewicz, Jin P

    2015-08-18

    Copy-number variants (CNVs) are a major form of genetic variation and a risk factor for various human diseases, so it is crucial to accurately detect and characterize them. It is conceivable that allele-specific reads from high-throughput sequencing data could be leveraged to both enhance CNV detection and produce allele-specific copy number (ASCN) calls. Although statistical methods have been developed to detect CNVs using whole-genome sequence (WGS) and/or whole-exome sequence (WES) data, information from allele-specific read counts has not yet been adequately exploited. In this paper, we develop an integrated method, called AS-GENSENG, which incorporates allele-specific read counts in CNV detection and estimates ASCN using either WGS or WES data. To evaluate the performance of AS-GENSENG, we conducted extensive simulations, generated empirical data using existing WGS and WES data sets and validated predicted CNVs using an independent methodology. We conclude that AS-GENSENG not only predicts accurate ASCN calls but also improves the accuracy of total copy number calls, owing to its unique ability to exploit information from both total and allele-specific read counts while accounting for various experimental biases in sequence data. Our novel, user-friendly and computationally efficient method and a complete analytic protocol is freely available at https://sourceforge.net/projects/asgenseng/. PMID:25883151

  7. Estimation of allele frequencies for VNTR loci.

    OpenAIRE

    Devlin, B; Risch, N; Roeder, K

    1991-01-01

    VNTR loci provide valuable information for a number of fields of study involving human genetics, ranging from forensics (DNA fingerprinting and paternity testing) to linkage analysis and population genetics. Alleles of a VNTR locus are simply fragments obtained from a particular portion of the DNA molecule and are defined in terms of their length. The essential element of a VNTR fragment is the repeat, which is a short sequence of basepairs. The core of the fragment is composed of a variable ...

  8. Quantitative threefold allele-specific PCR (QuanTAS-PCR) for highly sensitive JAK2 V617F mutant allele detection

    International Nuclear Information System (INIS)

    The JAK2 V617F mutation is the most frequent somatic change in myeloproliferative neoplasms, making it an important tumour-specific marker for diagnostic purposes and for the detection of minimal residual disease. Sensitive quantitative assays are required for both applications, particularly for the monitoring of minimal residual disease, which requires not only high sensitivity but also very high specificity. We developed a highly sensitive probe-free quantitative mutant-allele detection method, Quantitative Threefold Allele-Specific PCR (QuanTAS-PCR), that is performed in a closed-tube system, thus eliminating the manipulation of PCR products. QuantTAS-PCR uses a threefold approach to ensure allele-specific amplification of the mutant sequence: (i) a mutant allele-specific primer, (ii) a 3′dideoxy blocker to suppress false-positive amplification from the wild-type template and (iii) a PCR specificity enhancer, also to suppress false-positive amplification from the wild-type template. Mutant alleles were quantified relative to exon 9 of JAK2. We showed that the addition of the 3′dideoxy blocker suppressed but did not eliminate false-positive amplification from the wild-type template. However, the addition of the PCR specificity enhancer near eliminated false-positive amplification from the wild-type allele. Further discrimination between true and false positives was enabled by using the quantification cycle (Cq) value of a single mutant template as a cut-off point, thus enabling robust distinction between true and false positives. As 10,000 JAK2 templates were used per replicate, the assay had a sensitivity of 1/10-4 per replicate. Greater sensitivity could be reached by increasing the number of replicates analysed. Variation in replicates when low mutant-allele templates were present necessitated the use of a statistics-based approach to estimate the load of mutant JAK2 copies. QuanTAS-PCR showed comparable quantitative results when validated against a

  9. Frequencies of HID-ion ampliseq ancestry panel markers among greenlanders.

    Science.gov (United States)

    Espregueira Themudo, Gonçalo; Smidt Mogensen, Helle; Børsting, Claus; Morling, Niels

    2016-09-01

    The HID-Ion AmpliSeq Ancestry Panel from Life Techologies includes 123 SNPs from the Seldin panel and 55 SNPs from Kidd panel in a single multiplex assay that helps to determine the continental biogeographic ancestry of individuals. We tested the panel on 104 Greenlanders, divided into a training set of 89 individuals and a test set of 15 individuals. All loci showed genotype distributions consistent with Hardy-Weinberg expectations. Linkage disequilibrium tests indicated that 14 pairs of loci were in association in Greenlanders. Population assignment of the training set to populations included in the HID SNP genotyper plugin placed most individuals in American, Asian, and in a few cases European populations. By including the genotype frequencies of this training set as a possible population of origin, all 15 individuals from the test set were correctly predicted to be Greenlanders using the Seldin SNPs, and nine were classified as Greenlanders using the Kidd SNPs. Population structure analysis indicated that Greenlanders have a genetic profile that is distinguishable from those of populations from America or Asia. PMID:27326551

  10. Biogeographic ancestry, self-identified race, and admixture-phenotype associations in the Heart SCORE Study.

    Science.gov (United States)

    Halder, Indrani; Kip, Kevin E; Mulukutla, Suresh R; Aiyer, Aryan N; Marroquin, Oscar C; Huggins, Gordon S; Reis, Steven E

    2012-07-15

    Large epidemiologic studies examining differences in cardiovascular disease (CVD) risk factor profiles between European Americans and African Americans have exclusively used self-identified race (SIR) to classify individuals. Recent genetic epidemiology studies of some CVD risk factors have suggested that biogeographic ancestry (BGA) may be a better predictor of CVD risk than SIR. This hypothesis was investigated in 464 African Americans and 771 European Americans enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) Study in March and April 2010. Individual West African and European BGA were ascertained by means of a panel of 1,595 genetic ancestry informative markers. Individual BGA varied significantly among African Americans and to a lesser extent among European Americans. In the total cohort, BGA was not found to be a better predictor of CVD risk factors than SIR. Both measures predicted differences in the presence of the metabolic syndrome, waist circumference, triglycerides, body mass index, very low density lipoprotein cholesterol, lipoprotein A, and systolic and diastolic blood pressure between European Americans and African Americans. These results suggest that for most nongenetic cardiovascular epidemiology studies, SIR is sufficient for predicting CVD risk factor differences between European Americans and African Americans. However, higher body mass index and diastolic blood pressure were significantly associated with West African BGA among African Americans, suggesting that BGA should be considered in genetic cardiovascular epidemiology studies carried out among African Americans. PMID:22771727

  11. Highly discrepant proportions of female and male Scandinavian and British Isles ancestry within the isolated population of the Faroe Islands

    DEFF Research Database (Denmark)

    Als, Thomas D; Jorgensen, Tove H; Børglum, Anders D;

    2006-01-01

    The Faroe Islands in the North Atlantic Ocean are inhabited by a small population, whose origin is thought to date back to the Viking Age. Historical, archaeological and linguistic evidence indicates that the present population of the Faroe Islands may have a mixture of Scandinavian and British...... frequency-based admixture approach taking private haplotypes into account by the use of phylogenetic information. While previous studies have suggested an excess of Scandinavian ancestry among the male settlers of the Faroe Islands, the current study indicates an excess of British Isles ancestry among the...

  12. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

    DEFF Research Database (Denmark)

    Kato, Norihiro; Loh, Marie; Takeuchi, Fumihiko;

    2015-01-01

    We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(...

  13. Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained.

    Directory of Open Access Journals (Sweden)

    Ying Wu

    2013-03-01

    Full Text Available Genome-wide association studies (GWAS have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG, high-density lipoprotein cholesterol (HDL-C, and low-density lipoprotein cholesterol (LDL-C, respectively, in individuals of African American (n = 6,832, East Asian (n = 9,449, and European (n = 10,829 ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1 × 10(-4 in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies.

  14. Variation in genetic admixture and population structure among Latinos: the Los Angeles Latino eye study (LALES

    Directory of Open Access Journals (Sweden)

    Le Marchand Loic

    2009-11-01

    Full Text Available Abstract Background Population structure and admixture have strong confounding effects on genetic association studies. Discordant frequencies for age-related macular degeneration (AMD risk alleles and for AMD incidence and prevalence rates are reported across different ethnic groups. We examined the genomic ancestry characterizing 538 Latinos drawn from the Los Angeles Latino Eye Study [LALES] as part of an ongoing AMD-association study. To help assess the degree of Native American ancestry inherited by Latino populations we sampled 25 Mayans and 5 Mexican Indians collected through Coriell's Institute. Levels of European, Asian, and African descent in Latinos were inferred through the USC Multiethnic Panel (USC MEP, formed from a sample from the Multiethnic Cohort (MEC study, the Yoruba African samples from HapMap II, the Singapore Chinese Health Study, and a prospective cohort from Shanghai, China. A total of 233 ancestry informative markers were genotyped for 538 LALES Latinos, 30 Native Americans, and 355 USC MEP individuals (African Americans, Japanese, Chinese, European Americans, Latinos, and Native Hawaiians. Sensitivity of ancestry estimates to relative sample size was considered. Results We detected strong evidence for recent population admixture in LALES Latinos. Gradients of increasing Native American background and of correspondingly decreasing European ancestry were observed as a function of birth origin from North to South. The strongest excess of homozygosity, a reflection of recent population admixture, was observed in non-US born Latinos that recently populated the US. A set of 42 SNPs especially informative for distinguishing between Native Americans and Europeans were identified. Conclusion These findings reflect the historic migration patterns of Native Americans and suggest that while the 'Latino' label is used to categorize the entire population, there exists a strong degree of heterogeneity within that population, and that

  15. Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes.

    Science.gov (United States)

    Miller, F W; Chen, W; O'Hanlon, T P; Cooper, R G; Vencovsky, J; Rider, L G; Danko, K; Wedderburn, L R; Lundberg, I E; Pachman, L M; Reed, A M; Ytterberg, S R; Padyukov, L; Selva-O'Callaghan, A; Radstake, T R; Isenberg, D A; Chinoy, H; Ollier, W E R; Scheet, P; Peng, B; Lee, A; Byun, J; Lamb, J A; Gregersen, P K; Amos, C I

    2015-10-01

    Autoimmune muscle diseases (myositis) comprise a group of complex phenotypes influenced by genetic and environmental factors. To identify genetic risk factors in patients of European ancestry, we conducted a genome-wide association study (GWAS) of the major myositis phenotypes in a total of 1710 cases, which included 705 adult dermatomyositis, 473 juvenile dermatomyositis, 532 polymyositis and 202 adult dermatomyositis, juvenile dermatomyositis or polymyositis patients with anti-histidyl-tRNA synthetase (anti-Jo-1) autoantibodies, and compared them with 4724 controls. Single-nucleotide polymorphisms showing strong associations (PAH8.1) defined essentially all the genetic risk in the phenotypes studied. Although the HLA DRB1*03:01 allele showed slightly stronger associations with adult and juvenile dermatomyositis, and HLA B*08:01 with polymyositis and anti-Jo-1 autoantibody-positive myositis, multiple alleles of AH8.1 were required for the full risk effects. Our findings establish that alleles of the AH8.1 comprise the primary genetic risk factors associated with the major myositis phenotypes in geographically diverse Caucasian populations. PMID:26291516

  16. Borrowed alleles and convergence in serpentine adaptation.

    Science.gov (United States)

    Arnold, Brian J; Lahner, Brett; DaCosta, Jeffrey M; Weisman, Caroline M; Hollister, Jesse D; Salt, David E; Bomblies, Kirsten; Yant, Levi

    2016-07-19

    Serpentine barrens represent extreme hazards for plant colonists. These sites are characterized by high porosity leading to drought, lack of essential mineral nutrients, and phytotoxic levels of metals. Nevertheless, nature forged populations adapted to these challenges. Here, we use a population-based evolutionary genomic approach coupled with elemental profiling to assess how autotetraploid Arabidopsis arenosa adapted to a multichallenge serpentine habitat in the Austrian Alps. We first demonstrate that serpentine-adapted plants exhibit dramatically altered elemental accumulation levels in common conditions, and then resequence 24 autotetraploid individuals from three populations to perform a genome scan. We find evidence for highly localized selective sweeps that point to a polygenic, multitrait basis for serpentine adaptation. Comparing our results to a previous study of independent serpentine colonizations in the closely related diploid Arabidopsis lyrata in the United Kingdom and United States, we find the highest levels of differentiation in 11 of the same loci, providing candidate alleles for mediating convergent evolution. This overlap between independent colonizations in different species suggests that a limited number of evolutionary strategies are suited to overcome the multiple challenges of serpentine adaptation. Interestingly, we detect footprints of selection in A. arenosa in the context of substantial gene flow from nearby off-serpentine populations of A. arenosa, as well as from A. lyrata In several cases, quantitative tests of introgression indicate that some alleles exhibiting strong selective sweep signatures appear to have been introgressed from A. lyrata This finding suggests that migrant alleles may have facilitated adaptation of A. arenosa to this multihazard environment. PMID:27357660

  17. Tri-allelic pattern of short tandem repeats identifies the murderer among identical twins and suggests an embryonic mutational origin.

    Science.gov (United States)

    Wang, Li-Feng; Yang, Ying; Zhang, Xiao-Nan; Quan, Xiao-Liang; Wu, Yuan-Ming

    2015-05-01

    Monozygotic twins can be co-identified by genotyping of short tandem repeats (STRs); however, for distinguishing them, STR genotyping is ineffective, especially in the case of murder. Here, a rarely occurring tri-allelic pattern in the vWA locus (16, 18, 19) was identified only in the DNA of one identical twin, which could help to exonerate the innocent twin in a murder charge. This mutation was defined as primary through genotyping of the family and could be detected in blood, buccal and semen samples from the individual; however, two alternative allele-balanced di-allelic patterns (16, 18 or 16, 19) were detected in hair root sheath cells. Such a kind of segregation indicates a one-step mutation occurs in cell mitosis, which is after embryonic zygote formation and during the early development of the individual after the division of the blastocyte. Sequencing revealed the insertion between the allele 18 and 19 is a repeat unit of TAGA/TCTA (plus/minus strand), which belongs to "AGAT/ATCT"-based core repeats identified from all tri-allelic pattern reports recorded in the STR base and a detailed model was proposed for STR repeat length variation caused by false priming during DNA synthesis. Our model illustrates the possible origination of allele-balanced and unbalanced tri-allelic pattern, clarifies that the genotypes of parent-child mismatches, aberrant di-allelic patterns, and type 1 or 2 tri-allelic patterns should be considered as independent, but interconnected forms of STR mutation. PMID:25732248

  18. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

    DEFF Research Database (Denmark)

    Mahajan, Anubha; Go, Min Jin; Zhang, Weihua;

    2014-01-01

    To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We obs...

  19. The association between common genetic variation in the FTO gene and metabolic syndrome in Han Chinese

    Institute of Scientific and Technical Information of China (English)

    WANG Tong; ZHANG Li-li; ZHANG Yun; SUN Xiao-fang; ZHANG Qian; HUANG Yi; XIAO Xin-hua; WANG Duen-mei; DIAO Cheng-ming; ZHANG Feng; XU Ling-ling; ZHANG Yong-biao; LI Wen-hui

    2010-01-01

    Background Genome-wide association studies for type 2 diabetes mellitus (T2DM) identified FTO gene as a locus conferring increased risk for common obesity in many populations with European ancestry. However, the involvement of FTO gene in obesity or T2DM related metabolic traits has not been consistently established in Chinese populations. The objective of this study was to investigate the association of FTO genetic polymorphisms with metabolic syndrome (MetS) in Han Chinese.Methods We tested 41 FTO single nucleotide polymorphisms (SNPs) for association between FTO and MetS-related traits. There were a total of 236 unrelated subjects (108 cases and 128 controls), grouped according to the International Diabetes Federation (IDF) criteria.Results Of the 41 SNPs examined, only SNP rs8047395 exhibited statistical significance (P=0.026) under a recessive model, after Bonferroni adjustment for multiple testing (OR 1.64, 95% CI 1.11-2.42; P=0.014). The common distributions of this polymorphism among Chinese-with a minor allele frequency (MAF) of 36% in the control group versus 48% in the MetS group-greatly improved our test power in a relatively small sample size for an association study. Previously identified obesity-(or T2DM-) associated FTO SNPs were less common in Han Chinese and were not associated with MetS in this study. No significant associations were found between our FTO SNPs and any endophenotypes of MetS.Conclusions A more common risk-conferring variant of FTO for MetS was identified in Han Chinese. Our study substantiated that genetic variations in FTO locus are involved in the pathogenesis of MetS.

  20. Malagasy Genetic Ancestry Comes from an Historical Malay Trading Post in Southeast Borneo.

    Science.gov (United States)

    Brucato, Nicolas; Kusuma, Pradiptajati; Cox, Murray P; Pierron, Denis; Purnomo, Gludhug A; Adelaar, Alexander; Kivisild, Toomas; Letellier, Thierry; Sudoyo, Herawati; Ricaut, François-Xavier

    2016-09-01

    Malagasy genetic diversity results from an exceptional protoglobalization process that took place over a thousand years ago across the Indian Ocean. Previous efforts to locate the Asian origin of Malagasy highlighted Borneo broadly as a potential source, but so far no firm source populations were identified. Here, we have generated genome-wide data from two Southeast Borneo populations, the Banjar and the Ngaju, together with published data from populations across the Indian Ocean region. We find strong support for an origin of the Asian ancestry of Malagasy among the Banjar. This group emerged from the long-standing presence of a Malay Empire trading post in Southeast Borneo, which favored admixture between the Malay and an autochthonous Borneo group, the Ma'anyan. Reconciling genetic, historical, and linguistic data, we show that the Banjar, in Malay-led voyages, were the most probable Asian source among the analyzed groups in the founding of the Malagasy gene pool. PMID:27381999

  1. Ancestry inference in complex admixtures via variable-length Markov chain linkage models.

    Science.gov (United States)

    Rodriguez, Jesse M; Bercovici, Sivan; Elmore, Megan; Batzoglou, Serafim

    2013-03-01

    Inferring the ancestral origin of chromosomal segments in admixed individuals is key for genetic applications, ranging from analyzing population demographics and history, to mapping disease genes. Previous methods addressed ancestry inference by using either weak models of linkage disequilibrium, or large models that make explicit use of ancestral haplotypes. In this paper we introduce ALLOY, an efficient method that incorporates generalized, but highly expressive, linkage disequilibrium models. ALLOY applies a factorial hidden Markov model to capture the parallel process producing the maternal and paternal admixed haplotypes, and models the background linkage disequilibrium in the ancestral populations via an inhomogeneous variable-length Markov chain. We test ALLOY in a broad range of scenarios ranging from recent to ancient admixtures with up to four ancestral populations. We show that ALLOY outperforms the previous state of the art, and is robust to uncertainties in model parameters. PMID:23421795

  2. The Hmong Diaspora: preserved South-East Asian genetic ancestry in French Guianese Asians.

    Science.gov (United States)

    Brucato, Nicolas; Mazières, Stéphane; Guitard, Evelyne; Giscard, Pierre-Henri; Bois, Etienne; Larrouy, Georges; Dugoujon, Jean-Michel

    2012-01-01

    The Hmong Diaspora is one of the widest modern human migrations. Mainly localised in South-East Asia, the United States of America, and metropolitan France, a small community has also settled the Amazonian forest of French Guiana. We have biologically analysed 62 individuals of this unique Guianese population through three complementary genetic markers: mitochondrial DNA (HVS-I/II and coding region SNPs), Y-chromosome (SNPs and STRs), and the Gm allotypic system. All genetic systems showed a high conservation of the Asian gene pool (Asian ancestry: mtDNA=100.0%; NRY=99.1%; Gm=96.6%), without a trace of founder effect. When compared across various Asian populations, the highest correlations were observed with Hmong-Mien groups still living in South-East Asia (Fst<0.05; P-value<0.05). Despite a long history punctuated by exodus, the French Guianese Hmong have maintained their original genetic diversity. PMID:23199638

  3. The dynamics of mergers and acquisitions: ancestry as the seminal determinant.

    Science.gov (United States)

    Viegas, Eduardo; Cockburn, Stuart P; Jensen, Henrik J; West, Geoffrey B

    2014-11-01

    Understanding the fundamental mechanisms behind the complex landscape of corporate mergers and acquisitions is of crucial importance to economies across the world. Adapting ideas from the fields of complexity and evolutionary dynamics to analyse business ecosystems, we show here that ancestry, i.e. the cumulative sum of historical mergers across all ancestors, is the key characteristic to company mergers and acquisitions. We verify this by comparing an agent-based model to an extensive range of business data, covering the period from the 1830s to the present day and a range of industries and geographies. This seemingly universal mechanism leads to imbalanced business ecosystems, with the emergence of a few very large, but sluggish 'too big to fail' entities, and very small, niche entities, thereby creating a paradigm where a configuration akin to effective oligopoly or monopoly is a likely outcome for free market systems. PMID:25383025

  4. Race, Common Genetic Variation, and Therapeutic Response Disparities in Heart Failure

    OpenAIRE

    Taylor, Mathew R.; Sun, Albert Y.; Davis, Gordon; Fiuzat, Mona; Liggett, Stephen B.; Bristow, Michael R.

    2014-01-01

    Because of its relatively recent evolution, Homo sapiens exhibits relatively little within-species genomic diversity. However, because of genome size, a proportionally small amount of variation creates ample opportunity for both rare mutations that may be disease-causative as well as more common genetic variation that may be important in disease modification or pharmacogenetics. Primarily because of the East African origin of modern humans, individuals of African ancestry (AA) exhibit greater...

  5. Association of the BANK1 R61H variant with systemic lupus erythematosus in Americans of European and African ancestry

    Directory of Open Access Journals (Sweden)

    Struan FA Grant

    2008-12-01

    Full Text Available Struan FA Grant1,2,3, Michelle Petri4, Jonathan P Bradfield1, Cecilia E Kim1, Erin Santa1, Kiran Annaiah1, Edward C Frackelton1, Joseph T Glessner1, F George Otieno1, Julie L Shaner1, Ryan M Smith1, Andrew W Eckert1, Rosetta M Chiavacci1, Marcin Imielinski1, Kathleen E Sullivan5, Hakon Hakonarson1,2,31Center for Applied Genomics, Abramson Research Center, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA; 2Department of Pediatrics and Division of Human Genetics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA; 3Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; 4Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, MD, USA; 5Division of Allergy and Immunology, Abramson Research Center, The Children’s Hospital of Philadelphia, Philadelphia, PA, USAAbstract: Recently an association was demonstrated between the single nucleotide polymorphism (SNP, rs10516487, within the B-cell gene BANK1 and systemic lupus erythematosus (SLE as a consequence of a genome wide association study of this disease in European and Argentinean populations. In a bid for replication, we examined the effects of the R61H non-synonymous variant with respect to SLE in our genotyped American cohorts of European and African ancestry. Utilizing data from our ongoing genome-wide association study in our cohort of 178 Caucasian SLE cases and 1808 Caucasian population-based controls plus 148 African American (AA SLE cases and 1894 AA population-based controls we investigated the association of the previously described non-synonymous SNP at the BANK1 locus with the disease in the two ethnicities separately. Using a Fisher’s exact test, the minor allele frequency (MAF of rs10516487 in the Caucasian cases was 22.6% while it was 31.2% in Caucasian controls, yielding a protective odds ratio (OR of 0.64 (95% CI 0.49–0.85; one-sided p = 7.07 × 10−4. Furthermore, the MAF of rs10516487 in the

  6. DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status

    DEFF Research Database (Denmark)

    Weiner Lachmi, Karin; Lin, Ling; Kornum, Birgitte Rahbek;

    2012-01-01

    The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression in per...

  7. Evolutionary ancestry and novel functions of the mammalian glucose transporter (GLUT family

    Directory of Open Access Journals (Sweden)

    Patron Nicola

    2010-05-01

    Full Text Available Abstract Background In general, sugar porters function by proton-coupled symport or facilitative transport modes. Symporters, coupled to electrochemical energy, transport nutrients against a substrate gradient. Facilitative carriers transport sugars along a concentration gradient, thus transport is dependent upon extracellular nutrient levels. Across bacteria, fungi, unicellular non-vertebrates and plants, proton-coupled hexose symport is a crucial process supplying energy under conditions of nutrient flux. In mammals it has been assumed that evolution of whole body regulatory mechanisms would eliminate this need. To determine whether any isoforms bearing this function might be conserved in mammals, we investigated the relationship between the transporters of animals and the proton-coupled hexose symporters found in other species. Results We took a comparative genomic approach and have performed the first comprehensive and statistically supported phylogenetic analysis of all mammalian glucose transporter (GLUT isoforms. Our data reveals the mammalian GLUT proteins segregate into five distinct classes. This evolutionary ancestry gives insight to structure, function and transport mechanisms within the groups. Combined with biological assays, we present novel evidence that, in response to changing nutrient availability and environmental pH, proton-coupled, active glucose symport function is maintained in mammalian cells. Conclusions The analyses show the ancestry, evolutionary conservation and biological importance of the GLUT classes. These findings significantly extend our understanding of the evolution of mammalian glucose transport systems. They also reveal that mammals may have conserved an adaptive response to nutrient demand that would have important physiological implications to cell survival and growth.

  8. ObStruct: a method to objectively analyse factors driving population structure using Bayesian ancestry profiles.

    Directory of Open Access Journals (Sweden)

    Velimir Gayevskiy

    Full Text Available Bayesian inference methods are extensively used to detect the presence of population structure given genetic data. The primary output of software implementing these methods are ancestry profiles of sampled individuals. While these profiles robustly partition the data into subgroups, currently there is no objective method to determine whether the fixed factor of interest (e.g. geographic origin correlates with inferred subgroups or not, and if so, which populations are driving this correlation. We present ObStruct, a novel tool to objectively analyse the nature of structure revealed in Bayesian ancestry profiles using established statistical methods. ObStruct evaluates the extent of structural similarity between sampled and inferred populations, tests the significance of population differentiation, provides information on the contribution of sampled and inferred populations to the observed structure and crucially determines whether the predetermined factor of interest correlates with inferred population structure. Analyses of simulated and experimental data highlight ObStruct's ability to objectively assess the nature of structure in populations. We show the method is capable of capturing an increase in the level of structure with increasing time since divergence between simulated populations. Further, we applied the method to a highly structured dataset of 1,484 humans from seven continents and a less structured dataset of 179 Saccharomyces cerevisiae from three regions in New Zealand. Our results show that ObStruct provides an objective metric to classify the degree, drivers and significance of inferred structure, as well as providing novel insights into the relationships between sampled populations, and adds a final step to the pipeline for population structure analyses.

  9. The influence of climate on age at menarche: Augmented with the influence of ancestry.

    Science.gov (United States)

    Sohn, Kitae

    2016-08-01

    Samples representative of South Korea, Indonesia, and Peninsular Malaysia were analyzed and the influence of climate on age at menarche was investigated. The sample size was 24,651 for Korea (birth years 1941-1992), for Indonesia 8331 (birth years 1944-1988) plus 20,519 (birth years 1978-1997), and 2842 for Peninsular Malaysia (birth years 1927-1968). Respondents recalled their age at menarche. The mean age at menarche was calculated for each birth year by country, and for Malaysia, additionally by ancestry. It has been found that mean ages at menarche for the early birth years were much younger in Indonesia than in Korea despite similar levels of socioeconomic conditions (proxied by GDP per capita). For example, for the birth year 1944, the mean age at menarche was 14.45 years for Indonesia and 16.19 years for Korea-a difference of 1.74 years. It was necessary to double the Korean GDP per capita to make the Korean mean age at menarche the same as the Indonesian one. Chinese and Malay women in Peninsular Malaysia were further analyzed, and the results provided indirect evidence that the difference between Korea and Indonesia was not due to ancestry differences. Results in multivariate settings provided consistent results. It has been concluded that climate exerts a significant influence on age at menarche because the relatively easy availability of food in the tropics increases energy intake while the absence of cold weather decreases energy expenditure on maintenance and activity. PMID:27369814

  10. Skin color variation in Orang Asli tribes of Peninsular Malaysia.

    Directory of Open Access Journals (Sweden)

    Khai C Ang

    Full Text Available Pigmentation is a readily scorable and quantitative human phenotype, making it an excellent model for studying multifactorial traits and diseases. Convergent human evolution from the ancestral state, darker skin, towards lighter skin colors involved divergent genetic mechanisms in people of European vs. East Asian ancestry. It is striking that the European mechanisms result in a 10-20-fold increase in skin cancer susceptibility while the East Asian mechanisms do not. Towards the mapping of genes that contribute to East Asian pigmentation there is need for one or more populations that are admixed for ancestral and East Asian ancestry, but with minimal European contribution. This requirement is fulfilled by the Senoi, one of three indigenous tribes of Peninsular Malaysia collectively known as the Orang Asli. The Senoi are thought to be an admixture of the Negrito, an ancestral dark-skinned population representing the second of three Orang Asli tribes, and regional Mongoloid populations of Indo-China such as the Proto-Malay, the third Orang Asli tribe. We have calculated skin reflectance-based melanin indices in 492 Orang Asli, which ranged from 28 (lightest to 75 (darkest; both extremes were represented in the Senoi. Population averages were 56 for Negrito, 42 for Proto-Malay, and 46 for Senoi. The derived allele frequencies for SLC24A5 and SLC45A2 in the Senoi were 0.04 and 0.02, respectively, consistent with greater South Asian than European admixture. Females and individuals with the A111T mutation had significantly lighter skin (p = 0.001 and 0.0039, respectively. Individuals with these derived alleles were found across the spectrum of skin color, indicating an overriding effect of strong skin lightening alleles of East Asian origin. These results suggest that the Senoi are suitable for mapping East Asian skin color genes.

  11. Geographical distribution of GmTfl1 alleles in Chinese soybean varieties

    Institute of Scientific and Technical Information of China (English)

    Guifeng; Liu; Lin; Zhao; Benjamin; J.Averitt; Ying; Liu; Bo; Zhang; Ruzhen; Chang; Yansong; Ma; Xiaoyan; Luan; Rongxia; Guan; Lijuan; Qiu

    2015-01-01

    Stem growth habit is an important agronomic trait in soybean and is subject to artificial selection. This study aimed to provide a theory for genotypic selection of stem growth habit for breeding purposes by analyzing the alleles of Gm Tfl1 gene in Chinese soybean varieties and establishing a database of Gm Tfl1 variation. Using knowledge of insertion and deletion(Indel) in the non-coding region and four single-nucleotide polymorphisms(SNPs) in the coding sequences of the Gm Tfl1 gene, four CAPS and one Indel markers were developed and used to test 1120 Chinese soybean varieties. We found that the dominant Gm Tfl1 allele was prevalent in accessions from the Northern ecoregion, whereas the recessive allele, Gmtfl1, was more common in the Southern ecoregion, and the proportions of Gm Tfl1 and recessive alleles were respectively 40.1% and 59.9% in the Huang-Huai ecoregion. The proportion of Gm Tfl1 decreased and that of Gmtfl1 increased, gradually from north to south. Allele Gm Tfl1-a was present in higher proportions in the Huang-Huai spring, Huang-Huai summer, and Northern spring sub-ecoregions than that in the other sub-ecoregions. Gm Tfl1-b was common in the Northeast spring, Northern spring and Southern summer sub-ecoregions. Gmtfl1-ta was found mainly in the Huang-Huai spring,Huang-Huai summer and Southern spring sub-ecoregions. The Gmtfl1-ab allele was distributed in all six soybean sub-ecoregions. The Gmtfl1-bb allele was distributed mainly in the Huang-Huai spring and summer and Southern spring and summer sub-ecoregions,but the Gmtfl1-tb allele was detected only in the Huang-Huai summer sub-ecoregion. The distributions of Gm Tfl1 and Gmtfl1 have shown no large changes in nearly 60 years of breeding, but the frequency of the recessive genotype Gmtfl1 has shown a rising trend in the last 20 years. This study provides a theoretical foundation for breeding new soybean varieties for different ecoregions.

  12. SNP GENOTYPING BY TAQMAN ALLELE DISCRIMINATION TECHNIQUE

    Directory of Open Access Journals (Sweden)

    Lucian Negura

    2015-07-01

    Full Text Available Breast cancer is the most frequent neoplasm in women worldwide and the principal cause of deaths by cancer, the majority being by metastatic disease. About half of breast tumors are hormone dependent, and in post-menopause women the preferred first line treatment uses third generation aromatase inhibitors. Aromatase is encoded by CYP19 gene on 15q21.1, and there is strong evidence that mutations in this gene affect its expression, with directconsequences on cancer phenotype and response to treatment. Several single nucleotide polymorphisms have beenstudied on CYP19A1 transcription variant, notably rs727479, rs10046, rs4646 and rs700518. We implemented a Taqman-based allele discrimination assay for the rapid investigation of the 4 SNPs in CYP19A1. We genotyped 22 metastaticbreast cancer patients by the technique described.

  13. Nomenclature for human CYP2D6 alleles.

    Science.gov (United States)

    Daly, A K; Brockmöller, J; Broly, F; Eichelbaum, M; Evans, W E; Gonzalez, F J; Huang, J D; Idle, J R; Ingelman-Sundberg, M; Ishizaki, T; Jacqz-Aigrain, E; Meyer, U A; Nebert, D W; Steen, V M; Wolf, C R; Zanger, U M

    1996-06-01

    To standardize CYP2D6 allele nomenclature, and to conform with international human gene nomenclature guidelines, an alternative to the current arbitrary system is described. Based on recommendations for human genome nomenclature, we propose that alleles be designated by CYP2D6 followed by an asterisk and a combination of roman letters and arabic numerals distinct for each allele with the number specifying the key mutation and, where appropriate, a letter specifying additional mutations. Criteria for classification as a separate allele and protein nomenclature are also presented. PMID:8807658

  14. Identification of Multiple Alleles at the Wx Locus and Development of Single Segment Substitution Lines for the Alleles in Rice

    Institute of Scientific and Technical Information of China (English)

    ZENG Rui-zhen; ZHANG Ze-min; HE Feng-hua; XI Zhang-ying; Akshay TALUKDAR; SHI Jun-qiong; QIN Li-jun; HUANG Chao-feng; ZHANG Gui-quan

    2006-01-01

    The microsatellite markers 484/485 and 484/W2R were used to identify the multiple alleles at the Wx locus in rice germplasm. Fifteen alleles were identified in 278 accessions by using microsatellite class and G-T polymorphism. Among these alleles, (CT)12-G, (CT)15-G, (CT)16-G, (CT)17-G, (CT)18-G and (CT)21-G have not been reported. Seventy-two single-segment substitution lines (SSSLs) carrying different alleles at the Wx locus were developed by using Huajingxian 74 with the (CT)11-G allele as a recipient and 20 accessions containing 12 different alleles at the Wx locus as donors. The estimated length of the substituted segments ranged from 2.2 to 77.3 cM with an average of 17.4 cM.

  15. A loss-of-function allele of OsHMA3 associated with high cadmium accumulation in shoots and grain of Japonica rice cultivars.

    Science.gov (United States)

    Yan, Jiali; Wang, Peitong; Wang, Peng; Yang, Meng; Lian, Xingming; Tang, Zhong; Huang, Chao-Feng; Salt, David E; Zhao, Fang Jie

    2016-09-01

    Excessive cadmium (Cd) accumulation in rice poses a risk to food safety. OsHMA3 plays an important role in restricting Cd translocation from roots to shoots. A non-functional allele of OsHMA3 has been reported in some Indica rice cultivars with high Cd accumulation, but it is not known if OsHMA3 allelic variation is associated with Cd accumulation in Japonica cultivars. In this study, we identified a Japonica cultivar with consistently high Cd accumulation in shoots and grain in both field and greenhouse experiments. The cultivar possesses an OsHMA3 allele with a predicted amino acid mutation at the 380(th) position from Ser to Arg. The haplotype had no Cd transport activity when the gene was expressed in yeast, and the allele did not complement a known nonfunctional allele of OsHMA3 in F1 test. The allele is present only in temperate Japonica cultivars among diversity panels of 1483 rice cultivars. Different cultivars possessing this allele showed greatly increased root-to-shoot Cd translocation and a shift in root Cd speciation from Cd-S to Cd-O bonding determined by synchrotron X-ray absorption spectroscopy. Our study has identified a new loss-of-function allele of OsHMA3 in Japonica rice cultivars leading to high Cd accumulation in shoots and grain. PMID:27038090

  16. Allelic imbalance metre (Allim), a new tool for measuring allele-specific gene expression with RNA-seq data

    OpenAIRE

    Pandey, Ram Vinay; Franssen, Susanne U.; Futschik, Andreas; Schlötterer, Christian

    2013-01-01

    Estimating differences in gene expression among alleles is of high interest for many areas in biology and medicine. Here, we present a user-friendly software tool, Allim, to estimate allele-specific gene expression. Because mapping bias is a major problem for reliable estimates of allele-specific gene expression using RNA-seq, Allim combines two different strategies to account for the mapping biases. In order to reduce the mapping bias, Allim first generates a polymorphism-aware reference gen...

  17. Indices of Paraoxonase and Oxidative Status Do Not Enhance the Prediction of Subclinical Cardiovascular Disease in Mixed-Ancestry South Africans

    Directory of Open Access Journals (Sweden)

    M. Macharia

    2014-01-01

    Full Text Available We evaluated the association of indices of paraoxonase (PON1 and oxidative status with subclinical cardiovascular disease (CVD in mixed-ancestry South Africans. Participants were 491 adults (126 men who were stratified by diabetes status and body mass index (BMI. Carotid intima-media thickness (CIMT was used as a measure of subclinical CVD. Indices of PON1 and oxidative status were determined by measuring levels and activities (paraoxonase and arylesterase of PON1, antioxidant activity (ferric reducing antioxidant power and trolox equivalent antioxidant capacity, and lipid peroxidation markers (malondialdehyde and oxidized LDL. Diabetic subjects (28.9% displayed a significant decrease in PON1 status and antioxidant activity as well as increase in oxidized LDL and malondialdehyde. A similar profile was apparent across increasing BMI categories. CIMT was higher in diabetic than nondiabetic subjects (P<0.0001  but showed no variation across BMI categories. Overall, CIMT correlated negatively with indices of antioxidant activity and positively with measures of lipid oxidation. Sex, age, BMI, and diabetes altogether explained 29.2% of CIMT, with no further improvement from adding PON1 and/or antioxidant status indices. Though indices of PON1 and oxidative status correlate with CIMT, their measurements may not be useful for identifying subjects at high CVD risk in this population.

  18. Habitual diets rich in dark-green vegetables are associated with an increased response to ω-3 fatty acid supplementation in Americans of African ancestry.

    Science.gov (United States)

    O'Sullivan, Aifric; Armstrong, Patrice; Schuster, Gertrud U; Pedersen, Theresa L; Allayee, Hooman; Stephensen, Charles B; Newman, John W

    2014-02-01

    Although substantial variation exists in individual responses to omega-3 (ω-3) (n-3) fatty acid supplementation, the causes for differences in response are largely unknown. Here we investigated the associations between the efficacy of ω-3 fatty acid supplementation and a broad range of nutritional and clinical factors collected during a double-blind, placebo-controlled trial in participants of African ancestry, randomly assigned to receive either 2 g eicosapentaenoic acid (EPA) + 1 g docosahexaenoic acid (n = 41) or corn/soybean oil placebo (n = 42) supplements for 6 wk. Food-frequency questionnaires were administered, and changes in erythrocyte lipids, lipoproteins, and monocyte 5-lipoxygenase-dependent metabolism were measured before and after supplementation. Mixed-mode linear regression modeling identified high (n = 28) and low (n = 13) ω-3 fatty acid response groups on the basis of changes in erythrocyte EPA abundance (P orange vegetables and legumes (P = 0.01) and a lower intake of vegetables (P = 0.02), particularly dark-green vegetables (P = 0.002). Because the findings reported here are associative in nature, prospective studies are needed to determine if dietary dark-green vegetables or nutrients contained in these foods can enhance the efficacy of ω-3 fatty acid supplements. This trial was registered at clinicaltrials.gov as NCT00536185. PMID:24259553

  19. Risk alleles for systemic lupus erythematosus in a large case-control collection and associations with clinical subphenotypes.

    Directory of Open Access Journals (Sweden)

    Kimberly E Taylor

    2011-02-01

    Full Text Available Systemic lupus erythematosus (SLE is a genetically complex disease with heterogeneous clinical manifestations. Recent studies have greatly expanded the number of established SLE risk alleles, but the distribution of multiple risk alleles in cases versus controls and their relationship to subphenotypes have not been studied. We studied 22 SLE susceptibility polymorphisms with previous genome-wide evidence of association (p < 5 x 10⁻¹²⁸ in 1919 SLE cases from 9 independent Caucasian SLE case series and 4813 independent controls. The mean number of risk alleles in cases was 15.1 (SD 3.1 while the mean in controls was 13.1 (SD 2.8, with trend p = 4 x 10⁻⁸. We defined a genetic risk score (GRS for SLE as the number of risk alleles with each weighted by the SLE risk odds ratio (OR. The OR for high-low GRS tertiles, adjusted for intra-European ancestry, sex, and parent study, was 4.4 (95% CI 3.8-5.1. We studied associations of individual SNPs and the GRS with clinical manifestations for the cases: age at diagnosis, the 11 American College of Rheumatology classification criteria, and double-stranded DNA antibody (anti-dsDNA production. Six subphenotypes were significantly associated with the GRS, most notably anti-dsDNA (OR(high-low = 2.36, p = 9e-9, the immunologic criterion (OR(high-low = 2.23, p = 3e-7, and age at diagnosis (OR(high-low = 1.45, p = 0.0060. Finally, we developed a subphenotype-specific GRS (sub-GRS for each phenotype with more power to detect cumulative genetic associations. The sub-GRS was more strongly associated than any single SNP effect for 5 subphenotypes (the above plus hematologic disorder and oral ulcers, while single loci are more significantly associated with renal disease (HLA-DRB1, OR = 1.37, 95% CI 1.14-1.64 and arthritis (ITGAM, OR = 0.72, 95% CI 0.59-0.88. We did not observe significant associations for other subphenotypes, for individual loci or the sub-GRS. Thus our

  20. Genetic Variants and Allele Frequencies of Kappa Casein in Egyptian Cattle and Buffalo Using PCR-RFLP

    OpenAIRE

    Eman M. Gouda; Mona Kh. Galal; Samy A. Abdelaziz

    2013-01-01

    Kappa casein (K-Ca) genetic variations affected quality and composition of the milk. Several variants of Kappa casein (K-Ca) gene locus IV have been reported with special interest for the ‘B’ allele for its relation to the milk protein and fat yields. Genotyping and allelic frequencies of K-Ca among Native Egyptian breeds of cattle and buffalo were the aim of the present study. PCR amplification of DNA isolated from 300 blood samples collected from Holstein and Baladi cattle and buffalo were ...

  1. Reliable allele detection using SNP-based PCR primers containing Locked Nucleic Acid: application in genetic mapping

    Directory of Open Access Journals (Sweden)

    Trognitz Friederike

    2007-02-01

    Full Text Available Abstract Background The diploid, Solanum caripense, a wild relative of potato and tomato, possesses valuable resistance to potato late blight and we are interested in the genetic base of this resistance. Due to extremely low levels of genetic variation within the S. caripense genome it proved impossible to generate a dense genetic map and to assign individual Solanum chromosomes through the use of conventional chromosome-specific SSR, RFLP, AFLP, as well as gene- or locus-specific markers. The ease of detection of DNA polymorphisms depends on both frequency and form of sequence variation. The narrow genetic background of close relatives and inbreds complicates the detection of persisting, reduced polymorphism and is a challenge to the development of reliable molecular markers. Nonetheless, monomorphic DNA fragments representing not directly usable conventional markers can contain considerable variation at the level of single nucleotide polymorphisms (SNPs. This can be used for the design of allele-specific molecular markers. The reproducible detection of allele-specific markers based on SNPs has been a technical challenge. Results We present a fast and cost-effective protocol for the detection of allele-specific SNPs by applying Sequence Polymorphism-Derived (SPD markers. These markers proved highly efficient for fingerprinting of individuals possessing a homogeneous genetic background. SPD markers are obtained from within non-informative, conventional molecular marker fragments that are screened for SNPs to design allele-specific PCR primers. The method makes use of primers containing a single, 3'-terminal Locked Nucleic Acid (LNA base. We demonstrate the applicability of the technique by successful genetic mapping of allele-specific SNP markers derived from monomorphic Conserved Ortholog Set II (COSII markers mapped to Solanum chromosomes, in S. caripense. By using SPD markers it was possible for the first time to map the S. caripense alleles

  2. Genome-wide association of body fat distribution in African ancestry populations suggests new loci.

    Directory of Open Access Journals (Sweden)

    Ching-Ti Liu

    Full Text Available Central obesity, measured by waist circumference (WC or waist-hip ratio (WHR, is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS of fat distribution among those of predominantly African ancestry (AA. We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1. Overall, 25 SNPs with single genomic control (GC-corrected p-values<5.0 × 10(-6 were followed-up (stage 2 in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10(-8 for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10(-8 for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5 × 10(-8; RREB1: p = 5.7 × 10(-8. Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN. Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02. In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept

  3. ACTN3 allele frequency in humans covaries with global latitudinal gradient.

    Directory of Open Access Journals (Sweden)

    Scott M Friedlander

    Full Text Available A premature stop codon in ACTN3 resulting in α-actinin-3 deficiency (the ACTN3 577XX genotype is common in humans and reduces strength, muscle mass, and fast-twitch fiber diameter, but increases the metabolic efficiency of skeletal muscle. Linkage disequilibrium data suggest that the ACTN3 R577X allele has undergone positive selection during human evolution. The allele has been hypothesized to be adaptive in environments with scarce resources where efficient muscle metabolism would be selected. Here we test this hypothesis by using recently developed comparative methods that account for evolutionary relatedness and gene flow among populations. We find evidence that the ACTN3 577XX genotype evolved in association with the global latitudinal gradient. Our results suggest that environmental variables related to latitudinal variation, such as species richness and mean annual temperature, may have influenced the adaptive evolution of ACTN3 577XX during recent human history.

  4. Differences in optic nerve structure between individuals of predominantly African and European ancestry: Implications for disease detection and pathogenesis

    Directory of Open Access Journals (Sweden)

    Christopher A Girkin

    2008-03-01

    Full Text Available Christopher A GirkinUniversity of Alabama at Birmingham School of Medicine, Birmingham, AL, USAAbstract: Glaucoma disproportionately affects individual of African ancestry. Additionally, racial differences in the optic nerve head have been well described that may alter the vulnerability to intraocular pressure related injury and, in addition, alter the clinical ability to detect the presence of early optic nerve injury. This paper will review the literature describing racial differences in the optic nerve head between individuals of African and European ancestry with regards to the potential effects of these differences on the ability to detect glaucoma in different racial groups and to potential differences in the pathogenesis of glaucomatous injury.Keywords: primary open angle glaucoma, African American, optic nerve, optic disc, retinal nerve fiber layer

  5. 雅加达非华裔大学生中文学习动机调查 JAKARTA NON-CHINESE ANCESTRY INDONESIAN STUDENTSMOTIVATION OF CHINESE STUDYING

    OpenAIRE

    Fu Ruomei; Huang Yan; Ye Mei

    2011-01-01

    More and more non-Chinese ancestry Indonesian begin to learn Chinese,some of them even choose Chinese as their major in University.The survey of four major Chinese departments in Jakarta shows that intrinsic motivation is the most important motivation of Chinese studying. Interests and passion to Chinese language and culture encouraged the non-Chinese ancestry Indonesian students to study Chinese. To assist them overcome their difficulties in studying is very important for Chinese education i...

  6. Drop-out probabilities of IrisPlex SNP alleles

    DEFF Research Database (Denmark)

    Andersen, Jeppe Dyrberg; Tvedebrink, Torben; Mogensen, Helle Smidt;

    2013-01-01

    true alleles is possible. As part of the validation of the IrisPlex assay in our ISO17025 accredited, forensic genetic laboratory, we estimated the probability of drop-out of specific SNP alleles using 29 and 30 PCR cycles and 25, 50 and 100 Single Base Extension (SBE) cycles. We observed no drop...

  7. Rescue of progeria in trichothiodystrophy by homozygous lethal Xpd alleles.

    Directory of Open Access Journals (Sweden)

    Jaan-Olle Andressoo

    2006-10-01

    Full Text Available Although compound heterozygosity, or the presence of two different mutant alleles of the same gene, is common in human recessive disease, its potential to impact disease outcome has not been well documented. This is most likely because of the inherent difficulty in distinguishing specific biallelic effects from differences in environment or genetic background. We addressed the potential of different recessive alleles to contribute to the enigmatic pleiotropy associated with XPD recessive disorders in compound heterozygous mouse models. Alterations in this essential helicase, with functions in both DNA repair and basal transcription, result in diverse pathologies ranging from elevated UV sensitivity and cancer predisposition to accelerated segmental progeria. We report a variety of biallelic effects on organismal phenotype attributable to combinations of recessive Xpd alleles, including the following: (i the ability of homozygous lethal Xpd alleles to ameliorate a variety of disease symptoms when their essential basal transcription function is supplied by a different disease-causing allele, (ii differential developmental and tissue-specific functions of distinct Xpd allele products, and (iii interallelic complementation, a phenomenon rarely reported at clinically relevant loci in mammals. Our data suggest a re-evaluation of the contribution of "null" alleles to XPD disorders and highlight the potential of combinations of recessive alleles to affect both normal and pathological phenotypic plasticity in mammals.

  8. The genetic legacy of Lonesome George survives: Giant tortoises with Pinta Island ancestry identified in Galápagos

    OpenAIRE

    Edwards, DL; Benavides, E; Garrick, RC; Gibbs, JP; Russello, MA; Dion, KB; Hyseni, C; Flanagan, JP; Tapia, W. (ed.); Caccone, A

    2013-01-01

    The death of Lonesome George, the last known purebred individual of Chelonoidis abingdoni native to Pinta Island, marked the extinction of one of 10 surviving giant tortoise species from the Galápagos Archipelago. Using a DNA reference dataset including historical C. abingdoni and >1600 living Volcano Wolf tortoise samples, a site on Isabela Island known to harbor hybrid tortoises, we discovered 17 individuals with ancestry in C. abingdoni. These animals belong to various hybrid categories, i...

  9. Sex-specific Effects of Exercise Ancestry on Metabolic, Morphological, and Gene Expression Phenotypes in Multiple Generations of Mouse Offspring

    OpenAIRE

    Guth, Lisa M.; Andrew T. Ludlow; Witkowski, Sarah; Marshall, Mallory R.; Lima, Laila C. J.; Venezia, Andrew C.; Xiao, Tao; Lee, Mei-Ling Ting; Spangenburg, Espen E.; Roth, Stephen M.

    2013-01-01

    Early life and pre-conception environmental stimuli can affect adult health-related phenotypes. Exercise training is an environmental stimulus affecting many systems throughout the body and appears to alter offspring phenotypes. The aim of this study was to examine the influence of parental exercise training, or “exercise ancestry,” on morphological and metabolic phenotypes in two generations of mouse offspring. F0 C57BL/6 mice were exposed to voluntary exercise or sedentary lifestyle and bre...

  10. Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.

    OpenAIRE

    Amidou N'Diaye; Chen, Gary K.; Palmer, Cameron D; Bing Ge; Bamidele Tayo; Rasika A Mathias; Jingzhong Ding; Michael A Nalls; Adebowale Adeyemo; Véronique Adoue; Ambrosone, Christine B.; Larry Atwood; Bandera, Elisa V.; Becker, Lewis C.; Berndt, Sonja I.

    2011-01-01

    Adult height is a classic polygenic trait of high heritability (h(2) approximately 0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain approximately10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analy...

  11. Identification, Replication, and Fine-Mapping of Loci Associated with Adult Height in Individuals of African Ancestry

    OpenAIRE

    N'Diaye, Amidou; Chen, Gary K.; Palmer, Cameron D; Ge, Bing; Tayo, Bamidele; Rasika A Mathias; Ding, Jingzhong; Michael A Nalls; Adeyemo, Adebowale; Adoue, Véronique; Ambrosone, Christine B.; Atwood, Larry; Bandera, Elisa V.; Becker, Lewis C.; Berndt, Sonja I.

    2011-01-01

    Author Summary Adult height is an ideal phenotype to improve our understanding of the genetic architecture of complex diseases and traits: it is easily measured and usually available in large cohorts, relatively stable, and mostly influenced by genetics (narrow-sense heritability of height h 2∼0.8). Genome-wide association (GWA) studies in individuals of European ancestry have identified >180 single nucleotide polymorphisms (SNPs) associated with height. In the current study, we continued to ...

  12. Development of a panel of genome-wide ancestry informative markers to study admixture throughout the Americas.

    Directory of Open Access Journals (Sweden)

    Joshua Mark Galanter

    Full Text Available Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R² > 0.9 for ancestral components with significant between-subject variance. Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region.

  13. Development of a Panel of Genome-Wide Ancestry Informative Markers to Study Admixture Throughout the Americas

    Science.gov (United States)

    Galanter, Joshua Mark; Fernandez-Lopez, Juan Carlos; Gignoux, Christopher R.; Barnholtz-Sloan, Jill; Fernandez-Rozadilla, Ceres; Via, Marc; Hidalgo-Miranda, Alfredo; Contreras, Alejandra V.; Figueroa, Laura Uribe; Raska, Paola; Jimenez-Sanchez, Gerardo; Silva Zolezzi, Irma; Torres, Maria; Ponte, Clara Ruiz; Ruiz, Yarimar; Salas, Antonio; Nguyen, Elizabeth; Eng, Celeste; Borjas, Lisbeth; Zabala, William; Barreto, Guillermo; Rondón González, Fernando; Ibarra, Adriana; Taboada, Patricia; Porras, Liliana; Moreno, Fabián; Bigham, Abigail; Gutierrez, Gerardo; Brutsaert, Tom; León-Velarde, Fabiola; Moore, Lorna G.; Vargas, Enrique; Cruz, Miguel; Escobedo, Jorge; Rodriguez-Santana, José; Rodriguez-Cintrón, William; Chapela, Rocio; Ford, Jean G.; Bustamante, Carlos; Seminara, Daniela; Shriver, Mark; Ziv, Elad; Gonzalez Burchard, Esteban; Haile, Robert

    2012-01-01

    Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R2>0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region. PMID:22412386

  14. Empirical Selection of Informative Microsatellite Markers within Co-ancestry Pig Populations Is Required for Improving the Individual Assignment Efficiency

    OpenAIRE

    Y. H. Li; Chu, H. P.; Jiang, Y. N.; Lin, C.Y.; Li, S. H.; Li, K. T.; Weng, G. J.; Cheng, C. C.; Lu, D. J.; Ju, Y. T.

    2014-01-01

    The Lanyu is a miniature pig breed indigenous to Lanyu Island, Taiwan. It is distantly related to Asian and European pig breeds. It has been inbred to generate two breeds and crossed with Landrace and Duroc to produce two hybrids for laboratory use. Selecting sets of informative genetic markers to track the genetic qualities of laboratory animals and stud stock is an important function of genetic databases. For more than two decades, Lanyu derived breeds of common ancestry and crossbreeds hav...

  15. Comparing genetic ancestry and self-reported race/ethnicity in a multiethnic population in New York City

    Indian Academy of Sciences (India)

    Yin Leng Lee; Susan Teitelbaum; Mary S. Wolff; James G. Wetmur; Jia Chen

    2010-12-01

    Self-reported race/ethnicity is frequently used in epidemiological studies to assess an individual’s background origin. However, in admixed populations such as Hispanic, self-reported race/ethnicity may not accurately represent them genetically because they are admixed with European, African and Native American ancestry. We estimated the proportions of genetic admixture in an ethnically diverse population of 396 mothers and 188 of their children with 35 ancestry informative markers (AIMs) using the STRUCTURE version 2.2 program. The majority of the markers showed significant deviation from Hardy–Weinberg equilibrium in our study population. In mothers self-identified as Black and White, the imputed ancestry proportions were 77.6% African and 75.1% European respectively, while the racial composition among self-identified Hispanics was 29.2% European, 26.0% African, and 44.8% Native American.We also investigated the utility of AIMs by showing the improved fitness of models in paraoxanase-1 genotype–phenotype associations after incorporating AIMs; however, the improvement was moderate at best. In summary, a minimal set of 35 AIMs is sufficient to detect population stratification and estimate the proportion of individual genetic admixture; however, the utility of these markers remains questionable.

  16. Empirical testing of a 23-AIMs panel of SNPs for ancestry evaluations in four major US populations.

    Science.gov (United States)

    Zeng, Xiangpei; Warshauer, David H; King, Jonathan L; Churchill, Jennifer D; Chakraborty, Ranajit; Budowle, Bruce

    2016-07-01

    Ancestry informative markers (AIMs) can be used to determine population affiliation of the donors of forensic samples. In order to examine ancestry evaluations of the four major populations in the USA, 23 highly informative AIMs were identified from the International HapMap project. However, the efficacy of these 23 AIMs could not be fully evaluated in silico. In this study, these 23 SNPs were multiplexed to test their actual performance in ancestry evaluations. Genotype data were obtained from 189 individuals collected from four American populations. One SNP (rs12149261) on chromosome 16 was removed from this panel because it was duplicated on chromosome 1. The resultant 22-AIMs panel was able to empirically resolve the four major populations as in the in silico study. Eight individuals were assigned to a different group than indicated on their samples. The assignments of the 22 AIMs for these samples were consistent with AIMs results from the ForenSeq(TM) panel. No departures from Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD) were detected for all 22 SNPs in four US populations (after removing the eight problematic samples). The principal component analysis (PCA) results indicated that 181 individuals from these populations were assigned to the expected groups. These 22 SNPs can contribute to the candidate AIMs pool for potential forensic identification purposes in major US populations. PMID:26914801

  17. Color, race, and genomic ancestry in Brazil: dialogues between anthropology and genetics.

    Science.gov (United States)

    Santos, Ricardo Ventura; Fry, Peter H; Monteiro, Simone; Maio, Marcos Chor; Rodrigues, José Carlos; Bastos-Rodrigues, Luciana; Pena, Sérgio D J

    2009-12-01

    In the contemporary world, "race" narratives are so multifaceted that at times, different views of the concept appear mutually incompatible. In recent decades biologists, especially geneticists, have repeatedly stated that the notion of race does not apply to the human species. On the other hand, social scientists claim that race is highly significant in cultural, historical, and socioeconomic terms because it molds everyday social relations and because it is a powerful motivator for social and political movements based on race differences. In this paper we present the results of an interdisciplinary research project incorporating approaches from genetics and anthropology. Our objective is to explore the interface between information about biology/genetics and perceptions about color/ race in Rio de Janeiro, Brazil. We argue that the data and interpretation of our research resonate far beyond the local level, stimulating discussion about methodological, theoretical, and political issues of wider national and international relevance. Topics addressed include the complex terminology of color/race classification in Brazil, perceptions about ancestry in the context of ideologies of Brazilian national identity, and the relationship between genetic information about the Brazilian population and a sociopolitical agenda that turns on questions of race and racism. PMID:20614657

  18. Genomic microsatellites identify shared Jewish ancestry intermediate between Middle Eastern and European populations

    Directory of Open Access Journals (Sweden)

    Hillel Jossi

    2009-12-01

    Full Text Available Abstract Background Genetic studies have often produced conflicting results on the question of whether distant Jewish populations in different geographic locations share greater genetic similarity to each other or instead, to nearby non-Jewish populations. We perform a genome-wide population-genetic study of Jewish populations, analyzing 678 autosomal microsatellite loci in 78 individuals from four Jewish groups together with similar data on 321 individuals from 12 non-Jewish Middle Eastern and European populations. Results We find that the Jewish populations show a high level of genetic similarity to each other, clustering together in several types of analysis of population structure. Further, Bayesian clustering, neighbor-joining trees, and multidimensional scaling place the Jewish populations as intermediate between the non-Jewish Middle Eastern and European populations. Conclusion These results support the view that the Jewish populations largely share a common Middle Eastern ancestry and that over their history they have undergone varying degrees of admixture with non-Jewish populations of European descent.

  19. Afro-derived Amazonian populations: inferring continental ancestry and population substructure.

    Science.gov (United States)

    Lopes Maciel, Luana Gomes; Ribeiro Rodrigues, Elzemar Martins; Carneiro Dos Santos, Ney Pereira; Ribeiro Dos Santos, Ândrea; Guerreiro, João Farias; Santos, Sidney

    2011-10-01

    A panel of Ancestry Informative Markers (AIMs) was used to identify population substructure and estimate individual and overall interethnic admixture in 294 individuals from seven African-derived communities of the Brazilian Amazon. A panel of 48 biallelic markers, representing the insertion (IN) or the deletion (DEL) of small DNA fragments, was employed for this purpose. Overall interethnic admixture estimates showed high miscegenation with other ethnic groups in all populations (between 46% and 64%). The proportion of ancestral genes varied significantly among individuals of the sample: the contribution of African genes varied between 12% and 75%; of European genes between 10% and 73%; and of Amerindians genes between 8% and 66%. The obtained data reveal a high contribution of Amerindian genes in these communities, unlike in other African-derived communities of the Northeast and the South of Brazil. In addition, the majority of the Amerindian contribution may result from the preferential inclusion of indigenous women in the African descent groups. High heterogeneity of the proportion of interethnic admixture among analyzed individuals was found when the proportion of ancestral genes of each individual of the sample was estimated. This heterogeneity is reflected in the fact that four populations can be considered as substructured and that the global African descent sample is possibly formed by two subpopulations. PMID:22146065

  20. A SNP test to identify Africanized honeybees via proportion of 'African' ancestry.

    Science.gov (United States)

    Chapman, Nadine C; Harpur, Brock A; Lim, Julianne; Rinderer, Thomas E; Allsopp, Michael H; Zayed, Amro; Oldroyd, Benjamin P

    2015-11-01

    The honeybee, Apis mellifera, is the world's most important pollinator and is ubiquitous in most agricultural ecosystems. Four major evolutionary lineages and at least 24 subspecies are recognized. Commercial populations are mainly derived from subspecies originating in Europe (75-95%). The Africanized honeybee is a New World hybrid of A. m. scutellata from Africa and European subspecies, with the African component making up 50-90% of the genome. Africanized honeybees are considered undesirable for bee-keeping in most countries, due to their extreme defensiveness and poor honey production. The international trade in honeybees is restricted, due in part to bans on the importation of queens (and semen) from countries where Africanized honeybees are extant. Some desirable strains from the United States of America that have been bred for traits such as resistance to the mite Varroa destructor are unfortunately excluded from export to countries such as Australia due to the presence of Africanized honeybees in the USA. This study shows that a panel of 95 single nucleotide polymorphisms, chosen to differentiate between the African, Eastern European and Western European lineages, can detect Africanized honeybees with a high degree of confidence via ancestry assignment. Our panel therefore offers a valuable tool to mitigate the risks of spreading Africanized honeybees across the globe and may enable the resumption of queen and bee semen imports from the Americas. PMID:25846634

  1. Genome-Wide DNA Methylation in Mixed Ancestry Individuals with Diabetes and Prediabetes from South Africa

    Science.gov (United States)

    Pheiffer, Carmen; Humphries, Stephen E.; Gamieldien, Junaid; Erasmus, Rajiv T.

    2016-01-01

    Aims. To conduct a genome-wide DNA methylation in individuals with type 2 diabetes, individuals with prediabetes, and control mixed ancestry individuals from South Africa. Methods. We used peripheral blood to perform genome-wide DNA methylation analysis in 3 individuals with screen detected diabetes, 3 individuals with prediabetes, and 3 individuals with normoglycaemia from the Bellville South Community, Cape Town, South Africa, who were age-, gender-, body mass index-, and duration of residency-matched. Methylated DNA immunoprecipitation (MeDIP) was performed by Arraystar Inc. (Rockville, MD, USA). Results. Hypermethylated DMRs were 1160 (81.97%) and 124 (43.20%), respectively, in individuals with diabetes and prediabetes when both were compared to subjects with normoglycaemia. Our data shows that genes related to the immune system, signal transduction, glucose transport, and pancreas development have altered DNA methylation in subjects with prediabetes and diabetes. Pathway analysis based on the functional analysis mapping of genes to KEGG pathways suggested that the linoleic acid metabolism and arachidonic acid metabolism pathways are hypomethylated in prediabetes and diabetes. Conclusions. Our study suggests that epigenetic changes are likely to be an early process that occurs before the onset of overt diabetes. Detailed analysis of DMRs that shows gradual methylation differences from control versus prediabetes to prediabetes versus diabetes in a larger sample size is required to confirm these findings.

  2. Mitochondrial control region genetic diversity and maternal ancestry of a Brangus-Ibage cattle populations

    Directory of Open Access Journals (Sweden)

    Luiz Ernani Henkes

    2005-03-01

    Full Text Available The genetic diversity of 277 nucleotides in the mitochondrial DNA control region (nt 15,964 to 16,240 in reference sequence was analyzed in crossbreed beef cattle (Brangus-Ibage, 5/8 Bos primigenius taurus x 3/8 Bos primigenius indicus as well as in some Nellore samples (B. p. indicus. Fifty-seven mutations were found in Brangus-Ibage comprising 18 haplotypes (haplotype diversity, h = 0.851 ± 0.041 and nucleotide diversity, ntd = 0.009 ± 0.006 and 66 in Nellore (h = 1.00 ± 0.27, ntd = 0.014 ± 0.012. These data indicated sequence identities of 99.6 and 92.1% between the B. p. taurus' reference sequence and Brangus-Ibage and Nellore, respectively. The comparison of our data with sequence data for 612 individuals recovered from GenBank showed a total of 205 haplotypes defined by 99 polymorphic sites. Most of the variability (53% was due to differentiation within breeds. The phylogenetic tree constructed using the neighbor-joining method showed clearly the well-known dichotomy between B. p. taurus and B. p. indicus. The Brangus-Ibage clustered with B. p. taurus lineages; however, the displacement of Nellore from B. p. indicus branch probably indicates a substantial B. p. taurus maternal ancestry in some Nellore samples (obtained from GenBank and reflects the primarily male-driven introduction of this breed in Brazil.

  3. Genetic evidence for a mitochondriate ancestry in the 'amitochondriate' flagellate Trimastix pyriformis.

    Directory of Open Access Journals (Sweden)

    Vladimir Hampl

    Full Text Available Most modern eukaryotes diverged from a common ancestor that contained the alpha-proteobacterial endosymbiont that gave rise to mitochondria. The 'amitochondriate' anaerobic protist parasites that have been studied to date, such as Giardia and Trichomonas harbor mitochondrion-related organelles, such as mitosomes or hydrogenosomes. Yet there is one remaining group of mitochondrion-lacking flagellates known as the Preaxostyla that could represent a primitive 'pre-mitochondrial' lineage of eukaryotes. To test this hypothesis, we conducted an expressed sequence tag (EST survey on the preaxostylid flagellate Trimastix pyriformis, a poorly-studied free-living anaerobe. Among the ESTs we detected 19 proteins that, in other eukaryotes, typically function in mitochondria, hydrogenosomes or mitosomes, 12 of which are found exclusively within these organelles. Interestingly, one of the proteins, aconitase, functions in the tricarboxylic acid cycle typical of aerobic mitochondria, whereas others, such as pyruvate:ferredoxin oxidoreductase and [FeFe] hydrogenase, are characteristic of anaerobic hydrogenosomes. Since Trimastix retains genetic evidence of a mitochondriate ancestry, we can now say definitively that all known living eukaryote lineages descend from a common ancestor that had mitochondria.

  4. Genetic evidence for a mitochondriate ancestry in the 'amitochondriate' flagellate Trimastix pyriformis.

    Science.gov (United States)

    Hampl, Vladimir; Silberman, Jeffrey D; Stechmann, Alexandra; Diaz-Triviño, Sara; Johnson, Patricia J; Roger, Andrew J

    2008-01-01

    Most modern eukaryotes diverged from a common ancestor that contained the alpha-proteobacterial endosymbiont that gave rise to mitochondria. The 'amitochondriate' anaerobic protist parasites that have been studied to date, such as Giardia and Trichomonas harbor mitochondrion-related organelles, such as mitosomes or hydrogenosomes. Yet there is one remaining group of mitochondrion-lacking flagellates known as the Preaxostyla that could represent a primitive 'pre-mitochondrial' lineage of eukaryotes. To test this hypothesis, we conducted an expressed sequence tag (EST) survey on the preaxostylid flagellate Trimastix pyriformis, a poorly-studied free-living anaerobe. Among the ESTs we detected 19 proteins that, in other eukaryotes, typically function in mitochondria, hydrogenosomes or mitosomes, 12 of which are found exclusively within these organelles. Interestingly, one of the proteins, aconitase, functions in the tricarboxylic acid cycle typical of aerobic mitochondria, whereas others, such as pyruvate:ferredoxin oxidoreductase and [FeFe] hydrogenase, are characteristic of anaerobic hydrogenosomes. Since Trimastix retains genetic evidence of a mitochondriate ancestry, we can now say definitively that all known living eukaryote lineages descend from a common ancestor that had mitochondria. PMID:18167542

  5. Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts.

    Science.gov (United States)

    Schwantes-An, Tae-Hwi; Zhang, Juan; Chen, Li-Shiun; Hartz, Sarah M; Culverhouse, Robert C; Chen, Xiangning; Coon, Hilary; Frank, Josef; Kamens, Helen M; Konte, Bettina; Kovanen, Leena; Latvala, Antti; Legrand, Lisa N; Maher, Brion S; Melroy, Whitney E; Nelson, Elliot C; Reid, Mark W; Robinson, Jason D; Shen, Pei-Hong; Yang, Bao-Zhu; Andrews, Judy A; Aveyard, Paul; Beltcheva, Olga; Brown, Sandra A; Cannon, Dale S; Cichon, Sven; Corley, Robin P; Dahmen, Norbert; Degenhardt, Louisa; Foroud, Tatiana; Gaebel, Wolfgang; Giegling, Ina; Glatt, Stephen J; Grucza, Richard A; Hardin, Jill; Hartmann, Annette M; Heath, Andrew C; Herms, Stefan; Hodgkinson, Colin A; Hoffmann, Per; Hops, Hyman; Huizinga, David; Ising, Marcus; Johnson, Eric O; Johnstone, Elaine; Kaneva, Radka P; Kendler, Kenneth S; Kiefer, Falk; Kranzler, Henry R; Krauter, Ken S; Levran, Orna; Lucae, Susanne; Lynskey, Michael T; Maier, Wolfgang; Mann, Karl; Martin, Nicholas G; Mattheisen, Manuel; Montgomery, Grant W; Müller-Myhsok, Bertram; Murphy, Michael F; Neale, Michael C; Nikolov, Momchil A; Nishita, Denise; Nöthen, Markus M; Nurnberger, John; Partonen, Timo; Pergadia, Michele L; Reynolds, Maureen; Ridinger, Monika; Rose, Richard J; Rouvinen-Lagerström, Noora; Scherbaum, Norbert; Schmäl, Christine; Soyka, Michael; Stallings, Michael C; Steffens, Michael; Treutlein, Jens; Tsuang, Ming; Wall, Tamara L; Wodarz, Norbert; Yuferov, Vadim; Zill, Peter; Bergen, Andrew W; Chen, Jingchun; Cinciripini, Paul M; Edenberg, Howard J; Ehringer, Marissa A; Ferrell, Robert E; Gelernter, Joel; Goldman, David; Hewitt, John K; Hopfer, Christian J; Iacono, William G; Kaprio, Jaakko; Kreek, Mary Jeanne; Kremensky, Ivo M; Madden, Pamela A F; McGue, Matt; Munafò, Marcus R; Philibert, Robert A; Rietschel, Marcella; Roy, Alec; Rujescu, Dan; Saarikoski, Sirkku T; Swan, Gary E; Todorov, Alexandre A; Vanyukov, Michael M; Weiss, Robert B; Bierut, Laura J; Saccone, Nancy L

    2016-03-01

    The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for "general" substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day >20 vs. ≤ 10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95% C.I. [0.83-0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses. PMID:26392368

  6. Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin

    Science.gov (United States)

    Seiser, Eric L; van Leeuwen, Nienke; Tavendale, Roger; Bennett, Amanda J; Groves, Christopher J; Coleman, Ruth L; van der Heijden, Amber A; Beulens, Joline W; de Keyser, Catherine E; Zaharenko, Linda; Rotroff, Daniel M; Out, Mattijs; Jablonski, Kathleen A; Chen, Ling; Javorský, Martin; Židzik, Jozef; Levin, Albert M; Williams, L Keoki; Dujic, Tanja; Semiz, Sabina; Kubo, Michiaki; Chien, Huan-Chieh; Maeda, Shiro; Witte, John S; Wu, Longyang; Tkáč, Ivan; Kooy, Adriaan; van Schaik, Ron H N; Stehouwer, Coen D A; Logie, Lisa; Sutherland, Calum; Klovins, Janis; Pirags, Valdis; Hofman, Albert; Stricker, Bruno H; Motsinger-Reif, Alison A; Wagner, Michael J; Innocenti, Federico; 't Hart, Leen M; Holman, Rury R; McCarthy, Mark I; Hedderson, Monique M; Palmer, Colin N A; Florez, Jose C; Giacomini, Kathleen M; Pearson, Ewan R

    2016-01-01

    Metformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear1. Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome-wide association study (GWAS), consisting of 13,123 participants of different ancestries. The C allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (p=6.6×10−14) greater metformin-induced in haemoglobin A1c (HbA1c) in 10,577 participants of European ancestry. rs8192675 is the top cis expression quantitative trait locus (cis-eQTL) for SLC2A2 in 1,226 human liver samples, suggesting a key role for hepatic GLUT2 in regulation of metformin action. Among obese individuals, C-allele homozygotes at rs8192675 had a 0.33% (3.6 mmol/mol) greater absolute HbA1c reduction than T-allele homozygotes. This was about half the effect seen with the addition of a DPP-4 inhibitor, and equated to a dose difference of 550mg of metformin, suggesting rs8192675 as a potential biomarker for stratified medicine. PMID:27500523

  7. GST M1-T1 null allele frequency patterns in geographically assorted human populations: a phylogenetic approach.

    Directory of Open Access Journals (Sweden)

    Senthilkumar Pitchalu Kasthurinaidu

    Full Text Available Genetic diversity in drug metabolism and disposition is mainly considered as the outcome of the inter-individual genetic variation in polymorphism of drug-xenobiotic metabolizing enzyme (XME. Among the XMEs, glutathione-S-transferases (GST gene loci are an important candidate for the investigation of diversity in allele frequency, as the deletion mutations in GST M1 and T1 genotypes are associated with various cancers and genetic disorders of all major Population Affiliations (PAs. Therefore, the present population based phylogenetic study was focused to uncover the frequency distribution pattern in GST M1 and T1 null genotypes among 45 Geographically Assorted Human Populations (GAHPs. The frequency distribution pattern for GST M1 and T1 null alleles have been detected in this study using the data derived from literatures representing 44 populations affiliated to Africa, Asia, Europe, South America and the genome of PA from Gujarat, a region in western India. Allele frequency counting for Gujarat PA and scattered plot analysis for geographical distribution among the PAs were performed in SPSS-21. The GST M1 and GST T1 null allele frequencies patterns of the PAs were computed in Seqboot, Gendist program of Phylip software package (3.69 versions and Unweighted Pair Group method with Arithmetic Mean in Mega-6 software. Allele frequencies from South African Xhosa tribe, East African Zimbabwe, East African Ethiopia, North African Egypt, Caucasian, South Asian Afghanistan and South Indian Andhra Pradesh have been identified as the probable seven patterns among the 45 GAHPs investigated in this study for GST M1-T1 null genotypes. The patternized null allele frequencies demonstrated in this study for the first time addresses the missing link in GST M1-T1 null allele frequencies among GAHPs.

  8. A Risk Allele for Nicotine Dependence in CHRNA5 Is a Protective Allele for Cocaine Dependence

    Science.gov (United States)

    Grucza, Richard A; Wang, Jen C.; Stitzel, Jerry A.; Hinrichs, Anthony L.; Saccone, Scott F.; Saccone, Nancy L.; Bucholz, Kathleen K.; Cloninger, C. Robert; Neuman, Rosalind J.; Budde, John P.; Fox, Louis; Bertelsen, Sarah; Kramer, John; Hesselbrock, Victor; Tischfield, Jay; Nurnberger, John. I.; Almasy, Laura; Porjesz, Bernice; Kuperman, Samuel; Schuckit, Marc A.; Edenberg, Howard J.; Rice, John P.; Goate, Alison M.; Bierut, Laura J.

    2008-01-01

    Background A non-synonymous coding polymorphism, rs16969968, of the CHRNA5 gene which encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR) has been found to be associated with nicotine dependence (20). The goal of the present study is to examine the association of this variant with cocaine dependence. Methods Genetic association analysis in two, independent samples of unrelated cases and controls; 1.) 504 European-American participating in the Family Study on Cocaine Dependence (FSCD); 2.) 814 European Americans participating in the Collaborative Study on the Genetics of Alcoholsim (COGA). Results In the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (OR = 0.67 per allele, p = 0.0045, assuming an additive genetic model), but in the reverse direction compared to that previously observed for nicotine dependence. In multivariate analyses that controlled for the effects of nicotine dependence, both the protective effect for cocaine dependence and the previously documented risk effect for nicotine dependence were statistically significant. The protective effect for cocaine dependence was replicated in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype for nicotine dependence, were consistent with those observed in FSCD. Conclusion The minor (A) allele of rs16969968, relative to the major G allele, appears to be both a risk factor for nicotine dependence and a protective factor for cocaine dependence. The biological plausibility of such a bidirectional association stems from the involvement of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward pathways. PMID:18519132

  9. AllelicImbalance: An R/ bioconductor package for detecting, managing, and visualizing allele expression imbalance data from RNA sequencing

    DEFF Research Database (Denmark)

    Gådin, Jesper R.; van't Hooft, Ferdinand M.; Eriksson, Per;

    2015-01-01

    Background: One aspect in which RNA sequencing is more valuable than microarray-based methods is the ability to examine the allelic imbalance of the expression of a gene. This process is often a complex task that entails quality control, alignment, and the counting of reads over heterozygous single...... possible biases. Results: We present AllelicImblance, a software program that is designed to detect, manage, and visualize allelic imbalances comprehensively. The purpose of this software is to allow users to pose genetic questions in any RNA sequencing experiment quickly, enhancing the general utility of...... RNA sequencing. The visualization features can reveal notable, non-trivial allelic imbalance behavior over specific regions, such as exons. Conclusions: The software provides a complete framework to perform allelic imbalance analyses of aligned RNA sequencing data, from detection to visualization...

  10. Are ???Endurance??? Alleles ???Survival??? Alleles? Insights from the ACTN3 R577X Polymorphism

    OpenAIRE

    Fiuza-Luces, Carmen; Ruiz, Jonatan R.; Rodr??guez-Romo, Gabriel; Santiago, Catalina; G??mez-Gallego, F??lix; Yvert, Thomas; Cano-Nieto, Amalia; Garatechea, Nuria; Mor??n, Mar??a; Luc??a, Alejandro

    2011-01-01

    Exercise phenotypes have played a key role for ensuring survival over human evolution. We speculated that some genetic variants that influence exercise phenotypes could be associated with exceptional survival (i.e. reaching ???100years of age). Owing to its effects on muscle structure/function, a potential candidate is the Arg(R)577Ter(X) polymorphism (rs1815739) in ACTN3, the structural gene encoding the skeletal muscle protein ??-actinin-3. We compared the ACTN3 R577X genotype/allele freque...

  11. Interactions between SNP Alleles at Multiple Loci Contribute to Skin Color Differences between Caucasoid and Mongoloid Subjects

    Directory of Open Access Journals (Sweden)

    Sumiko Anno, Takashi Abe, Takushi Yamamoto

    2008-01-01

    Full Text Available This study aimed to identify single nucleotide polymorphism (SNP alleles at multiple loci associated with racial differences in skin color using SNP genotyping. A total of 122 Caucasians in Toledo, Ohio and 100 Mongoloids in Japan were genotyped for 20 SNPs in 7 candidate genes, encoding the Agouti signaling protein (ASIP, tyrosinase-related protein 1 (TYRP1, tyrosinase (TYR, melanocortin 1 receptor (MC1R, oculocutaneous albinism II (OCA2, microphthalmia-associated transcription factor (MITF, and myosin VA (MYO5A. Data were used to analyze associations between the 20 SNP alleles using linkage disequilibrium (LD. Combinations of SNP alleles were jointly tested under LD for associations with racial groups by performing a χ2 test for independence. Results showed that SNP alleles at multiple loci can be considered the haplotype that contributes to significant differences between the two population groups and suggest a high probability of LD. Confirmation of these findings requires further study with other ethnic groups to analyze the associations between SNP alleles at multiple loci and skin color variation among races.

  12. Association of Circulating Renin and Aldosterone With Osteocalcin and Bone Mineral Density in African Ancestry Families.

    Science.gov (United States)

    Kuipers, Allison L; Kammerer, Candace M; Pratt, J Howard; Bunker, Clareann H; Wheeler, Victor W; Patrick, Alan L; Zmuda, Joseph M

    2016-05-01

    Hypertension is associated with accelerated bone loss, and the renin-angiotensin-aldosterone system is a key regulator of blood pressure. Although components of this system are expressed in human bone cells, studies in humans are sparse. Thus, we studied the association of circulating renin and aldosterone with osteocalcin and bone mineral density. We recruited 373 African ancestry family members without regard to health status from 6 probands (mean family size: 62 and relative pairs: 1687). Participants underwent a clinical examination, dual-energy x-ray absorptiometry, and quantitative computed tomographic scans. Renin activity, aldosterone concentration, and osteocalcin were measured in fasting blood samples. Aldosterone/renin ratio was calculated as aldosterone concentration/renin activity. All models were analyzed using pedigree-based variance components methods. Full models included adjustment for age, sex, body composition, comorbidities, lifestyle factors, blood pressure, and antihypertensive medication. Higher renin activity was significantly associated with lower total osteocalcin and with higher trabecular bone mineral density (bothP<0.01). There were also significant genetic correlations between renin activity and whole-body bone mineral density. There were no associations with aldosterone concentration in any model and results for aldosterone/renin ratio were similar to those for renin activity. This is the first study to report a significant association between renin activity and a marker of bone turnover and bone mineral density in generally healthy individuals. Also, there is evidence for significant genetic pleiotropy and, thus, there may be a shared biological mechanism underlying both the renin-angiotensin-aldosterone system and bone metabolism that is independent of hypertension. PMID:26975710

  13. Counting the Founders: The Matrilineal Genetic Ancestry of the Jewish Diaspora

    Science.gov (United States)

    Behar, Doron M.; Metspalu, Ene; Kivisild, Toomas; Rosset, Saharon; Tzur, Shay; Hadid, Yarin; Yudkovsky, Guennady; Rosengarten, Dror; Pereira, Luisa; Amorim, Antonio; Kutuev, Ildus; Gurwitz, David; Bonne-Tamir, Batsheva; Villems, Richard; Skorecki, Karl

    2008-01-01

    The history of the Jewish Diaspora dates back to the Assyrian and Babylonian conquests in the Levant, followed by complex demographic and migratory trajectories over the ensuing millennia which pose a serious challenge to unraveling population genetic patterns. Here we ask whether phylogenetic analysis, based on highly resolved mitochondrial DNA (mtDNA) phylogenies can discern among maternal ancestries of the Diaspora. Accordingly, 1,142 samples from 14 different non-Ashkenazi Jewish communities were analyzed. A list of complete mtDNA sequences was established for all variants present at high frequency in the communities studied, along with high-resolution genotyping of all samples. Unlike the previously reported pattern observed among Ashkenazi Jews, the numerically major portion of the non-Ashkenazi Jews, currently estimated at 5 million people and comprised of the Moroccan, Iraqi, Iranian and Iberian Exile Jewish communities showed no evidence for a narrow founder effect, which did however characterize the smaller and more remote Belmonte, Indian and the two Caucasus communities. The Indian and Ethiopian Jewish sample sets suggested local female introgression, while mtDNAs in all other communities studied belong to a well-characterized West Eurasian pool of maternal lineages. Absence of sub-Saharan African mtDNA lineages among the North African Jewish communities suggests negligible or low level of admixture with females of the host populations among whom the African haplogroup (Hg) L0-L3 sub-clades variants are common. In contrast, the North African and Iberian Exile Jewish communities show influence of putative Iberian admixture as documented by mtDNA Hg HV0 variants. These findings highlight striking differences in the demographic history of the widespread Jewish Diaspora. PMID:18446216

  14. Early B-cell differentiation in Merkel cell carcinomas: clues to cellular ancestry.

    Science.gov (United States)

    Zur Hausen, Axel; Rennspiess, Dorit; Winnepenninckx, Veronique; Speel, Ernst-Jan; Kurz, Anna Kordelia

    2013-08-15

    Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine nonmelanoma skin cancer, which is associated with the Merkel cell polyoma virus (MCPyV). Recently, expression of the terminal deoxynucleotidyl transferase (TdT) and the paired box gene 5 (PAX 5) has been consistently reported in the majority of MCCs. We tested 21 MCCs for the expression of MCPyV, TdT, PAX5, IgG, IgM, IgA, kappa, and lambda by immunohistochemistry and assessed IgH and Igk rearrangement in all 21 MCCs. All of the MCCs revealed specific expression of PAX5 and 72.8% of the MCCs expressed TdT. In addition, most of the MCCs revealed specific expression of one or more Ig subclasses and kappa or lambda. One MCC did reveal monoclonal IgH and Igk rearrangement next to two other MCCs showing Igk rearrangement. As coexpression of TdT and PAX5 under physiologic circumstances is restricted to pro/pre- and pre-B cells we propose, on the basis of our results, that the cell of origin of MCCs is a pro/pre- or pre-B cell rather than the postmitotic Merkel cells. MCPyV infection and transformation of pro-/pre-B cells are likely to induce the expression of simple cytokeratins as has been shown for SV40 in other nonepithelial cells. This model of cellular ancestry of MCCs might impact therapy and possibly helps to understand why approximately 20% of MCCs are MCPyV-negative. PMID:23576560

  15. African Ancestry Analysis and Admixture Genetic Mapping for Proliferative Diabetic Retinopathy in African Americans

    Science.gov (United States)

    Tandon, Arti; Chen, Ching J.; Penman, Alan; Hancock, Heather; James, Maurice; Husain, Deeba; Andreoli, Christopher; Li, Xiaohui; Kuo, Jane Z.; Idowu, Omolola; Riche, Daniel; Papavasilieou, Evangelia; Brauner, Stacey; Smith, Sataria O.; Hoadley, Suzanne; Richardson, Cole; Kieser, Troy; Vazquez, Vanessa; Chi, Cheryl; Fernandez, Marlene; Harden, Maegan; Cotch, Mary Frances; Siscovick, David; Taylor, Herman A.; Wilson, James G.; Reich, David; Wong, Tien Y.; Klein, Ronald; Klein, Barbara E. K.; Rotter, Jerome I.; Patterson, Nick; Sobrin, Lucia

    2015-01-01

    Purpose. To examine the relationship between proportion of African ancestry (PAA) and proliferative diabetic retinopathy (PDR) and to identify genetic loci associated with PDR using admixture mapping in African Americans with type 2 diabetes (T2D). Methods. Between 1993 and 2013, 1440 participants enrolled in four different studies had fundus photographs graded using the Early Treatment Diabetic Retinopathy Study scale. Cases (n = 305) had PDR while controls (n = 1135) had nonproliferative diabetic retinopathy (DR) or no DR. Covariates included diabetes duration, hemoglobin A1C, systolic blood pressure, income, and education. Genotyping was performed on the Affymetrix platform. The association between PAA and PDR was evaluated using logistic regression. Genome-wide admixture scanning was performed using ANCESTRYMAP software. Results. In the univariate analysis, PDR was associated with increased PAA (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.16–1.59, P = 0.0002). In multivariate regression adjusting for traditional DR risk factors, income and education, the association between PAA and PDR was attenuated and no longer significant (OR = 1.21, 95% CI = 0.59–2.47, P = 0.61). For the admixture analyses, the maximum genome-wide score was 1.44 on chromosome 1. Conclusions. In this largest study of PDR in African Americans with T2D to date, an association between PAA and PDR is not present after adjustment for clinical, demographic, and socioeconomic factors. No genome-wide significant locus (defined as having a locus-genome statistic > 5) was identified with admixture analysis. Further analyses with even larger sample sizes are needed to definitively assess if any admixture signal for DR is present. PMID:26098467

  16. Deciphering and dating the red panda's ancestry and early adaptive radiation of Musteloidea.

    Science.gov (United States)

    Sato, Jun J; Wolsan, Mieczyslaw; Minami, Shinji; Hosoda, Tetsuji; Sinaga, Martua H; Hiyama, Kozue; Yamaguchi, Yasunori; Suzuki, Hitoshi

    2009-12-01

    Few species have been of more disputed affinities than the red or lesser panda (Ailurus fulgens), an endangered endemic Southeast Asian vegetarian member of the placental mammalian order Carnivora. This peculiar carnivoran has mostly been classified with raccoons (Procyonidae) or bears (Ursidae), grouped with the giant panda (Ailuropoda melanoleuca) in their own family, or considered a separate lineage of equivocal ancestry. Recent molecular studies have indicated a close affinity of the red panda to a clade of procyonids and mustelids (weasels, otters, martens, badgers, and allies), but have failed to unambiguously resolve the position of this species relative to mephitids (skunks and stink badgers). We examined the relationship of the red panda to other extant species of the carnivoran suborder Caniformia using a set of concatenated approximately 5.5-kb sequences from protein-coding exons of five nuclear genes. Bayesian, maximum likelihood, and parsimony phylogenetic analyses strongly supported the red panda as the closest living relative of a clade containing Procyonidae and Mustelidae to the exclusion of Mephitidae. These three families together with the red panda (which is classified here as a single extant species of a distinct family, Ailuridae) compose the superfamily Musteloidea, a clade strongly supported by all our phylogenetic analyses as sister to the monophyletic Pinnipedia (seals, sea lions, walruses). The approximately unbiased, Kishino-Hasegawa, and Templeton topology tests rejected (Pfossil evidence that extends the early adaptive radiation of the total clade of musteloids to the Eocene-Oligocene transition and also suggests Asia as a center of this radiation. PMID:19699810

  17. Naturally occurring allele diversity allows potato cultivation in northern latitudes.

    Science.gov (United States)

    Kloosterman, Bjorn; Abelenda, José A; Gomez, María del Mar Carretero; Oortwijn, Marian; de Boer, Jan M; Kowitwanich, Krissana; Horvath, Beatrix M; van Eck, Herman J; Smaczniak, Cezary; Prat, Salomé; Visser, Richard G F; Bachem, Christian W B

    2013-03-14

    Potato (Solanum tuberosum L.) originates from the Andes and evolved short-day-dependent tuber formation as a vegetative propagation strategy. Here we describe the identification of a central regulator underlying a major-effect quantitative trait locus for plant maturity and initiation of tuber development. We show that this gene belongs to the family of DOF (DNA-binding with one finger) transcription factors and regulates tuberization and plant life cycle length, by acting as a mediator between the circadian clock and the StSP6A mobile tuberization signal. We also show that natural allelic variants evade post-translational light regulation, allowing cultivation outside the geographical centre of origin of potato. Potato is a member of the Solanaceae family and is one of the world's most important food crops. This annual plant originates from the Andean regions of South America. Potato develops tubers from underground stems called stolons. Its equatorial origin makes potato essentially short-day dependent for tuberization and potato will not make tubers in the long-day conditions of spring and summer in the northern latitudes. When introduced in temperate zones, wild material will form tubers in the course of the autumnal shortening of day-length. Thus, one of the first selected traits in potato leading to a European potato type is likely to have been long-day acclimation for tuberization. Potato breeders can exploit the naturally occurring variation in tuberization onset and life cycle length, allowing varietal breeding for different latitudes, harvest times and markets. PMID:23467094

  18. Demographic history and rare allele sharing among human populations

    Science.gov (United States)

    Gravel, Simon; Henn, Brenna M.; Gutenkunst, Ryan N.; Indap, Amit R.; Marth, Gabor T.; Clark, Andrew G.; Yu, Fuli; Gibbs, Richard A.; Bustamante, Carlos D.; Altshuler, David L.; Durbin, Richard M.; Abecasis, Gonçalo R.; Bentley, David R.; Chakravarti, Aravinda; Clark, Andrew G.; Collins, Francis S.; De La Vega, Francisco M.; Donnelly, Peter; Egholm, Michael; Flicek, Paul; Gabriel, Stacey B.; Gibbs, Richard A.; Knoppers, Bartha M.; Lander, Eric S.; Lehrach, Hans; Mardis, Elaine R.; McVean, Gil A.; Nickerson, Debbie A.; Peltonen, Leena; Schafer, Alan J.; Sherry, Stephen T.; Wang, Jun; Wilson, Richard K.; Gibbs, Richard A.; Deiros, David; Metzker, Mike; Muzny, Donna; Reid, Jeff; Wheeler, David; Wang, Jun; Li, Jingxiang; Jian, Min; Li, Guoqing; Li, Ruiqiang; Liang, Huiqing; Tian, Geng; Wang, Bo; Wang, Jian; Wang, Wei; Yang, Huanming; Zhang, Xiuqing; Zheng, Huisong; Lander, Eric S.; Altshuler, David L.; Ambrogio, Lauren; Bloom, Toby; Cibulskis, Kristian; Fennell, Tim J.; Gabriel, Stacey B.; Jaffe, David B.; Shefler, Erica; Sougnez, Carrie L.; Bentley, David R.; Gormley, Niall; Humphray, Sean; Kingsbury, Zoya; Koko-Gonzales, Paula; Stone, Jennifer; McKernan, Kevin J.; Costa, Gina L.; Ichikawa, Jeffry K.; Lee, Clarence C.; Sudbrak, Ralf; Lehrach, Hans; Borodina, Tatiana A.; Dahl, Andreas; Davydov, Alexey N.; Marquardt, Peter; Mertes, Florian; Nietfeld, Wilfiried; Rosenstiel, Philip; Schreiber, Stefan; Soldatov, Aleksey V.; Timmermann, Bernd; Tolzmann, Marius; Egholm, Michael; Affourtit, Jason; Ashworth, Dana; Attiya, Said; Bachorski, Melissa; Buglione, Eli; Burke, Adam; Caprio, Amanda; Celone, Christopher; Clark, Shauna; Conners, David; Desany, Brian; Gu, Lisa; Guccione, Lorri; Kao, Kalvin; Kebbel, Andrew; Knowlton, Jennifer; Labrecque, Matthew; McDade, Louise; Mealmaker, Craig; Minderman, Melissa; Nawrocki, Anne; Niazi, Faheem; Pareja, Kristen; Ramenani, Ravi; Riches, David; Song, Wanmin; Turcotte, Cynthia; Wang, Shally; Mardis, Elaine R.; Wilson, Richard K.; Dooling, David; Fulton, Lucinda; Fulton, Robert; Weinstock, George; Durbin, Richard M.; Burton, John; Carter, David M.; Churcher, Carol; Coffey, Alison; Cox, Anthony; Palotie, Aarno; Quail, Michael; Skelly, Tom; Stalker, James; Swerdlow, Harold P.; Turner, Daniel; De Witte, Anniek; Giles, Shane; Gibbs, Richard A.; Wheeler, David; Bainbridge, Matthew; Challis, Danny; Sabo, Aniko; Yu, Fuli; Yu, Jin; Wang, Jun; Fang, Xiaodong; Guo, Xiaosen; Li, Ruiqiang; Li, Yingrui; Luo, Ruibang; Tai, Shuaishuai; Wu, Honglong; Zheng, Hancheng; Zheng, Xiaole; Zhou, Yan; Li, Guoqing; Wang, Jian; Yang, Huanming; Marth, Gabor T.; Garrison, Erik P.; Huang, Weichun; Indap, Amit; Kural, Deniz; Lee, Wan-Ping; Leong, Wen Fung; Quinlan, Aaron R.; Stewart, Chip; Stromberg, Michael P.; Ward, Alistair N.; Wu, Jiantao; Lee, Charles; Mills, Ryan E.; Shi, Xinghua; Daly, Mark J.; DePristo, Mark A.; Altshuler, David L.; Ball, Aaron D.; Banks, Eric; Bloom, Toby; Browning, Brian L.; Cibulskis, Kristian; Fennell, Tim J.; Garimella, Kiran V.; Grossman, Sharon R.; Handsaker, Robert E.; Hanna, Matt; Hartl, Chris; Jaffe, David B.; Kernytsky, Andrew M.; Korn, Joshua M.; Li, Heng; Maguire, Jared R.; McCarroll, Steven A.; McKenna, Aaron; Nemesh, James C.; Philippakis, Anthony A.; Poplin, Ryan E.; Price, Alkes; Rivas, Manuel A.; Sabeti, Pardis C.; Schaffner, Stephen F.; Shefler, Erica; Shlyakhter, Ilya A.; Cooper, David N.; Ball, Edward V.; Mort, Matthew; Phillips, Andrew D.; Stenson, Peter D.; Sebat, Jonathan; Makarov, Vladimir; Ye, Kenny; Yoon, Seungtai C.; Bustamante, Carlos D.; Clark, Andrew G.; Boyko, Adam; Degenhardt, Jeremiah; Gravel, Simon; Gutenkunst, Ryan N.; Kaganovich, Mark; Keinan, Alon; Lacroute, Phil; Ma, Xin; Reynolds, Andy; Clarke, Laura; Flicek, Paul; Cunningham, Fiona; Herrero, Javier; Keenen, Stephen; Kulesha, Eugene; Leinonen, Rasko; McLaren, William M.; Radhakrishnan, Rajesh; Smith, Richard E.; Zalunin, Vadim; Zheng-Bradley, Xiangqun; Korbel, Jan O.; Stütz, Adrian M.; Humphray, Sean; Bauer, Markus; Cheetham, R. Keira; Cox, Tony; Eberle, Michael; James, Terena; Kahn, Scott; Murray, Lisa; Chakravarti, Aravinda; Ye, Kai; De La Vega, Francisco M.; Fu, Yutao; Hyland, Fiona C. L.; Manning, Jonathan M.; McLaughlin, Stephen F.; Peckham, Heather E.; Sakarya, Onur; Sun, Yongming A.; Tsung, Eric F.; Batzer, Mark A.; Konkel, Miriam K.; Walker, Jerilyn A.; Sudbrak, Ralf; Albrecht, Marcus W.; Amstislavskiy, Vyacheslav S.; Herwig, Ralf; Parkhomchuk, Dimitri V.; Sherry, Stephen T.; Agarwala, Richa; Khouri, Hoda M.; Morgulis, Aleksandr O.; Paschall, Justin E.; Phan, Lon D.; Rotmistrovsky, Kirill E.; Sanders, Robert D.; Shumway, Martin F.; Xiao, Chunlin; McVean, Gil A.; Auton, Adam; Iqbal, Zamin; Lunter, Gerton; Marchini, Jonathan L.; Moutsianas, Loukas; Myers, Simon; Tumian, Afidalina; Desany, Brian; Knight, James; Winer, Roger; Craig, David W.; Beckstrom-Sternberg, Steve M.; Christoforides, Alexis; Kurdoglu, Ahmet A.; Pearson, John V.; Sinari, Shripad A.; Tembe, Waibhav D.; Haussler, David; Hinrichs, Angie S.; Katzman, Sol J.; Kern, Andrew; Kuhn, Robert M.; Przeworski, Molly; Hernandez, Ryan D.; Howie, Bryan; Kelley, Joanna L.; Melton, S. Cord; Abecasis, Gonçalo R.; Li, Yun; Anderson, Paul; Blackwell, Tom; Chen, Wei; Cookson, William O.; Ding, Jun; Kang, Hyun Min; Lathrop, Mark; Liang, Liming; Moffatt, Miriam F.; Scheet, Paul; Sidore, Carlo; Snyder, Matthew; Zhan, Xiaowei; Zöllner, Sebastian; Awadalla, Philip; Casals, Ferran; Idaghdour, Youssef; Keebler, John; Stone, Eric A.; Zilversmit, Martine; Jorde, Lynn; Xing, Jinchuan; Eichler, Evan E.; Aksay, Gozde; Alkan, Can; Hajirasouliha, Iman; Hormozdiari, Fereydoun; Kidd, Jeffrey M.; Sahinalp, S. Cenk; Sudmant, Peter H.; Mardis, Elaine R.; Chen, Ken; Chinwalla, Asif; Ding, Li; Koboldt, Daniel C.; McLellan, Mike D.; Dooling, David; Weinstock, George; Wallis, John W.; Wendl, Michael C.; Zhang, Qunyuan; Durbin, Richard M.; Albers, Cornelis A.; Ayub, Qasim; Balasubramaniam, Senduran; Barrett, Jeffrey C.; Carter, David M.; Chen, Yuan; Conrad, Donald F.; Danecek, Petr; Dermitzakis, Emmanouil T.; Hu, Min; Huang, Ni; Hurles, Matt E.; Jin, Hanjun; Jostins, Luke; Keane, Thomas M.; Le, Si Quang; Lindsay, Sarah; Long, Quan; MacArthur, Daniel G.; Montgomery, Stephen B.; Parts, Leopold; Stalker, James; Tyler-Smith, Chris; Walter, Klaudia; Zhang, Yujun; Gerstein, Mark B.; Snyder, Michael; Abyzov, Alexej; Balasubramanian, Suganthi; Bjornson, Robert; Du, Jiang; Grubert, Fabian; Habegger, Lukas; Haraksingh, Rajini; Jee, Justin; Khurana, Ekta; Lam, Hugo Y. K.; Leng, Jing; Mu, Xinmeng Jasmine; Urban, Alexander E.; Zhang, Zhengdong; Li, Yingrui; Luo, Ruibang; Marth, Gabor T.; Garrison, Erik P.; Kural, Deniz; Quinlan, Aaron R.; Stewart, Chip; Stromberg, Michael P.; Ward, Alistair N.; Wu, Jiantao; Lee, Charles; Mills, Ryan E.; Shi, Xinghua; McCarroll, Steven A.; Banks, Eric; DePristo, Mark A.; Handsaker, Robert E.; Hartl, Chris; Korn, Joshua M.; Li, Heng; Nemesh, James C.; Sebat, Jonathan; Makarov, Vladimir; Ye, Kenny; Yoon, Seungtai C.; Degenhardt, Jeremiah; Kaganovich, Mark; Clarke, Laura; Smith, Richard E.; Zheng-Bradley, Xiangqun; Korbel, Jan O.; Humphray, Sean; Cheetham, R. Keira; Eberle, Michael; Kahn, Scott; Murray, Lisa; Ye, Kai; De La Vega, Francisco M.; Fu, Yutao; Peckham, Heather E.; Sun, Yongming A.; Batzer, Mark A.; Konkel, Miriam K.; Walker, Jerilyn A.; Xiao, Chunlin; Iqbal, Zamin; Desany, Brian; Blackwell, Tom; Snyder, Matthew; Xing, Jinchuan; Eichler, Evan E.; Aksay, Gozde; Alkan, Can; Hajirasouliha, Iman; Hormozdiari, Fereydoun; Kidd, Jeffrey M.; Chen, Ken; Chinwalla, Asif; Ding, Li; McLellan, Mike D.; Wallis, John W.; Hurles, Matt E.; Conrad, Donald F.; Walter, Klaudia; Zhang, Yujun; Gerstein, Mark B.; Snyder, Michael; Abyzov, Alexej; Du, Jiang; Grubert, Fabian; Haraksingh, Rajini; Jee, Justin; Khurana, Ekta; Lam, Hugo Y. K.; Leng, Jing; Mu, Xinmeng Jasmine; Urban, Alexander E.; Zhang, Zhengdong; Gibbs, Richard A.; Bainbridge, Matthew; Challis, Danny; Coafra, Cristian; Dinh, Huyen; Kovar, Christie; Lee, Sandy; Muzny, Donna; Nazareth, Lynne; Reid, Jeff; Sabo, Aniko; Yu, Fuli; Yu, Jin; Marth, Gabor T.; Garrison, Erik P.; Indap, Amit; Leong, Wen Fung; Quinlan, Aaron R.; Stewart, Chip; Ward, Alistair N.; Wu, Jiantao; Cibulskis, Kristian; Fennell, Tim J.; Gabriel, Stacey B.; Garimella, Kiran V.; Hartl, Chris; Shefler, Erica; Sougnez, Carrie L.; Wilkinson, Jane; Clark, Andrew G.; Gravel, Simon; Grubert, Fabian; Clarke, Laura; Flicek, Paul; Smith, Richard E.; Zheng-Bradley, Xiangqun; Sherry, Stephen T.; Khouri, Hoda M.; Paschall, Justin E.; Shumway, Martin F.; Xiao, Chunlin; McVean, Gil A.; Katzman, Sol J.; Abecasis, Gonçalo R.; Blackwell, Tom; Mardis, Elaine R.; Dooling, David; Fulton, Lucinda; Fulton, Robert; Koboldt, Daniel C.; Durbin, Richard M.; Balasubramaniam, Senduran; Coffey, Allison; Keane, Thomas M.; MacArthur, Daniel G.; Palotie, Aarno; Scott, Carol; Stalker, James; Tyler-Smith, Chris; Gerstein, Mark B.; Balasubramanian, Suganthi; Chakravarti, Aravinda; Knoppers, Bartha M.; Abecasis, Gonçalo R.; Bustamante, Carlos D.; Gharani, Neda; Gibbs, Richard A.; Jorde, Lynn; Kaye, Jane S.; Kent, Alastair; Li, Taosha; McGuire, Amy L.; McVean, Gil A.; Ossorio, Pilar N.; Rotimi, Charles N.; Su, Yeyang; Toji, Lorraine H.; TylerSmith, Chris; Brooks, Lisa D.; Felsenfeld, Adam L.; McEwen, Jean E.; Abdallah, Assya; Juenger, Christopher R.; Clemm, Nicholas C.; Collins, Francis S.; Duncanson, Audrey; Green, Eric D.; Guyer, Mark S.; Peterson, Jane L.; Schafer, Alan J.; Abecasis, Gonçalo R.; Altshuler, David L.; Auton, Adam; Brooks, Lisa D.; Durbin, Richard M.; Gibbs, Richard A.; Hurles, Matt E.; McVean, Gil A.

    2011-01-01

    High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2–4× coverage data for 179 samples from HapMap European, Asian, and African panels as well as high-coverage target sequencing of the exons of 800 genes from 697 individuals in seven populations. We use the site frequency spectra obtained from these data to infer demographic parameters for an Out-of-Africa model for populations of African, European, and Asian descent and to predict, by a jackknife-based approach, the amount of genetic diversity that will be discovered as sample sizes are increased. We predict that the number of discovered nonsynonymous coding variants will reach 100,000 in each population after ∼1,000 sequenced chromosomes per population, whereas ∼2,500 chromosomes will be needed for the same number of synonymous variants. Beyond this point, the number of segregating sites in the European and Asian panel populations is expected to overcome that of the African panel because of faster recent population growth. Overall, we find that the majority of human genomic variable sites are rare and exhibit little sharing among diverged populations. Our results emphasize that replication of disease association for specific rare genetic variants across diverged populations must overcome both reduced statistical power because of rarity and higher population divergence. PMID:21730125

  19. Analysis of Rare, Exonic Variation amongst Subjects with Autism Spectrum Disorders and Population Controls

    OpenAIRE

    Liu, Li; Sabo, Aniko; Neale, Benjamin Michael; Nagaswamy, Uma; Stevens, Christine; Lim, Elaine; Bodea, Corneliu A.; Muzny, Donna; Reid, Jeffrey G.; Banks, Eric; Coon, Hillary; Depristo, Mark; Dinh, Huyen; Fennel, Tim; Flannick, Jason A.

    2013-01-01

    We report on results from whole-exome sequencing (WES) of 1,039 subjects diagnosed with autism spectrum disorders (ASD) and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by ...

  20. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility

    DEFF Research Database (Denmark)

    Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B;

    2016-01-01

    Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and.......5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry....

  1. A New Electrophoresis Technique to Seperate Microsatellite Alleles

    Science.gov (United States)

    Traditional agarose and polyacrylamide gel electrophoresis have been used commonly for microsatellite (simple sequence repeats, SSRs) analysis, but they are labor- intensive and not always able to provide accurate sizes for different alleles. Capillary sequencers provide automated analysis and accur...

  2. Are 'endurance' alleles 'survival' alleles? Insights from the ACTN3 R577X polymorphism.

    Directory of Open Access Journals (Sweden)

    Carmen Fiuza-Luces

    Full Text Available Exercise phenotypes have played a key role for ensuring survival over human evolution. We speculated that some genetic variants that influence exercise phenotypes could be associated with exceptional survival (i.e. reaching ≥100 years of age. Owing to its effects on muscle structure/function, a potential candidate is the Arg(R577Ter(X polymorphism (rs1815739 in ACTN3, the structural gene encoding the skeletal muscle protein α-actinin-3. We compared the ACTN3 R577X genotype/allele frequencies between the following groups of ethnically-matched (Spanish individuals: centenarians (cases, n = 64; 57 female; age range: 100-108 years, young healthy controls (n = 283, 67 females, 216 males; 21±2 years, and humans who are at the two end-points of exercise capacity phenotypes, i.e. muscle endurance (50 male professional road cyclists and muscle power (63 male jumpers/sprinters. Although there were no differences in genotype/allele frequencies between centenarians (RR:28.8%; RX:47.5%; XX:23.7%, and controls (RR:31.8%; RX:49.8%; XX:18.4% or endurance athletes (RR:28.0%; RX:46%; XX:26.0%, we observed a significantly higher frequency of the X allele (P = 0.019 and XX genotype (P = 0.011 in centenarians compared with power athletes (RR:47.6%; RX:36.5%;XX:15.9%. Notably, the frequency of the null XX (α-actinin-3 deficient genotype in centenarians was the highest ever reported in non-athletic Caucasian populations. In conclusion, despite there were no significant differences with the younger, control population, overall the ACTN3 genotype of centenarians resembles that of world-class elite endurance athletes and differs from that of elite power athletes. Our preliminary data would suggest a certain 'survival' advantage brought about by α-actinin-3 deficiency and the 'endurance'/oxidative muscle phenotype that is commonly associated with this condition.

  3. Random survey for RH allele polymorphism among 50 native Tibetans

    OpenAIRE

    Wei, Qing

    2006-01-01

    Rhesus D (RHD) allele distribution varied significantly among different population. However, no data are available for people, like Tibetans, living at extreme altitudes, where the oxygen density is decreased. A comprehensive study has been performed to define the Rhesus (RH) allele polymorphism and RH haplotype distribution in 50 native Tibetans. Nucleotide sequencing from genomic deoxyribonucleic acid (DNA) for 10 Rhesus D gene (RHD) exons in all of 50 samples plus 10 Rhesus CE gene (RHCE) ...

  4. ALLELIC POLYMORPHISM OF IFNγ GENE IN PATIENTS WITH PULMONARY TUBERCULOSIS

    OpenAIRE

    E. L. Nikulina; I. O. Naslednikova; Urazova, O. I.; O. V. Voronkova; V. V. Novitsky; E. V. Nekrasov; O. V. Filiniuk; E. G. Churina; K. O. Mikheyeva; R. R. Hasanova; V. A. Serebryakova; N. A. Sukhalentseva

    2014-01-01

    In present work, some immunogenetic aspects of pulmonary tuberculosis were studied, using modern techniques from molecular genetics and immunology. It is shown that carriage of Т allele and homozygous TT genotype in +874А/Т IFNγ gene polymorphism comprise a immunogenetic factor which correlated with a protective effect, regarding a susceptibility to pulmonary tuberculosis. Predisposition for tuberculosis infection is associated with A allele of this gene, as well as with АА and АТ genotypes o...

  5. Helicobacter pylori genotyping from American indigenous groups shows novel Amerindian vacA and cagA alleles and Asian, African and European admixture.

    Directory of Open Access Journals (Sweden)

    Margarita Camorlinga-Ponce

    Full Text Available It is valuable to extend genotyping studies of Helicobacter pylori to strains from indigenous communities across the world to better define adaption, evolution, and associated diseases. We aimed to genetically characterize both human individuals and their infecting H. pylori from indigenous communities of Mexico, and to compare them with those from other human groups. We studied individuals from three indigenous groups, Tarahumaras from the North, Huichols from the West and Nahuas from the center of Mexico. Volunteers were sampled at their community site, DNA was isolated from white blood cells and mtDNA, Y-chromosome, and STR alleles were studied. H. pylori was cultured from gastric juice, and DNA extracted for genotyping of virulence and housekeeping genes. We found Amerindian mtDNA haplogroups (A, B, C, and D, Y-chromosome DYS19T, and Amerindian STRs alleles frequent in the three groups, confirming Amerindian ancestry in these Mexican groups. Concerning H.pylori cagA phylogenetic analyses, although most isolates were of the Western type, a new Amerindian cluster neither Western nor Asian, was formed by some indigenous Mexican, Colombian, Peruvian and Venezuelan isolates. Similarly, vacA phylogenetic analyses showed the existence of a novel Amerindian type in isolates from Alaska, Mexico and Colombia. With hspA strains from Mexico and other American groups clustered within the three major groups, Asian, African or European. Genotyping of housekeeping genes confirmed that Mexican strains formed a novel Asian-related Amerindian group together with strains from remote Amazon Aborigines. This study shows that Mexican indigenous people with Amerindian markers are colonized with H. pylori showing admixture of Asian, European and African strains in genes known to interact with the gastric mucosa. We present evidence of novel Amerindian cagA and vacA alleles in indigenous groups of North and South America.

  6. Allele-specific MMP-3 transcription under in vivo conditions

    International Nuclear Information System (INIS)

    A common matrix metalloproteinases-3 (MMP-3) -1612 5A/6A promoter polymorphism is associated with risk for cardiovascular disease, rheumatoid arthritis, and other diseases. Here we used the haplotype chromatin immunoprecipitation method to study allele-specific MMP-3 expression under in vivo conditions in heterozygous THP-1 cells. Pyrosequencing was used to analyse the ratio of 5A-allele to 6A-allele after chromatin immunoprecipitation using an antibody against phosphorylated active RNA polymerase II. There was no allele-specific difference in transcriptional activity during basal conditions, i.e., in unstimulated monocytic THP-1 cells. However, after stimulation of MMP-3 expression by monocyte differentiation or incubation with IL-1β, the haplotype containing the 5A-allele was associated with higher transcriptional activity compared with the 6A-containing haplotype. Electromobility shift assay demonstrated increased binding of nuclear proteins to the 5A-allele after monocyte differentiation. In conclusion, the common MMP-3 5A/6A promoter polymorphism appears to be functional only during specific environmental conditions involving inflammation

  7. Ecological interactions and the fitness effect of water-use efficiency: Competition and drought alter the impact of natural MPK12 alleles in Arabidopsis.

    Science.gov (United States)

    Campitelli, Brandon E; Des Marais, David L; Juenger, Thomas E

    2016-04-01

    The presence of substantial genetic variation for water-use efficiency (WUE) suggests that natural selection plays a role in maintaining alleles that affect WUE. Soil water deficit can reduce plant survival, and is likely to impose selection to increase WUE, whereas competition for resources may select for decreased WUE to ensure water acquisition. We tested the fitness consequences of natural allelic variation in a single gene (MPK12) that influences WUE in Arabidopsis, using transgenic lines contrasting in MPK12 alleles, under four treatments; drought/competition, drought/no competition, well-watered/competition, well-watered/no competition. Results revealed an allele × environment interaction: Low WUE plants performed better in competition, resulting from increased resource consumption. Contrastingly, high WUE individuals performed better in no competition, irrespective of water availability, presumably from enhanced water conservation and nitrogen acquisition. Our findings suggest that selection can influence MPK12 evolution, and represents the first assessment of plant fitness resulting from natural allelic variation at a single locus affecting WUE. PMID:26868103

  8. Inter-laboratory evaluation of the EUROFORGEN Global ancestry-informative SNP panel by massively parallel sequencing using the Ion PGM™.

    Science.gov (United States)

    Eduardoff, M; Gross, T E; Santos, C; de la Puente, M; Ballard, D; Strobl, C; Børsting, C; Morling, N; Fusco, L; Hussing, C; Egyed, B; Souto, L; Uacyisrael, J; Syndercombe Court, D; Carracedo, Á; Lareu, M V; Schneider, P M; Parson, W; Phillips, C; Parson, W; Phillips, C

    2016-07-01

    The EUROFORGEN Global ancestry-informative SNP (AIM-SNPs) panel is a forensic multiplex of 128 markers designed to differentiate an individual's ancestry from amongst the five continental population groups of Africa, Europe, East Asia, Native America, and Oceania. A custom multiplex of AmpliSeq™ PCR primers was designed for the Global AIM-SNPs to perform massively parallel sequencing using the Ion PGM™ system. This study assessed individual SNP genotyping precision using the Ion PGM™, the forensic sensitivity of the multiplex using dilution series, degraded DNA plus simple mixtures, and the ancestry differentiation power of the final panel design, which required substitution of three original ancestry-informative SNPs with alternatives. Fourteen populations that had not been previously analyzed were genotyped using the custom multiplex and these studies allowed assessment of genotyping performance by comparison of data across five laboratories. Results indicate a low level of genotyping error can still occur from sequence misalignment caused by homopolymeric tracts close to the target SNP, despite careful scrutiny of candidate SNPs at the design stage. Such sequence misalignment required the exclusion of component SNP rs2080161 from the Global AIM-SNPs panel. However, the overall genotyping precision and sensitivity of this custom multiplex indicates the Ion PGM™ assay for the Global AIM-SNPs is highly suitable for forensic ancestry analysis with massively parallel sequencing. PMID:27208666

  9. Strong genetic admixture in the Altai at the Middle Bronze Age revealed by uniparental and ancestry informative markers.

    Science.gov (United States)

    Hollard, Clémence; Keyser, Christine; Giscard, Pierre-Henri; Tsagaan, Turbat; Bayarkhuu, Noost; Bemmann, Jan; Crubézy, Eric; Ludes, Bertrand

    2014-09-01

    The Altai Mountains have been a long-term boundary zone between the Eurasian Steppe populations and South and East Asian populations. To disentangle some of the historical population movements in this area, 14 ancient human specimens excavated in the westernmost part of the Mongolian Altai were studied. Thirteen of them were dated from the Middle to the End of the Bronze Age and one of them to the Eneolithic period. The environmental conditions encountered in this region led to the good preservation of DNA in the human remains. Therefore, a multi-markers approach was adopted for the genetic analysis of identity, ancestry and phenotype markers. Mitochondrial DNA analyses revealed that the ancient Altaians studied carried both Western (H, U, T) and Eastern (A, C, D) Eurasian lineages. In the same way, the patrilineal gene pool revealed the presence of different haplogroups (Q1a2a1-L54, R1a1a1b2-Z93 and C), probably marking different origins for the male paternal lineages. To go further in the search of the origin of these ancient specimens, phenotypical characters (i.e. hair and eye color) were determined. For this purpose, we adapted the HIrisPlex assay recently described to MALDI-TOF mass spectrometry. In addition, some ancestry informative markers were analyzed with this assay. The results revealed mixed phenotypes among this group confirming the probable admixed ancestry of the studied Altaian population at the Middle Bronze Age. The good results obtained from ancient DNA samples suggest that this approach might be relevant for forensic casework too. PMID:25016250

  10. Allelic imbalance analysis by high-density single-nucleotide polymorphic allele (SNP) array with whole genome amplified DNA

    OpenAIRE

    Wong, Kwong-Kwok; Tsang, Yvonne T.M.; Shen, Jianhe; Cheng, Rita S.; Chang, Yi-Mieng; Man, Tsz-Kwong; Lau, Ching C.

    2004-01-01

    Besides their use in mRNA expression profiling, oligonucleotide microarrays have also been applied to single-nucleotide polymorphism (SNP) and loss of heterozygosity (LOH) or allelic imbalance studies. In this report, we evaluate the reliability of using whole genome amplified DNA for analysis with an oligonucleotide microarray containing 11 560 SNPs to detect allelic imbalance and chromosomal copy number abnormalities. Whole genome SNP analyses were performed with DNA extracted from osteosar...

  11. Characterization of a New Pm2 Allele Conferring Powdery Mildew Resistance in the Wheat Germplasm Line FG-1

    Science.gov (United States)

    Ma, Pengtao; Xu, Hongxng; Li, Lihui; Zhang, Hongxia; Han, Guohao; Xu, Yunfeng; Fu, Xiaoyi; Zhang, Xiaotian; An, Diaoguo

    2016-01-01

    Powdery mildew has a negative impact on wheat production. Novel host resistance increases the diversity of resistance genes and helps to control the disease. In this study, wheat line FG-1 imported from France showed a high level of powdery mildew resistance at both the seedling and adult stages. An F2 population and F2:3 families from the cross FG-1 × Mingxian 169 both fit Mendelian ratios for a single dominant resistance gene when tested against multiple avirulent Blumeria tritici f. sp. tritici (Bgt) races. This gene was temporarily designated PmFG. PmFG was mapped on the multi-allelic Pm2 locus of chromosome 5DS using seven SSR, 10 single nucleotide polymorphism (SNP)-derived and two SCAR markers with the flanking markers Xbwm21/Xcfd81/Xscar112 (distal) and Xbwm25 (proximal) at 0.3 and 0.5 cM being the closest. Marker SCAR203 co-segregated with PmFG. Allelism tests between PmFG and documented Pm2 alleles confirmed that PmFG was allelic with Pm2. Line FG-1 produced a significantly different reaction pattern compared to other lines with genes at or near Pm2 when tested against 49 Bgt isolates. The PmFG-linked marker alleles detected by the SNP-derived markers revealed significant variation between FG-1 and other lines with genes at or near Pm2. It was concluded that PmFG is a new allele at the Pm2 locus. Data from seven closely linked markers tested on 31 wheat cultivars indicated opportunities for marker-assisted pyramiding of this gene with other genes for powdery mildew resistance and additional traits. PMID:27200022

  12. Impriniting of human H19: Allele-specific CpG methylation, loss of the active allele in Wilms tumor, and potential for somatic allele switching

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y.; Shields, T.; Crenshaw, T.; Hao, Y.; Moulton, T.; Tycko, B. (Columbia Univ., New York (United States))

    1993-07-01

    Genomic imprinting and monoallelic gene expression appear to play a role in human genetic disease and tumorigenesis. The human H19 gene, at chromosome 11p15, has previously been shown to be monoallelically expressed. Since CpG methylation has been implicated in imprinting, the authors analyzed methylation of H19 DNA. In fetal and adult organs the transcriptionally silent H19 allele was extensively hypermethylated through the entire gene and its promoter, and, consistent with a functional role for DNA methylation, expression of an H19 promoter-reporter construct was inhibited by in vitro methylation. Gynogenetic ovarian teratomas were found to contain only hypomethylated H19 DNA, suggesting that the expressed H19 allele might be maternal. This was confirmed by analysis of 11p15 polymorphisms in a patient with Wilms tumor. The tumor had lost the maternal 11p15, and H19 expression in the normal kidney was exclusively from this allele. Imprinting of human H19 appears to be susceptible to tissue-specific modulation in somatic development; in one individual, cerebellar cells were found to express only the otherwise silent allele. Implications of these findings for the role of DNA methylation in imprinting and for H19 as a candidate imprinted tumor-suppressor gene are discussed. 57 refs., 7 figs.

  13. Body fatness and breast cancer risk in women of African ancestry

    International Nuclear Information System (INIS)

    Obesity has been shown to be inversely associated with breast cancer risk in premenopausal women, while increasing risk in postmenopausal women. However, the current evidence is largely based on studies in Caucasian populations. Associations in women of African ancestry (AA), who have a higher prevalence of obesity, have been evaluated in few studies and results suggest different effects. We evaluated the impact of body size, body fat distribution, and body composition on breast cancer risk among AA women (978 cases and 958 controls) participating in the Women’s Circle of Health Study, a multi-site case–control study in New York City (NYC) and New Jersey (NJ). Cases were newly diagnosed with histologically confirmed ductal carcinoma in situ or invasive breast cancer, age 20–75 yrs. In NYC, cases were recruited through hospitals with the largest referral patterns for AA women and controls through random digit dialing (RDD). In NJ, cases were identified in seven counties in NJ thorough the NJ State Cancer Registry, and controls through RDD and community-based recruitment. During in-person interviews, questionnaires were administered and detailed anthropometric measurements were obtained. Body composition was assessed by bioelectrical impedance analysis. BMI did not have a major impact on pre- or post-menopausal breast cancer, but was significantly associated with reduced risk of ER-/PR- tumors among postmenopausal women (OR: 0.37; 95% CI: 0.15-0.96 for BMI > 30 vs. BMI < 25). Furthermore, increased premenopausal breast cancer risk was found for higher waist and hip circumferences after adjusting for BMI, with ORs of 2.25 (95% CI: 1.07-4.74) and 2.91 (95% CI: 1.39-6.10), respectively, comparing the highest vs. lowest quartile. While ORs for higher fat mass and percent body fat among postmenopausal women were above one, confidence intervals included the null value. Our study suggests that in AA women BMI is generally unrelated to breast cancer. However, higher

  14. Inter-laboratory evaluation of the EUROFORGEN Global ancestry-informative SNP panel by massively parallel sequencing using the Ion PGM™

    DEFF Research Database (Denmark)

    Eduardoff, M; Gross, T E; Santos, C;

    2016-01-01

    the exclusion of component SNP rs2080161 from the Global AIM-SNPs panel. However, the overall genotyping precision and sensitivity of this custom multiplex indicates the Ion PGM™ assay for the Global AIM-SNPs is highly suitable for forensic ancestry analysis with massively parallel sequencing.......The EUROFORGEN Global ancestry-informative SNP (AIM-SNPs) panel is a forensic multiplex of 128 markers designed to differentiate an individual's ancestry from amongst the five continental population groups of Africa, Europe, East Asia, Native America, and Oceania. A custom multiplex of Ampli......Seq™ PCR primers was designed for the Global AIM-SNPs to perform massively parallel sequencing using the Ion PGM™ system. This study assessed individual SNP genotyping precision using the Ion PGM™, the forensic sensitivity of the multiplex using dilution series, degraded DNA plus simple mixtures, and the...

  15. Population genetic analysis of bi-allelic structural variants from low-coverage sequence data with an expectation-maximization algorithm

    Science.gov (United States)

    2014-01-01

    Background Population genetics and association studies usually rely on a set of known variable sites that are then genotyped in subsequent samples, because it is easier to genotype than to discover the variation. This is also true for structural variation detected from sequence data. However, the genotypes at known variable sites can only be inferred with uncertainty from low coverage data. Thus, statistical approaches that infer genotype likelihoods, test hypotheses, and estimate population parameters without requiring accurate genotypes are becoming popular. Unfortunately, the current implementations of these methods are intended to analyse only single nucleotide and short indel variation, and they usually assume that the two alleles in a heterozygous individual are sampled with equal probability. This is generally false for structural variants detected with paired ends or split reads. Therefore, the population genetics of structural variants cannot be studied, unless a painstaking and potentially biased genotyping is performed first. Results We present svgem, an expectation-maximization implementation to estimate allele and genotype frequencies, calculate genotype posterior probabilities, and test for Hardy-Weinberg equilibrium and for population differences, from the numbers of times the alleles are observed in each individual. Although applicable to single nucleotide variation, it aims at bi-allelic structural variation of any type, observed by either split reads or paired ends, with arbitrarily high allele sampling bias. We test svgem with simulated and real data from the 1000 Genomes Project. Conclusions svgem makes it possible to use low-coverage sequencing data to study the population distribution of structural variants without having to know their genotypes. Furthermore, this advance allows the combined analysis of structural and nucleotide variation within the same genotype-free statistical framework, thus preventing biases introduced by genotype

  16. Chloroplast genetics of chlamydomonas. I. Allelic segregation ratios

    International Nuclear Information System (INIS)

    This paper presents allelic segregation data from a series of 16 crosses segregated for nuclear and chloroplast genes. By means of pedigree analysis, segregants of chloroplast genes. By means of pedigree analysis, segregants of chloroplast markers occurring in the zygote have been distinguished from those occurring in zoospore clones. The genes ac1, ac2, and tm1 showed little if any deviation from 1:1 either in zygotic segregation or in zoospore clones. The genes sm2, ery, and spc showed a significant excess of the allele from the mt+ parent in zygotes. However, in zoospores, mt+ excess was seen only when the allele was the mutant (resistant) form but not when it was wild type (sensitive). These results show that the extent of preferential segregation differs in zygotes and in zoospores, and that preferential segregation is influenced by map location and by allele specificity. A comparison of progeny from zygotes mated after 0, 15'', 30'', and 50'' uv irradiation of the mt+ gametes demonstrated the lack of an effect of uv upon allelic segregation ratios. In total, these results exclude the multi-copy model of chloroplast genome segregation suggested by Gillham. Boynton and Lee (1974) and support the diploid model we have previously proposed

  17. Chloroplast genetics of chlamydomonas. I. Allelic segregation ratios. [UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    Sager, R.; Ramanis, Z.

    1976-06-01

    This paper presents allelic segregation data from a series of 16 crosses segregated for nuclear and chloroplast genes. By means of pedigree analysis, segregants of chloroplast genes. By means of pedigree analysis, segregants of chloroplast markers occurring in the zygote have been distinguished from those occurring in zoospore clones. The genes ac1, ac2, and tm1 showed little if any deviation from 1:1 either in zygotic segregation or in zoospore clones. The genes sm2, ery, and spc showed a significant excess of the allele from the mt+ parent in zygotes. However, in zoospores, mt+ excess was seen only when the allele was the mutant (resistant) form but not when it was wild type (sensitive). These results show that the extent of preferential segregation differs in zygotes and in zoospores, and that preferential segregation is influenced by map location and by allele specificity. A comparison of progeny from zygotes mated after 0, 15'', 30'', and 50'' uv irradiation of the mt+ gametes demonstrated the lack of an effect of uv upon allelic segregation ratios. In total, these results exclude the multi-copy model of chloroplast genome segregation suggested by Gillham. Boynton and Lee (1974) and support the diploid model we have previously proposed.

  18. HLA-G allele and haplotype frequencies in a healthy population of Iran.

    Science.gov (United States)

    Kuroshli, Zahra; Gourabi, Hamid; Bazrgar, Masoud; Sanati, Mohammad Hossein; Bahraminejad, Elmira; Anisi, Khadije

    2014-06-01

    The human leukocyte antigen (HLA)-G molecule is expressed in cytotrophoblast cells, adult thymic epithelial cells, erythroblasts, pancreatic islets and mesenchymal stem cells. Although, HLA-G expression in allotransplanted patients is correlated with a better allograft acceptance, it is associated with an advanced grade of the tumor in cancer. In addition to the role on the immune system, HLA-G is also involved in successful pregnancy through the embryo implantation, fetal survival and the initial steps of hematopoiesis and angiogenesis. The aim of this study was determination of HLA-G allele frequencies in a healthy population of Iran. In this research, we selected 100 samples from healthy Iranian individuals and henceforth, we used polymerase chain reaction (PCR) followed by sequencing technique for exon 2, 3, 4 and intron 2 of the gene for evaluating the HLA-G alleles frequencies. Investigation of intronic (intron 2) variation is the novelty of our study. The obtained results indicated thirteen alleles of HLA-G in Iranian individuals including G*01:01:01:01, G*01:06, G*01:01:01:06, G*01:01:02, G*01:01:03, G*01:01:05, G*01:01:06, G*01:01:07, G*01:01:08, G*01:03, G*01:04:01, G*01:04:03, and G*01:04:04. According to this study, the most prevalent alleles in the Iranian population were G*01:01:01:01 (52.5%), G*01:01:02 (16%) and G*01:04:03 (14.5%) and also the lowest alleles regarding the frequency were G*01:01:01:06 (0.5%) and G*01:03 (0.5%). The results of G*01:01:01:01 and G*01:04:01 frequencies showed some similarities with the polish population. Our results were similar to the north Indian population for the frequencies of G*01:06 and G*01:01:02. PMID:24659125

  19. A strategy to discover genes that carry multi-allelic or mono-allelic risk for common diseases: A cohort allelic sums test (CAST)

    International Nuclear Information System (INIS)

    A method is described to discover if a gene carries one or more allelic mutations that confer risk for any specified common disease. The method does not depend upon genetic linkage of risk-conferring mutations to high frequency genetic markers such as single nucleotide polymorphisms. Instead, the sums of allelic mutation frequencies in case and control cohorts are determined and a statistical test is applied to discover if the difference in these sums is greater than would be expected by chance. A statistical model is presented that defines the ability of such tests to detect significant gene-disease relationships as a function of case and control cohort sizes and key confounding variables: zygosity and genicity, environmental risk factors, errors in diagnosis, limits to mutant detection, linkage of neutral and risk-conferring mutations, ethnic diversity in the general population and the expectation that among all exonic mutants in the human genome greater than 90% will be neutral with regard to any effect on disease risk. Means to test the null hypothesis for, and determine the statistical power of, each test are provided. For this 'cohort allelic sums test' or 'CAST', the statistical model and test are provided as an Excel (TM) program, CASTAT (C) at http://epidemiology.mit.edu. Based on genetics, technology and statistics, a strategy of enumerating the mutant alleles carried in the exons and splice sites of the estimated ∼25,000 human genes in case cohort samples of 10,000 persons for each of 100 common diseases is proposed and evaluated: A wide range of possible conditions of multi-allelic or mono-allelic and monogenic, multigenic or polygenic (including epistatic) risk are found to be detectable using the statistical criteria of 1 or 10 ''false positive'' gene associations per 25,000 gene-disease pair-wise trials and a statistical power of >0.8. Using estimates of the distribution of both neutral and gene-inactivating nondeleterious mutations in humans and

  20. Implication of HLA-DMA Alleles in Corsican IDDM

    Directory of Open Access Journals (Sweden)

    P. Cucchi-Mouillot

    1998-01-01

    Full Text Available The HLA-DM molecule catalyses the CLIP/antigen peptide exchange in the classical class II peptide-binding groove. As such, DM is an antigen presentation regulator and may be linked to autoimmune diseases. Using PCR derived methods, a relationship was revealed between DM gene polymorphism and IDDM, in a Corsican population. The DMA*0101 allele was observed to confer a significant predisposition to this autoimmune disease while the DMA*0102 allele protected significantly. Experiments examining polymorphism of the HLA-DRB1 gene established that these relationships are not a consequence of linkage disequilibrium with HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore be an additional tool for early IDDM diagnosis in the Corsican population.

  1. A common mutation associated with the Duarte galactosemia allele

    Energy Technology Data Exchange (ETDEWEB)

    Elsas, L.J.; Dembure, P.P.; Langley, S.; Paulk, E.M.; Hjelm, L.N.; Fridovich-Keil, J. (Emory Univ. School of Medicine, Atlanta, GA (United States))

    1994-06-01

    The human cDNA and gene for galactose-1-phosphate uridyl transferase (GALT) have been cloned and sequenced. A prevalant mutation (Q188R) is known to cause classic galactosemia (G/G). G/G galactosemia has an incidence of 1/38,886 in 1,396,766 Georgia live-born infants, but a more common variant of galactosemia, Duarte, has an unknown incidence. The proposed Duarte biochemical phenotypes of GALT are as follows: D/N, D/D, and D/G, which have [approximately]75%, 50%, and 25% of normal GALT activity, respectively. In addition, the D allele has isoforms of its enzyme that have more acidic pI than normal. Here the authors systematically determine (a) the prevalence of an A-to-G transition at base pair 2744 of exon 10 in the GALT gene, a transition that produces a codon change converting asparagine to aspartic acid at position 314 (N314D), and (b) the association of this mutation with the Duarte biochemical phenotype. The 2744G nucleotide change adds an AvaII (SinI) cut site, which was identified in PCR-amplified DNA. In 111 biochemically unphenotyped controls with no history of galactosemia, 13 N314D alleles were identified (prevalence 5.9%). In a prospective study, 40 D alleles were biochemically phenotyped, and 40 N314D alleles were found. By contrast, in 36 individuals known not to have the Duarte biochemical phenotype, no N314D alleles were found. The authors conclude that the N314D mutation is a common allele that probably causes the Duarte GALT biochemical phenotype and occurs in a predominantly Caucasian, nongalactosemic population, with a prevalence of 5.9%. 36 refs., 3 figs., 2 tabs.

  2. The inheritance of resistance alleles in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Sreeram V Ramagopalan

    2007-09-01

    Full Text Available Multiple sclerosis (MS is a complex trait in which alleles at or near the class II loci HLA-DRB1 and HLA-DQB1 contribute significantly to genetic risk. HLA-DRB1*15 and HLA-DRB1*17-bearing haplotypes and interactions at the HLA-DRB1 locus increase risk of MS but it has taken large samples to identify resistance HLA-DRB1 alleles. In this investigation of 7,093 individuals from 1,432 MS families, we have assessed the validity, mode of inheritance, associated genotypes, and the interactions of HLA-DRB1 resistance alleles. HLA-DRB1*14-, HLA-DRB1*11-, HLA-DRB1*01-, and HLA-DRB1*10-bearing haplotypes are protective overall but they appear to operate by different mechanisms. The first type of resistance allele is characterised by HLA-DRB1*14 and HLA-DRB1*11. Each shows a multiplicative mode of inheritance indicating a broadly acting suppression of risk, but a different degree of protection. In contrast, a second type is exemplified by HLA-DRB1*10 and HLA-DRB1*01. These alleles are significantly protective when they interact specifically in trans with HLA-DRB1*15-bearing haplotypes. HLA-DRB1*01 and HLA-DRB1*10 do not interact with HLA-DRB1*17, implying that several mechanisms may be operative in major histocompatibility complex-associated MS susceptibility, perhaps analogous to the resistance alleles. There are major practical implications for risk and for the exploration of mechanisms in animal models. Restriction of antigen presentation by HLA-DRB1*15 seems an improbably simple mechanism of major histocompatibility complex-associated susceptibility.

  3. Distribution of a pseudodeficiency allele among Tay-Sachs carriers

    Energy Technology Data Exchange (ETDEWEB)

    Tomczak, J.; Grebner, E.E. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Boogen, C. (Univ. of Essen Medical School (Germany))

    1993-08-01

    Recently Triggs-Raine et al. (1992) identified a new mutation in the gene coding for the [alpha]-subunit of [beta]-hexosaminidase A (hex A), the enzyme whose deficiency causes Tay-Sachs disease. This mutation, a C[sub 739]-to-T transition in exon 7, results in an altered enzyme that is active (albeit at reduced levels) in cells but that has essentially no activity in serum. This so-called pseudodeficient allele was first detected in compound heterozygotes who also carried a Tay-Sachs disease allele and therefore had no detectable hex A in their serum but who were in good health. Carriers of this apparently benign mutation are generally indistinguishable from carriers of a lethal mutation by means of routine enzyme-based screening tests, because the product of the pseudodeficient allele is not detectable in serum and has decreased activity in cells. This suggests that some individuals who have been classified as Tay-Sachs carriers are actually carriers of the pseudodeficient allele and are not at risk to have a child affected with Tay-Sachs disease. The pseudodeficient allele may also be responsible for some inconclusive diagnoses, where leukocyte values fall below the normal range but are still above the carrier range. The fact that there are now two mutant alleles (the psuedodeficient and the adult) that are indistinguishable from the lethal infantile mutations by means of enzyme assay yet that are phenotypically very different and that together may account for as much as 12% of enzyme-defined carriers on the basis of the data here suggests that DNA analysis should be part of a comprehensive screening program. It will be particularly useful to identify the mutations in couples at risk, before they undergo prenatal diagnosis. DNA analysis will also resolve some inconclusive diagnoses.

  4. Bonobos fall within the genomic variation of chimpanzees.

    Directory of Open Access Journals (Sweden)

    Anne Fischer

    Full Text Available To gain insight into the patterns of genetic variation and evolutionary relationships within and between bonobos and chimpanzees, we sequenced 150,000 base pairs of nuclear DNA divided among 15 autosomal regions as well as the complete mitochondrial genomes from 20 bonobos and 58 chimpanzees. Except for western chimpanzees, we found poor genetic separation of chimpanzees based on sample locality. In contrast, bonobos consistently cluster together but fall as a group within the variation of chimpanzees for many of the regions. Thus, while chimpanzees retain genomic variation that predates bonobo-chimpanzee speciation, extensive lineage sorting has occurred within bonobos such that much of their genome traces its ancestry back to a single common ancestor that postdates their origin as a group separate from chimpanzees.

  5. Platelet antigen allele frequencies in Australian aboriginal and Caucasian populations.

    Science.gov (United States)

    Chen, Z; Lester, S; Boettcher, B; McCluskey, J

    1997-11-01

    We have applied genotyping methods of PCR-SSOP and PCR-RFLP to three, bi-allelic platelet specific antigen systems HPA-1 (Pla), HPA-3 (Bak) and HPA-5 (Br). This combination of techniques offers flexibility for high volume or rapid typing. The phenotype and genotype frequencies of alleles from the three systems differ significantly between the Yuendumu Australian Aboriginals (Wailbri) and Australian Caucasians. The major differences are the very low frequencies of HPA-1b and HPA-3b in Yuendumu Aboriginals which are potentially relevant to platelet transfusion in patients of Australian Aboriginal descent. PMID:9423221

  6. A common allele on chromosome 9 associated with coronary heartdisease

    Energy Technology Data Exchange (ETDEWEB)

    McPherson, Ruth; Pertsemlidis, Alexander; Kavaslar, Nihan; Stewart, Alexandre; Roberts, Robert; Cox, David R.; Hinds, David; Pennachio, Len; Tybjaerg-Hansen, Anne; Folsom, Aaron R.; Boerwinkle,Eric; Hobbs, Helen H.; Cohen, Jonathan C.

    2007-03-01

    Coronary heart disease (CHD) is a major cause of death in Western countries. Here we used genome-wide association scanning to identify a 58 kb interval on chromosome 9 that was consistently associated with CHD in six independent samples. The interval contains no annotated genes and is not associated with established CHD risk factors such as plasma lipoproteins, hypertension or diabetes. Homozygotes for the risk allele comprise 20-25% of Caucasians and have a {approx}30-40% increased risk of CHD. These data indicate that the susceptibility allele acts through a novel mechanism to increase CHD risk in a large fraction of the population.

  7. Results of Expedicion Humana. I. Analysis of HLA class II (DRB1-DQA1-DPB1) alleles and DR-DQ haplotypes in nine Amerindian populations from Colombia.

    Science.gov (United States)

    Trachtenberg, E A; Keyeux, G; Bernal, J E; Rhodas, M C; Erlich, H A

    1996-09-01

    HLA class II variation was analyzed in nine Native American populations of Colombia using PCR/SSOP typing methods. Under the auspices of the Expedition Humana, approximately 30 unrelated native Colombia Indian samples each from the Tule (NW Pacific Coast), Kogui (Sierra Nevada). Ijka (Sierra Nevada), Ingano (Amazonas), Coreguaje (Amazonas), Nukak (Amazonas), Waunana (Pacific), Embera (Pacific) and Sikuani (Northeastern Plains) were collected and analyzed at the DRBI, DQA1, DQB1 and DPB1 loci. The number of different DRB1, DQA1, DQB1 and DPB1 alleles in the Colombian Indians is markedly reduced in comparison with neighboring African Colombian populations, which exhibit a very high degree of class II variability, as discussed in an accompanying paper. In the Colombian Amerindian groups, DR2 (DRB1*1602), DR4 (DRB1*0407, *0404, *0403 AND *0411), DR6 (DRB1*1402) and DR8 (DRB1*0802) comprise > 95% of all DRB1 alleles. We also found an absence of DR3 in all populations, and DR1, DR7 and DR9 allelic groups were either very rare or absent. Each Colombian Amerindian population has a predominant DRB1 allele (f = approximately 0.22-0.65) and DRB1-DQA1-DQB1 haplotype. Several novel DR-DQ haplotypes were also found. At the DPB1 locus, DPB1*0402 (f = 0.28-0.82), *1401 (f = 0.03-0.45), and *3501 (f = 0.03-0.27), were the three most prevalent alleles, each population maintaining one of these three alleles as the predominant (f > 0.26) DPB1 allele. The reduction of diversity for the HLA class II alleles in the Colombian Indians is suggestive of a population bottleneck during the colonization of the Americans, with little to no subsequent admixture with neighboring African Colombian populations in the last approximately 300 years. PMID:8896175

  8. A WIDE DISTRIBUTION OF A NEW VRN-B1c ALLELE OF WHEAT TRITICUM AESTIVUM L. IN RUSSIA, UKRAINE AND ADJACENT REGIONS: A LINK WITH THE HEADING TIME AND ADAPTIVE POTENTIAL

    Directory of Open Access Journals (Sweden)

    Shcherban A.

    2012-08-01

    Full Text Available The adaptation of common wheat (T. aestivum L. to diverse environmental conditions is greatly under the control of genes involved in determination of vernalization response (Vrn-1 genes. It was found that the variation in common wheat heading time is affected not only by combination of Vrn-1 homoeoalleles but also by multiple alleles at a separate Vrn-1 locus. Previously, we described the Vrn-B1c allele from T.aestivum cv. 'Saratovskaya 29' and found significant differences in the structure of the first (1st intron of this allele when compared to another highly abundant Vrn-B1a allele, specifically, the deletion of 0.8 kb coupled with the duplication of 0.4 kb. We suggested that the changes in the intron 1 of Vrn-B1c allele caused earlier ear emergence in the near-isogenic line and cultivars, carrying this allele. In this study we investigate the distribution of the Vrn-B1c allele in a wide set of spring wheat cultivars from Russia, Ukraine and adjacent regions. The analysis revealed that 40% of Russian and 53% of Ukranian spring wheat cultivars contain the Vrn-B1c allele. The high distribution of the Vrn-B1c allele can be explained by a frequent using of 'Saratovskaya 29' in the breeding process inside the studied area. From the other hand, the predominance of the Vrn-B1c allele among cultivars cultivated in West Siberia and Kazakhstan may be due to the selective advantage of this allele for the region where there is a high risk of early fall frosts.

  9. Allelic Variation within Single Podded Gene Characterized by STMS Marker in Chickpea

    Institute of Scientific and Technical Information of China (English)

    H. Ali; M.A. Haq; N. Iqbal; A. Hameed; T.M. Shah; B.M. Atta

    2007-01-01

    @@ Chickpea (Cicer arietinum L.), is an important grain legume crop throughout the world especially in developing countries. However the average yield worldwide is considered to be lower than its potential yield (Singh et al.,1994).

  10. Comparative systems biology reveals allelic variation modulating tocochromanol profiles in barley

    Science.gov (United States)

    Background: Tocochromanols are recognized for beneficial effects in plant stress response, seed storage longevity, and nutritional content. Efforts to elucidate specific bioactive forms and develop new crops with beneficial amounts and ratios have been hindered due to costly analytical methods. Obje...

  11. Allelic variation in CRHR1 predisposes to panic disorder : evidence for biased fear processing

    OpenAIRE

    Weber, Heike; Richter, Jan; Straube, Benjamin; Lueken, Ulrike; Domschke, Katharina; Schartner, Christoph; Klauke, Benedikt; Baumann, Christian; Pané-Farré, Christiane; Jacob, Christian P; Scholz, Claus-Jürgen; Zwanger, Peter; Lang, Thomas; Fehm, Lydia; Jansen, Andreas

    2015-01-01

    This work is part of the German multicenter trial ‘Mechanisms of Action in CBT (MAC)’. The MAC study is funded by the German Federal Ministry of Education and Research (BMBF; project no. 01GV0615) as part of the BMBF Psychotherapy Research Funding Initiative. The study was further supported by the DFG (Grant RE1632/5-1 and KFO 125 to AR; SFB TRR 58 Z02 to JD, PP and AR; C02 to JD and KD; DE357/4-1 to JD, AR, JR and AH; RTG 1256 to AR, JD and PP; IZKF-Würzburg Z-6 to HW).

  12. Is black coat color in wolves of Iran an evidence of admixed ancestry with dogs?

    Science.gov (United States)

    Khosravi, Rasoul; Asadi Aghbolaghi, Marzieh; Rezaei, Hamid Reza; Nourani, Elham; Kaboli, Mohammad

    2015-02-01

    Melanism is not considered a typical characteristic in wolves of Iran and dark wolves are believed to have originated from crossbreeding with dogs. Such hybrid individuals can be identified with the combined use of genetic and morphological markers. We analyzed two black wolves using a 544 base pairs (bp) fragment of the mtDNA control region and 15 microsatellite loci in comparison with 28 dogs, 28 wolves, and four known hybrids. The artificial neural networks (ANNs) method was applied to microsatellite data to separate genetically differentiated samples of wolves, dogs, and hybrids, and to determine the correct class for the black specimens. Individual assignments based on ANNs showed that black samples were genetically closer to wolves. Also, in the neighbor-joining network of mtDNA haplotypes, wolves and dogs were separated, with the dark specimens located in the wolf branch as two separate haplotypes. Furthermore, we compared 20 craniometrical characters of the two black individuals with 14 other wolves. The results showed that craniometrical measures of the two black wolves fall within the range of wolf skulls. We found no trace of recent hybridization with free-ranging dogs in the two black wolves. Dark coat color might be the result of a natural combination of alleles in the coat-color-determining gene, mutation in the K locus due to past hybridization with free-ranging dogs, or the effect of ecological factors and adaption to habitat conditions. PMID:25085671

  13. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

    DEFF Research Database (Denmark)

    Paternoster, Lavinia; Standl, Marie; Waage, Johannes;

    2015-01-01

    Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases...

  14. Multifragment alleles in DNA fingerprints of the parrot, Amazona ventralis

    Science.gov (United States)

    Brock, M.K.; White, B.N.

    1991-01-01

    Human DNA probes that identify variable numbers of tandem repeat loci are being used to generate DNA fingerprints in many animal and plant species. In most species the majority of the sc rable autoradiographic bands of the DNA fingerprint represent alleles from numerous unlinked loci. This study was initiated to use DNA fingerprints to determine the amount of band-sharing among captive Hispaniolan parrots (Amazona ventralis) with known genetic relationships. This would form the data base to examine DNA fingerprints of the closely related and endangered Puerto Rican parrot (A. vittata) and to estimate the degree of inbreeding in the relic population. We found by segregation analysis of the bands scored in the DNA fingerprints of the Hispaniolan parrots that there may be as few as two to five loci identified by the human 33.15 probe. Furthermore, at one locus we identified seven alleles, one of which is represented by as many as 19 cosegregating bands. It is unknown how common multiband alleles might be in natural populations, and their existence will cause problems in the assessment of relatedness by band-sharing analysis. We believe, therefore, that a pedigree analysis should be included in all DNA fingerprinting studies, where possible, in order to estimate the number of loci identified by a minisatellite DNA probe and to examine the nature of their alleles.

  15. Distribution of forensic marker allelic frequencies in Pernambuco, Northestern Brazil.

    Science.gov (United States)

    Santos, S M; Souza, C A; Rabelo, K C N; Souza, P R E; Moura, R R; Oliveira, T C; Crovella, S

    2015-01-01

    Pernambuco is one of the 27 federal units of Brazil, ranking seventh in the number of inhabitants. We examined the allele frequencies of 13 short tandem repeat loci (CFS1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, TH01, vWA, and TPOX), the minimum recommended by the Federal Bureau of Investigation and commonly used in forensic genetics laboratories in Brazil, in a sample of 609 unrelated individuals from all geographic regions of Pernambuco. The allele frequencies ranged from 5 to 47.2%. No significant differences for any loci analyzed were observed compared with other publications in other various regions of Brazil. Most of the markers observed were in Hardy-Weinberg equilibrium. The occurrence of the allele 47.2 (locus FGA) and alleles 35.1 and 39 (locus D21S11), also described in a single study of the Brazilian population, was observed. The other forensic parameters analyzed (matching probability, power of discrimination, polymorphic information content, paternity exclusion, complement factor I, observed heterozygosity, expected heterozygosity) indicated that the studied markers are very informative for human forensic identification purposes in the Pernambuco population. PMID:25966202

  16. Disease-Causing Allele-Specific Silencing by RNA Interference

    Directory of Open Access Journals (Sweden)

    Hirohiko Hohjoh

    2013-04-01

    Full Text Available Small double-stranded RNAs (dsRNAs of approximately 21-nucleotides in size, referred to as small interfering RNA (siRNA duplexes, can induce sequence-specific posttranscriptional gene silencing, or RNA interference (RNAi. Since chemically synthesized siRNA duplexes were found to induce RNAi in mammalian cells, RNAi has become a powerful reverse genetic tool for suppressing the expression of a gene of interest in mammals, including human, and its application has been expanding to various fields. Recent studies further suggest that synthetic siRNA duplexes have the potential for specifically inhibiting the expression of an allele of interest without suppressing the expression of other alleles, i.e., siRNA duplexes likely confer allele-specific silencing. Such gene silencing by RNAi is an advanced technique with very promising applications. In this review, I would like to discuss the potential utility of allele-specific silencing by RNAi as a therapeutic method for dominantly inherited diseases, and describe possible improvements in siRNA duplexes for enhancing their efficacy.

  17. Short mucin 6 alleles are associated with H pylori infection

    Institute of Scientific and Technical Information of China (English)

    Thai V Nguyen; Marcel JR Janssen; Paulien Gritters; René HM te Morsche; Joost PH Drenth; Henri van Asten; Robert JF Laheij; Jan BMJ Jansen

    2006-01-01

    AIM: To investigate the relationship between mucin 6(MUC6) VNTR length and H pylori infection.METHODS: Blood samples were collected from patients visiting the Can Tho General Hospital for upper gastrointestinal endoscopy. DNA was isolated from whole blood, the repeated section was cut out using a restriction enzyme (Pvu Ⅱ) and the length of the allele fragments was determined by Southern blotting. H pylori infection was diagnosed by 14C urea breath test. For analysis, MUC6 allele fragment length was dichotomized as being either long (> 13.5 kbp) or short (≤ 13.5 kbp)and patients were classified according to genotype [long-long (LL), long-short (LS), short-short (SS)].RESULTS: 160 patients were studied (mean age 43years, 36% were males, 58% H pylori positive). MUC6Pvu Ⅱ-restricted allele fragment lengths ranged from 7 to 19 kbp. Of the patients with the LL, LS, SS MUC6genotype, 43% (24/56), 57% (25/58) and 76% (11/46)were infected with H pylori, respectively (P = 0.003).CONCLUSION: Short MUC6 alleles are associated with H pylori infection.

  18. Impact of autoimmune risk alleles on the immune system

    OpenAIRE

    Ray, John P.; Hacohen, Nir

    2015-01-01

    Genetic analyses of autoimmune diseases have revealed hundreds of disease-associated DNA variants, but the identity and function of the causal variants are understudied and warrant deeper mechanistic studies. Here, we highlight methods for deciphering how alleles that are associated with autoimmune disease alter the human immune system, and suggest strategies for future autoimmune genetic research.

  19. On universal common ancestry, sequence similarity, and phylogenetic structure: the sins of P-values and the virtues of Bayesian evidence

    Directory of Open Access Journals (Sweden)

    Theobald Douglas L

    2011-11-01

    Full Text Available Abstract Background The universal common ancestry (UCA of all known life is a fundamental component of modern evolutionary theory, supported by a wide range of qualitative molecular evidence. Nevertheless, recently both the status and nature of UCA has been questioned. In earlier work I presented a formal, quantitative test of UCA in which model selection criteria overwhelmingly choose common ancestry over independent ancestry, based on a dataset of universally conserved proteins. These model-based tests are founded in likelihoodist and Bayesian probability theory, in opposition to classical frequentist null hypothesis tests such as Karlin-Altschul E-values for sequence similarity. In a recent comment, Koonin and Wolf (K&W claim that the model preference for UCA is "a trivial consequence of significant sequence similarity". They support this claim with a computational simulation, derived from universally conserved proteins, which produces similar sequences lacking phylogenetic structure. The model selection tests prefer common ancestry for this artificial data set. Results For the real universal protein sequences, hierarchical phylogenetic structure (induced by genealogical history is the overriding reason for why the tests choose UCA; sequence similarity is a relatively minor factor. First, for cases of conflicting phylogenetic structure, the tests choose independent ancestry even with highly similar sequences. Second, certain models, like star trees and K&W's profile model (corresponding to their simulation, readily explain sequence similarity yet lack phylogenetic structure. However, these are extremely poor models for the real proteins, even worse than independent ancestry models, though they explain K&W's artificial data well. Finally, K&W's simulation is an implementation of a well-known phylogenetic model, and it produces sequences that mimic homologous proteins. Therefore the model selection tests work appropriately with the artificial

  20. Functional alleles of the flowering time regulator FRIGIDA in the Brassica oleracea genome

    Directory of Open Access Journals (Sweden)

    Irwin Judith A

    2012-02-01

    Full Text Available Abstract Background Plants adopt different reproductive strategies as an adaptation to growth in a range of climates. In Arabidopsis thaliana FRIGIDA (FRI confers a vernalization requirement and thus winter annual habit by increasing the expression of the MADS box transcriptional repressor FLOWERING LOCUS C (FLC. Variation at FRI plays a major role in A. thaliana life history strategy, as independent loss-of-function alleles that result in a rapid-cycling habit in different accessions, appear to have evolved many times. The aim of this study was to identify and characterize orthologues of FRI in Brassica oleracea. Results We describe the characterization of FRI from Brassica oleracea and identify the two B. oleracea FRI orthologues (BolC.FRI.a and BolC.FRI.b. These show extensive amino acid conservation in the central and C-terminal regions to FRI from other Brassicaceae, including A. thaliana, but have a diverged N-terminus. The genes map to two of the three regions of B. oleracea chromosomes syntenic to part of A. thaliana chromosome 5 suggesting that one of the FRI copies has been lost since the ancient triplication event that formed the B. oleracea genome. This genomic position is not syntenic with FRI in A. thaliana and comparative analysis revealed a recombination event within the A. thaliana FRI promoter. This relocated A. thaliana FRI to chromosome 4, very close to the nucleolar organizer region, leaving a fragment of FRI in the syntenic location on A. thaliana chromosome 5. Our data show this rearrangement occurred after the divergence from A. lyrata. We explored the allelic variation at BolC.FRI.a within cultivated B. oleracea germplasm and identified two major alleles, which appear equally functional both to each other and A. thaliana FRI, when expressed as fusions in A. thaliana. Conclusions We identify the two Brassica oleracea FRI genes, one of which we show through A. thaliana complementation experiments is functional, and show

  1. ALLELE DISTRIBUTION OF FIVE X-CHROMOSOME SHORT TANDEM REPEAT LOCI IN EWENKE POPULATION OF NORTH CHINA

    Institute of Scientific and Technical Information of China (English)

    Shan-zhi Gu; Teng Chen; Qing-bo Liu; Bing Yu; Sheng-bin Li

    2005-01-01

    Objective To study the allele genetic polymorphism of five short tandem repeat (STR) loci on X-chromosome in Ewenke population of north China and to provide basic data for forensic identification.Methods Genomic DNA was extracted from EDTA-whole blood of Ewenke population by Chelex-100. The DNA samples were amplified by PCR and were analyzed by polyacrylamide gel electrophoresis and silver staining. The sequence length variations of DXS6799, DXS8378, DXS101, HPRTB, and DXS6789 loci on X-chromosome in 98unrelated Ewenke individuals were investigated.Results All five loci analyzed showed high polymorphism and genetic stability. The data of the five X-chromosome STR loci in Ewenke ethnic group of China was in accordance with Hardy-Weinberg equilibrium by Chi-square test.Conclusion Allele polymorphism of five X-chromosome STR loci can be used as a genetic marker for forensic identification and population genetic research.

  2. On the Bayesness, minimaxity and admissibility of point estimators of allelic frequencies.

    Science.gov (United States)

    Martínez, Carlos Alberto; Khare, Kshitij; Elzo, Mauricio A

    2015-10-21

    In this paper, decision theory was used to derive Bayes and minimax decision rules to estimate allelic frequencies and to explore their admissibility. Decision rules with uniformly smallest risk usually do not exist and one approach to solve this problem is to use the Bayes principle and the minimax principle to find decision rules satisfying some general optimality criterion based on their risk functions. Two cases were considered, the simpler case of biallelic loci and the more complex case of multiallelic loci. For each locus, the sampling model was a multinomial distribution and the prior was a Beta (biallelic case) or a Dirichlet (multiallelic case) distribution. Three loss functions were considered: squared error loss (SEL), Kulback-Leibler loss (KLL) and quadratic error loss (QEL). Bayes estimators were derived under these three loss functions and were subsequently used to find minimax estimators using results from decision theory. The Bayes estimators obtained from SEL and KLL turned out to be the same. Under certain conditions, the Bayes estimator derived from QEL led to an admissible minimax estimator (which was also equal to the maximum likelihood estimator). The SEL also allowed finding admissible minimax estimators. Some estimators had uniformly smaller variance than the MLE and under suitable conditions the remaining estimators also satisfied this property. In addition to their statistical properties, the estimators derived here allow variation in allelic frequencies, which is closer to the reality of finite populations exposed to evolutionary forces. PMID:26271891

  3. Minor Allele Frequency Changes the Nature of Genotype by Environment Interactions.

    Science.gov (United States)

    Verhulst, Brad; Neale, Michael C

    2016-09-01

    In the classical twin study, phenotypic variation is often partitioned into additive genetic (A), common (C) and specific environment (E) components. From genetical theory, the outcome of genotype by environment interaction is expected to inflate A when the interacting factor is shared (i.e., C) between the members of a twin pair. We show that estimates of both A and C can be inflated. When the shared interacting factor changes the size of the difference between homozygotes' means, the expected sibling or DZ twin correlation is .5 if and only if the minor allele frequency (MAF) is .5; otherwise the expected DZ correlation is greater than this value, consistent (and confounded) with some additional effect of C. This result is considered in the light of the distribution of minor allele frequencies for polygenic traits. Also discussed is whether such interactions take place at the locus level or affect an aggregated biological structure or system. Interactions with structures or endophenotypes that result from the aggregated effects of many loci will generally emerge as part of the A estimate. PMID:27105628

  4. Determining the effects and challenges of incorporating genetic testing into primary care management of hypertensive patients with African ancestry.

    Science.gov (United States)

    Horowitz, C R; Abul-Husn, N S; Ellis, S; Ramos, M A; Negron, R; Suprun, M; Zinberg, R E; Sabin, T; Hauser, D; Calman, N; Bagiella, E; Bottinger, E P

    2016-03-01

    People of African ancestry (Blacks) have increased risk of kidney failure due to numerous socioeconomic, environmental, and clinical factors. Two variants in the APOL1 gene are now thought to account for much of the racial disparity associated with hypertensive kidney failure in Blacks. However, this knowledge has not been translated into clinical care to help improve patient outcomes and address disparities. GUARDD is a randomized trial to evaluate the effects and challenges of incorporating genetic risk information into primary care. Hypertensive, non-diabetic, adults with self-reported African ancestry, without kidney dysfunction, are recruited from diverse clinical settings and randomized to undergo APOL1 genetic testing at baseline (intervention) or at one year (waitlist control). Providers are educated about genomics and APOL1. Guided by a genetic counselor, trained staff return APOL1 results to patients and provide low-literacy educational materials. Real-time clinical decision support tools alert clinicians of their patients' APOL1 results and associated risk status at the point of care. Our academic-community-clinical partnership designed a study to generate information about the impact of genetic risk information on patient care (blood pressure and renal surveillance) and on patient and provider knowledge, attitudes, beliefs, and behaviors. GUARDD will help establish the effective implementation of APOL1 risk-informed management of hypertensive patients at high risk of CKD, and will provide a robust framework for future endeavors to implement genomic medicine in diverse clinical practices. It will also add to the important dialog about factors that contribute to and may help eliminate racial disparities in kidney disease. PMID:26747051

  5. The COMT Val158 allele is associated with impaired delayed-match-to-sample performance in ADHD

    Directory of Open Access Journals (Sweden)

    Matthews Natasha

    2012-05-01

    Full Text Available Abstract Background This study explored the association between three measures of working memory ability and genetic variation in a range of catecholamine genes in a sample of children with ADHD. Methods One hundred and eighteen children with ADHD performed three working memory measures taken from the CANTAB battery (Spatial Span, Delayed-match-to-sample, and Spatial Working Memory. Associations between performance on working memory measures and allelic variation in catecholamine genes (including those for the noradrenaline transporter [NET1], the dopamine D4 and D2 receptor genes [DRD4; DRD2], the gene encoding dopamine beta hydroxylase [DBH] and catechol-O-methyl transferase [COMT] were investigated using regression models that controlled for age, IQ, gender and medication status on the day of test. Results Significant associations were found between performance on the delayed-match-to-sample task and COMT genotype. More specifically, val/val homozygotes produced significantly more errors than did children who carried a least one met allele. There were no further associations between allelic variants and performance across the other working memory tasks. Conclusions The working memory measures employed in the present study differed in the degree to which accurate task performance depended upon either the dynamic updating and/or manipulation of items in working memory, as in the spatial span and spatial working memory tasks, or upon the stable maintenance of representations, as in the delay-match–to-sample task. The results are interpreted as evidence of a relationship between tonic dopamine levels associated with the met COMT allele and the maintenance of stable working memory representations required to perform the delayed-match-to-sample-task.

  6. Allelic divergence and cultivar-specific SSR alleles revealed by capillary electrophoresis using fluorescence-labeled SSR markers in sugarcane

    Science.gov (United States)

    Though sugarcane cultivars (Saccharum spp. hybrids) are complex aneu-polyploid hybrids, genetic evaluation and tracking of clone- or cultivar-specific alleles become possible due to capillary electrophoregrams (CE) using fluorescence-labeled SSR primer pairs. Twenty-four sugarcane cultivars, 12 each...

  7. KIR2DL2/2DL3-E35 alleles are functionally stronger than -Q35 alleles

    Science.gov (United States)

    Bari, Rafijul; Thapa, Rajoo; Bao, Ju; Li, Ying; Zheng, Jie; Leung, Wing

    2016-03-01

    KIR2DL2 and KIR2DL3 segregate as alleles of a single locus in the centromeric motif of the killer cell immunoglobulin-like receptor (KIR) gene family. Although KIR2DL2/L3 polymorphism is known to be associated with many human diseases and is an important factor for donor selection in allogeneic hematopoietic stem cell transplantation, the molecular determinant of functional diversity among various alleles is unclear. In this study we found that KIR2DL2/L3 with glutamic acid at position 35 (E35) are functionally stronger than those with glutamine at the same position (Q35). Cytotoxicity assay showed that NK cells from HLA-C1 positive donors with KIR2DL2/L3-E35 could kill more target cells lacking their ligands than NK cells with the weaker -Q35 alleles, indicating better licensing of KIR2DL2/L3+ NK cells with the stronger alleles. Molecular modeling analysis reveals that the glutamic acid, which is negatively charged, interacts with positively charged histidine located at position 55, thereby stabilizing KIR2DL2/L3 dimer and reducing entropy loss when KIR2DL2/3 binds to HLA-C ligand. The results of this study will be important for future studies of KIR2DL2/L3-associated diseases as well as for donor selection in allogeneic stem cell transplantation.

  8. Mannose-binding lectin variant alleles and HLA-DR4 alleles are associated with giant cell arteritis

    DEFF Research Database (Denmark)

    Jacobsen, Soren; Baslund, Bo; Madsen, Hans Ole;

    2002-01-01

    To determine whether variant alleles of the mannose-binding lectin (MBL) gene causing low serum concentrations of MBL and/or polymorphisms of HLA-DRB1 are associated with increased susceptibility to polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) or particular clinical phenotypes of PMR/GCA....

  9. Functional and genetic analysis in type 2 diabetes of Liver X receptor alleles – a cohort study

    Directory of Open Access Journals (Sweden)

    Gustafsson Jan-Åke

    2009-03-01

    Full Text Available Abstract Background Liver X receptor alpha (LXRA and beta (LXRB regulate glucose and lipid homeostasis in model systems but their importance in human physiology is poorly understood. This project aimed to determine whether common genetic variations in LXRA and LXRB associate with type 2 diabetes (T2D and quantitative measures of glucose homeostasis, and, if so, reveal the underlying mechanisms. Methods Eight common single nucleotide polymorphisms in LXRA and LXRB were analyzed for association with T2D in one French cohort (N = 988 cases and 941 controls, and for association with quantitative measures reflecting glucose homeostasis in two non-diabetic population-based samples comprising N = 697 and N = 1344 adults. Investigated quantitative phenotypes included fasting plasma glucose, serum insulin, and HOMAIR as measure of overall insulin resistance. An oral glucose tolerance test was performed in N = 1344 of adults. The two alleles of the proximal LXRB promoter, differing only at the SNP rs17373080, were cloned into reporter vectors and transiently transfected, whereupon allele-specific luciferase activity was measured. rs17373080 overlapped, according to in silico analysis, with a binding site for Nuclear factor 1 (NF1. Promoter alleles were tested for interaction with NF1 using direct DNA binding and transactivation assays. Results Genotypes at two LXRB promoter SNPs, rs35463555 and rs17373080, associated nominally with T2D (P values 0.047 and 0.026. No LXRA or LXRB SNP associated with quantitative measures reflecting glucose homeostasis. The rs17373080 C allele displayed higher basal transcription activity (P value LXRB gene promoter, but there was no difference between promoter alleles in NF1 induced transactivation activity. Conclusion Variations in the LXRB gene promoter may be part of the aetiology of T2D. However, the association between LXRB rs35463555 and rs17373080, and T2D are preliminary and needs to be investigated in additional

  10. Genomic reticulation indicates mixed ancestry in Southern-Hemisphere #Mytilus$ spp. mussels

    OpenAIRE

    Borsa, Philippe; Daguin, Claire; Bierne, Nicolas

    2007-01-01

    Previous surveys of allozyme variation in smooth-shell Mytilus spp. mussels have reported the presence in the Southern Hemisphere of both Mytilus edulis and Mytilus galloprovincialis mussels. In the present study, nuclear DNA markers mac-1 and Glu-5'/Glu-3', both diagnostic for Northern-Hemisphere M. edulis and M. galloprovincialis, were used to further characterize the nuclear genomes of M. edulis from Kerguelen and M. galloprovincialis from Tasmania. Genomic reticulation was observed, with ...

  11. Floral volatile alleles can contribute to pollinator-mediated reproductive isolation in monkeyflowers (Mimulus).

    Science.gov (United States)

    Byers, Kelsey J R P; Vela, James P; Peng, Foen; Riffell, Jeffrey A; Bradshaw, Harvey D

    2014-12-01

    Pollinator-mediated reproductive isolation is a major factor in driving the diversification of flowering plants. Studies of floral traits involved in reproductive isolation have focused nearly exclusively on visual signals, such as flower color. The role of less obvious signals, such as floral scent, has been studied only recently. In particular, the genetics of floral volatiles involved in mediating differential pollinator visitation remains unknown. The bumblebee-pollinated Mimulus lewisii and hummingbird-pollinated Mimulus cardinalis are a model system for studying reproductive isolation via pollinator preference. We have shown that these two species differ in three floral terpenoid volatiles - d-limonene, β-myrcene, and E-β-ocimene - that are attractive to bumblebee pollinators. By genetic mapping and in vitro analysis of enzyme activity we demonstrate that these interspecific differences are consistent with allelic variation at two loci, LIMONENE-MYRCENE SYNTHASE (LMS) and OCIMENE SYNTHASE (OS). Mimulus lewisii LMS (MlLMS) and OS (MlOS) are expressed most strongly in floral tissue in the last stages of floral development. Mimulus cardinalis LMS (McLMS) is weakly expressed and has a nonsense mutation in exon 3. Mimulus cardinalis OS (McOS) is expressed similarly to MlOS, but the encoded McOS enzyme produces no E-β-ocimene. Recapitulating the M. cardinalis phenotype by reducing the expression of MlLMS by RNA interference in transgenic M. lewisii produces no behavioral difference in pollinating bumblebees; however, reducing MlOS expression produces a 6% decrease in visitation. Allelic variation at the OCIMENE SYNTHASE locus is likely to contribute to differential pollinator visitation, and thus promote reproductive isolation between M. lewisii and M. cardinalis. OCIMENE SYNTHASE joins a growing list of 'speciation genes' ('barrier genes') in flowering plants. PMID:25319242

  12. Clinical and pharmacogenomic implications of genetic variation in a Southern Ethiopian population.

    Science.gov (United States)

    Tekola-Ayele, F; Adeyemo, A; Aseffa, A; Hailu, E; Finan, C; Davey, G; Rotimi, C N; Newport, M J

    2015-02-01

    Africa is home to genetically diverse human populations. We compared the genetic structure of the Wolaita ethnic population from Southern Ethiopia (WETH, n=120) with HapMap populations using genome-wide variants. We investigated allele frequencies of 443 clinically and pharmacogenomically relevant genetic variants in WETH compared with HapMap populations. We found that WETH were genetically most similar to the Kenya Maasai and least similar to the Japanese in HapMap. Variant alleles associated with increased risk of adverse reactions to drugs used for treating tuberculosis (rs1799929 and rs1495741 in NAT2), thromboembolism (rs7294, rs9923231 and rs9934438 in VKORC1), and HIV/AIDS and solid tumors (rs2242046 in SLC28A1) had significantly higher frequencies in WETH compared with African ancestry HapMap populations. Our results illustrate that clinically relevant pharmacogenomic loci display allele frequency differences among African populations. We conclude that drug dosage guidelines for important global health diseases should be validated in genetically diverse African populations. PMID:25069476

  13. Early allelic selection in maize as revealed by ancient DNA.

    Science.gov (United States)

    Jaenicke-Després, Viviane; Buckler, Ed S; Smith, Bruce D; Gilbert, M Thomas P; Cooper, Alan; Doebley, John; Pääbo, Svante

    2003-11-14

    Maize was domesticated from teosinte, a wild grass, by approximately 6300 years ago in Mexico. After initial domestication, early farmers continued to select for advantageous morphological and biochemical traits in this important crop. However, the timing and sequence of character selection are, thus far, known only for morphological features discernible in corn cobs. We have analyzed three genes involved in the control of plant architecture, storage protein synthesis, and starch production from archaeological maize samples from Mexico and the southwestern United States. The results reveal that the alleles typical of contemporary maize were present in Mexican maize by 4400 years ago. However, as recently as 2000 years ago, allelic selection at one of the genes may not yet have been complete. PMID:14615538

  14. Recurrent BRCA1 and BRCA2 mutations in breast cancer patients of African ancestry.

    Science.gov (United States)

    Zhang, Jing; Fackenthal, James D; Zheng, Yonglan; Huo, Dezheng; Hou, Ningqi; Niu, Qun; Zvosec, Cecilia; Ogundiran, Temidayo O; Hennis, Anselm J; Leske, Maria Cristina; Nemesure, Barbara; Wu, Suh-Yuh; Olopade, Olufunmilayo I

    2012-07-01

    Recurrent mutations constituted nearly three quarters of all BRCA1 mutations and almost half of all BRCA2 mutations identified in the first cohort of the Nigerian Breast Cancer Study. To further characterize breast/ovarian cancer risks associated with BRCA1/BRCA2 mutations in the African diaspora, we genotyped recurrent mutations among Nigerian, African American, and Barbadian breast cancer patients. A replication cohort of 356 Nigerian breast cancer patients was genotyped for 12 recurrent BRCA1/2 mutant alleles (Y101X, 1742insG, 4241delTG, M1775R, 4359insC, C64Y, 1623delTTAAA, Q1090X, and 943ins10 from BRCA1, and 1538delAAGA, 2630del11, and 9045delGAAA from BRCA2) by means of SNaPshot followed by direct sequencing or by direct sequencing alone. In addition, 260 African Americans and 118 Barbadians were genotyped for six of the recurrent BRCA1 mutations by SNaPshot assay. Of all the BRCA1/2 recurrent mutations we identified in the first cohort, six were identified in 11 patients in the replication study. These mutation carriers constitute 3.1 % [95 % Confidence Interval (CI) 1.6-5.5 %] of the replication cohort. By comparison, 6.9 % (95 % CI 4.7-9.7 %) of the discovery cohort carried BRCA1/2 recurrent mutations. For the subset of recurrent mutations we tested in breast cancer cases from Barbados or the United States, only two 943ins10 carriers were identified in African Americans. Nigerian breast cancer patients from Ibadan carry a broad and unique spectrum of BRCA1/2 mutations. Our data suggest that BRCA1/2 mutation testing limited to recurrent mutations is not sufficient to understand the BRCA1/2-associated breast cancer risk in African populations in the diaspora. As the cost of Sanger sequencing is considerably reduced, deploying innovative technologies such as high throughput DNA sequencing of BRCA1/2 and other cancer susceptibility genes will be essential for identifying high-risk individuals and families to reduce the burden of aggressive early onset breast

  15. Allele-selective inhibition of trinucleotide repeat genes

    OpenAIRE

    Matsui, Masayuki; Corey, David R.

    2012-01-01

    Expanded trinucleotide repeats cause Huntington’s disease (HD) and many other neurodegenerative disorders. There are no cures for these devastating illnesses and treatments are urgently needed. Each trinucleotide repeat disorder is the result of the mutation of just one gene, and agents that block expression of the mutant gene offer a promising option for treatment. Therapies that block expression of both mutant and wild-type alleles can have adverse effects, challenging researchers to develo...

  16. Multiplex allele-specific target amplification based on PCR suppression

    OpenAIRE

    Broude, Natalia E.; Zhang, Lingang; Woodward, Karen; Englert, David; Cantor, Charles R.

    2001-01-01

    We have developed a strategy for multiplex PCR based on PCR suppression. PCR suppression allows DNA target amplification with only one sequence-specific primer per target and a second primer that is common for all targets. Therefore, an n-plex PCR would require only n + 1 primers. We have demonstrated uniform, efficient amplification of targeted sequences in 14-plex PCR. The high specificity of suppression PCR also provides multiplexed amplification with allele specifi...

  17. Effect of wheat puroindoline alleles on functional properties of starch

    OpenAIRE

    Brites, Carla Moita; Santos, Carla Alexandra Lourenço; Bagulho, Ana Sofia; Beirão-da-Costa, Maria Luisa

    2008-01-01

    Puroindoline a and b (Pina, Pinb) form the molecular basis of bread wheat grain hardness. Varieties with a softer endosperm and a wild genotype, in which both Pina and Pinb were present, seemed to produce less damaged starch Xour than hard varieties, where Pin mutations occurred and changed the starch rheological properties. The functional property of starch samples extracted from wheat varieties with diVerent Pin alleles was evaluated. Starch morphology was characteri...

  18. Allelic diversity of the population of Phytophthora infestans in China

    OpenAIRE

    Li, Y; Huang, S.; Lee; Kessel, G.J.T.; Jacobsen, E.; Zhang, R.; Jin, G.; Lan, C.; Zhao, Z.; Kamoun, S

    2009-01-01

    Introduction of resistance genes from wild Solanum species into potato cultivars is considered the most promising and environmentally safe approach to achieve late blight resistance. An R-gene stacking breeding program using cisgenesis is planning to trial its products in China. To adapt this approach to local conditions, we propose to assess the allelic diversity of known avirulent genes of P. infestans from the intended introduction regions of the GM-potatoes in China. So far, we have a lar...

  19. Allele-Specific DNA Methylation Detection by Pyrosequencing®

    DEFF Research Database (Denmark)

    Sommer Kristensen, Lasse; Johansen, Jens Vilstrup; Grønbæk, Kirsten

    2015-01-01

    DNA methylation is an epigenetic modification that plays important roles in healthy as well as diseased cells, by influencing the transcription of genes. In spite the fact that human somatic cells are diploid, most of the currently available methods for the study of DNA methylation do not provide......-effective protocol for allele-specific DNA methylation detection based on Pyrosequencing(®) of methylation-specific PCR (MSP) products including a single nucleotide polymorphism (SNP) within the amplicon....

  20. Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots

    Czech Academy of Sciences Publication Activity Database

    Baker, C.L.; Petkova, P.; Walker, M.; Flachs, Petr; Mihola, Ondřej; Trachtulec, Zdeněk; Petkov, P.M.; Paigen, K.

    2015-01-01

    Roč. 11, č. 9 (2015), e1005512-e1005512. ISSN 1553-7390 R&D Projects: GA ČR GAP305/10/1931; GA ČR(CZ) GA14-20728S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : recombination * PRDM9 * allelic competition Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.528, year: 2014

  1. Gene identification and allele-specific marker development for two allelic low phytic acid mutations in rice (Oryza sativa L.)

    International Nuclear Information System (INIS)

    Phytic acid (PA, myo-inositol 1,2,3,4,5,6-hexakisphosphate) is an important anti-nutritional component in cereal and legume grains. PA forms of phosphorus (P) and its salts with micronutrient cations, such as iron and zinc, are indigestible in humans and non-ruminant animals, and hence could affect food/feed nutritional value and cause P pollution of ground water from animal waste. We previously developed a set of low phytic acid (LPA) rice mutants with the aim to increase their nutritional quality. Among them, one line, i.e., Os-lpa -XQZ-1 (hereafter lpa 1-2), was identified to have a mutation allelic to the KBNT lpa 1-1 mutation (hereafter lpa 1-1), which was already delimited to a 47-kb region on chromosome 2. In this study, we searched the candidate gene for these two allelic LPA mutations using T-DNA insertion mutants, mutation detection by CEL I facilitated mismatch cleavage, and gene sequencing. The TIGR locus LOCOs02g57400 was revealed as the candidate gene hosting these two mutations. Sequence analysis showed that the lpa 1-1 is a single base pair substitution mutation, while lpa 1-2 involves a 1,475-bp fragment deletion. A CAPS marker (LPA1CAPS) was developed for distinguishing the lpa 1-1 allele from lpa 1-2 and WT alleles, and InDel marker (LPA1InDel) was developed for differentiating the lpa 1-2 allele from lpa 1-1 and WT ones. Analysis of two populations derived from the two mutants with wild-type varieties confirmed the complete co-segregation of these two markers and LPA phenotype. The LOCOs02g57400 is predicted to encode, through alternative splicing, four possible proteins that are homologous to the 2-phosphoglycerate kinase reported in hyperthermophilic and thermophilic bacteria. The identification of the LPA gene and development of allele-specific markers are of importance not only for breeding LPA varieties, but also for advancing genetics and genomics of phytic acid biosynthesis in rice and other plant species. (author)

  2. Variational MCMC

    OpenAIRE

    De Freitas, Nando; Hojen-Sorensen, Pedro; Jordan, Michael I.; Russell, Stuart

    2013-01-01

    We propose a new class of learning algorithms that combines variational approximation and Markov chain Monte Carlo (MCMC) simulation. Naive algorithms that use the variational approximation as proposal distribution can perform poorly because this approximation tends to underestimate the true variance and other features of the data. We solve this problem by introducing more sophisticated MCMC algorithms. One of these algorithms is a mixture of two MCMC kernels: a random walk Metropolis kernel ...

  3. Tracing pastoralist migrations to southern Africa with lactase persistence alleles.

    Science.gov (United States)

    Macholdt, Enrico; Lede, Vera; Barbieri, Chiara; Mpoloka, Sununguko W; Chen, Hua; Slatkin, Montgomery; Pakendorf, Brigitte; Stoneking, Mark

    2014-04-14

    Although southern African Khoisan populations are often assumed to have remained largely isolated during prehistory, there is growing evidence for a migration of pastoralists from eastern Africa some 2,000 years ago, prior to the arrival of Bantu-speaking populations in southern Africa. Eastern Africa harbors distinctive lactase persistence (LP) alleles, and therefore LP alleles in southern African populations may be derived from this eastern African pastoralist migration. We sequenced the lactase enhancer region in 457 individuals from 18 Khoisan and seven Bantu-speaking groups from Botswana, Namibia, and Zambia and additionally genotyped four short tandem repeat (STR) loci that flank the lactase enhancer region. We found nine single-nucleotide polymorphisms, of which the most frequent is -14010(∗)C, which was previously found to be associated with LP in Kenya and Tanzania and to exhibit a strong signal of positive selection. This allele occurs in significantly higher frequency in pastoralist groups and in Khoe-speaking groups in our study, supporting the hypothesis of a migration of eastern African pastoralists that was primarily associated with Khoe speakers. Moreover, we find a signal of ongoing positive selection in all three pastoralist groups in our study, as well as (surprisingly) in two foraging groups. PMID:24704073

  4. The protease inhibitor PI*S allele and COPD

    DEFF Research Database (Denmark)

    Hersh, C P; Ly, N P; Berkey, C S; Silverman, E K; Nordestgaard, B G; Dahl, Morten; Dahl, M

    2005-01-01

    In many countries, the protease inhibitor (SERPINA1) PI*S allele is more common than PI*Z, the allele responsible for most cases of chronic obstructive pulmonary disease (COPD) due to severe alpha 1-antitrypsin deficiency. However, the risk of COPD due to the PI*S allele is not clear. The current...... authors located studies that addressed the risk of COPD or measured lung function in individuals with the PI SZ, PI MS and PI SS genotypes. A separate meta-analysis for each genotype was performed. Aggregating data from six studies, the odds ratio (OR) for COPD in PI SZ compound heterozygotes compared...... with PI MM (normal) individuals was significantly increased at 3.26 (95% confidence intervals (CI): 1.24-8.57). In 17 cross-sectional and case-control studies, the OR for COPD in PI MS heterozygotes was 1.19 (95%CI: 1.02-1.38). However, PI MS genotype was not associated with COPD risk after correcting...

  5. HLA- DR Alleles in Pakistani Patients of Pemphigus Vulgaris

    International Nuclear Information System (INIS)

    Objective: To determine frequency of HLA-DR alleles in Pakistani patients of pemphigus vulgaris in comparison with local healthy controls. Study Design: Cross-sectional, comparative study. Place and Duration of Study: Department of Immunology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from January 2011 to January 2014. Methodology: Twenty eight patients with biopsy proven diagnosis of pemphigus vulgaris referred from Department of Dermatology, Military Hospital, Rawalpindi were included. Patients were compared with a group of 150 unrelated local healthy subjects. DNA was extracted from peripheral blood collected in Tri-potassium EDTA. HLA-DRB1 typing was carried out on allele level (DRB1*01 - DRB1*16) using SSP (sequence specific primers). HLA type was determined by agarose gel electrophoresis and results recorded. Phenotype frequency of various alleles among patient group and control group was calculated by direct counting and significance of their association was determined by Fisher's exact test/ Chi square test. Results: A total of 12 male and 16 female patients, with age ranging from 21 to 34 (mean 23.4 years) were genotype for HLA-DRB1 loci. A statistically significant association of the disease with HLA-DRB1*04 was observed (50% versus 20.7% in controls, p < 0.05). Conclusion: There is a strong association of HLA-DRB1*04 with pemphigus vulgaris in Pakistani population. (author)

  6. Sporadic inclusion body myositis: HLA-DRB1 allele interactions influence disease risk and clinical phenotype.

    Science.gov (United States)

    Mastaglia, Frank L; Needham, Merrilee; Scott, Adrian; James, Ian; Zilko, Paul; Day, Timothy; Kiers, Lynette; Corbett, Alastair; Witt, Campbell S; Allcock, Richard; Laing, Nigel; Garlepp, Michael; Christiansen, Frank T

    2009-11-01

    Susceptibility to sIBM is strongly associated with the HLA-DRB1*03 allele and the 8.1 MHC ancestral haplotype (HLA-A1, B8, DRB1*03) but little is known about the effects of allelic interactions at the DRB1 locus or disease-modifying effects of HLA alleles. HLA-A, B and DRB1 genotyping was performed in 80 Australian sIBM cases and the frequencies of different alleles and allele combinations were compared with those in a group of 190 healthy controls. Genotype-phenotype correlations were also investigated. Amongst carriers of the HLA-DRB1*03 allele, DRB1*03/*01 heterozygotes were over-represented in the sIBM group (pHLA-DRB1*03 allele and other alleles at the DRB1 locus can influence disease susceptibility and the clinical phenotype in sIBM. PMID:19720533

  7. The evolution of skin pigmentation and hair texture in people of African ancestry.

    Science.gov (United States)

    Jablonski, Nina G; Chaplin, George

    2014-04-01

    Our species, Homo sapiens, evolved in Africa, and humanity's highest levels of genetic diversity are maintained there today. Underlying genetic diversity combined with the great range of solar regimes and climatic conditions found in Africa has contributed to a wide range of human integumentary phenotypes within the continent. Millions of Africans have moved, voluntarily and involuntarily, to other continents in the past 2000 years, and the range of integumentary phenotypes among admixed African diaspora populations is enormous. In this contribution, we do not catalog this variation, but provide basic evolutionary background as to how it developed in the first place. PMID:24679998

  8. Human genetic variation database, a reference database of genetic variations in the Japanese population

    Science.gov (United States)

    Higasa, Koichiro; Miyake, Noriko; Yoshimura, Jun; Okamura, Kohji; Niihori, Tetsuya; Saitsu, Hirotomo; Doi, Koichiro; Shimizu, Masakazu; Nakabayashi, Kazuhiko; Aoki, Yoko; Tsurusaki, Yoshinori; Morishita, Shinichi; Kawaguchi, Takahisa; Migita, Osuke; Nakayama, Keiko; Nakashima, Mitsuko; Mitsui, Jun; Narahara, Maiko; Hayashi, Keiko; Funayama, Ryo; Yamaguchi, Daisuke; Ishiura, Hiroyuki; Ko, Wen-Ya; Hata, Kenichiro; Nagashima, Takeshi; Yamada, Ryo; Matsubara, Yoichi; Umezawa, Akihiro; Tsuji, Shoji; Matsumoto, Naomichi; Matsuda, Fumihiko

    2016-01-01

    Whole-genome and -exome resequencing using next-generation sequencers is a powerful approach for identifying genomic variations that are associated with diseases. However, systematic strategies for prioritizing causative variants from many candidates to explain the disease phenotype are still far from being established, because the population-specific frequency spectrum of genetic variation has not been characterized. Here, we have collected exomic genetic variation from 1208 Japanese individuals through a collaborative effort, and aggregated the data into a prevailing catalog. In total, we identified 156 622 previously unreported variants. The allele frequencies for the majority (88.8%) were lower than 0.5% in allele frequency and predicted to be functionally deleterious. In addition, we have constructed a Japanese-specific major allele reference genome by which the number of unique mapping of the short reads in our data has increased 0.045% on average. Our results illustrate the importance of constructing an ethnicity-specific reference genome for identifying rare variants. All the collected data were centralized to a newly developed database to serve as useful resources for exploring pathogenic variations. Public access to the database is available at http://www.genome.med.kyoto-u.ac.jp/SnpDB/. PMID:26911352

  9. A Δ11 desaturase gene genealogy reveals two divergent allelic classes within the European corn borer (Ostrinia nubilalis

    Directory of Open Access Journals (Sweden)

    Harrison Richard G

    2010-04-01

    Full Text Available Abstract Background Moth pheromone mating systems have been characterized at the molecular level, allowing evolutionary biologists to study how changes in protein sequence or gene expression affect pheromone phenotype, patterns of mating, and ultimately, the formation of barriers to gene exchange. Recent studies of Ostrinia pheromones have focused on the diversity of sex pheromone desaturases and their role in the specificity of pheromone production. Here we produce a Δ11 desaturase genealogy within Ostrinia nubilalis. We ask what has been the history of this gene, and whether this history suggests that changes in Δ11 desaturase have been involved in the divergence of the E and Z O. nubilalis pheromone strains. Results The Δ11 desaturase gene genealogy does not differentiate O. nubilalis pheromone strains. However, we find two distinct clades, separated by 2.9% sequence divergence, that do not sort with pheromone strain, geographic origin, or emergence time. We demonstrate that these clades do not represent gene duplicates, but rather allelic variation at a single gene locus. Conclusions Analyses of patterns of variation at the Δ11 desaturase gene in ECB suggest that this enzyme does not contribute to reproductive isolation between pheromone strains (E and Z. However, our genealogy reveals two deeply divergent allelic classes. Standing variation at loci that contribute to mate choice phenotypes may permit novel pheromone mating systems to arise in the presence of strong stabilizing selection.

  10. HLA Dr beta 1 alleles in Pakistani patients with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Objective: To determine frequencies of HLA DR beta 1 alleles in rheumatoid arthritis in Pakistani patients. Study Design: Cross sectional / analytical study. Place and Duration of Study: Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi in collaboration with Rheumatology departments of Military Hospital, Rawalpindi and Fauji Foundation Hospital, Rawalpindi, from January 2009 to January 2010. Methodology: HLA DR beta 1 genotyping of one hundred Pakistani patients, diagnosed as having RA as per American College of Rheumatology revised criteria 1987, was done. HLA DR beta 1 genotyping was carried out at allele group level (DR beta 1*01-DR beta 1*16) by sequence specific primers in RA patients. Comparison of HLA DR beta 1 allele frequencies between patients and control groups was made using Pearson's chi-square test to find possible association of HLA DR?1 alleles with RA in Pakistani rheumatoid patients. Results: HLA DR beta 1*04 was expressed with significantly increased frequency in patients with rheumatoid arthritis (p <0.05). HLA DR?1*11 was expressed statistically significantly more in control group as compared to rheumatoid patients indicating a possible protective effect. There was no statistically significant difference observed in frequencies of HLA DR beta 1 allele *01, DR beta 1 allele *03, DR beta 1 allele *07, DR beta 1 allele *08, DR beta 1 allele *09, DR beta 1 allele *10, DR beta 1 allele *12, DR beta 1 allele *13, DR beta 1 allele *14, DR?1 allele *15 and DR beta 1 allele *16 between patients and control groups. Conclusion: The identification of susceptible HLA DR beta 1 alleles in Pakistani RA patients may help physicians to make early decisions regarding initiation of early intensive therapy with disease modifying anti rheumatic medicines and biological agents decreasing disability in RA patients. (author)

  11. Conditional Allele Mouse Planner (CAMP): software to facilitate the planning and design of breeding strategies involving mice with conditional alleles.

    Science.gov (United States)

    Hoffert, Jason D; Pisitkun, Trairak; Miller, R Lance

    2012-06-01

    Transgenic and conditional knockout mouse models play an important role in biomedical research and their use has grown exponentially in the last 5-10 years. Generating conditional knockouts often requires breeding multiple alleles onto the background of a single mouse or group of mice. Breeding these mice depends on parental genotype, litter size, transmission frequency, and the number of breeding rounds. Therefore, a well planned breeding strategy is critical for keeping costs to a minimum. However, designing a viable breeding strategy can be challenging. With so many different variables this would be an ideal task for a computer program. To facilitate this process, we created a Java-based program called Conditional Allele Mouse Planner (CAMP). CAMP is designed to provide an estimate of the number of breeders, amount of time, and costs associated with generating mice of a particular genotype. We provide a description of CAMP, how to use it, and offer it freely as an application. PMID:21870117

  12. Identification of a Novel Allele of TaCKX6a02 Associated with Grain Size, Filling Rate and Weight of Common Wheat

    Science.gov (United States)

    Zhang, Hai-Ping; Wang, Sheng-Xing; Sun, Genlou; Xiao, Shi-He; Ma, Chuan-Xi

    2015-01-01

    Cytokinin oxidase (CKX) plays a crucial role in plant growth and development by reversibly inactivating cytokinin (CTK). Twenty-four primer pairs, designed from ESTs of the TaCKX genes family of common wheat, were used to identify their allelic variations associated with grain size, weight, and filling rate in 169 recombinant inbred lines (RIL) derived from Jing 411 × Hongmangchun 21. TaCKX6a02, a member of TaCKX gene family, amplified by primer pair T31–32, showed a close association with grain traits in this RIL population. Statistical analysis indicated that allelic variation of TaCKX6a02 had significant correlation with grain size, weight, and filling rate (GFR; P cropping seasons. 12.8~35.1% of phenotypic variations were estimated for these genotypes. A novel 29-bp InDel behind the stop codon was detected by DNA sequence analysis between the two alleles of TaCKX6a02-D1. The gene-specific marker, TKX3D, was designed according to the novel variation, and can be used in marker-assisted selection (MAS) for grain size, weight, and GFR in common wheat. PMID:26657796

  13. Divergence, convergence, and the ancestry of feral populations in the domestic rock pigeon.

    Science.gov (United States)

    Stringham, Sydney A; Mulroy, Elisabeth E; Xing, Jinchuan; Record, David; Guernsey, Michael W; Aldenhoven, Jaclyn T; Osborne, Edward J; Shapiro, Michael D

    2012-02-21

    Domestic pigeons are spectacularly diverse and exhibit variation in more traits than any other bird species [1]. In The Origin of Species, Charles Darwin repeatedly calls attention to the striking variation among domestic pigeon breeds-generated by thousands of years of artificial selection on a single species by human breeders-as a model for the process of natural divergence among wild populations and species [2]. Darwin proposed a morphology-based classification of domestic pigeon breeds [3], but the relationships among major groups of breeds and their geographic origins remain poorly understood [4, 5]. We used a large, geographically diverse sample of 361 individuals from 70 domestic pigeon breeds and two free-living populations to determine genetic relationships within this species. We found unexpected relationships among phenotypically divergent breeds as well as convergent evolution of derived traits among several breed groups. Our findings also illuminate the geographic origins of breed groups in India and the Middle East and suggest that racing breeds have made substantial contributions to feral pigeon populations. PMID:22264611

  14. Novel method for analysis of allele specific expression in triploid Oryzias latipes reveals consistent pattern of allele exclusion.

    Directory of Open Access Journals (Sweden)

    Tzintzuni I Garcia

    Full Text Available Assessing allele-specific gene expression (ASE on a large scale continues to be a technically challenging problem. Certain biological phenomena, such as X chromosome inactivation and parental imprinting, affect ASE most drastically by completely shutting down the expression of a whole set of alleles. Other more subtle effects on ASE are likely to be much more complex and dependent on the genetic environment and are perhaps more important to understand since they may be responsible for a significant amount of biological diversity. Tools to assess ASE in a diploid biological system are becoming more reliable. Non-diploid systems are, however, not uncommon. In humans full or partial polyploid states are regularly found in both healthy (meiotic cells, polynucleated cell types and diseased tissues (trisomies, non-disjunction events, cancerous tissues. In this work we have studied ASE in the medaka fish model system. We have developed a method for determining ASE in polyploid organisms from RNAseq data and we have implemented this method in a software tool set. As a biological model system we have used nuclear transplantation to experimentally produce artificial triploid medaka composed of three different haplomes. We measured ASE in RNA isolated from the livers of two adult, triploid medaka fish that showed a high degree of similarity. The majority of genes examined (82% shared expression more or less evenly among the three alleles in both triploids. The rest of the genes (18% displayed a wide range of ASE levels. Interestingly the majority of genes (78% displayed generally consistent ASE levels in both triploid individuals. A large contingent of these genes had the same allele entirely suppressed in both triploids. When viewed in a chromosomal context, it is revealed that these genes are from large sections of 4 chromosomes and may be indicative of some broad scale suppression of gene expression.

  15. Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein metabolism in women and USF1 expression in atherosclerotic plaque

    Science.gov (United States)

    Fan, Yue-Mei; Hernesniemi, Jussi; Oksala, Niku; Levula, Mari; Raitoharju, Emma; Collings, Auni; Hutri-Kähönen, Nina; Juonala, Markus; Marniemi, Jukka; Lyytikäinen, Leo-Pekka; Seppälä, Ilkka; Mennander, Ari; Tarkka, Matti; Kangas, Antti J.; Soininen, Pasi; Salenius, Juha Pekka; Klopp, Norman; Illig, Thomas; Laitinen, Tomi; Ala-Korpela, Mika; Laaksonen, Reijo; Viikari, Jorma; Kähönen, Mika; Raitakari, Olli T.; Lehtimäki, Terho

    2014-01-01

    Upstream transcription factor 1 (USF1) allelic variants significantly influence future risk of cardiovascular disease and overall mortality in females. We investigated sex-specific effects of USF1 gene allelic variants on serum indices of lipoprotein metabolism, early markers of asymptomatic atherosclerosis and their changes during six years of follow-up. In addition, we investigated the cis-regulatory role of these USF1 variants in artery wall tissues in Caucasians. In the Cardiovascular Risk in Young Finns Study, 1,608 participants (56% women, aged 31.9 ± 4.9) with lipids and cIMT data were included. For functional study, whole genome mRNA expression profiling was performed in 91 histologically classified atherosclerotic samples. In females, serum total, LDL cholesterol and apoB levels increased gradually according to USF1 rs2516839 genotypes TT < CT < CC and rs1556259 AA < AG < GG as well as according to USF1 H3 (GCCCGG) copy number 0 < 1 < 2. Furthermore, the carriers of minor alleles of rs2516839 (C) and rs1556259 (G) of USF1 gene had decreased USF1 expression in atherosclerotic plaques (P = 0.028 and 0.08, respectively) as compared to non-carriers. The genetic variation in USF1 influence USF1 transcript expression in advanced atherosclerosis and regulates levels and metabolism of circulating apoB and apoB-containing lipoprotein particles in sex-dependent manner, but is not a major determinant of early markers of atherosclerosis. PMID:24722012

  16. A high-throughput method for genotyping S-RNase alleles in apple

    DEFF Research Database (Denmark)

    Larsen, Bjarne; Ørgaard, Marian; Toldam-Andersen, Torben Bo; Pedersen, Carsten

    2016-01-01

    We present a new efficient screening tool for detection of S-alleles in apple. The protocol using general and multiplexed primers for PCR reaction and fragment detection on an automatized capillary DNA sequencer exposed a higher number of alleles than any previous studies. Analysis of alleles is...

  17. Studies on recombination between allele in the ml-o locus of barley and on pleiotropic effects of the alleles

    International Nuclear Information System (INIS)

    Five independently arisen genes, which are functionally allelic in the m1-o locus and conditioning resistance to the powdery mildew fungus, were tested for structural allelism by recombination. Two heteroallelic crosses produced susceptible recombinants in F2 with a frequency of 8.6 and 2.0 x 10-4, respectively, showing that m1-o 1 is structurally non-allelic to m1-o 5 and to m1-o 9. Homozygous resistant populations derived from crossing different m1-o resistant barleys with susceptible varieties were exposed to two successive cycles of selection against necrotic leaf spotting. Field experiments with selected F5 lines and their parents showed that the m1-o resistant parents differed in severity of spotting, and that the spotting can be reduced or eliminated by crossing and subsequent selection. It appears that a reduction in the necrotic leaf spotting is accopanied by an increase in grain yield. Two new experiments designed to further elucidate the interallelic recombination in m1-o and the pleiotropic effects are briefly described. (author)

  18. Theoretical studies of gene substitution, geographic variation, and speciation

    Energy Technology Data Exchange (ETDEWEB)

    Felsenstein, J.

    1977-07-31

    Brief comments are given on the results of a research program dealing with population genetics of evolutionary processes. The various subjects studied included genetic variation in clines; speciation and disruptive selection; parapatric speciation in clines; macroevolutionary laws in a model ecosystem; migration matrices; lethal allelism; estimation of number of loci in quantitative inheritance; numerical taxonomy methods; and new mutants in Lesch-Nyhan disease.

  19. Variational analysis

    CERN Document Server

    Rockafellar, R Tyrrell

    1998-01-01

    From its origins in the minimization of integral functionals, the notion of 'variations' has evolved greatly in connection with applications in optimization, equilibrium, and control. It refers not only to constrained movement away from a point, but also to modes of perturbation and approximation that are best describable by 'set convergence', variational convergence of functions and the like. This book develops a unified framework and, in finite dimension, provides a detailed exposition of variational geometry and subdifferential calculus in their current forms beyond classical and convex analysis. Also covered are set-convergence, set-valued mappings, epi-convergence, duality, maximal monotone mappings, second-order subderivatives, measurable selections and normal integrands. The changes in this 3rd printing mainly concern various typographical corrections, and reference omissions that came to light in the previous printings. Many of these reached the authors' notice through their own re-reading, that of th...

  20. Expression and loss of alleles in cultured mouse embryonic fibroblasts and stem cells carrying allelic fluorescent protein genes

    Directory of Open Access Journals (Sweden)

    Stringer Saundra L

    2006-10-01

    Full Text Available Abstract Background Loss of heterozygosity (LOH contributes to many cancers, but the rate at which these events occur in normal cells of the body is not clear. LOH would be detectable in diverse cell types in the body if this event were to confer an obvious cellular phenotype. Mice that carry two different fluorescent protein genes as alleles of a locus would seem to be a useful tool for addressing this issue because LOH would change a cell's phenotype from dichromatic to monochromatic. In addition, LOH caused by mitotic crossing over might be discernable in tissues because this event produces a pair of neighboring monochromatic cells that are different colors. Results As a step in assessing the utility of this approach, we derived primary embryonic fibroblast populations and embryonic stem cell lines from mice that carried two different fluorescent protein genes as alleles at the chromosome 6 locus, ROSA26. Fluorescence activated cell sorting (FACS showed that the vast majority of cells in each line expressed the two marker proteins at similar levels, and that populations exhibited expression noise similar to that seen in bacteria and yeast. Cells with a monochromatic phenotype were present at frequencies on the order of 10-4 and appeared to be produced at a rate of approximately 10-5 variant cells per mitosis. 45 of 45 stably monochromatic ES cell clones exhibited loss of the expected allele at the ROSA26 locus. More than half of these clones retained heterozygosity at a locus between ROSA26 and the centromere. Other clones exhibited LOH near the centromere, but were disomic for chromosome 6. Conclusion Allelic fluorescent markers allowed LOH at the ROSA26 locus to be detected by FACS. LOH at this locus was usually not accompanied by LOH near the centromere, suggesting that mitotic recombination was the major cause of ROSA26 LOH. Dichromatic mouse embryonic cells provide a novel system for studying genetic/karyotypic stability and factors

  1. Variational principles

    CERN Document Server

    Moiseiwitsch, B L

    2004-01-01

    This graduate-level text's primary objective is to demonstrate the expression of the equations of the various branches of mathematical physics in the succinct and elegant form of variational principles (and thereby illuminate their interrelationship). Its related intentions are to show how variational principles may be employed to determine the discrete eigenvalues for stationary state problems and to illustrate how to find the values of quantities (such as the phase shifts) that arise in the theory of scattering. Chapter-by-chapter treatment consists of analytical dynamics; optics, wave mecha

  2. The ‘Stolen Generations' of Mothers and Daughters: Child Apprehension and Enhanced HIV Vulnerabilities for Sex Workers of Aboriginal Ancestry

    OpenAIRE

    Putu Duff; Brittany Bingham; Annick Simo; Delores Jury; Charlotte Reading; Kate Shannon

    2014-01-01

    Objectives The number of children in care of the state continues to grow in BC, Canada with a historical legacy of child apprehension among criminalized and marginalized populations, particularly women of Aboriginal ancestry and sex workers. However, there is a paucity of research investigating child apprehension experiences among marginalized mothers. The objective of the current analysis is to examine the prevalence and correlates of child apprehensions among female sex workers in Vanco...

  3. Genome-wide Association Study of Platelet Count Identifies Ancestry-Specific Loci in Hispanic/Latino Americans.

    Science.gov (United States)

    Schick, Ursula M; Jain, Deepti; Hodonsky, Chani J; Morrison, Jean V; Davis, James P; Brown, Lisa; Sofer, Tamar; Conomos, Matthew P; Schurmann, Claudia; McHugh, Caitlin P; Nelson, Sarah C; Vadlamudi, Swarooparani; Stilp, Adrienne; Plantinga, Anna; Baier, Leslie; Bien, Stephanie A; Gogarten, Stephanie M; Laurie, Cecelia A; Taylor, Kent D; Liu, Yongmei; Auer, Paul L; Franceschini, Nora; Szpiro, Adam; Rice, Ken; Kerr, Kathleen F; Rotter, Jerome I; Hanson, Robert L; Papanicolaou, George; Rich, Stephen S; Loos, Ruth J F; Browning, Brian L; Browning, Sharon R; Weir, Bruce S; Laurie, Cathy C; Mohlke, Karen L; North, Kari E; Thornton, Timothy A; Reiner, Alex P

    2016-02-01

    Platelets play an essential role in hemostasis and thrombosis. We performed a genome-wide association study of platelet count in 12,491 participants of the Hispanic Community Health Study/Study of Latinos by using a mixed-model method that accounts for admixture and family relationships. We discovered and replicated associations with five genes (ACTN1, ETV7, GABBR1-MOG, MEF2C, and ZBTB9-BAK1). Our strongest association was with Amerindian-specific variant rs117672662 (p value = 1.16 × 10(-28)) in ACTN1, a gene implicated in congenital macrothrombocytopenia. rs117672662 exhibited allelic differences in transcriptional activity and protein binding in hematopoietic cells. Our results underscore the value of diverse populations to extend insights into the allelic architecture of complex traits. PMID:26805783

  4. HLA-DR alleles among Pakistani patients of coeliac disease

    International Nuclear Information System (INIS)

    Objectives: To investigate whether certain DR alleles might also contribute to the genetic susceptibility among Coeliac disease patients in Pakistan. Methods: The case-control study was conducted at the Military Hospital, Rawalpindi, from October 2011 to January 2012, and analysed 25 children diagnosed to have coeliac disease as per the criteria set by the European Society of Paediatric Gastroenterology and Nutrition, which included histopathological alterations in duodenal biopsies, clinical response to gluten withdrawal, and presence of anti-endomyseal antibodies. Patients were compared with a group of 150 healthy subjects. Dioxyribonucleic acid was extracted from peripheral blood collected in ethylenediaminetetraacetic acid.K3. Human leukocyte antigen DRB1 typing was carried out on allele level (DRB1*01 - DRB1*16) using sequence specific primers. Human leukocyte antigen type was determined by agarose gel electrophoresis and results were recorded. Phenotype frequency of various alleles among the patient group and the control group was calculated by direct counting, and significance of their association was determined by Fisher Exact Test. Results: A total of 11 (44%) female paediatric coeliac patients in age range 1-9 (mean 7.2+-4.8 years) and 14 (56%) male paediatric patients in the age range 6-14 (mean 8.6+-5.1 years) were genotyped for HLA-DRB1 loci. A statistically significant positive association of the disease with HLA-DRB1*03 (n=23; 92% versus n=31; 21% in controls, p <0.01) was observed. Conclusion: HLA-DRB1*03 is associated with increased risk of developing coeliac disease. (author)

  5. The human genome retains relics of its prokaryotic ancestry: human genes of archaebacterial and eubacterial origin exhibit remarkable differences.

    Science.gov (United States)

    Alvarez-Ponce, David; McInerney, James O

    2011-01-01

    Eukaryotes are generally thought to stem from a fusion event involving an archaebacterium and a eubacterium. As a result of this event, contemporaneous eukaryotic genomes are chimeras of genes inherited from both endosymbiotic partners. These two coexisting gene repertoires have been shown to differ in a number of ways in yeast. Here we combine genomic and functional data in order to determine if and how human genes that have been inherited from both prokaryotic ancestors remain distinguishable. We show that, despite being fewer in number, human genes of archaebacterial origin are more highly and broadly expressed across tissues, are more likely to have lethal mouse orthologs, tend to be involved in informational processes, are more selectively constrained, and encode shorter and more central proteins in the protein-protein interaction network than eubacterium-like genes. Furthermore, consistent with endosymbiotic theory, we show that proteins tend to interact with those encoded by genes of the same ancestry. Most interestingly from a human health perspective, archaebacterial genes are less likely to be involved in heritable human disease. Taken together, these results show that more than 2 billion years after eukaryogenesis, the human genome retains at least two somewhat distinct communities of genes. PMID:21795752

  6. NERO’S ANCESTRY AND THE CONSTRUCTION OF IMPERIAL IDEOLOGY IN THE EARLY EMPIRE. A METHODOLOGICAL CASE STUDY

    Directory of Open Access Journals (Sweden)

    Olivier Hekster

    2015-01-01

    Full Text Available Within the discipline of ancient history, diverse types of sources, such as coins, inscriptions, portraits and texts, are often combined to create a coherent image of a particular ruler. A good example of how such a process works is the way in which reconstructions by modern scholars of the emperor Nero tend to look for a clearly defined ‘Neronian image’, by bringing together various types of primary evidence without paying sufficient attention to these sources’ medial contexts. This article argues that such a reconstruction does not do justice to the complex and multi-layered image of the last Julio-Claudian. By focusing on one particular aspect of Neronian imagery, the propagation of this emperor’s ancestry, we will argue that different types of sources, stemming from varying contexts and addressing different groups, cannot unproblematically be combined. Through an investigation of the ancestral messages spread by imperial and provincial coins, epigraphic evidence and portraiture, it becomes clear that systematic analysis of ancient media, their various contexts and inconsistencies is needed before combining them. Such an analysis reveals patterns within the different sources and shows that, in creating imperial images, rulers were constrained by both medial and local traditions. Modern studies of ancient images should therefore consider this medial and geographical variety in order to do justice to the multi-faceted phenomenon of imperial representation.

  7. Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations.

    Science.gov (United States)

    Hayes, M Geoffrey; Urbanek, Margrit; Ehrmann, David A; Armstrong, Loren L; Lee, Ji Young; Sisk, Ryan; Karaderi, Tugce; Barber, Thomas M; McCarthy, Mark I; Franks, Stephen; Lindgren, Cecilia M; Welt, Corrine K; Diamanti-Kandarakis, Evanthia; Panidis, Dimitrios; Goodarzi, Mark O; Azziz, Ricardo; Zhang, Yi; James, Roland G; Olivier, Michael; Kissebah, Ahmed H; Stener-Victorin, Elisabet; Legro, Richard S; Dunaif, Andrea

    2015-01-01

    Polycystic ovary syndrome (PCOS) is a common, highly heritable complex disorder of unknown aetiology characterized by hyperandrogenism, chronic anovulation and defects in glucose homeostasis. Increased luteinizing hormone relative to follicle-stimulating hormone secretion, insulin resistance and developmental exposure to androgens are hypothesized to play a causal role in PCOS. Here we map common genetic susceptibility loci in European ancestry women for the National Institutes of Health PCOS phenotype, which confers the highest risk for metabolic morbidities, as well as reproductive hormone levels. Three loci reach genome-wide significance in the case-control meta-analysis, two novel loci mapping to chr 8p23.1 [Corrected] and chr 11p14.1, and a chr 9q22.32 locus previously found in Chinese PCOS. The same chr 11p14.1 SNP, rs11031006, in the region of the follicle-stimulating hormone B polypeptide (FSHB) gene strongly associates with PCOS diagnosis and luteinizing hormone levels. These findings implicate neuroendocrine changes in disease pathogenesis. PMID:26284813

  8. Genomic study of the Ket: a Paleo-Eskimo-related ethnic group with significant ancient North Eurasian ancestry.

    Science.gov (United States)

    Flegontov, Pavel; Changmai, Piya; Zidkova, Anastassiya; Logacheva, Maria D; Altınışık, N Ezgi; Flegontova, Olga; Gelfand, Mikhail S; Gerasimov, Evgeny S; Khrameeva, Ekaterina E; Konovalova, Olga P; Neretina, Tatiana; Nikolsky, Yuri V; Starostin, George; Stepanova, Vita V; Travinsky, Igor V; Tříska, Martin; Tříska, Petr; Tatarinova, Tatiana V

    2016-01-01

    The Kets, an ethnic group in the Yenisei River basin, Russia, are considered the last nomadic hunter-gatherers of Siberia, and Ket language has no transparent affiliation with any language family. We investigated connections between the Kets and Siberian and North American populations, with emphasis on the Mal'ta and Paleo-Eskimo ancient genomes, using original data from 46 unrelated samples of Kets and 42 samples of their neighboring ethnic groups (Uralic-speaking Nganasans, Enets, and Selkups). We genotyped over 130,000 autosomal SNPs, identified mitochondrial and Y-chromosomal haplogroups, and performed high-coverage genome sequencing of two Ket individuals. We established that Nganasans, Kets, Selkups, and Yukaghirs form a cluster of populations most closely related to Paleo-Eskimos in Siberia (not considering indigenous populations of Chukotka and Kamchatka). Kets are closely related to modern Selkups and to some Bronze and Iron Age populations of the Altai region, with all these groups sharing a high degree of Mal'ta ancestry. Implications of these findings for the linguistic hypothesis uniting Ket and Na-Dene languages into a language macrofamily are discussed. PMID:26865217

  9. Modulation of allele leakiness and adaptive mutability in Escherichia coli

    Indian Academy of Sciences (India)

    R. Jayaraman

    2000-08-01

    It is shown that partial phenotypic suppression of two ochre mutations (argE3 and lacZU118) and an amber mutation (in argE) by sublethal concentrations of streptomycin in an rpsL+ (streptomycin-sensitive) derivative of the Escherichia coli strain AB1157 greatly enhances their adaptive mutability under selection. Streptomycin also increases adaptive mutability brought about by the ppm mutation described earlier. Inactivation of recA affects neither phenotypic suppression by streptomycin nor replication-associated mutagenesis but abolishes adaptive mutagenesis. These results indicate a causal relationship between allele leakiness and adaptive mutability.

  10. Allelic drop-out probabilities estimated by logistic regression

    DEFF Research Database (Denmark)

    Tvedebrink, Torben; Eriksen, Poul Svante; Asplund, Maria;

    2012-01-01

    We discuss the model for estimating drop-out probabilities presented by Tvedebrink et al. [7] and the concerns, that have been raised. The criticism of the model has demonstrated that the model is not perfect. However, the model is very useful for advanced forensic genetic work, where allelic drop......-out is occurring. With this discussion, we hope to improve the drop-out model, so that it can be used for practical forensic genetics and stimulate further discussions. We discuss how to estimate drop-out probabilities when using a varying number of PCR cycles and other experimental conditions....

  11. Effects of the APOE ε2 Allele on Mortality and Cognitive Function in the Oldest Old

    DEFF Research Database (Denmark)

    Lindahl-Jacobsen, Rune; Tan, Qihua; Mengel-From, Jonas;

    2013-01-01

    Some studies indicate that the APOE ε2 allele may have a protective effect on mortality and mental health among the elderly adults. We investigated the effect of the APOE ε2 allele on cognitive function and mortality in 1651 members of the virtually extinct Danish 1905 birth cohort. We found...... no protective effect of the APOE ε2 allele on mortality compared with the APOE ε3 allele. The point estimates indicated an increased protection against cognitive decline over time for persons with the APOE ε2 allele. Cognitive score did not significantly modify the mortality risk of the various APOE genotypes....... We did not find a protective effect of the APOE ε2 allele on mortality among the oldest old, but in agreement with our previous findings, we found a 22% increased mortality risk for APOE ε4 carriers. The APOE ε2 allele may be protective on cognitive decline among the oldest old....

  12. Longitudinal Trajectories of Cholesterol from Midlife through Late Life according to Apolipoprotein E Allele Status

    Directory of Open Access Journals (Sweden)

    Brian Downer

    2014-10-01

    Full Text Available Background: Previous research indicates that total cholesterol levels increase with age during young adulthood and middle age and decline with age later in life. This is attributed to changes in diet, body composition, medication use, physical activity, and hormone levels. In the current study we utilized data from the Framingham Heart Study Original Cohort to determine if variations in apolipoprotein E (APOE, a gene involved in regulating cholesterol homeostasis, influence trajectories of total cholesterol, HDL cholesterol, and total: HDL cholesterol ratio from midlife through late life. Methods: Cholesterol trajectories from midlife through late life were modeled using generalized additive mixed models and mixed-effects regression models. Results: APOE e2+ subjects had lower total cholesterol levels, higher HDL cholesterol levels, and lower total: HDL cholesterol ratios from midlife to late life compared to APOE e3 and APOE e4+ subjects. Statistically significant differences in life span cholesterol trajectories according to gender and use of cholesterol-lowering medications were also detected. Conclusion: The findings from this research provide evidence that variations in APOE modify trajectories of serum cholesterol from midlife to late life. In order to efficiently modify cholesterol through the life span, it is important to take into account APOE allele status.

  13. Allele-specific methylation occurs at genetic variants associated with complex disease.

    Directory of Open Access Journals (Sweden)

    John N Hutchinson

    Full Text Available We hypothesize that the phenomenon of allele-specific methylation (ASM may underlie the phenotypic effects of multiple variants identified by Genome-Wide Association studies (GWAS. We evaluate ASM in a human population and document its genome-wide patterns in an initial screen at up to 380,678 sites within the genome, or up to 5% of the total genomic CpGs. We show that while substantial inter-individual variation exists, 5% of assessed sites show evidence of ASM in at least six samples; the majority of these events (81% are under genetic influence. Many of these cis-regulated ASM variants are also eQTLs in peripheral blood mononuclear cells and monocytes and/or in high linkage-disequilibrium with variants linked to complex disease. Finally, focusing on autoimmune phenotypes, we extend this initial screen to confirm the association of cis-regulated ASM with multiple complex disease-associated variants in an independent population using next-generation bisulfite sequencing. These four variants are implicated in complex phenotypes such as ulcerative colitis and AIDS progression disease (rs10491434, Celiac disease (rs2762051, Crohn's disease, IgA nephropathy and early-onset inflammatory bowel disease (rs713875 and height (rs6569648. Our results suggest cis-regulated ASM may provide a mechanistic link between the non-coding genetic changes and phenotypic variation observed in these diseases and further suggests a route to integrating DNA methylation status with GWAS results.

  14. PLCL1 rs7595412 variation is not associated with hip bone size variation in postmenopausal Danish women

    Directory of Open Access Journals (Sweden)

    Karsdal Morten A

    2009-12-01

    Full Text Available Abstract Background Bone size (BS variation is under strong genetic control and plays an important role in determining bone strength and fracture risk. Recently, a genome-wide association study identified polymorphisms associated with hip BS variation in the PLCL1 (phospholipase c-like 1 locus. Carriers of the major A allele of the most significant polymorphism, rs7595412, have around 17% larger hip BS than non-carriers. We therefore hypothesized that this polymorphism may also influence postmenopausal complications. Methods The effects of rs7595412 on hip BS, bone mineral density (BMD, vertebral fractures, serum Crosslaps and osteocalcin levels were analyzed in 1,191 postmenopausal Danish women. Results This polymorphism had no influence on hip and spine BS as well as on femur and spine BMD. Women carrying at least one copy of the A allele had lower levels of serum osteocalcin as compared with those homozygous for the G allele (p = 0.03 whereas no effect on serum Crosslaps was detected. Furthermore, women homozygous for the A allele were more affected by vertebral fractures than those carrying at least one copy of the G allele (p = 0.04. Conclusions In postmenopausal women, our results suggest that the PLCL1 rs7595412 polymorphism has no obvious effect on hip BS or BMD but may be nominally associated with increased proportion of vertebral fracture and increased levels of osteocalcin.

  15. Effect of the allelic variants of aldehyde dehydrogenase ALDH2*2 and alcohol dehydrogenase ADH1B*2 on blood acetaldehyde concentrations

    OpenAIRE

    Peng Giia-Sheun; Yin Shih-Jiun

    2009-01-01

    Abstract Alcoholism is a complex behavioural disorder. Molecular genetics studies have identified numerous candidate genes associated with alcoholism. It is crucial to verify the disease susceptibility genes by correlating the pinpointed allelic variations to the causal phenotypes. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal enzymes responsible for ethanol metabolism in humans. Both ADH and ALDH exhibit functional polymorphisms among racial populations; the...

  16. Mechanisms and Disease Associations of Haplotype-Dependent Allele-Specific DNA Methylation.

    Science.gov (United States)

    Do, Catherine; Lang, Charles F; Lin, John; Darbary, Huferesh; Krupska, Izabela; Gaba, Aulona; Petukhova, Lynn; Vonsattel, Jean-Paul; Gallagher, Mary P; Goland, Robin S; Clynes, Raphael A; Dwork, Andrew; Kral, John G; Monk, Catherine; Christiano, Angela M; Tycko, Benjamin

    2016-05-01

    Haplotype-dependent allele-specific methylation (hap-ASM) can impact disease susceptibility, but maps of this phenomenon using stringent criteria in disease-relevant tissues remain sparse. Here we apply array-based and Methyl-Seq approaches to multiple human tissues and cell types, including brain, purified neurons and glia, T lymphocytes, and placenta, and identify 795 hap-ASM differentially methylated regions (DMRs) and 3,082 strong methylation quantitative trait loci (mQTLs), most not previously reported. More than half of these DMRs have cell type-restricted ASM, and among them are 188 hap-ASM DMRs and 933 mQTLs located near GWAS signals for immune and neurological disorders. Targeted bis-seq confirmed hap-ASM in 12/13 loci tested, including CCDC155, CD69, FRMD1, IRF1, KBTBD11, and S100A(∗)-ILF2, associated with immune phenotypes, MYT1L, PTPRN2, CMTM8 and CELF2, associated with neurological disorders, NGFR and HLA-DRB6, associated with both immunological and brain disorders, and ZFP57, a trans-acting regulator of genomic imprinting. Polymorphic CTCF and transcription factor (TF) binding sites were over-represented among hap-ASM DMRs and mQTLs, and analysis of the human data, supplemented by cross-species comparisons to macaques, indicated that CTCF and TF binding likelihood predicts the strength and direction of the allelic methylation asymmetry. These results show that hap-ASM is highly tissue specific; an important trans-acting regulator of genomic imprinting is regulated by this phenomenon; and variation in CTCF and TF binding sites is an underlying mechanism, and maps of hap-ASM and mQTLs reveal regulatory sequences underlying supra- and sub-threshold GWAS peaks in immunological and neurological disorders. PMID:27153397

  17. Protective effect of the AT137RQ and ARQK176 PrP alleles against classical scrapie in Sarda breed sheep

    Science.gov (United States)

    Vaccari, Gabriele; Scavia, Gaia; Sala, Marcello; Cosseddu, Gianmario; Chiappini, Barbara; Conte, Michela; Esposito, Elena; Lorenzetti, Raniero; Perfetti, Gabriella; Marconi, Paola; Scholl, Francesco; Barbaro, Katia; Bella, Antonino; Nonno, Romolo; Agrimi, Umberto

    2009-01-01

    The susceptibility of sheep to scrapie is under the control of the host’s prion protein (PrP) gene and is also influenced by the strain of the agent. PrP polymorphisms at codons 136 (A/V), 154 (R/H) and 171 (Q/R/H) are the main determinants of susceptibility/resistance of sheep to classical scrapie. They are combined in four main variants of the wild-type ARQ allele: VRQ, AHQ, ARH and ARR. Breeding programmes have been undertaken on this basis in the European Union and the USA to increase the frequency of the resistant ARR allele in sheep populations. Herein, we report the results of a multi-flock study showing the protective effect of polymorphisms other than those at codons 136, 154 and 171 in Sarda breed sheep. All ARQ/ARQ affected sheep (n = 154) and 378 negative ARQ/ARQ controls from four scrapie outbreaks were submitted to sequencing of the PrP gene. The distribution of variations other than those at the standard three codons, between scrapie cases and negative controls, was statistically different in all flocks. In particular, the AT137RQ and ARQK176 alleles showed a clear protective effect. This is the first study demonstrating a protective influence of alleles other than ARR under field conditions. If further investigations in other sheep breeds and with other scrapie sources confirm these findings, the availability of various protective alleles in breeding programmes of sheep for scrapie resistance could be useful in breeds with a low frequency of the ARR allele and would allow maintaining a wider variability of the PrP gene. PMID:19171116

  18. Low frequency of the scrapile resistance-associated allele and presence of lysine-171 allele of the prion protein gene in Italian Biellese ovine breed

    NARCIS (Netherlands)

    Acutis, P.L.; Sbaiz, L.; Verburg, F.J.; Riina, M.V.; Ru, G.; Moda, G.; Caramelli, M.; Bossers, A.

    2004-01-01

    Frequencies of polymorphisms at codons 136, 154 and 171 of the prion protein (PrP) gene were studied in 1207 pure-bred and cross-bred Italian Biellese rams, a small ovine breed of about 65 000 head in Italy. Aside from the five most common alleles (VRQ, ARQ, ARR, AHQ and ARH), the rare ARK allele wa

  19. African ancestry and its correlation to type 2 diabetes in African Americans: a genetic admixture analysis in three U.S. population cohorts.

    Directory of Open Access Journals (Sweden)

    Ching-Yu Cheng

    Full Text Available The risk of type 2 diabetes is approximately 2-fold higher in African Americans than in European Americans even after adjusting for known environmental risk factors, including socioeconomic status (SES, suggesting that genetic factors may explain some of this population difference in disease risk. However, relatively few genetic studies have examined this hypothesis in a large sample of African Americans with and without diabetes. Therefore, we performed an admixture analysis using 2,189 ancestry-informative markers in 7,021 African Americans (2,373 with type 2 diabetes and 4,648 without from the Atherosclerosis Risk in Communities Study, the Jackson Heart Study, and the Multiethnic Cohort to 1 determine the association of type 2 diabetes and its related quantitative traits with African ancestry controlling for measures of SES and 2 identify genetic loci for type 2 diabetes through a genome-wide admixture mapping scan. The median percentage of African ancestry of diabetic participants was slightly greater than that of non-diabetic participants (study-adjusted difference = 1.6%, P<0.001. The odds ratio for diabetes comparing participants in the highest vs. lowest tertile of African ancestry was 1.33 (95% confidence interval 1.13-1.55, after adjustment for age, sex, study, body mass index (BMI, and SES. Admixture scans identified two potential loci for diabetes at 12p13.31 (LOD = 4.0 and 13q14.3 (Z score = 4.5, P = 6.6 × 10(-6. In conclusion, genetic ancestry has a significant association with type 2 diabetes above and beyond its association with non-genetic risk factors for type 2 diabetes in African Americans, but no single gene with a major effect is sufficient to explain a large portion of the observed population difference in risk of diabetes. There undoubtedly is a complex interplay among specific genetic loci and non-genetic factors, which may both be associated with overall admixture, leading to the observed ethnic differences in diabetes

  20. Variation at APOE and STH loci and Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Kranzler Henry R

    2006-04-01

    Full Text Available Abstract Background The apolipoprotein E (APOE and tau proteins play important roles in the pathological development of Alzheimer's disease (AD. Many studies have shown an association between the APOE gene and AD. Association between AD and the newly discovered saitohin (STH gene, nested within the intron of the tau gene, has been reported. The present study aimed to elucidate the association between APOE and AD, and between STH and AD in our sample. Methods The functional polymorphisms, rs429358 and rs7412, in the APOE gene (which together define the ε2, ε3, and ε4 alleles, and the Q7R SNP in the STH gene, were genotyped in 369 patients with AD and 289 healthy European-Americans. The associations between these two genes and AD were analyzed in a case-control design. Results Consistent with previously reported results, the frequencies of the APOE ε4 allele, ε4/ε4 genotype and ε3/ε4 genotype were significantly higher in AD cases than controls; the ε4/ε4 genotype frequency was significantly higher in early-onset AD (EOAD than late-onset AD (LOAD; the frequencies of the ε2 allele, ε3 allele, ε3/ε3 genotype and ε2/ε3 genotype were significantly lower in AD cases than controls. Positive likelihood ratios (LRs+ of APOE alleles and genotypes increased in a linear trend with the number of ε4 alleles and decreased in a linear trend with the number of ε2 or ε3 alleles. There was no significant difference in the STH allele and genotype frequency distributions between AD cases and controls. Conclusion This study confirmed that the ε4 allele is a dose-response risk factor for AD and the ε4/ε4 genotype was associated with a significantly earlier age of onset. Moreover, we found that the ε2 allele was a dose-response protective factor for AD and the ε3 allele exerted a weaker dose-response protective effect for risk of AD compared with ε2. In a clinical setting, APOE genotyping could offer additional biological evidence of whether a

  1. Arabidopsis semidwarfs evolved from independent mutations in GA20ox1, ortholog to green revolution dwarf alleles in rice and barley.

    Science.gov (United States)

    Barboza, Luis; Effgen, Sigi; Alonso-Blanco, Carlos; Kooke, Rik; Keurentjes, Joost J B; Koornneef, Maarten; Alcázar, Rubén

    2013-09-24

    Understanding the genetic bases of natural variation for developmental and stress-related traits is a major goal of current plant biology. Variation in plant hormone levels and signaling might underlie such phenotypic variation occurring even within the same species. Here we report the genetic and molecular basis of semidwarf individuals found in natural Arabidopsis thaliana populations. Allelism tests demonstrate that independent loss-of-function mutations at GA locus 5 (GA5), which encodes gibberellin 20-oxidase 1 (GA20ox1) involved in the last steps of gibberellin biosynthesis, are found in different populations from southern, western, and northern Europe; central Asia; and Japan. Sequencing of GA5 identified 21 different loss-of-function alleles causing semidwarfness without any obvious general tradeoff affecting plant performance traits. GA5 shows signatures of purifying selection, whereas GA5 loss-of-function alleles can also exhibit patterns of positive selection in specific populations as shown by Fay and Wu's H statistics. These results suggest that antagonistic pleiotropy might underlie the occurrence of GA5 loss-of-function mutations in nature. Furthermore, because GA5 is the ortholog of rice SD1 and barley Sdw1/Denso green revolution genes, this study illustrates the occurrence of conserved adaptive evolution between wild A.thaliana and domesticated plants. PMID:24023067

  2. Allele mining and enhanced genetic recombination for rice breeding.

    Science.gov (United States)

    Leung, Hei; Raghavan, Chitra; Zhou, Bo; Oliva, Ricardo; Choi, Il Ryong; Lacorte, Vanica; Jubay, Mona Liza; Cruz, Casiana Vera; Gregorio, Glenn; Singh, Rakesh Kumar; Ulat, Victor Jun; Borja, Frances Nikki; Mauleon, Ramil; Alexandrov, Nickolai N; McNally, Kenneth L; Sackville Hamilton, Ruaraidh

    2015-12-01

    Traditional rice varieties harbour a large store of genetic diversity with potential to accelerate rice improvement. For a long time, this diversity maintained in the International Rice Genebank has not been fully used because of a lack of genome information. The publication of the first reference genome of Nipponbare by the International Rice Genome Sequencing Project (IRGSP) marked the beginning of a systematic exploration and use of rice diversity for genetic research and breeding. Since then, the Nipponbare genome has served as the reference for the assembly of many additional genomes. The recently completed 3000 Rice Genomes Project together with the public database (SNP-Seek) provides a new genomic and data resource that enables the identification of useful accessions for breeding. Using disease resistance traits as case studies, we demonstrated the power of allele mining in the 3,000 genomes for extracting accessions from the GeneBank for targeted phenotyping. Although potentially useful landraces can now be identified, their use in breeding is often hindered by unfavourable linkages. Efficient breeding designs are much needed to transfer the useful diversity to breeding. Multi-parent Advanced Generation InterCross (MAGIC) is a breeding design to produce highly recombined populations. The MAGIC approach can be used to generate pre-breeding populations with increased genotypic diversity and reduced linkage drag. Allele mining combined with a multi-parent breeding design can help convert useful diversity into breeding-ready genetic resources. PMID:26606925

  3. Allele frequency of CODIS 13 in Indonesian population.

    Science.gov (United States)

    Untoro, Evi; Atmadja, Djaja Surya; Pu, Chang-En; Wu, Fang-Chi

    2009-04-01

    Since the first application of DNA technology in 1985 in forensic cases, and the acceptance of this technology in 1988 at court, the DNA typing is widely used in personal identification, parentage cases and tracing the source of biological samples found in the crime scene. The FBI on 1990 had recommended the forensic labs to used 13 loci of Short Tandem Repeats (STR), known as CODIS 13, as the loci of choice for forensic use. The research on the population DNA database on these loci is extremely important for calculating the Paternity Index as well as Matching Probability for forensic application of DNA technology. As many as 402 unrelated persons, consisted of 322 from western part of Indonesia and 80 from eastern part of Indonesia, were chosen as the respondents of this research, after signing the informed consent. The peripheral blood sample was taken using sterile lancets and dropped onto FTA classic cards. The DNA was extracted by FTA purification solution (3x) and TE(-1) (2x), and amplified by PCR mix, either Cofiler or Profiler Plus (Perkin Elmers), followed by sequencing using ABI Prism type 3100 Avant Genetic Analyzer. The analysis showed that the alleles frequencies of Indonesian is specific, different with the other Asian populations with some specific alleles and microvariant were found. PMID:19261522

  4. Expression and loss of alleles in cultured mouse embryonic fibroblasts and stem cells carrying allelic fluorescent protein genes

    OpenAIRE

    Stringer Saundra L; Fischer Jared M; Yin Moying; Larson Jon S; Stringer James R

    2006-01-01

    Abstract Background Loss of heterozygosity (LOH) contributes to many cancers, but the rate at which these events occur in normal cells of the body is not clear. LOH would be detectable in diverse cell types in the body if this event were to confer an obvious cellular phenotype. Mice that carry two different fluorescent protein genes as alleles of a locus would seem to be a useful tool for addressing this issue because LOH would change a cell's phenotype from dichromatic to monochromatic. In a...

  5. Single-Nucleotide Polymorphisms in LPA Explain Most of the Ancestry-Specific Variation in Lp(a) Levels in African Americans

    OpenAIRE

    Deo, Rahul C.; Wilson, James G; Xing, Chao; Lawson, Kim; Kao, W.H. Linda; Reich, David; Tandon, Arti; Akylbekova, Ermeg; Patterson, Nick; Mosley, Thomas H (Jr); Boerwinkle, Eric; Taylor, Herman A.

    2011-01-01

    Lipoprotein(a) (Lp(a)) is an important causal cardiovascular risk factor, with serum Lp(a) levels predicting atherosclerotic heart disease and genetic determinants of Lp(a) levels showing association with myocardial infarction. Lp(a) levels vary widely between populations, with African-derived populations having nearly 2-fold higher Lp(a) levels than European Americans. We investigated the genetic basis of this difference in 4464 African Americans from the Jackson Heart Study (JHS) using a pa...

  6. Variant Toll-Like Receptor4 (Asp299Gly and Thr399Ile Alleles and Toll-Like Receptor2 (Arg753Gln and Arg677Trp Alleles in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Homa Davoodi

    2011-06-01

    Full Text Available The innate immune system recognizes the presence of bacterial products through the expression of a family of membrane receptors known as Toll-like receptors (TLRs. Polymorphisms in TLRs have been shown to be associated with increased susceptibility to diseases such as inflammatory bowel disease.The aim of this study was to determine whether there was a correlation between polymorphisms of TLR4 (Asp299Gly; Thr399Ile and TLR2 (Arg677Trp; Arg753Gln genes and risk of colorectal cancer. DNA from 60 colorectal carcinoma patients from 3 major races in Malaysia  (22  Malays,  20  Chinese  and  18  Indians  and  blood  from  50  apparently  healthy individuals were evaluated. Control group were matched to study group by race and age. The polymorphisms were determined by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP.Genotyping results showed two out of sixty tumor specimens (3.3% harbored both variant TLR4 Asp299Gly and Thr399Ile alleles. In contrast, DNA isolated from blood cells of 50 apparently healthy individuals harbored wild type TLR4. In the case of TLR2 Arg753Gln genotyping, all of the fifty normal and 60 tumors were of the wild type genotype. TLR2 Arg677Trp genotyping showed a heterozygous pattern in all samples. However, this may not be a true polymorphism of the TLR2 gene as it is likely due to a variation of a duplicated (pseudogene region. There was only a low incidence (2/60; 3.3% of TLR4 polymorphism at the Asp299Gly and Thr399Ile alleles in colorectal cancer patients. All normal and tumor samples harbored the wild type TLR2 Arg753 allele.Our study suggests that variant TLR4 (Asp299Gly and Thr399Ile alleles as well as TLR2 (Arg753Gln allele are not associated with risk of colorectal cancer.

  7. Experimental evidence for ecological selection on genome variation in the wild

    OpenAIRE

    Zachariah Gompert; Comeault, Aaron A.; Farkas, Timothy E; Feder, Jeffrey L.; Parchman, Thomas L.; C. Alex Buerkle; Patrik Nosil

    2014-01-01

    Understanding natural selection's effect on genetic variation is a major goal in biology, but the genome-scale consequences of contemporary selection are not well known. In a release and recapture field experiment we transplanted stick insects to native and novel host plants and directly measured allele frequency changes within a generation at 186 576 genetic loci. We observed substantial, genome-wide allele frequency changes during the experiment, most of which could be attributed to random ...

  8. A new analysis tool for individual-level allele frequency for genomic studies

    Directory of Open Access Journals (Sweden)

    Pan Wen-Harn

    2010-07-01

    Full Text Available Abstract Background Allele frequency is one of the most important population indices and has been broadly applied to genetic/genomic studies. Estimation of allele frequency using genotypes is convenient but may lose data information and be sensitive to genotyping errors. Results This study utilizes a unified intensity-measuring approach to estimating individual-level allele frequencies for 1,104 and 1,270 samples genotyped with the single-nucleotide-polymorphism arrays of the Affymetrix Human Mapping 100K and 500K Sets, respectively. Allele frequencies of all samples are estimated and adjusted by coefficients of preferential amplification/hybridization (CPA, and large ethnicity-specific and cross-ethnicity databases of CPA and allele frequency are established. The results show that using the CPA significantly improves the accuracy of allele frequency estimates; moreover, this paramount factor is insensitive to the time of data acquisition, effect of laboratory site, type of gene chip, and phenotypic status. Based on accurate allele frequency estimates, analytic methods based on individual-level allele frequencies are developed and successfully applied to discover genomic patterns of allele frequencies, detect chromosomal abnormalities, classify sample groups, identify outlier samples, and estimate the purity of tumor samples. The methods are packaged into a new analysis tool, ALOHA (Allele-frequency/Loss-of-heterozygosity/Allele-imbalance. Conclusions This is the first time that these important genetic/genomic applications have been simultaneously conducted by the analyses of individual-level allele frequencies estimated by a unified intensity-measuring approach. We expect that additional practical applications for allele frequency analysis will be found. The developed databases and tools provide useful resources for human genome analysis via high-throughput single-nucleotide-polymorphism arrays. The ALOHA software was written in R and R GUI and

  9. The lost p1 allele in sh2 sweet corn: Quantitative effects of p1 and a1 genes on the concentrations of maysin, apimaysin, methoxymaysin, and chlorogenic acid in maize silk, and the antibiotic activity against corn earworm

    Science.gov (United States)

    The flavor of sh2 super-sweet corn is preferred by consumers. Unfortunately, sh2 sweet corn has very little genetic variation for resistance to insects. This presentation will review and summarize the studies of the functions of two loci, p1 and a1. The P1 allele can have a major role in the resista...

  10. Genetic variations in the CLU and PICALM genes are associated with cognitive function in the oldest old

    DEFF Research Database (Denmark)

    Mengel-From, Jonas; Christensen, Kaare; McGue, Matt;

    2011-01-01

    (PICALM) gene and one variation, rs6656401, in the complement component (3b/4b) receptor 1 (CR) gene were associated with AD. Here, we replicate these associations with cognitive functioning in 1380 individuals from the Danish (1905) birth cohort study of the oldest old (92-93 years at intake) using...... measures of Mini Mental State Examination (MMSE) and a cognitive composite score. We found a significant association between the highly frequent CLU rs11136000 T allele (38%) and better performance on the cognitive composite score (p = 0.016) explaining 0.5% of the mean variation in cognitive composite...... score, and for men a significant association between the highly frequent PICALM rs3851179 A allele (38%). Better performance was found (p = 0.024), explaining 1.4% of the mean variation in cognitive composite score in men. These alleles correspond to the minor alleles initially found more frequent...

  11. Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.

    Science.gov (United States)

    Nettleton, Jennifer A; Follis, Jack L; Ngwa, Julius S; Smith, Caren E; Ahmad, Shafqat; Tanaka, Toshiko; Wojczynski, Mary K; Voortman, Trudy; Lemaitre, Rozenn N; Kristiansson, Kati; Nuotio, Marja-Liisa; Houston, Denise K; Perälä, Mia-Maria; Qi, Qibin; Sonestedt, Emily; Manichaikul, Ani; Kanoni, Stavroula; Ganna, Andrea; Mikkilä, Vera; North, Kari E; Siscovick, David S; Harald, Kennet; Mckeown, Nicola M; Johansson, Ingegerd; Rissanen, Harri; Liu, Yongmei; Lahti, Jari; Hu, Frank B; Bandinelli, Stefania; Rukh, Gull; Rich, Stephen; Booij, Lisanne; Dmitriou, Maria; Ax, Erika; Raitakari, Olli; Mukamal, Kenneth; Männistö, Satu; Hallmans, Göran; Jula, Antti; Ericson, Ulrika; Jacobs, David R; Van Rooij, Frank J A; Deloukas, Panos; Sjögren, Per; Kähönen, Mika; Djousse, Luc; Perola, Markus; Barroso, Inês; Hofman, Albert; Stirrups, Kathleen; Viikari, Jorma; Uitterlinden, André G; Kalafati, Ioanna P; Franco, Oscar H; Mozaffarian, Dariush; Salomaa, Veikko; Borecki, Ingrid B; Knekt, Paul; Kritchevsky, Stephen B; Eriksson, Johan G; Dedoussis, George V; Qi, Lu; Ferrucci, Luigi; Orho-Melander, Marju; Zillikens, M Carola; Ingelsson, Erik; Lehtimäki, Terho; Renström, Frida; Cupples, L Adrienne; Loos, Ruth J F; Franks, Paul W

    2015-08-15

    Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance. PMID:25994509

  12. Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry

    Science.gov (United States)

    Nettleton, Jennifer A.; Follis, Jack L.; Ngwa, Julius S.; Smith, Caren E.; Ahmad, Shafqat; Tanaka, Toshiko; Wojczynski, Mary K.; Voortman, Trudy; Lemaitre, Rozenn N.; Kristiansson, Kati; Nuotio, Marja-Liisa; Houston, Denise K.; Perälä, Mia-Maria; Qi, Qibin; Sonestedt, Emily; Manichaikul, Ani; Kanoni, Stavroula; Ganna, Andrea; Mikkilä, Vera; North, Kari E.; Siscovick, David S.; Harald, Kennet; Mckeown, Nicola M.; Johansson, Ingegerd; Rissanen, Harri; Liu, Yongmei; Lahti, Jari; Hu, Frank B.; Bandinelli, Stefania; Rukh, Gull; Rich, Stephen; Booij, Lisanne; Dmitriou, Maria; Ax, Erika; Raitakari, Olli; Mukamal, Kenneth; Männistö, Satu; Hallmans, Göran; Jula, Antti; Ericson, Ulrika; Jacobs,, David R.; Van Rooij, Frank J. A.; Deloukas, Panos; Sjögren, Per; Kähönen, Mika; Djousse, Luc; Perola, Markus; Barroso, Inês; Hofman, Albert; Stirrups, Kathleen; Viikari, Jorma; Uitterlinden, André G.; Kalafati, Ioanna P.; Franco, Oscar H.; Mozaffarian, Dariush; Salomaa, Veikko; Borecki, Ingrid B.; Knekt, Paul; Kritchevsky, Stephen B.; Eriksson, Johan G.; Dedoussis, George V.; Qi, Lu; Ferrucci, Luigi; Orho-Melander, Marju; Zillikens, M. Carola; Ingelsson, Erik; Lehtimäki, Terho; Renström, Frida; Cupples, L. Adrienne; Loos, Ruth J. F.; Franks, Paul W.

    2015-01-01

    Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist–hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006–0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance. PMID:25994509

  13. Allele discovery of ten candidate drought-response genes in Austrian oak using a systematically informatics approach based on 454 amplicon sequencing

    Directory of Open Access Journals (Sweden)

    Homolka Andreas

    2012-04-01

    Full Text Available Abstract Background Rise of temperatures and shortening of available water as result of predicted climate change will impose significant pressure on long-lived forest tree species. Discovering allelic variation present in drought related genes of two Austrian oak species can be the key to understand mechanisms of natural selection and provide forestry with key tools to cope with future challenges. Results In the present study we have used Roche 454 sequencing and developed a bioinformatic pipeline to process multiplexed tagged amplicons in order to identify single nucleotide polymorphisms and allelic sequences of ten candidate genes related to drought/osmotic stress from sessile oak (Quercus robur and sessile oak (Q. petraea individuals. Out of these, eight genes of 336 oak individuals growing in Austria have been detected with a total number of 158 polymorphic sites. Allele numbers ranged from ten to 52 with observed heterozygosity ranging from 0.115 to 0.640. All loci deviated from Hardy-Weinberg equilibrium and linkage disequilibrium was found among six combinations of loci. Conclusions We have characterized 183 alleles of drought related genes from oak species and detected first evidences of natural selection. Beside the potential for marker development, we have created an expandable bioinformatic pipeline for the analysis of next generation sequencing data.

  14. The miR9863 family regulates distinct Mla alleles in barley to attenuate NLR receptor-triggered disease resistance and cell-death signaling.

    Directory of Open Access Journals (Sweden)

    Jie Liu

    2014-12-01

    Full Text Available Barley (Hordeum vulgare L. Mla alleles encode coiled-coil (CC, nucleotide binding, leucine-rich repeat (NB-LRR receptors that trigger isolate-specific immune responses against the powdery mildew fungus, Blumeria graminis f. sp. hordei (Bgh. How Mla or NB-LRR genes in grass species are regulated at post-transcriptional level is not clear. The microRNA family, miR9863, comprises four members that differentially regulate distinct Mla alleles in barley. We show that miR9863 members guide the cleavage of Mla1 transcripts in barley, and block or reduce the accumulation of MLA1 protein in the heterologous Nicotiana benthamiana expression system. Regulation specificity is determined by variation in a unique single-nucleotide-polymorphism (SNP in mature miR9863 family members and two SNPs in the Mla miR9863-binding site that separates these alleles into three groups. Further, we demonstrate that 22-nt miR9863s trigger the biogenesis of 21-nt phased siRNAs (phasiRNAs and together these sRNAs form a feed-forward regulation network for repressing the expression of group I Mla alleles. Overexpression of miR9863 members specifically attenuates MLA1, but not MLA10-triggered disease resistance and cell-death signaling. We propose a key role of the miR9863 family in dampening immune response signaling triggered by a group of MLA immune receptors in barley.

  15. Sequence variation at the major histocompatibility complex locus DQ beta in beluga whales (Delphinapterus leucas)

    Science.gov (United States)

    Murray, B W; Malik, S; White, B N

    1995-07-01

    Genetic variation at the Major Histocompatibility Complex locus DQ beta was analyzed in 233 beluga whales (Delphinapterus leucas) from seven populations: St. Lawrence Estuary, eastern Beaufort Sea, eastern Chukchi Sea, western Hudson Bay, eastern Hudson Bay, southeastern Baffin Island, and High Arctic and in 12 narwhals (Monodon monoceros) sympatric with the High Arctic beluga population. Variation was assessed by amplification of the exon coding for the peptide binding region via the polymerase chain reaction, followed by either cloning and DNA sequencing or single-stranded conformation polymorphism analysis. Five alleles were found across the beluga populations and one in the narwhal. Pairwise comparisons of these alleles showed a 5:1 ratio of nonsynonymous to synonymous substitutions per site leading to eight amino acid differences, five of which were nonconservative substitutions, centered around positions previously shown to be important for peptide binding. Although the amount of allelic variation is low when compared with terrestrial mammals, the nature of the substitutions in the peptide binding sites indicates an important role for the DQ beta locus in the cellular immune response of beluga whales. Comparisons of allele frequencies among populations show the High Arctic population to be different (P Dele-DQ beta*0101-2, was found in 98% of the animals, while in the High Arctic it was found in only 52% of the animals. Two other alleles were found at high frequencies in the High Arctic population, one being very similar to the single allele found in narwhal. PMID:7659014

  16. Allele Frequency of D12S1632, D12S329, D12S96, D16S3096 and D16S2624 in four Ethnic Groups and Its Relationship With Metabolic Syndrome in Tehran Lipid and Glucose Study

    Directory of Open Access Journals (Sweden)

    Daneshpour

    2014-10-01

    Full Text Available Background Variation in drug resistance and susceptibility to various diseases may be related to difference in allele frequencies of the variants at the population level. Objectives The present study aimed to investigate the allele frequencies of five short tandem repeats (STR loci in two different chromosomes of candidates from Tehran Lipid and Glucose Study. Materials and Methods For this study, a representative sample of 563 individuals (130 affected by metabolic syndrome from Tehran, including four different ethnic groups of Iran, was selected. Five STRs including D12S1632, D12S329, D12S96, D16S3096 and D16S2624 were analyzed using the fragment analysis method. Allele frequency, polymorphism information content (PIC values, observed and expected heterozygosity, discrimination power, matching probability, power of discrimination, power of exclusion and paternity index were calculated for the whole sample. Results There was no significant deviation in allelic frequencies from Hardy-Weinberg equilibrium for all the studied markers except for D12S1632 and D12S329. The long alleles in D12S329 were significantly more frequent in patients with metabolic syndrome (P < 0.05. Conclusions This study revealed allele frequency of some STRs on chromosome 12 and 16 for the first time in Iran, and indicated differences between subjects with metabolic syndrome and subjects in the control group.

  17. Vitamin D receptor alleles and bone mineral density in a normal premenopausal Brazilian female population.

    Science.gov (United States)

    Lazaretti-Castro, M; Duarte-de-Oliveira, M A; Russo, E M; Vieira, J G

    1997-08-01

    Studies on the association between vitamin D receptor (VDR) polymorphism and bone mineral density (BMD) in different populations have produced conflicting results probably due to ethnic differences in the populations studied. The Brazilian population is characterized by a very broad genetic background and a high degree of miscegenation. Of an initial group of 164, we studied 127 women from the city of São Paulo, aged 20 to 47 years (median, 31 years), with normal menses, a normal diet and no history of diseases or use of any medication that could alter BMD. VDR genotype was assessed by PCR amplification followed by BsmI digestion of DNA isolated from peripheral leukocytes. BMD was measured using dual energy X-ray absorptiometry (Lunar DPX) at the lumbar site (L2-L4) and femoral neck. Most of the women (77.6%) were considered to be of predominantly European ancestry (20.6% of them reported also native American ancestry), 12.8% were of African-Brazilian ancestry and 9.6% of Asian ancestry, 41.0% (52) were classified as bb, 48.8% (62) as Bb and 10.2% (13) as BB. The BB, Bb and bb groups did not differ in age, height, weight, body mass index or age at menarche. Lumbar spine BMD was significantly higher in the bb group (1.22 +/- 0.16 g/cm2) than in the BB group (1.08 +/- 0.14; P < 0.05), and the Bb group presented an intermediate value (1.17 +/- 0.15). Femoral neck BMD was higher in the bb group (0.99 +/- 0.11 g/cm2) compared to Bb (0.93 +/- 0.12) and BB (0.90 +/- 0.09) (P < 0.05). These data indicate that there is a significant correlation between the VDR BsmI genotype and BMD in healthy Brazilian premenopausal females. PMID:9361720

  18. ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry

    OpenAIRE

    Bierut, Laura Jean; Goate, Alison M.; Breslau, Naomi; Johnson, Eric O.; Bertelsen, Sarah; Fox, Louis; Agrawal, Arpana; Bucholz, Kathleen K.; Grucza, Richard; Hesselbrock, Victor; Kramer, John; Kuperman, Samuel; Nurnberger, John; Porjesz, Bernice; Saccone, Nancy L.

    2011-01-01

    A coding variant in ADH1B (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American case-control studies in which alcohol dependence was defined by DSM-IV criteria, and demonstrated a strong protective effect of the Hi...

  19. Generation of humoral immune responses to multi-allele PfAMA1 vaccines; effect of adjuvant and number of component alleles on the breadth of response.

    Directory of Open Access Journals (Sweden)

    Kwadwo A Kusi

    Full Text Available There is increasing interest in multi-allele vaccines to overcome strain-specificity against polymorphic vaccine targets such as Apical Membrane Antigen 1 (AMA1. These have been shown to induce broad inhibitory antibodies in vitro and formed the basis for the design of three Diversity-Covering (DiCo proteins with similar immunological effects. The antibodies produced are to epitopes that are shared between vaccine alleles and theoretically, increasing the number of component AMA1 alleles is expected to broaden the antibody response. A plateau effect could however impose a limit on the number of alleles needed to achieve the broadest specificity. Moreover, production cost and the vaccine formulation process would limit the number of component alleles. In this paper, we compare rabbit antibody responses elicited with multi-allele vaccines incorporating seven (three DiCos and four natural AMA1 alleles and three (DiCo mix antigens for gains in broadened specificity. We also investigate the effect of three adjuvant platforms on antigen specificity and antibody functionality. Our data confirms a broadened response after immunisation with DiCo mix in all three adjuvants. Higher antibody titres were elicited with either CoVaccine HT™ or Montanide ISA 51, resulting in similar in vitro inhibition (65-82% of five out of six culture-adapted P. falciparum strains. The antigen binding specificities of elicited antibodies were also similar and independent of the adjuvant used or the number of vaccine component alleles. Thus neither the four extra antigens nor adjuvant had any observable benefits with respect to specificity broadening, although adjuvant choice influenced the absolute antibody levels and thus the extent of parasite inhibition. Our data confirms the feasibility and potential of multi-allele PfAMA1 formulations, and highlights the need for adjuvants with improved antibody potentiation properties for AMA1-based vaccines.

  20. Microsatellite polymorphism within pfcrt provides evidence of continuing evolution of chloroquine-resistant alleles in Papua New Guinea

    Directory of Open Access Journals (Sweden)

    Sharma Yagya D

    2007-03-01

    Full Text Available Abstract Background Polymorphism in the pfcrt gene underlies Plasmodium falciparum chloroquine resistance (CQR, as sensitive strains consistently carry lysine (K, while CQR strains carry threonine (T at the codon 76. Previous studies have shown that microsatellite (MS haplotype variation can be used to study the evolution of CQR polymorphism and to characterize intra- and inter-population dispersal of CQR in Papua New Guinea (PNG. Methods Here, following identification of new polymorphic MS in introns 2 and 3 within the pfcrt gene (msint2 and msint3, respectively, locus-by-locus and haplotype heterozygosity (H analyses were performed to determine the distribution of this intronic polymorphism among pfcrt chloroquine-sensitive and CQR alleles. Results For MS flanking the pfcrt CQR allele, H ranged from 0.07 (B5M77, -18 kb to 0.094 (9B12, +2 kb suggesting that CQ selection pressure was responsible for strong homogenisation of this gene locus. In a survey of 206 pfcrt-SVMNT allele-containing field samples from malaria-endemic regions of PNG, H for msint2 was 0.201. This observation suggests that pfcrt msint2 exhibits a higher level of diversity than what is expected from the analyses of pfcrt flanking MS. Further analyses showed that one of the three haplotypes present in the early 1980's samples has become the predominant haplotype (frequency = 0.901 in CQR parasite populations collected after 1995 from three PNG sites, when CQR had spread throughout malaria-endemic regions of PNG. Apparent localized diversification of pfcrt haplotypes at each site was also observed among samples collected after 1995, where minor CQR-associated haplotypes were found to be unique to each site. Conclusion In this study, a higher level of diversity at MS loci within the pfcrt gene was observed when compared with the level of diversity at pfcrt flanking MS. While pfcrt (K76T and its immediate flanking region indicate homogenisation in PNG CQR parasite populations

  1. An Allele Real-Coded Quantum Evolutionary Algorithm Based on Hybrid Updating Strategy

    Directory of Open Access Journals (Sweden)

    Yu-Xian Zhang

    2016-01-01

    Full Text Available For improving convergence rate and preventing prematurity in quantum evolutionary algorithm, an allele real-coded quantum evolutionary algorithm based on hybrid updating strategy is presented. The real variables are coded with probability superposition of allele. A hybrid updating strategy balancing the global search and local search is presented in which the superior allele is defined. On the basis of superior allele and inferior allele, a guided evolutionary process as well as updating allele with variable scale contraction is adopted. And Hε gate is introduced to prevent prematurity. Furthermore, the global convergence of proposed algorithm is proved by Markov chain. Finally, the proposed algorithm is compared with genetic algorithm, quantum evolutionary algorithm, and double chains quantum genetic algorithm in solving continuous optimization problem, and the experimental results verify the advantages on convergence rate and search accuracy.

  2. An Allele Real-Coded Quantum Evolutionary Algorithm Based on Hybrid Updating Strategy.

    Science.gov (United States)

    Zhang, Yu-Xian; Qian, Xiao-Yi; Peng, Hui-Deng; Wang, Jian-Hui

    2016-01-01

    For improving convergence rate and preventing prematurity in quantum evolutionary algorithm, an allele real-coded quantum evolutionary algorithm based on hybrid updating strategy is presented. The real variables are coded with probability superposition of allele. A hybrid updating strategy balancing the global search and local search is presented in which the superior allele is defined. On the basis of superior allele and inferior allele, a guided evolutionary process as well as updating allele with variable scale contraction is adopted. And H ε gate is introduced to prevent prematurity. Furthermore, the global convergence of proposed algorithm is proved by Markov chain. Finally, the proposed algorithm is compared with genetic algorithm, quantum evolutionary algorithm, and double chains quantum genetic algorithm in solving continuous optimization problem, and the experimental results verify the advantages on convergence rate and search accuracy. PMID:27057159

  3. Introgressive hybridization: brown bears as vectors for polar bear alleles.

    Science.gov (United States)

    Hailer, Frank

    2015-03-01

    The dynamics and consequences of introgression can inform about numerous evolutionary processes. Biologists have therefore long been interested in hybridization. One challenge, however, lies in the identification of nonadmixed genotypes that can serve as a baseline for accurate quantification of admixture. In this issue of Molecular Ecology, Cahill et al. (2015) analyse a genomic data set of 28 polar bears, eight brown bears and one American black bear. Polar bear alleles are found to be introgressed into brown bears not only near a previously identified admixture zone on the Alaskan Admiralty, Baranof and Chichagof (ABC) Islands, but also far into the North American mainland. Elegantly contrasting admixture levels at autosomal and X chromosomal markers, Cahill and colleagues infer that male-biased dispersal has spread these introgressed alleles away from the Late Pleistocene contact zone. Compared to a previous study on the ABC Island population in which an Alaskan brown bear served as a putatively admixture-free reference, Cahill et al. (2015) utilize a newly sequenced Swedish brown bear as admixture baseline. This approach reveals that brown bears have been impacted by introgression from polar bears to a larger extent (up to 8.8% of their genome), than previously known, including the bear that had previously served as admixture baseline. No evidence for introgression of brown bear into polar bear is found, which the authors argue could be a consequence of selection. Besides adding new exciting pieces to the puzzle of polar/brown bear evolutionary history, the study by Cahill and colleagues highlights that wildlife genomics is moving from analysing single genomes towards a landscape genomics approach. PMID:25775930

  4. Origins, distribution and expression of the Duarte-2 (D2) allele of galactose-1-phosphate uridylyltransferase

    OpenAIRE

    Carney, Amanda E.; Rebecca D Sanders; Garza, Kerry R.; McGaha, Lee Anne; Bean, Lora J. H.; Coffee, Bradford W.; Thomas, James W; Cutler, David J.; Kurtkaya, Natalie L.; Fridovich-Keil, Judith L.

    2009-01-01

    Duarte galactosemia is a mild to asymptomatic condition that results from partial impairment of galactose-1-phosphate uridylyltransferase (GALT). Patients with Duarte galactosemia demonstrate reduced GALT activity and carry one profoundly impaired GALT allele (G) along with a second, partially impaired GALT allele (Duarte-2, D2). Molecular studies reveal at least five sequence changes on D2 alleles: a p.N314D missense substitution, three intronic base changes and a 4 bp deletion in the 5′ pro...

  5. Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Lucotte, G.; David, F.; Berriche, S. [Regional Center of Neurogenetics, Reims (France)] [and others

    1994-09-15

    Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

  6. Identification of resistant carboxylesterase alleles in Culex pipiens complex via PCR-RFLP

    Directory of Open Access Journals (Sweden)

    Zhang Hanying

    2012-09-01

    Full Text Available Abstract Background Carboxylesterase overproduction is a frequently observed resistance mechanism of insects to organophosphate insecticides. As a major transmitter of human diseases, mosquitoes in the Culex pipiens complex have evolved 13 carboxylesterase alleles (Ester that confer organophosphate resistance. Six alleles, EsterB1, Ester2, Ester8, Ester9, EsterB10, and Ester11, have been observed in field populations in China, sometimes co-existing in one population. To differentiate the carboxylesterase alleles found in these field populations, PCR-RFLP was designed for use in resistance monitoring. Results Based on the DNA sequences of resistant and nonresistant carboxylesterase alleles, Ester B alleles were first amplified with PCR-specific primers and then digested with the restriction enzyme DraI. In this step, Ester2 and Ester11 were differentiated from the other Ester alleles. When the other Ester B alleles were digested with the restriction enzyme XbaI, EsterB1 and the susceptible C. p. pallens Ester were screened out. Ester8 and Ester9 were differentiated from EsterB10 and the susceptible C. p. quinquefasciatus esterase allele, respectively, by amplifying and digesting the Ester A alleles with the restriction enzyme ApaLI. The effectiveness of the custom-designed PCR-RFLP was verified in two field mosquito populations. Conclusions A PCR-RFLP based approach was developed to differentiate carboxylesterase alleles in Culex pipiens complex mosquitoes. These processes may be useful in monitoring the evolutionary dynamics of known carboxylesterase alleles as well as in the identification of new alleles in field populations.

  7. Age of an allele and gene genealogies of nested subsamples for populations admitting large offspring numbers

    OpenAIRE

    Eldon, Bjarki

    2012-01-01

    Coalescent processes, including mutation, are derived from Moran type population models admitting large offspring numbers. Including mutation in the coalescent process allows for quantifying the turnover of alleles by computing the distribution of the number of original alleles still segregating in the population at a given time in the past. The turnover of alleles is considered for specific classes of the Moran model admitting large offspring numbers. Versions of the Kingman coalescent are a...

  8. Allelic Spectra of Risk SNPs Are Different for Environment/Lifestyle Dependent versus Independent Diseases.

    Directory of Open Access Journals (Sweden)

    Ivan P Gorlov

    2015-07-01

    Full Text Available Genome-wide association studies (GWAS have generated sufficient data to assess the role of selection in shaping allelic diversity of disease-associated SNPs. Negative selection against disease risk variants is expected to reduce their frequencies making them overrepresented in the group of minor (<50% alleles. Indeed, we found that the overall proportion of risk alleles was higher among alleles with frequency <50% (minor alleles compared to that in the group of major alleles. We hypothesized that negative selection may have different effects on environment (or lifestyle-dependent versus environment (or lifestyle-independent diseases. We used an environment/lifestyle index (ELI to assess influence of environmental/lifestyle factors on disease etiology. ELI was defined as the number of publications mentioning "environment" or "lifestyle" AND disease per 1,000 disease-mentioning publications. We found that the frequency distributions of the risk alleles for the diseases with strong environmental/lifestyle components follow the distribution expected under a selectively neutral model, while frequency distributions of the risk alleles for the diseases with weak environmental/lifestyle influences is shifted to the lower values indicating effects of negative selection. We hypothesized that previously selectively neutral variants become risk alleles when environment changes. The hypothesis of ancestrally neutral, currently disadvantageous risk-associated alleles predicts that the distribution of risk alleles for the environment/lifestyle dependent diseases will follow a neutral model since natural selection has not had enough time to influence allele frequencies. The results of our analysis suggest that prediction of SNP functionality based on the level of evolutionary conservation may not be useful for SNPs associated with environment/lifestyle dependent diseases.

  9. Allele-specific enzymatic amplification of beta-globin genomic DNA for diagnosis of sickle cell anemia.

    OpenAIRE

    Wu, D Y; Ugozzoli, L; B..K. Pal; Wallace, R B

    1989-01-01

    A rapid nonradioactive approach to the diagnosis of sickle cell anemia is described based on an allele-specific polymerase chain reaction (ASPCR). This method allows direct detection of the normal or the sickle cell beta-globin allele in genomic DNA without additional steps of probe hybridization, ligation, or restriction enzyme cleavage. Two allele-specific oligonucleotide primers, one specific for the sickle cell allele and one specific for the normal allele, together with another primer co...

  10. Persistence of the common Hartnup disease D173N allele in populations of European origin.

    Science.gov (United States)

    Azmanov, Dimitar N; Rodgers, Helen; Auray-Blais, Christiane; Giguère, Robert; Bailey, Charles; Bröer, Stefan; Rasko, John E J; Cavanaugh, Juleen A

    2007-11-01

    Hartnup disorder is an aminoaciduria that results from mutations in the recently described gene SLC6A19 on chromosome 5p15.33. The disease is inherited in a simple recessive manner and ten different mutations have been described to date. One mutation, the D173N allele, is present in 42% of Hartnup chromosomes from apparently unrelated families from both Australia and North America. We report an investigation of the origins of the D173N allele using a unique combination of variants including SNPs, microsatellites, and a VNTR across 211 Kb spanning the SLC6A19 locus. All individuals who carry the mutant allele share an identical core haplotype suggesting a single common ancestor, indicating that the elevated frequency of the D173N allele is not a result of recurrent mutation. Analyses of these data indicate that the allele is more than 1000 years old. We compare the reasons for survival of this allele with other major alleles in some other common autosomal recessive diseases occurring in European Caucasians. We postulate that survival of this allele may be a consequence of failure of the allele to completely inactivate the transport of neutral amino acids. PMID:17555458

  11. Overdispersion in allelic counts and θ-correction in forensic genetics

    DEFF Research Database (Denmark)

    Tvedebrink, Torben

    2010-01-01

    We present a statistical model for incorporating the extra variability in allelic counts due to subpopulation structures. In forensic genetics, this effect is modelled by the identical-by-descent parameter θ, which measures the relationship between pairs of alleles within a population relative to...... the relationship of alleles between populations (Weir, 2007). In our statistical approach, we demonstrate that θ may be defined as an overdispersion parameter capturing the subpopulation effects. This formulation allows derivation of maximum likelihood estimates of the allele probabilities and θ...

  12. A quasi-exclusive European ancestry in the Senepol tropical cattle breed highlights the importance of the slick locus in tropical adaptation.

    Directory of Open Access Journals (Sweden)

    Laurence Flori

    Full Text Available BACKGROUND: The Senepol cattle breed (SEN was created in the early XX(th century from a presumed cross between a European (EUT breed (Red Poll and a West African taurine (AFT breed (N'Dama. Well adapted to tropical conditions, it is also believed trypanotolerant according to its putative AFT ancestry. However, such origins needed to be verified to define relevant husbandry practices and the genetic background underlying such adaptation needed to be characterized. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 153 SEN individuals on 47,365 SNPs and combined the resulting data with those available on 18 other populations representative of EUT, AFT and Zebu (ZEB cattle. We found on average 89% EUT, 10.4% ZEB and 0.6% AFT ancestries in the SEN genome. We further looked for footprints of recent selection using standard tests based on the extent of haplotype homozygosity. We underlined i three footprints on chromosome (BTA 01, two of which are within or close to the polled locus underlying the absence of horns and ii one footprint on BTA20 within the slick hair coat locus, involved in thermotolerance. Annotation of these regions allowed us to propose three candidate genes to explain the observed signals (TIAM1, GRIK1 and RAI14. CONCLUSIONS/SIGNIFICANCE: Our results do not support the accepted concept about the AFT origin of SEN breed. Initial AFT ancestry (if any might have been counter-selected in early generations due to breeding objectives oriented in particular toward meat production and hornless phenotype. Therefore, SEN animals are likely susceptible to African trypanosomes which questions the importation of SEN within the West African tsetse belt, as promoted by some breeding societies. Besides, our results revealed that SEN breed is predominantly a EUT breed well adapted to tropical conditions and confirmed the importance in thermotolerance of the slick locus.

  13. Association between Plasma 25-Hydroxyvitamin D, Ancestry and Aggressive Prostate Cancer among African Americans and European Americans in PCaP.

    Directory of Open Access Journals (Sweden)

    Susan E Steck

    Full Text Available African Americans (AAs have lower circulating 25-hydroxyvitamin D3 [25(OHD3] concentrations and higher prostate cancer (CaP aggressiveness than other racial/ethnic groups. The purpose of the current study was to examine the relationship between plasma 25(OHD3, African ancestry and CaP aggressiveness among AAs and European Americans (EAs.Plasma 25(OHD3 was measured using LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry in 537 AA and 663 EA newly-diagnosed CaP patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP classified as having either 'high' or 'low' aggressive disease based on clinical stage, Gleason grade and prostate specific antigen at diagnosis. Mean plasma 25(OHD3 concentrations were compared by proportion of African ancestry. Logistic regression was used to calculate multivariable adjusted odds ratios (OR and 95% confidence intervals (95%CI for high aggressive CaP by tertile of plasma 25(OHD3.AAs with highest percent African ancestry (>95% had the lowest mean plasma 25(OHD3 concentrations. Overall, plasma 25(OHD3 was associated positively with aggressiveness among AA men, an association that was modified by calcium intake (ORT 3vs.T1: 2.23, 95%CI: 1.26-3.95 among men with low calcium intake, and ORT 3vs.T1: 0.19, 95%CI: 0.05-0.70 among men with high calcium intake. Among EAs, the point estimates of the ORs were <1.0 for the upper tertiles with CIs that included the null.Among AAs, plasma 25(OHD3 was associated positively with CaP aggressiveness among men with low calcium intake and inversely among men with high calcium intake. The clinical significance of circulating concentrations of 25(OHD3 and interactions with calcium intake in the AA population warrants further study.

  14. Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype.

    Science.gov (United States)

    Krause, Amanda; Mitchell, Claire; Essop, Fahmida; Tager, Susan; Temlett, James; Stevanin, Giovanni; Ross, Christopher; Rudnicki, Dobrila; Margolis, Russell

    2015-10-01

    Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations. PMID:26079385

  15. Ageing: Cognitive change and the APOEe4 allele

    OpenAIRE

    Deary, Ian J; Whiteman, Martha C; Pattie, Alison; Starr, John M; Hayward, Caroline; Wright, Alan F.; Carothers, Andrew; Lawrence J Whalley

    2002-01-01

    There is a marked variation in whether people retain sufficient cognitive function to maintain their quality of life and independence in old age, even among those without dementia, so it would be valuable to identify the determinants of normal age-related cognitive change (1,2). We have retested non-demented 80-year-olds who were participants in the Scottish Mental Survey of 1932, and find that the variation in their non-pathological cognitive change from age ...

  16. Extensive sequence variation in rice blast resistance gene Pi54 makes it broad spectrum in nature

    Directory of Open Access Journals (Sweden)

    Shallu eThakur

    2015-05-01

    Full Text Available Rice blast resistant gene, Pi54 cloned from rice line, Tetep, is effective against diverse isolates of Magnaporthe oryzae. In this study, we prospected the allelic variants of the dominant blast resistance gene from a set of 92 rice lines to determine the nucleotide diversity, pattern of its molecular evolution, phylogenetic relationships and evolutionary dynamics, and to develop allele specific markers. High quality sequences were generated for homologs of Pi54 gene. Using comparative sequence analysis, InDels of variable sizes in all the alleles were observed. Profiling of the selected sites of SNP (Single Nucleotide Polymorphism and amino acids (N sites ≥ 10 exhibited constant frequency distribution of mutational and substitutional sites between the resistance and susceptible rice lines, respectively. A total of 50 new haplotypes based on the nucleotide polymorphism was also identified. A unique haplotype (H_3 was found to be linked to all the resistant alleles isolated from indica rice lines. Unique leucine zipper and tyrosine sulfation sites were identified in the predicted Pi54 proteins. Selection signals were observed in entire coding sequence of resistance alleles, as compared to LRR domains for susceptible alleles. This is a maiden report of extensive variability of Pi54 alleles in different landraces and cultivated varieties, possibly, attributing broad-spectrum resistance to Magnaporthe oryzae. The sequence variation in two consensus region: 163 bp and 144 bp were used for the development of allele specific DNA markers. Validated markers can be used for the selection and identification of better allele(s and their introgression in commercial rice cultivars employing marker assisted selection.

  17. Modeling variation in tumors in vivo

    OpenAIRE

    Stringer, James R.; Larson, Jon S.; Fischer, Jared M; Medvedovic, Mario; Hersh, Megan N; Boivin, Gregory P.; Stringer, Saundra L.

    2005-01-01

    Transgenic mice that allow mutant cells to be visualized in situ were used to study variation in tumors. These mice carry the G11 placental alkaline phosphatase (PLAP) transgene, a mutant allele rendered incapable of producing its enzyme product by a frameshift caused by insertion of a tract of G:C base pairs in a coding region. Spontaneous deletion of one G:C base pair from this tract restores gene function, and cells with PLAP activity can be detected histochemically. To study tumors, the G...

  18. Novel alleles among soybean Bowman-Birk proteinase inhibitor gene families

    Institute of Scientific and Technical Information of China (English)

    WANG YuePing; CHEN XiongTing; QIU LiJuan

    2008-01-01

    Trypsin inhibitors have been found in various animals, plants and microorganisms. There were two types of trypsin inhibitors in soybean including Bowman-Birk protease inhibitors (BBI) and Kunitz in-hibitors (KTI). The different BBI genes from wild soybean (G.soja) and cultivated soybean (G max) formed a multigene family. We constructed a cDNA library of cultivar 'SuiNong 14' seed at the R7 growth stage using the SMART Kit. Seventeen contigs or singletons were highly homologous to soy-bean protease inhibitors. Contigs of 5, 35, 8 and 9 were highly homologous to BBI family members BBI-A1, BBI-A2, BBI-C and BBI-D, respectively. Sequence analyses showed there were novel allelic varia-tions among the 4 BBI members in SuiNong 14. Based on the comparison of soybean seed cDNA li-braries from different developmental stages, it was apparent that the expression of trypsin inhibitors increased during seed development in soybean. Phylogenetic analysis of BBI gene sequences among dicotyledonous and monocotyledonous plants demonstrated that these genes shared a common pro-genitor.

  19. Allele-specific analysis of DNA replication origins in mammalian cells.

    Science.gov (United States)

    Bartholdy, Boris; Mukhopadhyay, Rituparna; Lajugie, Julien; Aladjem, Mirit I; Bouhassira, Eric E

    2015-01-01

    The mechanisms that control the location and timing of firing of replication origins are poorly understood. Using a novel functional genomic approach based on the analysis of SNPs and indels in phased human genomes, we observe that replication asynchrony is associated with small cumulative variations in the initiation efficiency of multiple origins between the chromosome homologues, rather than with the activation of dormant origins. Allele-specific measurements demonstrate that the presence of G-quadruplex-forming sequences does not correlate with the efficiency of initiation. Sequence analysis reveals that the origins are highly enriched in sequences with profoundly asymmetric G/C and A/T nucleotide distributions and are almost completely depleted of antiparallel triplex-forming sequences. We therefore propose that although G4-forming sequences are abundant in replication origins, an asymmetry in nucleotide distribution, which increases the propensity of origins to unwind and adopt non-B DNA structure, rather than the ability to form G4, is directly associated with origin activity. PMID:25987481

  20. A genome-wide scan for common alleles affecting risk for autism.

    LENUS (Irish Health Repository)

    Anney, Richard

    2010-10-15

    Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner\\'s curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.

  1. Disagreement in genotyping results of drug resistance alleles of the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) gene by allele-specific PCR (ASPCR) assays and Sanger sequencing.

    Science.gov (United States)

    Sharma, Divya; Lather, Manila; Dykes, Cherry L; Dang, Amita S; Adak, Tridibes; Singh, Om P

    2016-01-01

    The rapid spread of antimalarial drug resistance in Plasmodium falciparum over the past few decades has necessitated intensive monitoring of such resistance for an effective malaria control strategy. P. falciparum dihydropteroate synthase (Pfdhps) and P. falciparum dihydrofolate reductase (Pfdhfr) genes act as molecular markers for resistance against the antimalarial drugs sulphadoxine and pyrimethamine, respectively. Resistance to pyrimethamine which is used as a partner drug in artemisinin combination therapy (ACT) is associated with several mutations in the Pfdhfr gene, namely A16V, N51I, C59R, S108N/T and I164L. Therefore, routine monitoring of Pfdhfr-drug-resistant alleles in a population may help in effective drug resistance management. Allele-specific PCR (ASPCR) is one of the commonly used methods for molecular genotyping of these alleles. In this study, we genotyped 55 samples of P. falciparum for allele discrimination at four codons of Pfdhfr (N51, C59, S108 and I164) by ASPCR using published methods and by Sanger's DNA sequencing method. We found that the ASPCR identified a significantly higher number of mutant alleles as compared to the DNA sequencing method. Such discrepancies arise due to the non-specificity of some of the allele-specific primer sets and due to the lack of sensitivity of Sanger's DNA sequencing method to detect minor alleles present in multiple clone infections. This study reveals the need of a highly specific and sensitive method for genotyping and detecting minor drug-resistant alleles present in multiple clonal infections. PMID:26407876

  2. Dynamics of insecticide resistance alleles in house fly populations from New York and Florida.

    Science.gov (United States)

    Rinkevich, Frank D; Hamm, Ronda L; Geden, Christopher J; Scott, Jeffrey G

    2007-06-01

    The frequency of insecticide-resistance alleles for two genes (Vssc1 and CYP6D1) was studied in field collected populations of house flies from two different climates. While the frequency of these resistance alleles in flies at dairies from four states has recently been reported, there is no information on the relative change of these allele frequencies over time. House flies were collected during the 2003-2004 season from New York and Florida before the first application of permethrin, during the middle of the field season, after the final application, and again the following spring (following months without permethrin use). Bioassay results indicated that homozygous susceptible and extremely resistant flies were rare, while moderately and highly resistant individuals were relatively common at all times in both states. The frequency of resistance alleles at the New York dairy rose during the season and declined over the winter, suggesting an overwintering fitness cost associated with these alleles. The super-kdr allele was detected for the first time in North America at the end of 2003. In Florida the frequency of the resistance alleles did not increase during the spray season or decrease during the winter, suggesting there is substantial immigration of susceptible alleles to the Florida dairy and no overwintering fitness cost associated with resistance alleles in this climate. Resistance to permethrin correlated well with the frequency of the Vssc1 and CYP6D1 resistance alleles in flies from New York, but not as well in the population from Florida. This suggests there may be a new resistance mechanism or allele evolving in Florida. PMID:17517332

  3. Allele-mining and natural diversity in wheat powdery mildew resistance genes

    International Nuclear Information System (INIS)

    Using map-based cloning, we have isolated the Pm3b powdery mildew resistance gene from hexaploid bread wheat (Triticum aestivum L.). Based on haplotype studies, we have developed molecular tools to isolate all the 10 known Pm3 genes conferring resistance. We found that the Pm3 genes form a true allelic series and that they are highly conserved at the molecular level. The molecular work on Pm3 resistance genes has lead to very diagnostic tools for these genes which support the cloning of new functional alleles from this locus by allele-mining. We have used these tools to screen for new Pm3 alleles in the gene pools of (i) wild and domesticated tetraploid accessions and (ii) hexaploid wheat landraces. The Pm3 locus is conserved in tetraploid wheat, allowing a comparative evolutionary study of the same resistance locus in a domesticated species and one of its wild ancestors. We have identified 61 Pm3 allelic sequences from wild and domesticated tetraploid wheat subspecies. These alleles showed low sequence diversity, differing by few polymorphic sequence blocks that were further reshuffled between alleles by gene conversion and recombination. A new functional gene was identified in a wild wheat accession from Syria. This gene, Pm3k, conferred intermediate resistance to powdery mildew and consists of a mosaic of gene segments derived from non-functional alleles. From the hexaploid wheat gene pool, a set of 1320 landraces, mostly from Asia, was screened for powdery mildew resistance and the presence of a Pm3 haplotype. Most of these lines were found to contain a susceptible Pm3 allele which is closely related to the functional Pm3 resistance genes. We have also identified resistant lines with new types of Pm3 allelic sequences, resulting from point mutations, gene conversion and illegitimate recombination events. These new alleles are currently tested for resistance activity in a transient expression assay. (author)

  4. Cognitive and neural correlates of the 5-repeat allele of the dopamine D4 receptor gene in a population lacking the 7-repeat allele.

    Science.gov (United States)

    Takeuchi, Hikaru; Tomita, Hiroaki; Taki, Yasuyuki; Kikuchi, Yoshie; Ono, Chiaki; Yu, Zhiqian; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

    2015-04-15

    The 5-repeat allele of a common length polymorphism in the gene that encodes the dopamine D4 receptor (DRD4) is robustly associated with the risk of attention deficit hyperactivity disorder (ADHD) and substantially exists in Asian populations, which have a lower ADHD prevalence. In this study, we investigated the effect of this allele on microstructural properties of the brain and on its functional activity during externally directed attention-demanding tasks and creative performance in the 765 Asian subjects. For this purpose, we employed diffusion tensor imaging, N-back functional magnetic resonance imaging paradigms, and a test to measure creativity by divergent thinking. The 5-repeat allele was significantly associated with increased originality in the creative performance, increased mean diffusivity (the measure of how the tissue includes water molecules instead of neural and vessel components) in the widespread gray and white matter areas of extensive areas, particularly those where DRD4 is expressed, and reduced task-induced deactivation in the areas that are deactivated during the tasks in the course of both the attention-demanding working memory task and simple sensorimotor task. The observed neural characteristics of 5-repeat allele carriers may lead to an increased risk of ADHD and behavioral deficits. Furthermore, the increased originality of creative thinking observed in the 5-repeat allele carriers may support the notion of the side of adaptivity of the widespread risk allele of psychiatric diseases. PMID:25659462

  5. A transcriptional network associated with natural variation in Drosophila aggressive behavior

    OpenAIRE

    Edwards, Alexis C.; Ayroles, Julien F.; STONE, ERIC A.; Carbone, Mary Anna; Lyman, Richard F.; Mackay, Trudy FC

    2009-01-01

    Background Aggressive behavior is an important component of fitness in most animals. Aggressive behavior is genetically complex, with natural variation attributable to multiple segregating loci with allelic effects that are sensitive to the physical and social environment. However, we know little about the genes and genetic networks affecting natural variation in aggressive behavior. Populations of Drosophila melanogaster harbor quantitative genetic variation in aggressive behavior, providing...

  6. Individual Variation in Inbreeding Depression: The Roles of Inbreeding History and Mutation

    OpenAIRE

    Schultz, S. T.; Willis, J H

    1995-01-01

    We use mutation-selection recursion models to evaluate the relative contributions of mutation and inbreeding history to variation among individuals in inbreeding depression and the ability of experiments to detect associations between individual inbreeding depression and mating system genotypes within populations. Poisson mutation to deleterious additive or recessive alleles generally produces far more variation among individuals in inbreeding depression than variation in history of inbreedin...

  7. ZNF804A risk allele is associated with relatively intact gray matter volume in patients with schizophrenia.

    LENUS (Irish Health Repository)

    Donohoe, Gary

    2011-02-01

    ZNF804A rs1344706 is the first genetic risk variant to achieve genome wide significance for psychosis. Following earlier evidence that patients carrying the ZNF804A risk allele had relatively spared memory function compared to patient non-carriers, we investigated whether ZNF804A was also associated with variation in brain volume. In a sample of 70 patients and 38 healthy participants we used voxel based morphometry to compare homozygous (AA) carriers of the ZNF804A risk allele to heterozygous and homozygous (AC\\/CC) non-carriers for both whole brain volume and specific regions implicated in earlier ZNF804A studies-the dorsolateral pre-frontal cortex, the hippocampus, and the amygdala. For patients, but not for controls, we found that homozygous \\'AA\\' risk carriers had relatively larger gray matter volumes than heterozygous\\/homozygous non-carriers (AC\\/CC), particularly for hippocampal volumes. These data are consistent with our earlier behavioral data and suggest that ZNF804A is delineating a schizophrenia subtype characterized by relatively intact brain volume. Establishing if this represents a discrete molecular pathogenesis with consequences for nosology and treatment will be an important next step in understanding ZNF084A\\'s role in illness risk.

  8. Molecular detection and identification of intimin alleles in pathogenic Escherichia coli by multiplex PCR.

    Science.gov (United States)

    Reid, S D; Betting, D J; Whittam, T S

    1999-08-01

    A multiplex PCR was designed to detect the eae gene and simultaneously identify specific alleles in pathogenic Escherichia coli. The method was tested on 87 strains representing the diarrheagenic E. coli clones. The results show that the PCR assay accurately detects eae and resolves alleles encoding the alpha, beta, and gamma intimin variants. PMID:10405431

  9. Identification of novel alleles of the rice blast resistance gene Pi54

    Science.gov (United States)

    Vasudevan, Kumar; Gruissem, Wilhelm; Bhullar, Navreet K.

    2015-10-01

    Rice blast is one of the most devastating rice diseases and continuous resistance breeding is required to control the disease. The rice blast resistance gene Pi54 initially identified in an Indian cultivar confers broad-spectrum resistance in India. We explored the allelic diversity of the Pi54 gene among 885 Indian rice genotypes that were found resistant in our screening against field mixture of naturally existing M. oryzae strains as well as against five unique strains. These genotypes are also annotated as rice blast resistant in the International Rice Genebank database. Sequence-based allele mining was used to amplify and clone the Pi54 allelic variants. Nine new alleles of Pi54 were identified based on the nucleotide sequence comparison to the Pi54 reference sequence as well as to already known Pi54 alleles. DNA sequence analysis of the newly identified Pi54 alleles revealed several single polymorphic sites, three double deletions and an eight base pair deletion. A SNP-rich region was found between a tyrosine kinase phosphorylation site and the nucleotide binding site (NBS) domain. Together, the newly identified Pi54 alleles expand the allelic series and are candidates for rice blast resistance breeding programs.

  10. Mannose-binding lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Øhlenschlaeger, Tommy; Garred, Peter; Madsen, Hans O;

    2004-01-01

    Cardiovascular disease is an important complication in patients with systemic lupus erythematosus (SLE). Variant alleles of the mannose-binding lectin gene are associated with SLE as well as with severe atherosclerosis. We determined whether mannose-binding lectin variant alleles were associated...

  11. An Updated Collection of Sequence Barcoded Temperature-Sensitive Alleles of Yeast Essential Genes.

    Science.gov (United States)

    Kofoed, Megan; Milbury, Karissa L; Chiang, Jennifer H; Sinha, Sunita; Ben-Aroya, Shay; Giaever, Guri; Nislow, Corey; Hieter, Philip; Stirling, Peter C

    2015-09-01

    Systematic analyses of essential gene function using mutant collections in Saccharomyces cerevisiae have been conducted using collections of heterozygous diploids, promoter shut-off alleles, through alleles with destabilized mRNA, destabilized protein, or bearing mutations that lead to a temperature-sensitive (ts) phenotype. We previously described a method for construction of barcoded ts alleles in a systematic fashion. Here we report the completion of this collection of alleles covering 600 essential yeast genes. This resource covers a larger gene repertoire than previous collections and provides a complementary set of strains suitable for single gene and genomic analyses. We use deep sequencing to characterize the amino acid changes leading to the ts phenotype in half of the alleles. We also use high-throughput approaches to describe the relative ts behavior of the alleles. Finally, we demonstrate the experimental usefulness of the collection in a high-content, functional genomic screen for ts alleles that increase spontaneous P-body formation. By increasing the number of alleles and improving the annotation, this ts collection will serve as a community resource for probing new aspects of biology for essential yeast genes. PMID:26175450

  12. HLA-DRB1 allele polymorphisms in genetic susceptibility to esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun Lin; Chang-Sheng Deng; Jie Sun; Xian-Gong Zheng; Xing Huang; Yan Zhou; Ping Xiong; Ya-Ping Wang

    2003-01-01

    AIM: To probe into the genetic susceptibility of HLA-DRB1 alleles to esophageal carcinoma in Han Chinese in Hubei Province.METHODS: HLA-DRB1 allele polymorphisms were typed by polymerase chain reaction with sequence-specific primers (PCR-SSP) in 42 unrelated patients with esophageal cancer and 136 unrelated normal control subjects and the associated HLA-DRB1 allele was measured by nucleotide sequence analysis with PCR.SAS software was used in statistics.RESULTS: Allele frequency (AF) of HLA-DRB1·0901 was significantly higher in esophageal carcinoma patients than that in the normal controls (0.2500 vs0.1397, P=0.028, the odds ratio 2.053, etiologic fraction 0.1282). After analyzed the allele nucleotide sequence of HLA-DRB1·0901 which approachs to the corresponded exon 2 sequence of the allele in genebank. There was no association between patients and controls in the rested HLA-DRB1 alleles.CONCLUSION: HLA-DRB1·0901 allele is more common in the patients with esophageal carcinoma than in the healthy controls, which is positively associated with the patients of Hubei Han Chinese. Individuals carrying HLA-DRB1·0901may be susceptible to esophageal carcinoma.

  13. Correlation in chicken between the marker LEI0258 alleles and Major Histocompatibility Complex sequences

    DEFF Research Database (Denmark)

    Chazara, Olympe; Juul-Madsen, Helle Risdahl; Chang, Chi-Seng;

    Background The LEI0258 marker is located within the B region of the chicken Major Histocompatibility Complex (MHC), and is surprisingly well associated with serology. Therefore, the correlation between the LEI0258 alleles and the MHC class I and the class II alleles at the level of sequences is w...

  14. Salmonella Typhi shdA: pseudogene or allelic variant?

    Science.gov (United States)

    Urrutia, I M; Fuentes, J A; Valenzuela, L M; Ortega, A P; Hidalgo, A A; Mora, G C

    2014-08-01

    ShdA from Salmonella Typhimurium (ShdASTm) is a large outer membrane protein that specifically recognizes and binds to fibronectin. ShdASTm is involved in the colonization of the cecum and the Peyer's patches of terminal ileum in mice. On the other hand, shdA gene from Salmonella Typhi (shdASTy) has been considered a pseudogene (i.e. a nonfunctional sequence of genomic DNA) due to the presence of deletions and mutations that gave rise to premature stop codons. In this work we show that, despite the deletions and mutations, shdASTy is fully functional. S. Typhi ΔshdA mutants presented an impaired adherence and invasion of HEp-2 pre-treated with TGF-β1, an inducer of fibronectin production. Moreover, shdA from S. Typhi and S. Typhimurium seem to be equivalent since shdASTm restored the adherence and invasion of S. Typhi ΔshdA mutant to wild type levels. In addition, anti-FLAG mAbs interfered with the adherence and invasion of the S. Typhi shdA-3xFLAG strain. Finally, shdASTy encodes a detectable protein when heterologously expressed in Escherichia coli DH5α. The data presented here show that shdASTy is not a pseudogene, but a different functional allele compared with shdASTm. PMID:24859062

  15. Evidence for multiple alleles effecting muscling and fatness at the Ovine GDF8 locus

    Directory of Open Access Journals (Sweden)

    Oddy V Hutton

    2007-11-01

    Full Text Available Abstract Background The current investigation surveyed genetic polymorphism at the ovine GDF8 locus and determined its contribution to variation in muscling and fatness in sheep. Results Re-sequencing 2988 bp from a panel of 15 sires revealed a total of six SNP, none of which were located within exons of the gene. One of the identified SNP, g+6723G>A, is known to increase muscularity within the Belgian Texel. A genetic survey of 326 animals revealed that the mutation is near fixation within Australian Texels and present in additional breeds including White Suffolk, Poll Dorset and Lincoln. Using a resource population comprising 15 sires and 1191 half-sib progeny with genotypic data, the effect of this and other SNP was tested against a set of 50 traits describing growth, muscling, fatness, yield, meat and eating quality. The loss of function allele (g+6723A showed significant effects on slaughter measurements of muscling and fatness. No effect was detected on objectively assessed meat quality however evidence was found for an association between g+6723G>A, decreased intramuscular fat and reduced eating quality. Haplotype analysis using flanking microsatellites was performed to search for evidence of currently unidentified mutations which might affect production traits. Four haplotypes were identified that do not carry g+6723A but which showed significant associations with muscling and fatness. Conclusion The finding that g+6723G>A is present within Australian sheep facilitated an independent evaluation into its phenotypic consequence. Testing was conducted using a separate genetic background and animals raised in different environments to the Belgian Texel in which it was first identified. The observation that the direction and size of effects for g+6723A is approximately consistent represented a robust validation of the effects of the mutation. Based on observed allele frequencies within breeds, selection for g+6723A will have the largest

  16. Beneficial role of D allele in controlling ACE levels: a study among Brahmins of north India.

    Science.gov (United States)

    Kumari, Shobha; Sharma, Nidhi; Thakur, Sunil; Mondal, Prakash R; Saraswathy, Kallur N

    2016-06-01

    India being a country with vast diversity is expected to have different dietary and life style patterns which in turn may lead to population-specific environmental risk factors. Further, the interaction of these risk factors with the genetic makeup of population makes it either susceptible or resistant to cardiovascular disease. One such candidate gene is angiotensin converting enzyme (ACE) for various cardiovascular mechanisms. ACE is the key enzyme of the renin angiotensin aldosterone system pathway which maintains homeostasis blood pressure in the body and any variation in the levels is reported to be associated with various complex diseases. The DD genotype is found to increase ACE levels, which is associated with cardiovascular diseases and decrease in ACE levels are associated with kidney diseases. The aim of this study was to understand the distribution of ACE I/D polymorphism and ACE levels among Brahmins of National Capital Region (NCR) north India, with respect to age and sex ratio distribution. In this study, 136 subjects of which 50 males and 86 females, who were unrelated up to first cousin, aged 25 to70 years were studied. ACE gene was found to be polymorphic with high frequency of heterozygote (ID) followed by II and DD genotypes. The studied population was found to be in Hardy-Weinberg equilibrium with respect to ACE I/D polymorphism (P = 0.55). I allele frequency was found to be higher (0.560) than the D allele (0.44). The median level of ACE was found to be 65.96 ng/mL (48.12-86.24) which is towards lower side of the normal range. ACE levels were found to be increased among individual having either of the homozygotes that is II or DD and higher frequency of heterozygote (ID) is indicative of advantage in the population by maintaining lower ACE levels. The limitation of the present study is low sample size, however, the merit is that the subjects belonged to a Mendalian population with a common gene pool. PMID:27350671

  17. Beneficial role of D allele in controlling ACE levels: a study among Brahmins of north India

    Indian Academy of Sciences (India)

    SHOBHA KUMARI; NIDHI SHARMA; SUNIL THAKUR; PRAKASH R. MONDAL; KKALLUR N. SARASWATHY

    2016-06-01

    India being a country with vast diversity is expected to have different dietary and life style patterns which in turn may lead topopulation-specific environmental risk factors. Further, the interaction of these risk factors with the genetic makeup of pop-ulation makes it either susceptible or resistant to cardiovascular disease. One such candidate gene is angiotensin convertingenzyme (ACE) for various cardiovascular mechanisms. ACE is the key enzyme of the renin angiotensin aldosterone systempathway which maintains homeostasis blood pressure in the body and any variation in the levels is reported to be associatedwith various complex diseases. The DD genotype is found to increase ACE levels, which is associated with cardiovasculardiseases and decrease in ACE levels are associated with kidney diseases. The aim of this study was to understand the distribu-tion of ACE I/D polymorphism and ACE levels among Brahmins of National Capital Region (NCR) north India, with respectto age and sex ratio distribution. In this study, 136 subjects of which 50 males and 86 females, who were unrelated up to firstcousin, aged 25 to70 years were studied.ACEgene was found to be polymorphic with high frequency of heterozygote (ID)followed by II and DD genotypes. The studied population was found to be in Hardy–Weinberg equilibrium with respect toACE I/D polymorphism (P =0.55). I allele frequency was found to be higher (0.560) than the D allele (0.44). The medianlevel of ACE was found to be 65.96 ng/mL (48.12–86.24) which is towards lower side of the normal range. ACE levels werefound to be increased among individual having either of the homozygotes that is II or DD and higher frequency of heterozy-gote (ID) is indicative of advantage in the population by maintaining lower ACE levels. The limitation of the present study islow sample size, however, the merit is that the subjects belonged to a Mendalian population with a common gene pool

  18. Human cranial vault thickness in a contemporary sample of 1097 autopsy cases: relation to body weight, stature, age, sex and ancestry.

    Science.gov (United States)

    De Boer, H H Hans; Van der Merwe, A E Lida; Soerdjbalie-Maikoe, V Vidija

    2016-09-01

    The relation between human cranial vault thickness (CVT) and various elements of the physical anthropological biological profile is subject of ongoing discussion. Some results seem to indicate no correlation between CVT and the biological profile of the individual, whereas other results suggest that CVT measurements might be useful for identification purposes. This study assesses the correlation between CVT and body weight, stature, age, sex, and ancestry by reviewing data of 1097 forensic autopsies performed at the Netherlands Forensic Institute (NFI). In subadults (younger than 19 years of age at the time of death), all frontal, temporal, and occipital CVT measurements correlated moderately to strongly with indicators of growth (body weight, stature, and age). Neither sex nor ancestry correlated significantly with cranial thickness. In adults, body weight correlated with all CVT measurements. No meaningful correlation was found between CVT and stature or age. Females showed to have thicker frontal bones, and the occipital region was thicker in the Negroid subsample. All correlation in the adult group was weak, with the distribution of cranial thickness overlapping for a great deal between the groups. Based on these results, it was concluded that CVT generally cannot be used as an indicator for any part of the biological profile. PMID:26914798

  19. Power laws for heavy-tailed distributions: modeling allele and haplotype diversity for the national marrow donor program.

    Directory of Open Access Journals (Sweden)

    Noa Slater

    2015-04-01

    Full Text Available Measures of allele and haplotype diversity, which are fundamental properties in population genetics, often follow heavy tailed distributions. These measures are of particular interest in the field of hematopoietic stem cell transplant (HSCT. Donor/Recipient suitability for HSCT is determined by Human Leukocyte Antigen (HLA similarity. Match predictions rely upon a precise description of HLA diversity, yet classical estimates are inaccurate given the heavy-tailed nature of the distribution. This directly affects HSCT matching and diversity measures in broader fields such as species richness. We, therefore, have developed a power-law based estimator to measure allele and haplotype diversity that accommodates heavy tails using the concepts of regular variation and occupancy distributions. Application of our estimator to 6.59 million donors in the Be The Match Registry revealed that haplotypes follow a heavy tail distribution across all ethnicities: for example, 44.65% of the European American haplotypes are represented by only 1 individual. Indeed, our discovery rate of all U.S. European American haplotypes is estimated at 23.45% based upon sampling 3.97% of the population, leaving a large number of unobserved haplotypes. Population coverage, however, is much higher at 99.4% given that 90% of European Americans carry one of the 4.5% most frequent haplotypes. Alleles were found to be less diverse suggesting the current registry represents most alleles in the population. Thus, for HSCT registries, haplotype discovery will remain high with continued recruitment to a very deep level of sampling, but population coverage will not. Finally, we compared the convergence of our power-law versus classical diversity estimators such as Capture recapture, Chao, ACE and Jackknife methods. When fit to the haplotype data, our estimator displayed favorable properties in terms of convergence (with respect to sampling depth and accuracy (with respect to diversity

  20. The functional importance of sequence versus expression variability of MHC alleles in parasite resistance.

    Science.gov (United States)

    Axtner, Jan; Sommer, Simone

    2012-12-01

    Understanding selection processes driving the pronounced allelic polymorphism of the major histocompatibility complex (MHC) genes and its functional associations to parasite load have been the focus of many recent wildlife studies. Two main selection scenarios are currently debated which explain the susceptibility or resistance to parasite infections either by the effects of (1) specific MHC alleles which are selected frequency-dependent in space and time or (2) a heterozygote or divergent allele advantage. So far, most studies have focused only on structural variance in co-evolutionary processes although this might not be the only trait subject to natural selection. In the present study, we analysed structural variance stretching from exon1 through exon3 of MHC class II DRB genes as well as genotypic expression variance in relation to the gastrointestinal helminth prevalence and infection intensity in wild yellow-necked mice (Apodemus flavicollis). We found support for the functional importance of specific alleles both on the sequence and expression level. By resampling a previously investigated study population we identified specific MHC alleles affected by temporal shifts in parasite pressure and recorded associated changes in allele frequencies. The allele Apfl-DRB*23 was associated with resistance to infections by the oxyurid nematode Syphacia stroma and at the same time with susceptibility to cestode infection intensity. In line with our expectation, MHC mRNA transcript levels tended to be higher in cestode-infected animals carrying the allele Apfl-DRB*23. However, no support for a heterozygote or divergent allele advantage on the sequence or expression level was detected. The individual amino acid distance of genotypes did not explain individual differences in parasite loads and the genetic distance had no effect on MHC genotype expression. For ongoing studies on the functional importance of expression variance in parasite resistance, allele

  1. Analysis of Rare, Exonic Variation amongst Subjects with Autism Spectrum Disorders and Population Controls

    Science.gov (United States)

    Liu, Li; Sabo, Aniko; Neale, Benjamin M.; Nagaswamy, Uma; Stevens, Christine; Lim, Elaine; Bodea, Corneliu A.; Muzny, Donna; Reid, Jeffrey G.; Banks, Eric; Coon, Hillary; DePristo, Mark; Dinh, Huyen; Fennel, Tim; Flannick, Jason; Gabriel, Stacey; Garimella, Kiran; Gross, Shannon; Hawes, Alicia; Lewis, Lora; Makarov, Vladimir; Maguire, Jared; Newsham, Irene; Poplin, Ryan; Ripke, Stephan; Shakir, Khalid; Samocha, Kaitlin E.; Wu, Yuanqing; Boerwinkle, Eric; Buxbaum, Joseph D.; Cook, Edwin H.; Devlin, Bernie; Schellenberg, Gerard D.; Sutcliffe, James S.; Daly, Mark J.; Gibbs, Richard A.; Roeder, Kathryn

    2013-01-01

    We report on results from whole-exome sequencing (WES) of 1,039 subjects diagnosed with autism spectrum disorders (ASD) and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by fraction of missing data, read depth, and balance of alternative to reference reads. Results were evaluated using seven samples sequenced at both centers and by results from the association study. Next we addressed how the data and/or results from the centers should be combined. Gene-based analyses of association was an obvious choice, but should statistics for association be combined across centers (meta-analysis) or should data be combined and then analyzed (mega-analysis)? Because of the nature of many gene-based tests, we showed by theory and simulations that mega-analysis has better power than meta-analysis. Finally, before analyzing the data for association, we explored the impact of population structure on rare variant analysis in these data. Like other recent studies, we found evidence that population structure can confound case-control studies by the clustering of rare variants in ancestry space; yet, unlike some recent studies, for these data we found that principal component-based analyses were sufficient to control for ancestry and produce test statistics with appropriate distributions. After using a variety of gene-based tests and both meta- and mega-analysis, we found no new risk genes for ASD in this sample. Our results suggest that standard gene-based tests will require much larger samples of cases and controls before being effective for gene discovery, even for a disorder like ASD. PMID:23593035

  2. Analysis of rare, exonic variation amongst subjects with autism spectrum disorders and population controls.

    Directory of Open Access Journals (Sweden)

    Li Liu

    2013-04-01

    Full Text Available We report on results from whole-exome sequencing (WES of 1,039 subjects diagnosed with autism spectrum disorders (ASD and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by fraction of missing data, read depth, and balance of alternative to reference reads. Results were evaluated using seven samples sequenced at both centers and by results from the association study. Next we addressed how the data and/or results from the centers should be combined. Gene-based analyses of association was an obvious choice, but should statistics for association be combined across centers (meta-analysis or should data be combined and then analyzed (mega-analysis? Because of the nature of many gene-based tests, we showed by theory and simulations that mega-analysis has better power than meta-analysis. Finally, before analyzing the data for association, we explored the impact of population structure on rare variant analysis in these data. Like other recent studies, we found evidence that population structure can confound case-control studies by the clustering of rare variants in ancestry space; yet, unlike some recent studies, for these data we found that principal component-based analyses were sufficient to control for ancestry and produce test statistics with appropriate distributions. After using a variety of gene-based tests and both meta- and mega-analysis, we found no new risk genes for ASD in this sample. Our results suggest that standard gene-based tests will require much larger samples of cases and controls before being effective for gene discovery, even for a disorder like ASD.

  3. Oxytocin receptor genetic variation promotes human trust behavior

    Directory of Open Access Journals (Sweden)

    Frank Krueger

    2012-02-01

    Full Text Available Given that human trust behavior is heritable and intranasal administration of oxytocin enhances trust, the oxytocin receptor (OXTR gene is an excellent candidate to investigate genetic contributions to individual variations in trust behavior. Although a single-nucleotide polymorphism involving an adenine (A/ guanine (G transition (rs53576 has been associated with socio-emotional phenotypes, its link to trust behavior is unclear. We combined genotyping of healthy male students with the administration of a trust game experiment. Our results show that a naturally occurring genetic variation (rs53576 in the OXTR gene is reliably associated with trust behavior rather than a general increase in trustworthy or risk behaviors. Individuals homozygous for the G allele (GG showed higher trust behavior than individuals with A allele carriers (AA/AG. Although the molecular functionality of this polymorphism is still unknown, future research should clarify how the OXTR gene interacts with other genes and the environment in promoting socio-emotional behaviors.

  4. High-resolution copy-number variation map reflects human olfactory receptor diversity and evolution.

    Directory of Open Access Journals (Sweden)

    Yehudit Hasin

    2008-11-01

    Full Text Available Olfactory receptors (ORs, which are involved in odorant recognition, form the largest mammalian protein superfamily. The