Novel probabilistic models of spatial genetic ancestry with applications to stratification correction in genome-wide association studies.

Science.gov (United States)

Bhaskar, Anand; Javanmard, Adel; Courtade, Thomas A; Tse, David

2017-03-15

Genetic variation in human populations is influenced by geographic ancestry due to spatial locality in historical mating and migration patterns. Spatial population structure in genetic datasets has been traditionally analyzed using either model-free algorithms, such as principal components analysis (PCA) and multidimensional scaling, or using explicit spatial probabilistic models of allele frequency evolution. We develop a general probabilistic model and an associated inference algorithm that unify the model-based and data-driven approaches to visualizing and inferring population structure. Our spatial inference algorithm can also be effectively applied to the problem of population stratification in genome-wide association studies (GWAS), where hidden population structure can create fictitious associations when population ancestry is correlated with both the genotype and the trait. Our algorithm Geographic Ancestry Positioning (GAP) relates local genetic distances between samples to their spatial distances, and can be used for visually discerning population structure as well as accurately inferring the spatial origin of individuals on a two-dimensional continuum. On both simulated and several real datasets from diverse human populations, GAP exhibits substantially lower error in reconstructing spatial ancestry coordinates compared to PCA. We also develop an association test that uses the ancestry coordinates inferred by GAP to accurately account for ancestry-induced correlations in GWAS. Based on simulations and analysis of a dataset of 10 metabolic traits measured in a Northern Finland cohort, which is known to exhibit significant population structure, we find that our method has superior power to current approaches. Our software is available at https://github.com/anand-bhaskar/gap . abhaskar@stanford.edu or ajavanma@usc.edu. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved

Genetic ancestry effects on the distribution of toll-like receptors (TLRs) gene polymorphisms in a population of the Atlantic Forest, São Paulo, Brazil.

Science.gov (United States)

Guimarães, Lilian O; Bajay, Miklos Maximiliano; Monteiro, Eliana F; Wunderlich, Gerhard; Santos, Sidney E; Kirchgatter, Karin

2018-02-01

The innate immune system governed by toll-like receptors (TLRs) provides the first line of defense against pathogens. Surface-localized TLR1 and TLR6 are known to detect parasite components. TLR encoding genes were shown to display signatures of recent positive selection in Europeans and might be involved in local adaptation at immune-related genes. To verify the influence of Brazilian population admixture on the distribution of polymorphisms in TLRs, we analyzed the genotype frequencies of 24 polymorphisms distributed across five TLR genes in a Southeastern Brazilian population where autochthonous cases of malaria occur in small foci of transmission. The estimation of ancestry showed mainly European ancestry (63%) followed by African ancestry (22%). Mean proportions of European ancestry differed significantly between the genotypes of the TLR1 (I602S) gene and in the TLR6 (P249S) gene. The chance of having the G allele in TLR1 gene increases as European ancestry increases as well as the chance of having the T allele in the TLR6 gene. The 602S allele is related to a ''hypo-responsiveness'' possibly explaining the high prevalence of asymptomatic malaria cases in areas of Southeastern Brazil. Our results underline the necessity to include informative ancestry markers in genetic association studies in order to avoid biased results. Copyright © 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

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......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...

Properties of global- and local-ancestry adjustments in genetic association tests in admixed populations.

Science.gov (United States)

Martin, Eden R; Tunc, Ilker; Liu, Zhi; Slifer, Susan H; Beecham, Ashley H; Beecham, Gary W

2018-03-01

Population substructure can lead to confounding in tests for genetic association, and failure to adjust properly can result in spurious findings. Here we address this issue of confounding by considering the impact of global ancestry (average ancestry across the genome) and local ancestry (ancestry at a specific chromosomal location) on regression parameters and relative power in ancestry-adjusted and -unadjusted models. We examine theoretical expectations under different scenarios for population substructure; applying different regression models, verifying and generalizing using simulations, and exploring the findings in real-world admixed populations. We show that admixture does not lead to confounding when the trait locus is tested directly in a single admixed population. However, if there is more complex population structure or a marker locus in linkage disequilibrium (LD) with the trait locus is tested, both global and local ancestry can be confounders. Additionally, we show the genotype parameters of adjusted and unadjusted models all provide tests for LD between the marker and trait locus, but in different contexts. The local ancestry adjusted model tests for LD in the ancestral populations, while tests using the unadjusted and the global ancestry adjusted models depend on LD in the admixed population(s), which may be enriched due to different ancestral allele frequencies. Practically, this implies that global-ancestry adjustment should be used for screening, but local-ancestry adjustment may better inform fine mapping and provide better effect estimates at trait loci. © 2017 WILEY PERIODICALS, INC.

Dissecting the within-Africa ancestry of populations of African descent in the Americas.

Science.gov (United States)

Stefflova, Klara; Dulik, Matthew C; Barnholtz-Sloan, Jill S; Pai, Athma A; Walker, Amy H; Rebbeck, Timothy R

2011-01-06

The ancestry of African-descended Americans is known to be drawn from three distinct populations: African, European, and Native American. While many studies consider this continental admixture, few account for the genetically distinct sources of ancestry within Africa--the continent with the highest genetic variation. Here, we dissect the within-Africa genetic ancestry of various populations of the Americas self-identified as having primarily African ancestry using uniparentally inherited mitochondrial DNA. We first confirmed that our results obtained using uniparentally-derived group admixture estimates are correlated with the average autosomal-derived individual admixture estimates (hence are relevant to genomic ancestry) by assessing continental admixture using both types of markers (mtDNA and Y-chromosome vs. ancestry informative markers). We then focused on the within-Africa maternal ancestry, mining our comprehensive database of published mtDNA variation (∼5800 individuals from 143 African populations) that helped us thoroughly dissect the African mtDNA pool. Using this well-defined African mtDNA variation, we quantified the relative contributions of maternal genetic ancestry from multiple W/WC/SW/SE (West to South East) African populations to the different pools of today's African-descended Americans of North and South America and the Caribbean. Our analysis revealed that both continental admixture and within-Africa admixture may be critical to achieving an adequate understanding of the ancestry of African-descended Americans. While continental ancestry reflects gender-specific admixture processes influenced by different socio-historical practices in the Americas, the within-Africa maternal ancestry reflects the diverse colonial histories of the slave trade. We have confirmed that there is a genetic thread connecting Africa and the Americas, where each colonial system supplied their colonies in the Americas with slaves from African colonies they controlled

Fitness differences due to allelic variation at Esterase-4 Locus in ...

Indian Academy of Sciences (India)

Navya

2017-01-04

Jan 4, 2017 ... specific substrate (1-Naphthylacetate AR) and stain (Fast blue RR). On the basis of ... After 24 hr. each pair was transferred to fresh food vials .... derived from the natural populations harbour allelic variation that affects lifespan.

A Continuous Correlated Beta Process Model for Genetic Ancestry in Admixed Populations.

Science.gov (United States)

Gompert, Zachariah

2016-01-01

Admixture and recombination create populations and genomes with genetic ancestry from multiple source populations. Analyses of genetic ancestry in admixed populations are relevant for trait and disease mapping, studies of speciation, and conservation efforts. Consequently, many methods have been developed to infer genome-average ancestry and to deconvolute ancestry into continuous local ancestry blocks or tracts within individuals. Current methods for local ancestry inference perform well when admixture occurred recently or hybridization is ongoing, or when admixture occurred in the distant past such that local ancestry blocks have fixed in the admixed population. However, methods to infer local ancestry frequencies in isolated admixed populations still segregating for ancestry do not exist. In the current paper, I develop and test a continuous correlated beta process model to fill this analytical gap. The method explicitly models autocorrelations in ancestry frequencies at the population-level and uses discriminant analysis of SNP windows to take advantage of ancestry blocks within individuals. Analyses of simulated data sets show that the method is generally accurate such that ancestry frequency estimates exhibited low root-mean-square error and were highly correlated with the true values, particularly when large (±10 or ±20) SNP windows were used. Along these lines, the proposed method outperformed post hoc inference of ancestry frequencies from a traditional hidden Markov model (i.e., the linkage model in structure), particularly when admixture occurred more distantly in the past with little on-going gene flow or was followed by natural selection. The reliability and utility of the method was further assessed by analyzing genetic ancestry in an admixed human population (Uyghur) and three populations from a hybrid zone between Mus domesticus and M. musculus. Considerable variation in ancestry frequencies was detected within and among chromosomes in the Uyghur

Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.

Directory of Open Access Journals (Sweden)

Simon N Stacey

2010-07-01

Full Text Available We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1 genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case:control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively. Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2 x 10(-3, African (OR = 1.35, P = 0.014, and Asian (OR = 1.23, P = 2.9 x 10(-4 population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9 x 10(-7, was without significant heterogeneity between ancestries (P(het = 0.36 and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268, which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping.

Forensic genetic analysis of bio-geographical ancestry.

Science.gov (United States)

Phillips, Chris

2015-09-01

With the great strides made in the last ten years in the understanding of human population variation and the detailed characterization of the genome, it is now possible to identify sets of ancestry informative markers suitable for relatively small-scale PCR-based assays and use them to analyze the ancestry of an individual from forensic DNA. This review outlines some of the current understanding of past human population structure and how it may have influenced the complex distribution of contemporary human diversity. A simplified description of human diversity can provide a suitable basis for choosing the best ancestry-informative markers, which is important given the constraints of multiplex sizes in forensic DNA tests. It is also important to decide the level of geographic resolution that is realistic to ensure the balance between informativeness and an over-simplification of complex human diversity patterns. A detailed comparison is made of the most informative ancestry markers suitable for forensic use and assessments are made of the data analysis regimes that can provide statistical inferences of a DNA donor's bio-geographical ancestry. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium.

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Ng, Maggie C Y; Graff, Mariaelisa; Lu, Yingchang; Justice, Anne E; Mudgal, Poorva; Liu, Ching-Ti; Young, Kristin; Yanek, Lisa R; Feitosa, Mary F; Wojczynski, Mary K; Rand, Kristin; Brody, Jennifer A; Cade, Brian E; Dimitrov, Latchezar; Duan, Qing; Guo, Xiuqing; Lange, Leslie A; Nalls, Michael A; Okut, Hayrettin; Tajuddin, Salman M; Tayo, Bamidele O; Vedantam, Sailaja; Bradfield, Jonathan P; Chen, Guanjie; Chen, Wei-Min; Chesi, Alessandra; Irvin, Marguerite R; Padhukasahasram, Badri; Smith, Jennifer A; Zheng, Wei; Allison, Matthew A; Ambrosone, Christine B; Bandera, Elisa V; Bartz, Traci M; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Bottinger, Erwin P; Carpten, John; Chanock, Stephen J; Chen, Yii-Der Ida; Conti, David V; Cooper, Richard S; Fornage, Myriam; Freedman, Barry I; Garcia, Melissa; Goodman, Phyllis J; Hsu, Yu-Han H; Hu, Jennifer; Huff, Chad D; Ingles, Sue A; John, Esther M; Kittles, Rick; Klein, Eric; Li, Jin; McKnight, Barbara; Nayak, Uma; Nemesure, Barbara; Ogunniyi, Adesola; Olshan, Andrew; Press, Michael F; Rohde, Rebecca; Rybicki, Benjamin A; Salako, Babatunde; Sanderson, Maureen; Shao, Yaming; Siscovick, David S; Stanford, Janet L; Stevens, Victoria L; Stram, Alex; Strom, Sara S; Vaidya, Dhananjay; Witte, John S; Yao, Jie; Zhu, Xiaofeng; Ziegler, Regina G; Zonderman, Alan B; Adeyemo, Adebowale; Ambs, Stefan; Cushman, Mary; Faul, Jessica D; Hakonarson, Hakon; Levin, Albert M; Nathanson, Katherine L; Ware, Erin B; Weir, David R; Zhao, Wei; Zhi, Degui; Arnett, Donna K; Grant, Struan F A; Kardia, Sharon L R; Oloapde, Olufunmilayo I; Rao, D C; Rotimi, Charles N; Sale, Michele M; Williams, L Keoki; Zemel, Babette S; Becker, Diane M; Borecki, Ingrid B; Evans, Michele K; Harris, Tamara B; Hirschhorn, Joel N; Li, Yun; Patel, Sanjay R; Psaty, Bruce M; Rotter, Jerome I; Wilson, James G; Bowden, Donald W; Cupples, L Adrienne; Haiman, Christopher A; Loos, Ruth J F; North, Kari E

2017-04-01

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations.

Forensic genetic informativeness of an SNP panel consisting of 19 multi-allelic SNPs.

Science.gov (United States)

Gao, Zehua; Chen, Xiaogang; Zhao, Yuancun; Zhao, Xiaohong; Zhang, Shu; Yang, Yiwen; Wang, Yufang; Zhang, Ji

2018-05-01

Current research focusing on forensic personal identification, phenotype inference and ancestry information on single-nucleotide polymorphisms (SNPs) has been widely reported. In the present study, we focused on tetra-allelic SNPs in the Chinese Han population. A total of 48 tetra-allelic SNPs were screened out from the Chinese Han population of the 1000 Genomes Database, including Chinese Han in Beijing (CHB) and Chinese Han South (CHS). Considering the forensic genetic requirement for the polymorphisms, only 11 tetra-allelic SNPs with a heterozygosity >0.06 were selected for further multiplex panel construction. In order to meet the demands of personal identification and parentage identification, an additional 8 tri-allelic SNPs were combined into the final multiplex panel. To ensure application in the degraded DNA analysis, all the PCR products were designed to be 87-188 bp. Employing multiple PCR reactions and SNaPshot minisequencing, 511 unrelated Chinese Han individuals from Sichuan were genotyped. The combined match probability (CMP), combined discrimination power (CDP), and cumulative probability of exclusion (CPE) of the panel were 6.07 × 10 -11 , 0.9999999999393 and 0.996764, respectively. Based on the population data retrieved from the 1000 Genomes Project, Fst values between Chinese Han in Sichuan (SCH) and all the populations included in the 1000 Genomes Project were calculated. The results indicated that two SNPs in this panel may contain ancestry information and may be used as markers of forensic biogeographical ancestry inference. Copyright © 2018 Elsevier B.V. All rights reserved.

A Continuous Correlated Beta Process Model for Genetic Ancestry in Admixed Populations.

Directory of Open Access Journals (Sweden)

Zachariah Gompert

Full Text Available Admixture and recombination create populations and genomes with genetic ancestry from multiple source populations. Analyses of genetic ancestry in admixed populations are relevant for trait and disease mapping, studies of speciation, and conservation efforts. Consequently, many methods have been developed to infer genome-average ancestry and to deconvolute ancestry into continuous local ancestry blocks or tracts within individuals. Current methods for local ancestry inference perform well when admixture occurred recently or hybridization is ongoing, or when admixture occurred in the distant past such that local ancestry blocks have fixed in the admixed population. However, methods to infer local ancestry frequencies in isolated admixed populations still segregating for ancestry do not exist. In the current paper, I develop and test a continuous correlated beta process model to fill this analytical gap. The method explicitly models autocorrelations in ancestry frequencies at the population-level and uses discriminant analysis of SNP windows to take advantage of ancestry blocks within individuals. Analyses of simulated data sets show that the method is generally accurate such that ancestry frequency estimates exhibited low root-mean-square error and were highly correlated with the true values, particularly when large (±10 or ±20 SNP windows were used. Along these lines, the proposed method outperformed post hoc inference of ancestry frequencies from a traditional hidden Markov model (i.e., the linkage model in structure, particularly when admixture occurred more distantly in the past with little on-going gene flow or was followed by natural selection. The reliability and utility of the method was further assessed by analyzing genetic ancestry in an admixed human population (Uyghur and three populations from a hybrid zone between Mus domesticus and M. musculus. Considerable variation in ancestry frequencies was detected within and among

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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Allelic Variation of Risk for Anxiety Symptoms Moderates the Relation Between Adolescent Safety Behaviors and Social Anxiety Symptoms

Science.gov (United States)

Thomas, Sarah A.; Weeks, Justin W.; Dougherty, Lea R.; Lipton, Melanie F.; Daruwala, Samantha E.; Kline, Kathryn

2015-01-01

Social anxiety often develops in adolescence, and precedes the onset of depression and substance use disorders. The link between social anxiety and use of behaviors to minimize distress in social situations (i.e., safety behaviors) is strong and for some patients, this link poses difficulty for engaging in, and benefiting from, exposure-based treatment. Yet, little is known about whether individual differences may moderate links between social anxiety and safety behaviors, namely variations in genetic alleles germane to anxiety. We examined the relation between adolescent social anxiety and expressions of safety behaviors, and whether allelic variation for anxiety moderates this relation. Adolescents (n=75; ages 14–17) were recruited from two larger studies investigating measurement of family relationships or adolescent social anxiety. Adolescents completed self-report measures about social anxiety symptoms and use of safety behaviors. They also provided saliva samples to assess allelic variations for anxiety from two genetic polymorphisms (BDNF rs6265; TAQ1A rs1800497). Controlling for adolescent age and gender, we observed a significant interaction between social anxiety symptoms and allelic variation (β=0.37, t=2.41, p=.02). Specifically, adolescents carrying allelic variations for anxiety evidenced a statistically significant and relatively strong positive relation between social anxiety symptoms and safety behaviors (β=0.73), whereas adolescents not carrying allelic variation evidenced a statistically non-significant and relatively weak relation (β=0.22). These findings have important implications for treating adolescent social anxiety, in that we identified an individual difference variable that can be used to identify people who evidence a particularly strong link between use of safety behaviors and expressing social anxiety. PMID:26692635

Fine mapping of breast cancer genome-wide association studies loci in women of African ancestry identifies novel susceptibility markers.

Science.gov (United States)

Zheng, Yonglan; Ogundiran, Temidayo O; Falusi, Adeyinka G; Nathanson, Katherine L; John, Esther M; Hennis, Anselm J M; Ambs, Stefan; Domchek, Susan M; Rebbeck, Timothy R; Simon, Michael S; Nemesure, Barbara; Wu, Suh-Yuh; Leske, Maria Cristina; Odetunde, Abayomi; Niu, Qun; Zhang, Jing; Afolabi, Chibuzor; Gamazon, Eric R; Cox, Nancy J; Olopade, Christopher O; Olopade, Olufunmilayo I; Huo, Dezheng

2013-07-01

Numerous single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified by genome-wide association studies (GWAS). However, these SNPs were primarily discovered and validated in women of European and Asian ancestry. Because linkage disequilibrium is ancestry-dependent and heterogeneous among racial/ethnic populations, we evaluated common genetic variants at 22 GWAS-identified breast cancer susceptibility loci in a pooled sample of 1502 breast cancer cases and 1378 controls of African ancestry. None of the 22 GWAS index SNPs could be validated, challenging the direct generalizability of breast cancer risk variants identified in Caucasians or Asians to other populations. Novel breast cancer risk variants for women of African ancestry were identified in regions including 5p12 (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.11-1.76; P = 0.004), 5q11.2 (OR = 1.22, 95% CI = 1.09-1.36; P = 0.00053) and 10p15.1 (OR = 1.22, 95% CI = 1.08-1.38; P = 0.0015). We also found positive association signals in three regions (6q25.1, 10q26.13 and 16q12.1-q12.2) previously confirmed by fine mapping in women of African ancestry. In addition, polygenic model indicated that eight best markers in this study, compared with 22 GWAS-identified SNPs, could better predict breast cancer risk in women of African ancestry (per-allele OR = 1.21, 95% CI = 1.16-1.27; P = 9.7 × 10(-16)). Our results demonstrate that fine mapping is a powerful approach to better characterize the breast cancer risk alleles in diverse populations. Future studies and new GWAS in women of African ancestry hold promise to discover additional variants for breast cancer susceptibility with clinical implications throughout the African diaspora.

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

Directory of Open Access Journals (Sweden)

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.

Integrating common and rare genetic variation in diverse human populations.

Science.gov (United States)

Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Dermitzakis, Emmanouil; Schaffner, Stephen F; Yu, Fuli; Peltonen, Leena; Dermitzakis, Emmanouil; Bonnen, Penelope E; Altshuler, David M; Gibbs, Richard A; de Bakker, Paul I W; Deloukas, Panos; Gabriel, Stacey B; Gwilliam, Rhian; Hunt, Sarah; Inouye, Michael; Jia, Xiaoming; Palotie, Aarno; Parkin, Melissa; Whittaker, Pamela; Yu, Fuli; Chang, Kyle; Hawes, Alicia; Lewis, Lora R; Ren, Yanru; Wheeler, David; Gibbs, Richard A; Muzny, Donna Marie; Barnes, Chris; Darvishi, Katayoon; Hurles, Matthew; Korn, Joshua M; Kristiansson, Kati; Lee, Charles; McCarrol, Steven A; Nemesh, James; Dermitzakis, Emmanouil; Keinan, Alon; Montgomery, Stephen B; Pollack, Samuela; Price, Alkes L; Soranzo, Nicole; Bonnen, Penelope E; Gibbs, Richard A; Gonzaga-Jauregui, Claudia; Keinan, Alon; Price, Alkes L; Yu, Fuli; Anttila, Verneri; Brodeur, Wendy; Daly, Mark J; Leslie, Stephen; McVean, Gil; Moutsianas, Loukas; Nguyen, Huy; Schaffner, Stephen F; Zhang, Qingrun; Ghori, Mohammed J R; McGinnis, Ralph; McLaren, William; Pollack, Samuela; Price, Alkes L; Schaffner, Stephen F; Takeuchi, Fumihiko; Grossman, Sharon R; Shlyakhter, Ilya; Hostetter, Elizabeth B; Sabeti, Pardis C; Adebamowo, Clement A; Foster, Morris W; Gordon, Deborah R; Licinio, Julio; Manca, Maria Cristina; Marshall, Patricia A; Matsuda, Ichiro; Ngare, Duncan; Wang, Vivian Ota; Reddy, Deepa; Rotimi, Charles N; Royal, Charmaine D; Sharp, Richard R; Zeng, Changqing; Brooks, Lisa D; McEwen, Jean E

2010-09-02

Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of variation and its role in human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation.

Developing a novel panel of genome-wide ancestry informative markers for bio-geographical ancestry estimates.

Science.gov (United States)

Jia, Jing; Wei, Yi-Liang; Qin, Cui-Jiao; Hu, Lan; Wan, Li-Hua; Li, Cai-Xia

2014-01-01

Inferring the ancestral origin of DNA samples can be helpful in correcting population stratification in disease association studies or guiding crime investigations. Populations throughout the world vary in appearance features and biological characteristics. Based on this idea, we performed a genome-wide scan for SNPs within genes that are related to physical and biological traits. Using the HapMap database, we screened 52 genes and their flanking regions. Thirty-five SNPs that displayed highly contrasting allele frequencies (F(st)>0.3, linkage disequilibrium r(2)0.001) among Africans, Europeans, and East Asians were selected and validated. A multiplexed assay was developed to genotype these 35 SNPs in 357 individuals from 10 populations worldwide. This panel provided accurate estimates of individual ancestry proportions with balanced discriminatory power among the three continental ancestries: Africans, Europeans, and East Asians. It also proved very effective in evaluating admixed populations living in joint regions of continents (e.g., Uyghurs and Indians) and discriminating some subpopulations within each of the three continents. Structure analysis was performed to establish and evaluate the panel of ancestry-informative markers, and the components of each population were also described to indicate the structural composition. The 21 population structures in our study are consistent with geographic patterns, and individuals were properly assigned to their original ancestral populations with proportion analyses and random match probability calculations. Thus, the panel and its population information will be useful resources to minimize the effects of population stratification in association analyses and to assign the most likely origin of an unknown DNA contributor in forensic investigations. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Health and genetic ancestry testing: time to bridge the gap.

Science.gov (United States)

Smart, Andrew; Bolnick, Deborah A; Tutton, Richard

2017-01-09

It is becoming increasingly difficult to keep information about genetic ancestry separate from information about health, and consumers of genetic ancestry tests are becoming more aware of the potential health risks associated with particular ancestral lineages. Because some of the proposed associations have received little attention from oversight agencies and professional genetic associations, scientific developments are currently outpacing governance regimes for consumer genetic testing. We highlight the recent and unremarked upon emergence of biomedical studies linking markers of genetic ancestry to disease risks, and show that this body of scientific research is becoming part of public discourse connecting ancestry and health. For instance, data on genome-wide ancestry informative markers are being used to assess health risks, and we document over 100 biomedical research articles that propose associations between mitochondrial DNA and Y chromosome markers of genetic ancestry and a wide variety of disease risks. Taking as an example an association between coronary heart disease and British men belonging to Y chromosome haplogroup I, we show how this science was translated into mainstream and online media, and how it circulates among consumers of genetic tests for ancestry. We find wide variations in how the science is interpreted, which suggests the potential for confusion or misunderstanding. We recommend that stakeholders involved in creating and using estimates of genetic ancestry reconsider their policies for communicating with each other and with the public about the health implications of ancestry information.

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...... 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....... 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...

Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal

Science.gov (United States)

Cavalcante, Lourianne Nascimento; Stefano, Jose Tadeu; Machado, Mariana V; Mazo, Daniel F; Rabelo, Fabiola; Sandes, Kiyoko Abe; Carrilho, Flair José; Cortez-Pinto, Helena; Lyra, Andre Castro; de Oliveira, Claudia P

2015-01-01

AIM: To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal. METHODS: We included 131 subjects from Brazil [(n = 45 with simple steatosis (S. Steatosis) and n = 86 with nonalcoholic steatohepatitis (NASH)] and 90 patients from Portugal (n = 66, S. Steatosis; n = 24, NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis: simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers (AT3-I/D, LPL, Sb19.3, APO, FY-Null, PV92, and CKMM) with the greatest ethnic-geographical differential frequencies (≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP online and the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant (P 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 larger percentage of subjects in the S. Steatosis group (P = 0.003, respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort (Brazilian cohort: P = 0.75; Portuguese cohort: P = 0.97). Nonetheless, the genetic ancestry contribution of the Brazilian and Portuguese population were different, and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH

Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal.

Science.gov (United States)

Cavalcante, Lourianne Nascimento; Stefano, Jose Tadeu; Machado, Mariana V; Mazo, Daniel F; Rabelo, Fabiola; Sandes, Kiyoko Abe; Carrilho, Flair José; Cortez-Pinto, Helena; Lyra, Andre Castro; de Oliveira, Claudia P

2015-06-08

To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal. We included 131 subjects from Brazil [(n = 45 with simple steatosis (S. Steatosis) and n = 86 with nonalcoholic steatohepatitis (NASH)] and 90 patients from Portugal (n = 66, S. Steatosis; n = 24, NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis: simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers (AT3-I/D, LPL, Sb19.3, APO, FY-Null, PV92, and CKMM) with the greatest ethnic-geographical differential frequencies (≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP online and the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant (P 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 larger percentage of subjects in the S. Steatosis group (P = 0.003, respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort (Brazilian cohort: P = 0.75; Portuguese cohort: P = 0.97). Nonetheless, the genetic ancestry contribution of the Brazilian and Portuguese population were different, and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH and S

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

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.

Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc

International Nuclear Information System (INIS)

Adams, Scott V.; Barrick, Brian; Christopher, Emily P.; Shafer, Martin M.; Makar, Karen W.; Song, Xiaoling; Lampe, Johanna W.; Vilchis, Hugo; Ulery, April; Newcomb, Polly A.

2015-01-01

Background: Metallothionein (MT) proteins play critical roles in the physiological handling of both essential (Cu and Zn) and toxic (Cd) metals. MT expression is regulated by metal-regulatory transcription factor 1 (MTF1). Hence, genetic variation in the MT gene family and MTF1 might influence excretion of these metals. Methods: 321 women were recruited in Seattle, WA and Las Cruces, NM and provided demographic information, urine samples for measurement of metal concentrations by mass spectrometry and creatinine, and blood or saliva for extraction of DNA. Forty-one single nucleotide polymorphisms (SNPs) within the MTF1 gene region and the region of chromosome 16 encoding the MT gene family were selected for genotyping in addition to an ancestry informative marker panel. Linear regression was used to estimate the association of SNPs with urinary Cd, Cu, and Zn, adjusted for age, urinary creatinine, smoking history, study site, and ancestry. Results: Minor alleles of rs28366003 and rs10636 near the MT2A gene were associated with lower urinary Cd, Cu, and Zn. Minor alleles of rs8044719 and rs1599823, near MT1A and MT1B, were associated with lower urinary Cd and Zn, respectively. Minor alleles of rs4653329 in MTF1 were associated with lower urinary Cd. Conclusions: These results suggest that genetic variation in the MT gene region and MTF1 influences urinary Cd, Cu, and Zn excretion. - Highlights: • Genetic variation in metallothionein (MT) genes was assessed in two diverse populations. • Single nucleotide polymorphisms (SNPs) in MT genes were associated with mean urinary Cd, Cu and Zn. • Genetic variation may influence biomarkers of exposure, and associations of exposure with health.

Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc

Energy Technology Data Exchange (ETDEWEB)

Adams, Scott V., E-mail: sadams@fhcrc.org [Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States); Barrick, Brian [Department of Plant and Environmental Sciences, New Mexico State University, Box 30003 MSC 3Q, Las Cruces, NM 88003 (United States); Christopher, Emily P. [Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States); Shafer, Martin M. [Environmental Chemistry and Technology, Wisconsin State Laboratory of Hygiene, University of Wisconsin, 2601 Agriculture Dr., Madison, WI 53718 (United States); Makar, Karen W.; Song, Xiaoling [Public Health Science Biomarker Laboratory, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States); Lampe, Johanna W. [Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States); Vilchis, Hugo [Border Epidemiology and Environmental Health Center, New Mexico State University, Box 30001 MSC 3BEC, Las Cruces, NM 88003 (United States); Ulery, April [Department of Plant and Environmental Sciences, New Mexico State University, Box 30003 MSC 3Q, Las Cruces, NM 88003 (United States); Newcomb, Polly A. [Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States)

2015-12-15

Background: Metallothionein (MT) proteins play critical roles in the physiological handling of both essential (Cu and Zn) and toxic (Cd) metals. MT expression is regulated by metal-regulatory transcription factor 1 (MTF1). Hence, genetic variation in the MT gene family and MTF1 might influence excretion of these metals. Methods: 321 women were recruited in Seattle, WA and Las Cruces, NM and provided demographic information, urine samples for measurement of metal concentrations by mass spectrometry and creatinine, and blood or saliva for extraction of DNA. Forty-one single nucleotide polymorphisms (SNPs) within the MTF1 gene region and the region of chromosome 16 encoding the MT gene family were selected for genotyping in addition to an ancestry informative marker panel. Linear regression was used to estimate the association of SNPs with urinary Cd, Cu, and Zn, adjusted for age, urinary creatinine, smoking history, study site, and ancestry. Results: Minor alleles of rs28366003 and rs10636 near the MT2A gene were associated with lower urinary Cd, Cu, and Zn. Minor alleles of rs8044719 and rs1599823, near MT1A and MT1B, were associated with lower urinary Cd and Zn, respectively. Minor alleles of rs4653329 in MTF1 were associated with lower urinary Cd. Conclusions: These results suggest that genetic variation in the MT gene region and MTF1 influences urinary Cd, Cu, and Zn excretion. - Highlights: • Genetic variation in metallothionein (MT) genes was assessed in two diverse populations. • Single nucleotide polymorphisms (SNPs) in MT genes were associated with mean urinary Cd, Cu and Zn. • Genetic variation may influence biomarkers of exposure, and associations of exposure with health.

Sensitive detection of chromosomal segments of distinct ancestry in admixed populations.

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Alkes L Price

2009-06-01

Full Text Available Identifying the ancestry of chromosomal segments of distinct ancestry has a wide range of applications from disease mapping to learning about history. Most methods require the use of unlinked markers; but, using all markers from genome-wide scanning arrays, it should in principle be possible to infer the ancestry of even very small segments with exquisite accuracy. We describe a method, HAPMIX, which employs an explicit population genetic model to perform such local ancestry inference based on fine-scale variation data. We show that HAPMIX outperforms other methods, and we explore its utility for inferring ancestry, learning about ancestral populations, and inferring dates of admixture. We validate the method empirically by applying it to populations that have experienced recent and ancient admixture: 935 African Americans from the United States and 29 Mozabites from North Africa. HAPMIX will be of particular utility for mapping disease genes in recently admixed populations, as its accurate estimates of local ancestry permit admixture and case-control association signals to be combined, enabling more powerful tests of association than with either signal alone.

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.

Null alleles and sequence variations at primer binding sites of STR loci within multiplex typing systems.

Science.gov (United States)

Yao, Yining; Yang, Qinrui; Shao, Chengchen; Liu, Baonian; Zhou, Yuxiang; Xu, Hongmei; Zhou, Yueqin; Tang, Qiqun; Xie, Jianhui

2018-01-01

Rare variants are widely observed in human genome and sequence variations at primer binding sites might impair the process of PCR amplification resulting in dropouts of alleles, named as null alleles. In this study, 5 cases from routine paternity testing using PowerPlex ® 21 System for STR genotyping were considered to harbor null alleles at TH01, FGA, D5S818, D8S1179, and D16S539, respectively. The dropout of alleles was confirmed by using alternative commercial kits AGCU Expressmarker 22 PCR amplification kit and AmpFℓSTR ® . Identifiler ® Plus Kit, and sequencing results revealed a single base variation at the primer binding site of each STR locus. Results from the collection of previous reports show that null alleles at D5S818 were frequently observed in population detected by two PowerPlex ® typing systems and null alleles at D19S433 were mostly observed in Japanese population detected by two AmpFℓSTR™ typing systems. Furthermore, the most popular mutation type appeared the transition from C to T with G to A, which might have a potential relationship with DNA methylation. Altogether, these results can provide helpful information in forensic practice to the elimination of genotyping discrepancy and the development of primer sets. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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Gabriela E. S. Felix

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.

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.

Effect of Genetic African Ancestry on eGFR and Kidney Disease

Science.gov (United States)

Nadkarni, Girish N.; Belbin, Gillian; Lotay, Vaneet; Wyatt, Christina; Gottesman, Omri; Bottinger, Erwin P.; Kenny, Eimear E.; Peter, Inga

2015-01-01

Self-reported ancestry, genetically determined ancestry, and APOL1 polymorphisms are associated with variation in kidney function and related disease risk, but the relative importance of these factors remains unclear. We estimated the global proportion of African ancestry for 9048 individuals at Mount Sinai Medical Center in Manhattan (3189 African Americans, 1721 European Americans, and 4138 Hispanic/Latino Americans by self-report) using genome-wide genotype data. CKD-EPI eGFR and genotypes of three APOL1 coding variants were available. In admixed African Americans and Hispanic/Latino Americans, serum creatinine values increased as African ancestry increased (per 10% increase in African ancestry, creatinine values increased 1% in African Americans and 0.9% in Hispanic/Latino Americans; P≤1x10−7). eGFR was likewise significantly associated with African genetic ancestry in both populations. In contrast, APOL1 risk haplotypes were significantly associated with CKD, eGFRblack on the basis of ≥50% African ancestry resulted in higher eGFR for 14.7% of Hispanic/Latino Americans and lower eGFR for 4.1% of African Americans, affecting CKD staging in 4.3% and 1% of participants, respectively. Reclassified individuals had electrolyte values consistent with their newly assigned CKD stage. In summary, proportion of African ancestry was significantly associated with normal-range creatinine and eGFR, whereas APOL1 risk haplotypes drove the associations with CKD. Recalculation of eGFR on the basis of genetic ancestry affected CKD staging and warrants additional investigation. PMID:25349204

Genomic Features That Predict Allelic Imbalance in Humans Suggest Patterns of Constraint on Gene Expression Variation

Science.gov (United States)

Fédrigo, Olivier; Haygood, Ralph; Mukherjee, Sayan; Wray, Gregory A.

2009-01-01

Variation in gene expression is an important contributor to phenotypic diversity within and between species. Although this variation often has a genetic component, identification of the genetic variants driving this relationship remains challenging. In particular, measurements of gene expression usually do not reveal whether the genetic basis for any observed variation lies in cis or in trans to the gene, a distinction that has direct relevance to the physical location of the underlying genetic variant, and which may also impact its evolutionary trajectory. Allelic imbalance measurements identify cis-acting genetic effects by assaying the relative contribution of the two alleles of a cis-regulatory region to gene expression within individuals. Identification of patterns that predict commonly imbalanced genes could therefore serve as a useful tool and also shed light on the evolution of cis-regulatory variation itself. Here, we show that sequence motifs, polymorphism levels, and divergence levels around a gene can be used to predict commonly imbalanced genes in a human data set. Reduction of this feature set to four factors revealed that only one factor significantly differentiated between commonly imbalanced and nonimbalanced genes. We demonstrate that these results are consistent between the original data set and a second published data set in humans obtained using different technical and statistical methods. Finally, we show that variation in the single allelic imbalance-associated factor is partially explained by the density of genes in the region of a target gene (allelic imbalance is less probable for genes in gene-dense regions), and, to a lesser extent, the evenness of expression of the gene across tissues and the magnitude of negative selection on putative regulatory regions of the gene. These results suggest that the genomic distribution of functional cis-regulatory variants in the human genome is nonrandom, perhaps due to local differences in evolutionary

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

Science.gov (United States)

Astle, William J; Elding, Heather; Jiang, Tao; Allen, Dave; Ruklisa, Dace; Mann, Alice L; Mead, Daniel; Bouman, Heleen; Riveros-Mckay, Fernando; Kostadima, Myrto A; Lambourne, John J; Sivapalaratnam, Suthesh; Downes, Kate; Kundu, Kousik; Bomba, Lorenzo; Berentsen, Kim; Bradley, John R; Daugherty, Louise C; Delaneau, Olivier; Freson, Kathleen; Garner, Stephen F; Grassi, Luigi; Guerrero, Jose; Haimel, Matthias; Janssen-Megens, Eva M; Kaan, Anita; Kamat, Mihir; Kim, Bowon; Mandoli, Amit; Marchini, Jonathan; Martens, Joost H A; Meacham, Stuart; Megy, Karyn; O'Connell, Jared; Petersen, Romina; Sharifi, Nilofar; Sheard, Simon M; Staley, James R; Tuna, Salih; van der Ent, Martijn; Walter, Klaudia; Wang, Shuang-Yin; Wheeler, Eleanor; Wilder, Steven P; Iotchkova, Valentina; Moore, Carmel; Sambrook, Jennifer; Stunnenberg, Hendrik G; Di Angelantonio, Emanuele; Kaptoge, Stephen; Kuijpers, Taco W; Carrillo-de-Santa-Pau, Enrique; Juan, David; Rico, Daniel; Valencia, Alfonso; Chen, Lu; Ge, Bing; Vasquez, Louella; Kwan, Tony; Garrido-Martín, Diego; Watt, Stephen; Yang, Ying; Guigo, Roderic; Beck, Stephan; Paul, Dirk S; Pastinen, Tomi; Bujold, David; Bourque, Guillaume; Frontini, Mattia; Danesh, John; Roberts, David J; Ouwehand, Willem H; Butterworth, Adam S; Soranzo, Nicole

2016-11-17

Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal. Copyright © 2016 Elsevier Inc. All rights reserved.

What Is Genetic Ancestry Testing?

Science.gov (United States)

... What is genetic ancestry testing? What is genetic ancestry testing? Genetic ancestry testing, or genetic genealogy, is ... with other groups. For more information about genetic ancestry testing: The University of Utah provides video tutorials ...

Analysis of ancestry informative markers in three main ethnic groups from Ecuador supports a trihybrid origin of Ecuadorians.

Science.gov (United States)

Santangelo, Roberta; González-Andrade, Fabricio; Børsting, Claus; Torroni, Antonio; Pereira, Vania; Morling, Niels

2017-11-01

Ancestry inference is traditionally done using autosomal SNPs that present great allele frequency differences among populations from different geographic regions. These ancestry informative markers (AIMs) are useful for determining the most likely biogeographic ancestry or population of origin of an individual. Due to the growing interest in AIMs and their applicability in different fields, commercial companies have started to develop AIM multiplexes targeted for Massive Parallel Sequencing platforms. This project focused on the study of three main ethnic groups from Ecuador (Kichwa, Mestizo, and Afro-Ecuadorian) using the Precision ID Ancestry panel (Thermo Fisher Scientific). In total, 162 Ecuadorian individuals were investigated. The Afro-Ecuadorian and Mestizo showed higher average genetic diversities compared to the Kichwa. These results are consistent with the highly admixed nature of the first two groups. The Kichwa showed the highest proportion of Native Amerindian (NAM) ancestry relative to the other two groups. The Mestizo had an admixed ancestry of NAM and European with a larger European component, whereas the Afro-Ecuadorian were highly admixed presenting proportions of African, Native Amerindian, and European ancestries. The comparison of our results with previous studies based on uniparental markers (i.e. Y chromosome and mtDNA) highlighted the sex-biased admixture process in the Ecuadorian Mestizo. Overall, the data generated in this work represent one important step to assess the application of ancestry inference in admixed populations in a forensic context. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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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.

Allelic Variation of Bile Salt Hydrolase Genes in Lactobacillus salivarius Does Not Determine Bile Resistance Levels▿ †

Science.gov (United States)

Fang, Fang; Li, Yin; Bumann, Mario; Raftis, Emma J.; Casey, Pat G.; Cooney, Jakki C.; Walsh, Martin A.; O'Toole, Paul W.

2009-01-01

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. PMID:19592587

A single-tube 27-plex SNP assay for estimating individual ancestry and admixture from three continents.

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Wei, Yi-Liang; Wei, Li; Zhao, Lei; Sun, Qi-Fan; Jiang, Li; Zhang, Tao; Liu, Hai-Bo; Chen, Jian-Gang; Ye, Jian; Hu, Lan; Li, Cai-Xia

2016-01-01

A single-tube multiplex assay of a small set of ancestry-informative markers (AIMs) for effectively estimating individual ancestry and admixture is an ideal forensic tool to trace the population origin of an unknown DNA sample. We present a newly developed 27-plex single nucleotide polymorphism (SNP) panel with highly robust and balanced differential power to perfectly assign individuals to African, European, and East Asian ancestries. Evaluating 968 previously described intercontinental AIMs from three HapMap population genotyping datasets (Yoruban in Ibadan, Nigeria (YRI); Utah residents with Northern and Western European ancestry from the Centre de'Etude du Polymorphism Humain (CEPH) collection (CEU); and Han Chinese in Beijing, China (CHB)), the best set of markers was selected on the basis of Hardy-Weinberg equilibrium (p > 0.00001), population-specific allele frequency (two of three δ values >0.5), according to linkage disequilibrium (r (2) ancestry of the 11 populations in the HapMap project. Then, we tested the 27-plex SNP assay with 1164 individuals from 17 additional populations. The results demonstrated that the SNP panel was successful for ancestry inference of individuals with African, European, and East Asian ancestry. Furthermore, the system performed well when inferring the admixture of Eurasians (EUR/EAS) after analyzing admixed populations from Xinjiang (Central Asian) as follows: Tajik (68:27), Uyghur (49:46), Kirgiz (40:57), and Kazak (36:60). For individual analyses, we interpreted each sample with a three-ancestry component percentage and a population match probability sequence. This multiplex assay is a convenient and cost-effective tool to assist in criminal investigations, as well as to correct for the effects of population stratification for case-control studies.

Ancestry informative markers in Amerindians from Brazilian Amazon.

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Luizon, Marcelo Rizzatti; Mendes-Junior, Celso Teixeira; De Oliveira, Silviene Fabiana; Simões, Aguinaldo Luiz

2008-01-01

Ancestry informative markers (AIMs) are genetic loci with large frequency differences between the major ethnic groups and are very useful in admixture estimation. However, their frequencies are poorly known within South American indigenous populations, making it difficult to use them in admixture studies with Latin American populations, such as the trihybrid Brazilian population. To minimize this problem, the frequencies of the AIMs FY-null, RB2300, LPL, AT3-I/D, Sb19.3, APO, and PV92 were determined via PCR and PCR-RFLP in four tribes from Brazilian Amazon (Tikúna, Kashinawa, Baníwa, and Kanamarí), to evaluate their potential for discriminating indigenous populations from Europeans and Africans, as well as discriminating each tribe from the others. Although capable of differentiating tribes, as evidenced by the exact test of population differentiation, a neighbor-joining tree suggests that the AIMs are useless in obtaining reliable reconstructions of the biological relationships and evolutionary history that characterize the villages and tribes studied. The mean allele frequencies from these AIMs were very similar to those observed for North American natives. They discriminated Amerindians from Africans, but not from Europeans. On the other hand, the neighbor-joining dendrogram separated Africans and Europeans from Amerindians with a high statistical support (bootstrap = 0.989). The relatively low diversity (G(ST) = 0.042) among North American natives and Amerindians from Brazilian Amazon agrees with the lack of intra-ethnic variation previously reported for these markers. Despite genetic drift effects, the mean allelic frequencies herein presented could be used as Amerindian parental frequencies in admixture estimates in urban Brazilian populations. (c) 2007 Wiley-Liss, Inc.

Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection

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Elissa J. Chesler

2016-12-01

Full Text Available Multi-parent populations (MPPs capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution genetic mapping through the accumulation of recombination events over many generations. Breeding designs that maintain a large effective population size with randomized assignment of breeders at each generation can minimize the impact of selection, inbreeding, and genetic drift on allele frequencies. Small deviations from expected allele frequencies will have little effect on the power and precision of genetic analysis, but a major distortion could result in reduced power and loss of important functional alleles. We detected strong transmission ratio distortion in the Diversity Outbred (DO mouse population on chromosome 2, caused by meiotic drive favoring transmission of the WSB/EiJ allele at the R2d2 locus. The distorted region harbors thousands of polymorphisms derived from the seven non-WSB founder strains and many of these would be lost if the sweep was allowed to continue. To ensure the utility of the DO population to study genetic variation on chromosome 2, we performed an artificial selection against WSB/EiJ alleles at the R2d2 locus. Here, we report that we have purged the WSB/EiJ allele from the drive locus while preserving WSB/EiJ alleles in the flanking regions. We observed minimal disruption to allele frequencies across the rest of the autosomal genome. However, there was a shift in haplotype frequencies of the mitochondrial genome and an increase in the rate of an unusual sex chromosome aneuploidy. The DO population has been restored to genome-wide utility for genetic analysis, but our experience underscores that vigilant monitoring of similar genetic resource populations is needed to ensure their long-term utility.

Genomic structural variation-mediated allelic suppression causes hybrid male sterility in rice.

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Shen, Rongxin; Wang, Lan; Liu, Xupeng; Wu, Jiang; Jin, Weiwei; Zhao, Xiucai; Xie, Xianrong; Zhu, Qinlong; Tang, Huiwu; Li, Qing; Chen, Letian; Liu, Yao-Guang

2017-11-03

Hybrids between divergent populations commonly show hybrid sterility; this reproductive barrier hinders hybrid breeding of the japonica and indica rice (Oryza sativa L.) subspecies. Here we show that structural changes and copy number variation at the Sc locus confer japonica-indica hybrid male sterility. The japonica allele, Sc-j, contains a pollen-essential gene encoding a DUF1618-domain protein; the indica allele, Sc-i, contains two or three tandem-duplicated ~ 28-kb segments, each carrying an Sc-j-homolog with a distinct promoter. In Sc-j/Sc-i hybrids, the high-expression of Sc-i in sporophytic cells causes suppression of Sc-j expression in pollen and selective abortion of Sc-j-pollen, leading to transmission ratio distortion. Knocking out one or two of the three Sc-i copies by CRISPR/Cas9 rescues Sc-j expression and male fertility. Our results reveal the gene dosage-dependent allelic suppression as a mechanism of hybrid incompatibility, and provide an effective approach to overcome the reproductive barrier for hybrid breeding.

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

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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.

Interaction between common breast cancer susceptibility variants, genetic ancestry, and nongenetic risk factors in Hispanic women.

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Fejerman, Laura; Stern, Mariana C; John, Esther M; Torres-Mejía, Gabriela; Hines, Lisa M; Wolff, Roger K; Baumgartner, Kathy B; Giuliano, Anna R; Ziv, Elad; Pérez-Stable, Eliseo J; Slattery, Martha L

2015-11-01

Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population. We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions. We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74-1.20), 1.20 (0.94-1.53), and 1.49 (1.28-1.75) for current, former, and never hormone therapy users, respectively, Pinteraction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72-1.42), 1.19 (0.98-1.45), and 1.69 (1.26-2.26) for never, 12 months breastfeeding, respectively, Pinteraction 0.014]. The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women. These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and nongenetic risk factors and their contribution to breast cancer risk. ©2015 American Association for Cancer Research.

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

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Y. H. Li

2014-05-01

Full Text Available 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 have been used to examine the effectiveness of genetic marker selection and optimal approaches for individual assignment. In this paper, these pigs and the following breeds: Berkshire, Duroc, Landrace and Yorkshire, Meishan and Taoyuan, TLRI Black Pig No. 1, and Kaohsiung Animal Propagation Station Black pig are studied to build a genetic reference database. Nineteen microsatellite markers (loci provide information on genetic variation and differentiation among studied breeds. High differentiation index (FST and Cavalli-Sforza chord distances give genetic differentiation among breeds, including Lanyu’s inbred populations. Inbreeding values (FIS show that Lanyu and its derived inbred breeds have significant loss of heterozygosity. Individual assignment testing of 352 animals was done with different numbers of microsatellite markers in this study. The testing assigned 99% of the animals successfully into their correct reference populations based on 9 to 14 markers ranking D-scores, allelic number, expected heterozygosity (HE or FST, respectively. All miss-assigned individuals came from close lineage Lanyu breeds. To improve individual assignment among close lineage breeds, microsatellite markers selected from Lanyu populations with high polymorphic, heterozygosity, FST and D-scores were used. Only 6 to 8 markers ranking HE, FST or allelic number were required to obtain 99% assignment accuracy. This result suggests empirical examination of assignment-error rates

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

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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

2016-06-01

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. Copyright © 2016 Browning et al.

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.

An ancestry-based approach for detecting interactions.

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Park, Danny S; Eskin, Itamar; Kang, Eun Yong; Gamazon, Eric R; Eng, Celeste; Gignoux, Christopher R; Galanter, Joshua M; Burchard, Esteban; Ye, Chun J; Aschard, Hugues; Eskin, Eleazar; Halperin, Eran; Zaitlen, Noah

2018-02-01

Epistasis and gene-environment interactions are known to contribute significantly to variation of complex phenotypes in model organisms. However, their identification in human association studies remains challenging for myriad reasons. In the case of epistatic interactions, the large number of potential interacting sets of genes presents computational, multiple hypothesis correction, and other statistical power issues. In the case of gene-environment interactions, the lack of consistently measured environmental covariates in most disease studies precludes searching for interactions and creates difficulties for replicating studies. In this work, we develop a new statistical approach to address these issues that leverages genetic ancestry, defined as the proportion of ancestry derived from each ancestral population (e.g., the fraction of European/African ancestry in African Americans), in admixed populations. We applied our method to gene expression and methylation data from African American and Latino admixed individuals, respectively, identifying nine interactions that were significant at Pancestry can be a useful proxy for unknown and unmeasured covariates in the search for interaction effects. These results have important implications for our understanding of the genetic architecture of complex traits. © 2017 WILEY PERIODICALS, INC.

Haptoglobin genotyping of Vietnamese: global distribution of HP del, complete deletion allele of the HP gene.

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Soejima, Mikiko; Agusa, Tetsuro; Iwata, Hisato; Fujihara, Junko; Kunito, Takashi; Takeshita, Haruo; Lan, Vi Thi Mai; Minh, Tu Binh; Takahashi, Shin; Trang, Pham Thi Kim; Viet, Pham Hung; Tanabe, Shinsuke; Koda, Yoshiro

2015-01-01

The haptoglobin (HP) gene deletion allele (HP(del)) is responsible for anhaptoglobinemia and a genetic risk factor for anaphylaxis reaction after transfusion due to production of the anti-HP antibody. The distribution of this allele has been explored by several groups including ours. Here, we studied the frequency of HP(del) in addition to the distribution of common HP genotypes in 293 Vietnamese. The HP(del) was encountered with the frequency of 0.020. The present result suggested that this deletion allele is restricted to East and Southeast Asians. Thus, this allele seems to be a potential ancestry informative marker for these populations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals.

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Dan E Arking

2011-06-01

Full Text Available Sudden cardiac death (SCD continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000-300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10(-10. The risk allele, while ancestral, has a frequency of ~1.4%, suggesting strong negative selection and increases risk for SCD by 1.92-fold per allele (95% CI 1.57-2.34. We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals. Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006.

Genetic Ancestry and Susceptibility to Late-Onset Alzheimer Disease (LOAD) in the Admixed Colombian Population.

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Moreno, Diana J; Pino, Sebastián; Ríos, Ángela; Lopera, Francisco; Ostos, Henry; Via, Marc; Bedoya, Gabriel

2017-01-01

Differences in the prevalence of dementia among populations and in the effect of apolipoprotein E (APOE) on the emergence of Alzheimer disease (AD), which is the main type of dementia, have been reported. This study estimated the ancestry of a group of individuals with late-onset Alzheimer disease (LOAD) (N=280) and established whether there were any differences when compared with a control group (N=357) in a sample of the Colombian population. When the analyses were adjusted for known risk factors such as age, sex, presence of APOE[Latin Small Letter Open E]4, socioeconomic status, educational attainment, and place of birth, African ancestry was associated with an increased LOAD risk (odds ratio: 1.55; 95% confidence interval, 1.09-2.03; P=0.029), whereas Native American ancestry was associated with lower risk (odds ratio: 0.75; 95% confidence interval, 0.61-0.98; P=0.046), for every 10% increase in ancestry. In addition, there were significant differences in the proportion of Native American ancestry between carriers and noncarriers of the APOE[Latin Small Letter Open E]4 allele (Mann-Whitney U test, P=0.047), with noncarriers having higher mean Native American ancestry when compared with carriers. Our results are consistent with the presence of variants of African origin in the genome of the Colombian population and different from APOE[Latin Small Letter Open E]4 that represents a risk factor for the development of LOAD, whereas variants of Native American origin may be conferring protection. However, unknown environmental factors or epigenetic differences among continental groups could also explain the observed associations.

LAIT: a local ancestry inference toolkit.

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Hui, Daniel; Fang, Zhou; Lin, Jerome; Duan, Qing; Li, Yun; Hu, Ming; Chen, Wei

2017-09-06

Inferring local ancestry in individuals of mixed ancestry has many applications, most notably in identifying disease-susceptible loci that vary among different ethnic groups. Many software packages are available for inferring local ancestry in admixed individuals. However, most of these existing software packages require specific formatted input files and generate output files in various types, yielding practical inconvenience. We developed a tool set, Local Ancestry Inference Toolkit (LAIT), which can convert standardized files into software-specific input file formats as well as standardize and summarize inference results for four popular local ancestry inference software: HAPMIX, LAMP, LAMP-LD, and ELAI. We tested LAIT using both simulated and real data sets and demonstrated that LAIT provides convenience to run multiple local ancestry inference software. In addition, we evaluated the performance of local ancestry software among different supported software packages, mainly focusing on inference accuracy and computational resources used. We provided a toolkit to facilitate the use of local ancestry inference software, especially for users with limited bioinformatics background.

Influence of allelic variations in relation to norepinephrine and mineralocorticoid receptors on psychopathic traits: a pilot study

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Guillaume Durand

2018-03-01

Full Text Available Background Past findings support a relationship between abnormalities in the amygdala and the presence of psychopathic traits. Among other genes and biomarkers relevant to the amygdala, norepinephrine and mineralocorticoid receptors might both play a role in psychopathy due to their association with traits peripheral to psychopathy. The purpose is to examine if allelic variations in single nucleotide polymorphisms related to norepinephrine and mineralocorticoid receptors play a role in the display of psychopathic traits and executive functions. Methods Fifty-seven healthy participants from the community provided a saliva sample for SNP sampling of rs5522 and rs5569. Participants then completed the Psychopathic Personality Inventory–Short Form (PPI-SF and the Tower of Hanoi. Results Allelic variations of both rs5522 and rs5569 were significant when compared to PPI-SF total score and the fearless dominance component of the PPI-SF. A significant result was also obtained between rs5522 and the number of moves needed to complete the 5-disk Tower of Hanoi. Conclusion This pilot study offers preliminary results regarding the effect of allelic variations in SNPs related to norepinephrine and mineralocorticoid receptors on the presence of psychopathic traits. Suggestions are provided to enhance the reliability and validity of a larger-scale study.

Structural Analysis of Insulin Minisatellite Alleles Reveals Unusually Large Differences in Diversity between Africans and Non-Africans

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Stead, John D. H.; Jeffreys, Alec J.

2002-01-01

The insulin minisatellite (INS VNTR) associates with susceptibility to a variety of diseases. We have developed a high-resolution system for analyzing variant repeat distributions applicable to all known minisatellite alleles, irrespective of size, which allows lineages of related alleles to be identified. This system has previously revealed extremely low structural diversity in the minisatellite among northern Europeans from the United Kingdom, with all alleles belonging to one of only three highly diverged lineages called “I,” “IIIA,” and “IIIB.” To explore the origins of this remarkably limited lineage diversity, we have characterized an additional 780 alleles from three non-African and three African populations. In total, 22 highly diverged lineages were identified, with structural intermediates absent from extant populations, suggesting a bottleneck within the ancestry of all humans. The difference between levels of diversity in Africans and non-Africans is unusually large, with all 22 lineages identified in Africa compared with only three lineages seen not only in the United Kingdom but also in the other non-African populations. We also find evidence for overrepresentation of lineage I chromosomes in non-Africans. These data are consistent with a common out-of-Africa origin and an unusually tight bottleneck within the ancestry of all non-African populations, possibly combined with differential and positive selection for lineage I alleles in non-Africans. The important implications of these data for future disease-association studies are discussed. PMID:12404181

Ancestry inference using principal component analysis and spatial analysis: a distance-based analysis to account for population substructure.

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Byun, Jinyoung; Han, Younghun; Gorlov, Ivan P; Busam, Jonathan A; Seldin, Michael F; Amos, Christopher I

2017-10-16

Accurate inference of genetic ancestry is of fundamental interest to many biomedical, forensic, and anthropological research areas. Genetic ancestry memberships may relate to genetic disease risks. In a genome association study, failing to account for differences in genetic ancestry between cases and controls may also lead to false-positive results. Although a number of strategies for inferring and taking into account the confounding effects of genetic ancestry are available, applying them to large studies (tens thousands samples) is challenging. The goal of this study is to develop an approach for inferring genetic ancestry of samples with unknown ancestry among closely related populations and to provide accurate estimates of ancestry for application to large-scale studies. In this study we developed a novel distance-based approach, Ancestry Inference using Principal component analysis and Spatial analysis (AIPS) that incorporates an Inverse Distance Weighted (IDW) interpolation method from spatial analysis to assign individuals to population memberships. We demonstrate the benefits of AIPS in analyzing population substructure, specifically related to the four most commonly used tools EIGENSTRAT, STRUCTURE, fastSTRUCTURE, and ADMIXTURE using genotype data from various intra-European panels and European-Americans. While the aforementioned commonly used tools performed poorly in inferring ancestry from a large number of subpopulations, AIPS accurately distinguished variations between and within subpopulations. Our results show that AIPS can be applied to large-scale data sets to discriminate the modest variability among intra-continental populations as well as for characterizing inter-continental variation. The method we developed will protect against spurious associations when mapping the genetic basis of a disease. Our approach is more accurate and computationally efficient method for inferring genetic ancestry in the large-scale genetic studies.

A Panel of Ancestry Informative Markers for the Complex Five-Way Admixed South African Coloured Population

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Daya, Michelle; van der Merwe, Lize; Galal, Ushma; Möller, Marlo; Salie, Muneeb; Chimusa, Emile R.; Galanter, Joshua M.; van Helden, Paul D.; Henn, Brenna M.; Gignoux, Chris R.; Hoal, Eileen

2013-01-01

Admixture is a well known confounder in genetic association studies. If genome-wide data is not available, as would be the case for candidate gene studies, ancestry informative markers (AIMs) are required in order to adjust for admixture. The predominant population group in the Western Cape, South Africa, is the admixed group known as the South African Coloured (SAC). A small set of AIMs that is optimized to distinguish between the five source populations of this population (African San, African non-San, European, South Asian, and East Asian) will enable researchers to cost-effectively reduce false-positive findings resulting from ignoring admixture in genetic association studies of the population. Using genome-wide data to find SNPs with large allele frequency differences between the source populations of the SAC, as quantified by Rosenberg et. al's -statistic, we developed a panel of AIMs by experimenting with various selection strategies. Subsets of different sizes were evaluated by measuring the correlation between ancestry proportions estimated by each AIM subset with ancestry proportions estimated using genome-wide data. We show that a panel of 96 AIMs can be used to assess ancestry proportions and to adjust for the confounding effect of the complex five-way admixture that occurred in the South African Coloured population. PMID:24376522

Revision of the SNPforID 34-plex forensic ancestry test: Assay enhancements, standard reference sample genotypes and extended population studies.

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Fondevila, M; Phillips, C; Santos, C; Freire Aradas, A; Vallone, P M; Butler, J M; Lareu, M V; Carracedo, A

2013-01-01

A revision of an established 34 SNP forensic ancestry test has been made by swapping the under-performing rs727811 component SNP with the highly informative rs3827760 that shows a near-fixed East Asian specific allele. We collated SNP variability data for the revised SNP set in 66 reference populations from 1000 Genomes and HGDP-CEPH panels and used this as reference data to analyse four U.S. populations showing a range of admixture patterns. The U.S. Hispanics sample in particular displayed heterogeneous values of co-ancestry between European, Native American and African contributors, likely to reflect in part, the way this disparate group is defined using cultural as well as population genetic parameters. The genotyping of over 700 U.S. population samples also provided the opportunity to thoroughly gauge peak mobility variation and peak height ratios observed from routine use of the single base extension chemistry of the 34-plex test. Finally, the genotyping of the widely used DNA profiling Standard Reference Material samples plus other control DNAs completes the audit of the 34-plex assay to allow forensic practitioners to apply this test more readily in their own laboratories. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Robust Inference of Population Structure for Ancestry Prediction and Correction of Stratification in the Presence of Relatedness

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Conomos, Matthew P.; Miller, Mike; Thornton, Timothy

2016-01-01

Population structure inference with genetic data has been motivated by a variety of applications in population genetics and genetic association studies. Several approaches have been proposed for the identification of genetic ancestry differences in samples where study participants are assumed to be unrelated, including principal components analysis (PCA), multi-dimensional scaling (MDS), and model-based methods for proportional ancestry estimation. Many genetic studies, however, include individuals with some degree of relatedness, and existing methods for inferring genetic ancestry fail in related samples. We present a method, PC-AiR, for robust population structure inference in the presence of known or cryptic relatedness. PC-AiR utilizes genome-screen data and an efficient algorithm to identify a diverse subset of unrelated individuals that is representative of all ancestries in the sample. The PC-AiR method directly performs PCA on the identified ancestry representative subset and then predicts components of variation for all remaining individuals based on genetic similarities. In simulation studies and in applications to real data from Phase III of the HapMap Project, we demonstrate that PC-AiR provides a substantial improvement over existing approaches for population structure inference in related samples. We also demonstrate significant efficiency gains, where a single axis of variation from PC-AiR provides better prediction of ancestry in a variety of structure settings than using ten (or more) components of variation from widely used PCA and MDS approaches. Finally, we illustrate that PC-AiR can provide improved population stratification correction over existing methods in genetic association studies with population structure and relatedness. PMID:25810074

pfmdr1 Amplification and Fixation of pfcrt Chloroquine Resistance Alleles in Plasmodium falciparum in Venezuela ▿ †

Science.gov (United States)

Griffing, Sean; Syphard, Luke; Sridaran, Sankar; McCollum, Andrea M.; Mixson-Hayden, Tonya; Vinayak, Sumiti; Villegas, Leopoldo; Barnwell, John W.; Escalante, Ananias A.; Udhayakumar, Venkatachalam

2010-01-01

Molecular tools are valuable for determining evolutionary history and the prevalence of drug-resistant malaria parasites. These tools have helped to predict decreased sensitivity to antimalarials and fixation of multidrug resistance genotypes in some regions. In order to assess how historical drug policies impacted Plasmodium falciparum in Venezuela, we examined molecular changes in genes associated with drug resistance. We examined pfmdr1 and pfcrt in samples from Sifontes, Venezuela, and integrated our findings with earlier work describing dhfr and dhps in these samples. We characterized pfmdr1 genotypes and copy number variation, pfcrt genotypes, and proximal microsatellites in 93 samples originating from surveillance from 2003 to 2004. Multicopy pfmdr1 was found in 12% of the samples. Two pfmdr1 alleles, Y184F/N1042D/D1246Y (37%) and Y184F/S1034C/N1042D/D1246Y (63%), were found. These alleles share ancestry, and no evidence of strong selective pressure on mutations was found. pfcrt chloroquine resistance alleles are fixed with two alleles: StctVMNT (91%) and SagtVMNT (9%). These alleles are associated with strong selection. There was also an association between pfcrt, pfmdr1, dhfr, and dhps genotypes/haplotypes. Duplication of pfmdr1 suggests a potential shift in mefloquine sensitivity in this region, which warrants further study. A bottleneck occurred in P. falciparum in Sifontes, Venezuela, and multidrug resistance genotypes are present. This population could be targeted for malaria elimination programs to prevent the possible spread of multidrug-resistant parasites. PMID:20145087

Diversity of Wolbachia pipientis strain wPip in a genetically admixtured, above-ground Culex pipiens (Diptera: Culicidae) population: association with form molestus ancestry and host selection patterns.

Science.gov (United States)

Morningstar, Rebecca J; Hamer, Gabriel L; Goldberg, Tony L; Huang, Shaoming; Andreadis, Theodore G; Walker, Edward D

2012-05-01

Analysis of molecular genetic diversity in nine marker regions of five genes within the bacteriophage WO genomic region revealed high diversity of the Wolbachia pipentis strain wPip in a population of Culex pipiens L. sampled in metropolitan Chicago, IL. From 166 blood fed females, 50 distinct genetic profiles of wPip were identified. Rarefaction analysis suggested a maximum of 110 profiles out of a possible 512 predicted by combinations of the nine markers. A rank-abundance curve showed that few strains were common and most were rare. Multiple regression showed that markers associated with gene Gp2d, encoding a partial putative capsid protein, were significantly associated with ancestry of individuals either to form molestus or form pipiens, as determined by prior microsatellite allele frequency analysis. None of the other eight markers was associated with ancestry to either form, nor to ancestry to Cx. quinquefasciatus Say. Logistic regression of host choice (mammal vs. avian) as determined by bloodmeal analysis revealed that significantly fewer individuals that had fed on mammals had the Gp9a genetic marker (58.5%) compared with avian-fed individuals (88.1%). These data suggest that certain wPip molecular genetic types are associated with genetic admixturing in the Cx. pipiens complex of metropolitan Chicago, IL, and that the association extends to phenotypic variation related to host preference.

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

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

2014-09-01

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.

Variants in DENND1A are associated with polycystic ovary syndrome in women of European ancestry.

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Welt, Corrine K; Styrkarsdottir, Unnur; Ehrmann, David A; Thorleifsson, Gudmar; Arason, Gudmundur; Gudmundsson, Jens A; Ober, Carole; Rosenfield, Robert L; Saxena, Richa; Thorsteinsdottir, Unnur; Crowley, William F; Stefansson, Kari

2012-07-01

A genome-wide association study has identified three loci (five independent signals) that confer risk for polycystic ovary syndrome (PCOS) in Han Chinese women. Replication is necessary to determine whether the same variants confer risk for PCOS in women of European ancestry. The objective of the study was to test whether these PCOS risk variants in Han Chinese women confer risk for PCOS in women of European ancestry. This was a case-control study. The study was conducted at deCODE Genetics in Iceland and two academic medical centers in the United States. Cases were 376 Icelandic women and 565 and 203 women from Boston, MA, and Chicago, IL, respectively, all diagnosed with PCOS by the National Institutes of Health criteria. Controls were 16,947, 483, and 189 women not known to have PCOS from Iceland, Boston, and Chicago, respectively. There were no interventions. Main outcomes were allele frequencies for seven variants in PCOS cases and controls. Two strongly correlated Han Chinese PCOS risk variants on chromosome 9q33.3, rs10986105[C], and rs10818854[A], were replicated in samples of European ancestry with odds ratio of 1.68 (P = 0.00033) and odds ratio of 1.53 (P = 0.0019), respectively. Other risk variants at 2p16.3 (rs13405728), 2p21 (rs12468394, rs12478601, and rs13429458), and 9q33.3 (rs2479106), or variants correlated with them, did not associate with PCOS. The same allele of rs10986105 that increased the risk of PCOS also increased the risk of hyperandrogenism in women without PCOS from Iceland and demonstrated a stronger risk for PCOS defined by the National Institutes of Health criteria than the Rotterdam criteria. We replicated one of the five Chinese PCOS association signals, represented by rs10986105 and rs10818854 on 9q33, in individuals of European ancestry. Examination of the subjects meeting at least one of the Rotterdam criteria for PCOS suggests that the variant may be involved in the hyperandrogenism and possibly the irregular menses of PCOS.

Impact of ancestry categorisations on residential segregation measures using Swedish register data.

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Jarvis, Benjamin; Kawalerowicz, Juta; Valdez, Sarah

2017-07-01

Country-of-birth data contained in registers are often aggregated to create broad ancestry group categories. We examine how measures of residential segregation vary according to levels of aggregation. We use Swedish register data to calculate pairwise dissimilarity indices from 1990 to 2012 for ancestry groups defined at four nested levels of aggregation: (1) micro-groups containing 50 categories, (2) meso-groups containing 16 categories, (3) macro-groups containing six categories and (4) a broad Western/non-Western binary. We find variation in segregation levels between ancestry groups that is obscured by data aggregation. This study demonstrates that the practice of aggregating country-of-birth statistics in register data can hinder the ability to identify highly segregated groups and therefore design effective policy to remedy both intergroup and intergenerational inequalities.

Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case-control study.

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Traylor, Matthew; Curtis, Charles; Patel, Hamel; Breen, Gerome; Hyuck Lee, Sang; Xu, Xiaohui; Newhouse, Stephen; Dobson, Richard; Steer, Sophia; Cope, Andrew P; Markus, Hugh S; Lewis, Cathryn M; Scott, Ian C

2017-08-01

To evaluate whether genetic and environmental factors associated with RA in European and Asian ancestry populations are also associated with RA in African ancestry individuals. A case-control study was undertaken in 197 RA cases and 868 controls of African ancestry (Black African, Black Caribbean or Black British ethnicity) from South London. Smoking and alcohol consumption data at RA diagnosis was captured. Genotyping was undertaken (Multi-Ethnic Genotyping Array) and human leukocyte antigen (HLA) alleles imputed. The following European/Asian RA susceptibility factors were tested: 99 genome-wide loci combined into a genetic risk score; HLA region [20 haplotypes; shared epitope (SE)]; smoking; and alcohol consumption. The SE was tested for its association with radiological erosions. Logistic regression models were used, including ancestry-informative principal components, to control for admixture. European/Asian susceptibility loci were associated with RA in African ancestry individuals. The genetic risk score provided an odds ratio (OR) for RA of 1.53 (95% CI: 1.31, 1.79; P = 1.3 × 10 - 7 ). HLA haplotype ORs in European and African ancestry individuals were highly correlated ( r = 0.83, 95% CI: 0.56, 0.94; P = 1.1 × 10 - 4 ). Ever-smoking increased (OR = 2.36, 95% CI: 1.46, 3.82; P = 4.6 × 10 - 4 ) and drinking alcohol reduced (OR = 0.34, 95% CI: 0.20, 0.56; P = 2.7 × 10 - 5 ) RA risk in African ancestry individuals. The SE was associated with erosions (OR = 2.61, 95% CI: 1.36, 5.01; P = 3.9 × 10 - 3 ). Gene-environment RA risk factors identified in European/Asian ancestry populations are relevant in African ancestry individuals. As modern statistical methods facilitate analysing ancestrally diverse populations, future genetic studies should incorporate African ancestry individuals to ensure their implications for precision medicine are universally applicable. © The Author 2017. Published by Oxford University Press on behalf of the British Society for

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

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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.

Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population.

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Céspedes-Garro, Carolina; Rodrigues-Soares, Fernanda; Jiménez-Arce, Gerardo; Naranjo, María-Eugenia G; Tarazona-Santos, Eduardo; Fariñas, Humberto; Barrantes, Ramiro; Llerena, Adrián

2016-09-01

CYP2C9, CYP2C19 and CYP2D6 metabolize around 40% of drugs and their genes vary across populations. The Costa Rican population has a trihybrid ancestry and its key geographic location turns it into a suitable scenario to evaluate interethnic differences across populations. This study aims to describe the diversity of CYP2C9, CYP2C19 and CYP2D6 polymorphisms in Costa Rican populations in the context of their ancestry. A total of 448 healthy individuals were included in the study: Bribri (n= 47), Cabécar (n= 27), Maleku (n= 16), Guaymí (n= 30), Huetar (n= 48), Chorotega (n= 41), Admixed/Mestizos from the Central Valley/Guanacaste (n= 189), and Afro-Caribbeans (n= 50) from Limón. CYP2C9 (alleles *2, *3, *6) and CYP2C19 (*2, *3, *4, *5, *17) genotypes were determined by Real-Time PCR. African, European and Native American ancestry were inferred using 87 ancestry informative markers. The frequency of the decreased activity allele CYP2C9*2 is lower in the self-reported Amerindian groups compared to the admixed population, and the highest frequencies of CYP2C19*2 (null activity) and the CYP2C19*17 (increased activity) were found in the self-reported Afro-Caribbean population. Moreover, a frequency of 0.7 % CYP2C9 gPMs in the Admixed population and a variable frequency of CYP2C19 gUMs (0.0-32.6 %, more prevalent in Afro-Caribbeans) in Costa Rican populations, was found. Finally, the following alleles were positively correlated with genomic African ancestry and negatively correlated with genomic Native American ancestry: CYP2D6*5 (null activity), CYP2D6*17 (decreased activity), CYP2D6*29 (decreased activity) and CYP2C19*17 (increased activity). No correlation for CYP2C9 polymorphisms and genomic ancestry was found. Further studies assessing the CYP2C9 and CYP2C19 sequence in these populations, preferentially by sequencing these genes, are warranted.

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.

Inferring Genetic Ancestry: Opportunities, Challenges, and Implications

OpenAIRE

Royal, Charmaine D.; Novembre, John; Fullerton, Stephanie M.; Goldstein, David B.; Long, Jeffrey C.; Bamshad, Michael J.; Clark, Andrew G.

2010-01-01

Increasing public interest in direct-to-consumer (DTC) genetic ancestry testing has been accompanied by growing concern about issues ranging from the personal and societal implications of the testing to the scientific validity of ancestry inference. The very concept of “ancestry” is subject to misunderstanding in both the general and scientific communities. What do we mean by ancestry? How exactly is ancestry measured? How far back can such ancestry be defined and by which genetic tools? How ...

Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures

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Galanter, Joshua M; Gignoux, Christopher R; Oh, Sam S; Torgerson, Dara; Pino-Yanes, Maria; Thakur, Neeta; Eng, Celeste; Hu, Donglei; Huntsman, Scott; Farber, Harold J; Avila, Pedro C; Brigino-Buenaventura, Emerita; LeNoir, Michael A; Meade, Kelly; Serebrisky, Denise; Rodríguez-Cintrón, William; Kumar, Rajesh; Rodríguez-Santana, Jose R; Seibold, Max A; Borrell, Luisa N; Burchard, Esteban G; Zaitlen, Noah

2017-01-01

Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.2×10-64) of ethnicity-associated sites amongst loci previously associated environmental exposures, particularly maternal smoking during pregnancy. We conclude that differential methylation between ethnic groups is partially explained by the shared genetic ancestry but that environmental factors not captured by ancestry significantly contribute to variation in methylation. DOI: http://dx.doi.org/10.7554/eLife.20532.001 PMID:28044981

Allelic variation at the vernalization and photoperiod sensitivity loci in Chinese winter wheat cultivars (Triticum aestivum L.

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Xiangfen eZhang

2015-07-01

Full Text Available A total of 205 wheat cultivars from the Yellow and Huai valley of China were used to identify allelic variations of vernalization and photoperiod response genes, as well as the copy number variations (CNVs of Ppd-B1 and Vrn-A1 genes. A novel Vrn-D1 allele with 174-bp insertion in the promoter region of the recessive allele vrn-D1 was discovered in three Chinese wheat cultivars and designated as Vrn-D1c. Quantitative real-time polymerase chain reaction showed that cultivars with the Vrn-D1c allele exhibited significantly higher expression of the Vrn-D1 gene than that in cultivars with the recessive allele vrn-D1, indicating that the 174-bp insertion of Vrn-D1c contributed to the increase in Vrn-D1 gene expression and caused early heading and flowering. The five new cis-elements (Box II-like, 3-AF1 binding site, TC-rich repeats, Box-W1 and CAT-box in the 174-bp insertion possibly promoted the basal activity level of Vrn-D1 gene. Two new polymorphism combinations of photoperiod genes were identified and designated as Ppd-D1_Hapl-IX and Ppd-D1_Hapl-X. Association of the CNV of Ppd-B1 gene with the heading and flowering days showed that the cultivars with Ppd-B1_Hapl-VI demonstrated the earliest heading and flowering times, and those with Ppd-B1_Hapl-IV presented the latest heading and flowering times in three cropping seasons. Distribution of the vernalization and photoperiod response genes indicated that all recessive alleles at the four vernalization response loci, Ppd-B1_Hapl-I at Ppd-B1 locus, and Ppd-D1_Hapl-I at the Ppd-D1 locus were predominant in Chinese winter wheat cultivars. This study can provide useful information for wheat breeding programs to screen wheat cultivars with relatively superior adaptability and maturity.

SSR allelic variation of rice variety Hangxiangnuo bred by space mutation

International Nuclear Information System (INIS)

Yang Tifeng; Liu Chuanguang; Pan Dajian; Fan Zhilan; Li Chen; Chen Jianyou; Liu Bin; Jiang Yijun; Gao Yun; Zhou Hanqin

2011-01-01

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)

Ancestry prediction in Singapore population samples using the Illumina ForenSeq kit.

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Ramani, Anantharaman; Wong, Yongxun; Tan, Si Zhen; Shue, Bing Hong; Syn, Christopher

2017-11-01

The ability to predict bio-geographic ancestry can be valuable to generate investigative leads towards solving crimes. Ancestry informative marker (AIM) sets include large numbers of SNPs to predict an ancestral population. Massively parallel sequencing has enabled forensic laboratories to genotype a large number of such markers in a single assay. Illumina's ForenSeq DNA Signature Kit includes the ancestry informative SNPs reported by Kidd et al. In this study, the ancestry prediction capabilities of the ForenSeq kit through sequencing on the MiSeq FGx were evaluated in 1030 unrelated Singapore population samples of Chinese, Malay and Indian origin. A total of 59 ancestry SNPs and phenotypic SNPs with AIM properties were selected. The bio-geographic ancestry of the 1030 samples, as predicted by Illumina's ForenSeq Universal Analysis Software (UAS), was determined. 712 of the genotyped samples were used as a training sample set for the generation of an ancestry prediction model using STRUCTURE and Snipper. The performance of the prediction model was tested by both methods with the remaining 318 samples. Ancestry prediction in UAS was able to correctly classify the Singapore Chinese as part of the East Asian cluster, while Indians clustered with Ad-mixed Americans and Malays clustered in-between these two reference populations. Principal component analyses showed that the 59 SNPs were only able to account for 26% of the variation between the Singapore sub-populations. Their discriminatory potential was also found to be lower (G ST =0.085) than that reported in ALFRED (F ST =0.357). The Snipper algorithm was able to correctly predict bio-geographic ancestry in 91% of Chinese and Indian, and 88% of Malay individuals, while the success rates for the STRUCTURE algorithm were 94% in Chinese, 80% in Malay, and 91% in Indian individuals. Both these algorithms were able to provide admixture proportions when present. Ancestry prediction accuracy (in terms of likelihood ratio

Ancestry informative markers: inference of ancestry in aged bone samples using an autosomal AIM-Indel multiplex.

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Romanini, Carola; Romero, Magdalena; Salado Puerto, Mercedes; Catelli, Laura; Phillips, Christopher; Pereira, Rui; Gusmão, Leonor; Vullo, Carlos

2015-05-01

Ancestry informative markers (AIMs) can be useful to infer ancestry proportions of the donors of forensic evidence. The probability of success typing degraded samples, such as human skeletal remains, is strongly influenced by the DNA fragment lengths that can be amplified and the presence of PCR inhibitors. Several AIM panels are available amongst the many forensic marker sets developed for genotyping degraded DNA. Using a 46 AIM Insertion Deletion (Indel) multiplex, we analyzed human skeletal remains of post mortem time ranging from 35 to 60 years from four different continents (Sub-Saharan Africa, South and Central America, East Asia and Europe) to ascertain the genetic ancestry components. Samples belonging to non-admixed individuals could be assigned to their corresponding continental group. For the remaining samples with admixed ancestry, it was possible to estimate the proportion of co-ancestry components from the four reference population groups. The 46 AIM Indel set was informative enough to efficiently estimate the proportion of ancestry even in samples yielding partial profiles, a frequent occurrence when analyzing inhibited and/or degraded DNA extracts. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The common ancestry of life

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Wolf Yuri I

2010-11-01

Full Text Available Abstract Background It is common belief that all cellular life forms on earth have a common origin. This view is supported by the universality of the genetic code and the universal conservation of multiple genes, particularly those that encode key components of the translation system. A remarkable recent study claims to provide a formal, homology independent test of the Universal Common Ancestry hypothesis by comparing the ability of a common-ancestry model and a multiple-ancestry model to predict sequences of universally conserved proteins. Results We devised a computational experiment on a concatenated alignment of universally conserved proteins which shows that the purported demonstration of the universal common ancestry is a trivial consequence of significant sequence similarity between the analyzed proteins. The nature and origin of this similarity are irrelevant for the prediction of "common ancestry" of by the model-comparison approach. Thus, homology (common origin of the compared proteins remains an inference from sequence similarity rather than an independent property demonstrated by the likelihood analysis. Conclusion A formal demonstration of the Universal Common Ancestry hypothesis has not been achieved and is unlikely to be feasible in principle. Nevertheless, the evidence in support of this hypothesis provided by comparative genomics is overwhelming. Reviewers this article was reviewed by William Martin, Ivan Iossifov (nominated by Andrey Rzhetsky and Arcady Mushegian. For the complete reviews, see the Reviewers' Report section.

Anatomy, Medical Education, and Human Ancestral Variation

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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…

Denisovan Ancestry in East Eurasian and Native American Populations.

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Qin, Pengfei; Stoneking, Mark

2015-10-01

Although initial studies suggested that Denisovan ancestry was found only in modern human populations from island Southeast Asia and Oceania, more recent studies have suggested that Denisovan ancestry may be more widespread. However, the geographic extent of Denisovan ancestry has not been determined, and moreover the relationship between the Denisovan ancestry in Oceania and that elsewhere has not been studied. Here we analyze genome-wide single nucleotide polymorphism data from 2,493 individuals from 221 worldwide populations, and show that there is a widespread signal of a very low level of Denisovan ancestry across Eastern Eurasian and Native American (EE/NA) populations. We also verify a higher level of Denisovan ancestry in Oceania than that in EE/NA; the Denisovan ancestry in Oceania is correlated with the amount of New Guinea ancestry, but not the amount of Australian ancestry, indicating that recent gene flow from New Guinea likely accounts for signals of Denisovan ancestry across Oceania. However, Denisovan ancestry in EE/NA populations is equally correlated with their New Guinea or their Australian ancestry, suggesting a common source for the Denisovan ancestry in EE/NA and Oceanian populations. Our results suggest that Denisovan ancestry in EE/NA is derived either from common ancestry with, or gene flow from, the common ancestor of New Guineans and Australians, indicating a more complex history involving East Eurasians and Oceanians than previously suspected. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Population genetics models of local ancestry.

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Gravel, Simon

2012-06-01

Migrations have played an important role in shaping the genetic diversity of human populations. Understanding genomic data thus requires careful modeling of historical gene flow. Here we consider the effect of relatively recent population structure and gene flow and interpret genomes of individuals that have ancestry from multiple source populations as mosaics of segments originating from each population. This article describes general and tractable models for local ancestry patterns with a focus on the length distribution of continuous ancestry tracts and the variance in total ancestry proportions among individuals. The models offer improved agreement with Wright-Fisher simulation data when compared to the state-of-the art and can be used to infer time-dependent migration rates from multiple populations. Considering HapMap African-American (ASW) data, we find that a model with two distinct phases of "European" gene flow significantly improves the modeling of both tract lengths and ancestry variances.

Ancestry dependent DNA methylation and influence of maternal nutrition.

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Khyobeni Mozhui

Full Text Available There is extensive variation in DNA methylation between individuals and ethnic groups. These differences arise from a combination of genetic and non-genetic influences and potential modifiers include nutritional cues, early life experience, and social and physical environments. Here we compare genome-wide DNA methylation in neonatal cord blood from African American (AA; N = 112 and European American (EA; N = 91 participants of the CANDLE Study (Conditions Affecting Neurocognitive Development and Learning in Early Childhood. Our goal is to determine if there are replicable ancestry-specific methylation patterns that may implicate risk factors for diseases that have differential prevalence between populations. To identify the most robust ancestry-specific CpG sites, we replicate our results in lymphoblastoid cell lines from Yoruba African and CEPH European panels of HapMap. We also evaluate the influence of maternal nutrition--specifically, plasma levels of vitamin D and folate during pregnancy--on methylation in newborns. We define stable ancestry-dependent methylation of genes that include tumor suppressors and cell cycle regulators (e.g., APC, BRCA1, MCC. Overall, there is lower global methylation in African ancestral groups. Plasma levels of 25-hydroxy vitamin D are also considerably lower among AA mothers and about 60% of AA and 40% of EA mothers have concentrations below 20 ng/ml. Using a weighted correlation analysis, we define a network of CpG sites that is jointly modulated by ancestry and maternal vitamin D. Our results show that differences in DNA methylation patterns are remarkably stable and maternal micronutrients can exert an influence on the child epigenome.

Linkage disequilibrium in the insulin gene region: Size variation at the 5{prime} flanking polymorphism and bimodality among {open_quotes}Class I{close_quotes} alleles

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McGinnis, R.E.; Spielman, R.S. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)

1994-09-01

The 5{prime} flanking polymorphism (5{prime}FP), a hypervariable region at the 5{prime} end of the insulin gene, has {open_quotes}class 1{close_quotes} alleles (650-900 bp long) that are in positive linkage disequilibrium with insulin-dependent diabetes mellitus (IDDM). The authors report that precise sizing of the 5{prime}FP yields a bimodal frequency distribution of class 1 allele lengths. Class 1 alleles belonging to the lower component (650-750 bp) of the bimodal distribution were somewhat more highly associated with IDDM than were alleles from the upper component (760-900 bp), but the difference was not statistically significant. They also examined 5{prime}FP length variation in relation to allelic variation at nearby polymorphisms. At biallelic RFLPs on both sides of the 5{prime}FP, they found that one allele exhibits near-total association with the upper component of the 5FP class 1 distribution. Such associations represent a little-known but potentially wide-spread form of linkage disequilibrium. In this type of disequilibrium, a flanking allele has near-complete association with a single mode of VNTR alleles whose lengths represent consecutive numbers of tandem repeats (CNTR). Such extreme disequilibrium between a CNTR mode and flanking alleles may originate and persist because length mutations at some VNTR loci usually add or delete only one or two repeat units. 22 refs., 5 figs., 6 tabs.

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

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Santos, C; Fondevila, M; Ballard, D

2015-01-01

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...... 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...... 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 informative likelihood ratios for a third. Therefore, successful ancestry assignments were achieved by participants in 92 of 95...

Concordance of the ForenSeq™ system and characterisation of sequence-specific autosomal STR alleles across two major population groups.

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Devesse, Laurence; Ballard, David; Davenport, Lucinda; Riethorst, Immy; Mason-Buck, Gabriella; Syndercombe Court, Denise

2018-05-01

By using sequencing technology to genotype loci of forensic interest it is possible to simultaneously target autosomal, X and Y STRs as well as identity, ancestry and phenotypic informative SNPs, resulting in a breadth of data obtained from a single run that is considerable when compared to that generated with standard technologies. It is important however that this information aligns with the genotype data currently obtained using commercially available kits for CE-based investigations such that results are compatible with existing databases and hence can be of use to the forensic community. In this work, 400 samples were typed using commercially available STR kits and CE, as well as using the Ilumina ForenSeq™ DNA Signature Prep Kit and MiSeq ® FGx to assess concordance of autosomal STRs and population variability. Results show a concordance rate between the two technologies exceeding 99.98% while numerous novel sequence based alleles are described. In order to make use of the sequence variation observed, sequence specific allele frequencies were generated for White British and British Chinese populations. Copyright © 2017 Elsevier B.V. All rights reserved.

Selecting SNPs informative for African, American Indian and European Ancestry: application to the Family Investigation of Nephropathy and Diabetes (FIND).

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Williams, Robert C; Elston, Robert C; Kumar, Pankaj; Knowler, William C; Abboud, Hanna E; Adler, Sharon; Bowden, Donald W; Divers, Jasmin; Freedman, Barry I; Igo, Robert P; Ipp, Eli; Iyengar, Sudha K; Kimmel, Paul L; Klag, Michael J; Kohn, Orly; Langefeld, Carl D; Leehey, David J; Nelson, Robert G; Nicholas, Susanne B; Pahl, Madeleine V; Parekh, Rulan S; Rotter, Jerome I; Schelling, Jeffrey R; Sedor, John R; Shah, Vallabh O; Smith, Michael W; Taylor, Kent D; Thameem, Farook; Thornley-Brown, Denyse; Winkler, Cheryl A; Guo, Xiuqing; Zager, Phillip; Hanson, Robert L

2016-05-04

The presence of population structure in a sample may confound the search for important genetic loci associated with disease. Our four samples in the Family Investigation of Nephropathy and Diabetes (FIND), European Americans, Mexican Americans, African Americans, and American Indians are part of a genome- wide association study in which population structure might be particularly important. We therefore decided to study in detail one component of this, individual genetic ancestry (IGA). From SNPs present on the Affymetrix 6.0 Human SNP array, we identified 3 sets of ancestry informative markers (AIMs), each maximized for the information in one the three contrasts among ancestral populations: Europeans (HAPMAP, CEU), Africans (HAPMAP, YRI and LWK), and Native Americans (full heritage Pima Indians). We estimate IGA and present an algorithm for their standard errors, compare IGA to principal components, emphasize the importance of balancing information in the ancestry informative markers (AIMs), and test the association of IGA with diabetic nephropathy in the combined sample. A fixed parental allele maximum likelihood algorithm was applied to the FIND to estimate IGA in four samples: 869 American Indians; 1385 African Americans; 1451 Mexican Americans; and 826 European Americans. When the information in the AIMs is unbalanced, the estimates are incorrect with large error. Individual genetic admixture is highly correlated with principle components for capturing population structure. It takes ~700 SNPs to reduce the average standard error of individual admixture below 0.01. When the samples are combined, the resulting population structure creates associations between IGA and diabetic nephropathy. The identified set of AIMs, which include American Indian parental allele frequencies, may be particularly useful for estimating genetic admixture in populations from the Americas. Failure to balance information in maximum likelihood, poly-ancestry models creates biased

Influence of Human Leukocyte Antigen (HLA) Alleles and Killer Cell Immunoglobulin-Like Receptors (KIR) Types on Heparin-Induced Thrombocytopenia (HIT).

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Karnes, Jason H; Shaffer, Christian M; Cronin, Robert; Bastarache, Lisa; Gaudieri, Silvana; James, Ian; Pavlos, Rebecca; Steiner, Heidi E; Mosley, Jonathan D; Mallal, Simon; Denny, Joshua C; Phillips, Elizabeth J; Roden, Dan M

2017-09-01

Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT. HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. The p values for HLA and KIR association were corrected by using a false discovery rate qHIT cases and 350 matched controls were identified. No statistical differences in baseline characteristics were observed between cases and controls. The HLA-DRB3*01:01 allele was significantly associated with HIT in the overall population (odds ratio 2.81 [1.57-5.02], p=2.1×10 -4 , q=0.02) and in individuals with European ancestry, independent of other alleles. No KIR types were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is necessary. © 2017 Pharmacotherapy Publications, Inc.

African ancestry protects against Alzheimer's disease-related neuropathology.

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Schlesinger, D; Grinberg, L T; Alba, J G; Naslavsky, M S; Licinio, L; Farfel, J M; Suemoto, C K; de Lucena Ferretti, R E; Leite, R E P; de Andrade, M P; dos Santos, A C F; Brentani, H; Pasqualucci, C A; Nitrini, R; Jacob-Filho, W; Zatz, M

2013-01-01

Previous studies in dementia epidemiology have reported higher Alzheimer's disease rates in African-Americans when compared with White Americans. To determine whether genetically determined African ancestry is associated with neuropathological changes commonly associated with dementia, we analyzed a population-based brain bank in the highly admixed city of São Paulo, Brazil. African ancestry was estimated through the use of previously described ancestry-informative markers. Risk of presence of neuritic plaques, neurofibrillary tangles, small vessel disease, brain infarcts and Lewy bodies in subjects with significant African ancestry versus those without was determined. Results were adjusted for multiple environmental risk factors, demographic variables and apolipoprotein E genotype. African ancestry was inversely correlated with neuritic plaques (P=0.03). Subjects with significant African ancestry (n=112, 55.4%) showed lower prevalence of neuritic plaques in the univariate analysis (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.55-0.95, P=0.01) and when adjusted for age, sex, APOE genotype and environmental risk factors (OR 0.43, 95% CI 0.21-0.89, P=0.02). There were no significant differences for the presence of other neuropathological alterations. We show for the first time, using genetically determined ancestry, that African ancestry may be highly protective of Alzheimer's disease neuropathology, functioning through either genetic variants or unknown environmental factors. Epidemiological studies correlating African-American race/ethnicity with increased Alzheimer's disease rates should not be interpreted as surrogates of genetic ancestry or considered to represent African-derived populations from the developing nations such as Brazil.

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

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Umaima Al-Alem

Full Text Available 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.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.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.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/ethnic groups.

Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a Brazilian population with high African ancestry.

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do Rego Borges, Andrea; Sá, Jamile; Hoshi, Ryuichi; Viena, Camila Sane; Mariano, Lorena C; de Castro Veiga, Patricia; Medrado, Alena Peixoto; Machado, Renato Assis; de Aquino, Sibele Nascimento; Messetti, Ana Camila; Spritz, Richard A; Coletta, Ricardo D; Reis, Silvia R A

2015-10-01

Nonsyndromic cleft lip with or without cleft palate (NSCL ± P) is the most common orofacial birth defect, exhibiting variable prevalence around the world, often attributed to ethnic and environmental differences. Linkage analyses and genome-wide association studies have identified several genomic susceptibility regions for NSCL ± P, mostly in European-derived or Asian populations. Genetic predisposition to NSCL ± P is ethnicity-dependent, and the genetic basis of susceptibility to NSCL ± P likely varies among populations. The population of Brazil is highly admixed, with highly variable ancestry; thus, the genetic determinants of NSCL ± P susceptibility may be quite different. This study tested association of 8 single-nucleotide polymorphisms (SNPs), previously identified by genome-wide studies in other populations, with NSCL ± P in a Brazilian population with high African ancestry. SNPs rs560426, rs642961, rs1530300, rs987525, rs3758249, rs7078160, rs17085106, and rs13041247 were genotyped in 293 Brazilian patients with NSCL ± P and 352 unaffected Brazilian controls. Each sample was also genotyped for 40 biallelic short insertion/deletion polymorphic markers to characterize genetic ancestry. The average African ancestry background was 31.1% for the NSCL ± P group and 36.7% for the control group. After adjustment for ancestry and multiple testing, the minor alleles of rs3758249 (OR: 1.58, 95% CI: 1.25-2.01, P = 0.0001) and rs7078160 (OR: 1.59, 95% CI: 1.21-2.07, P = 0.0002) were significantly associated with risk of NSCL ± P. Polymorphisms located in IRF6 (rs642961) and 8q24 (rs1530300 and rs987525) showed marginal associations in this Brazilian population with high African ancestry. These results indicate that rs3758249 at 9q22 and rs7078160 at 10q25.3 represent risk loci for NSCL ± P in the Brazilian population with high African ancestry. © 2015 Wiley Periodicals, Inc.

Warfarin maintenance dose in older patients: higher average dose and wider dose frequency distribution in patients of African ancestry than those of European ancestry.

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Garwood, Candice L; Clemente, Jennifer L; Ibe, George N; Kandula, Vijay A; Curtis, Kristy D; Whittaker, Peter

2010-06-15

Studies report that warfarin doses required to maintain therapeutic anticoagulation decrease with age; however, these studies almost exclusively enrolled patients of European ancestry. Consequently, universal application of dosing paradigms based on such evidence may be confounded because ethnicity also influences dose. Therefore, we determined if warfarin dose decreased with age in Americans of African ancestry, if older African and European ancestry patients required different doses, and if their daily dose frequency distributions differed. Our chart review examined 170 patients of African ancestry and 49 patients of European ancestry cared for in our anticoagulation clinic. We calculated the average weekly dose required for each stable, anticoagulated patient to maintain an international normalized ratio of 2.0 to 3.0, determined dose averages for groups 80 years of age and plotted dose as a function of age. The maintenance dose in patients of African ancestry decreased with age (PAfrican ancestry required higher average weekly doses than patients of European ancestry: 33% higher in the 70- to 79-year-old group (38.2+/-1.9 vs. 28.8+/-1.7 mg; P=0.006) and 52% in the >80-year-old group (33.2+/-1.7 vs. 21.8+/-3.8 mg; P=0.011). Therefore, 43% of older patients of African ancestry required daily doses >5mg and hence would have been under-dosed using current starting-dose guidelines. The dose frequency distribution was wider for older patients of African ancestry compared to those of European ancestry (PAfrican ancestry indicate that strategies for initiating warfarin therapy based on studies of patients of European ancestry could result in insufficient anticoagulation and thereby potentially increase their thromboembolism risk. Copyright 2010 Elsevier Inc. All rights reserved.

Genetic variation among the Mapuche Indians from the Patagonian region of Argentina: mitochondrial DNA sequence variation and allele frequencies of several nuclear genes.

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Ginther, C; Corach, D; Penacino, G A; Rey, J A; Carnese, F R; Hutz, M H; Anderson, A; Just, J; Salzano, F M; King, M C

1993-01-01

DNA samples from 60 Mapuche Indians, representing 39 maternal lineages, were genetically characterized for (1) nucleotide sequences of the mtDNA control region; (2) presence or absence of a nine base duplication in mtDNA region V; (3) HLA loci DRB1 and DQA1; (4) variation at three nuclear genes with short tandem repeats; and (5) variation at the polymorphic marker D2S44. The genetic profile of the Mapuche population was compared to other Amerinds and to worldwide populations. Two highly polymorphic portions of the mtDNA control region, comprising 650 nucleotides, were amplified by the polymerase chain reaction (PCR) and directly sequenced. The 39 maternal lineages were defined by two or three generation families identified by the Mapuches. These 39 lineages included 19 different mtDNA sequences that could be grouped into four classes. The same classes of sequences appear in other Amerinds from North, Central, and South American populations separated by thousands of miles, suggesting that the origin of the mtDNA patterns predates the migration to the Americas. The mtDNA sequence similarity between Amerind populations suggests that the migration throughout the Americas occurred rapidly relative to the mtDNA mutation rate. HLA DRB1 alleles 1602 and 1402 were frequent among the Mapuches. These alleles also occur at high frequency among other Amerinds in North and South America, but not among Spanish, Chinese or African-American populations. The high frequency of these alleles throughout the Americas, and their specificity to the Americas, supports the hypothesis that Mapuches and other Amerind groups are closely related.(ABSTRACT TRUNCATED AT 250 WORDS)

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

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Lara E Sucheston

Full Text Available 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.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.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.Mean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity

Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.

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Jingjing Liang

2017-05-01

Full Text Available Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10-8 for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4 and multiple-trait analyses identified one novel locus (FRMD3 for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.

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

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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. © 2015 American Academy of Forensic Sciences.

Incomplete dominance of deleterious alleles contributes substantially to trait variation and heterosis in maize.

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Jinliang Yang

2017-09-01

Full Text Available Deleterious alleles have long been proposed to play an important role in patterning phenotypic variation and are central to commonly held ideas explaining the hybrid vigor observed in the offspring of a cross between two inbred parents. We test these ideas using evolutionary measures of sequence conservation to ask whether incorporating information about putatively deleterious alleles can inform genomic selection (GS models and improve phenotypic prediction. We measured a number of agronomic traits in both the inbred parents and hybrids of an elite maize partial diallel population and re-sequenced the parents of the population. Inbred elite maize lines vary for more than 350,000 putatively deleterious sites, but show a lower burden of such sites than a comparable set of traditional landraces. Our modeling reveals widespread evidence for incomplete dominance at these loci, and supports theoretical models that more damaging variants are usually more recessive. We identify haplotype blocks using an identity-by-decent (IBD analysis and perform genomic prediction analyses in which we weigh blocks on the basis of complementation for segregating putatively deleterious variants. Cross-validation results show that incorporating sequence conservation in genomic selection improves prediction accuracy for grain yield and other fitness-related traits as well as heterosis for those traits. Our results provide empirical support for an important role for incomplete dominance of deleterious alleles in explaining heterosis and demonstrate the utility of incorporating functional annotation in phenotypic prediction and plant breeding.

Incomplete dominance of deleterious alleles contributes substantially to trait variation and heterosis in maize.

Science.gov (United States)

Yang, Jinliang; Mezmouk, Sofiane; Baumgarten, Andy; Buckler, Edward S; Guill, Katherine E; McMullen, Michael D; Mumm, Rita H; Ross-Ibarra, Jeffrey

2017-09-01

Deleterious alleles have long been proposed to play an important role in patterning phenotypic variation and are central to commonly held ideas explaining the hybrid vigor observed in the offspring of a cross between two inbred parents. We test these ideas using evolutionary measures of sequence conservation to ask whether incorporating information about putatively deleterious alleles can inform genomic selection (GS) models and improve phenotypic prediction. We measured a number of agronomic traits in both the inbred parents and hybrids of an elite maize partial diallel population and re-sequenced the parents of the population. Inbred elite maize lines vary for more than 350,000 putatively deleterious sites, but show a lower burden of such sites than a comparable set of traditional landraces. Our modeling reveals widespread evidence for incomplete dominance at these loci, and supports theoretical models that more damaging variants are usually more recessive. We identify haplotype blocks using an identity-by-decent (IBD) analysis and perform genomic prediction analyses in which we weigh blocks on the basis of complementation for segregating putatively deleterious variants. Cross-validation results show that incorporating sequence conservation in genomic selection improves prediction accuracy for grain yield and other fitness-related traits as well as heterosis for those traits. Our results provide empirical support for an important role for incomplete dominance of deleterious alleles in explaining heterosis and demonstrate the utility of incorporating functional annotation in phenotypic prediction and plant breeding.

Is xenodontine snake reproduction shaped by ancestry, more than by ecology?

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Bellini, Gisela P; Arzamendia, Vanesa; Giraudo, Alejandro R

2017-01-01

One of the current challenges of evolutionary ecology is to understand the effects of phylogenetic history (PH) and/or ecological factors (EF) on the life-history traits of the species. Here, the effects of environment and phylogeny are tested for the first time on the reproductive biology of South American xenodontine snakes. We studied 60% of the tribes of this endemic and most representative clade in a temperate region of South America. A comparative method (canonical phylogenetic ordination-CPO) was used to find the relative contributions of EF and PH upon life-history aspects of snakes, comparing the reproductive mode, mean fecundity, reproductive potential, and frequency of nearly 1,000 specimens. CPO analysis showed that PH or ancestry explained most of the variation in reproduction, whereas EF explained little of this variation. The reproductive traits under study are suggested to have a strong phylogenetic signal in this clade, the ancestry playing a big role in reproduction. The EF also influenced the reproduction of South American xenodontines, although to a lesser extent. Our finding provides new evidence of how the evolutionary history is embodied in the traits of living species.

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

Energy Technology Data Exchange (ETDEWEB)

Tabasum, A; Iqbal, N; Hameed, A; Arshad, R [Nuclear Institute for Agriculture and Biology, Faisalabad (Pakistan)

2011-06-15

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)

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

International Nuclear Information System (INIS)

Tabasum, A.; Iqbal, N.; Hameed, A.; Arshad, R.

2011-01-01

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)

Ancestry Testing and the Practice of Genetic Counseling.

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Kirkpatrick, Brianne E; Rashkin, Misha D

2017-02-01

Ancestry testing is a home DNA test with many dimensions; in some cases, the implications and outcomes of testing cross over into the health sphere. Common reasons for seeking ancestry testing include determining an estimate of customer's ethnic background, identifying genetic relatives, and securing a raw DNA data file that can be used for other purposes. As the ancestry test marketplace continues to grow, and third-party vendors empower the general public to analyze their own genetic material, the role of the genetic counselor is likely to evolve dramatically. Roles of the genetic counselor may include assisting clients with the interpretation of and adaptation to these results, as well as advising the companies involved in this sector on the ethical, legal, and social issues associated with testing. This paper reviews the history, fundamentals, intended uses, and unintended consequences of ancestry genetic testing. It also discusses the types of information in an ancestry testing result, situations that might involve a clinical genetic counselor, and the benefits, limitations, and functions that ancestry genetic testing can play in a clinical genetics setting.

Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations.

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Yoneyama, S; Yao, J; Guo, X; Fernandez-Rhodes, L; Lim, U; Boston, J; Buzková, P; Carlson, C S; Cheng, I; Cochran, B; Cooper, R; Ehret, G; Fornage, M; Gong, J; Gross, M; Gu, C C; Haessler, J; Haiman, C A; Henderson, B; Hindorff, L A; Houston, D; Irvin, M R; Jackson, R; Kuller, L; Leppert, M; Lewis, C E; Li, R; Le Marchand, L; Matise, T C; Nguyen, K-Dh; Chakravarti, A; Pankow, J S; Pankratz, N; Pooler, L; Ritchie, M D; Bien, S A; Wassel, C L; Chen, Y-D I; Taylor, K D; Allison, M; Rotter, J I; Schreiner, P J; Schumacher, F; Wilkens, L; Boerwinkle, E; Kooperberg, C; Peters, U; Buyske, S; Graff, M; North, K E

2017-02-01

Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of body mass index (BMI) and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition. To identify the underlying functional genetic determinants of body fat distribution, we conducted an array-wide association meta-analysis among persons of African ancestry across seven studies/consortia participating in the Population Architecture using Genomics and Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine-mapping cardiovascular-associated loci, to explore novel array-wide associations with WC and WHR among 15 945 African descendants using all and sex-stratified groups. We further interrogated 17 known WHR regions for African ancestry-specific variants. Of the 17 WHR loci, eight single-nucleotide polymorphisms (SNPs) located in four loci were replicated in the sex-combined or sex-stratified meta-analyses. Two of these eight independently associated with WHR after conditioning on the known variant in European descendants (rs12096179 in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine-mapping assessment, the putative functional region was reduced across all four loci but to varying degrees (average 40% drop in number of putative SNPs and 20% drop in genomic region). Similar to previous studies, the significant SNPs in the female-stratified analysis were stronger than the significant SNPs from the sex-combined analysis. No novel associations were detected in the array-wide analyses. Of 17 previously identified loci, four loci replicated in the African ancestry populations of this

Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations

Science.gov (United States)

Yoneyama, Sachiko; Yao, Jie; Guo, Xiuqing; Fernandez-Rhodes, Lindsay; Lim, Unhee; Boston, Jonathan; Buzková, Petra; Carlson, Christopher S.; Cheng, Iona; Cochran, Barbara; Cooper, Richard; Ehret, Georg; Fornage, Myriam; Gong, Jian; Gross, Myron; Gu, C. Charles; Haessler, Jeff; Haiman, Christopher A.; Henderson, Brian; Hindorff, Lucia A.; Houston, Denise; Irvin, Marguerite R.; Jackson, Rebecca; Kuller, Lew; Leppert, Mark; Lewis, Cora E.; Li, Rongling; Le Marchand, Loic; Matise, Tara C.; Nguyen, Khanh-Dung H.; Chakravarti, Aravinda; Pankow, James S.; Pankratz, Nathan; Pooler, Loreall; Ritchie, Marylyn D.; Bien, Stephanie A.; Wassel, Christina L.; Chen, Yii-Der I.; Taylor, Kent D.; Allison, Matthew; Rotter, Jerome I.; Schreiner, Pamela J.; Schumacher, Fredrick; Wilkens, Lynne; Boerwinkle, Eric; Kooperberg, Charles; Peters, Ulrike; Buyske, Steven; Graff, Mariaelisa; North, Kari E.

2016-01-01

Background/Objectives Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of BMI and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition. Subjects/Methods To identify the underlying functional genetic determinants of body fat distribution, we conducted an array-wide association meta-analysis among persons of African ancestry across seven studies/consortia participating in the Population Architecture using Genomics and Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine mapping cardiovascular associated loci, to explore novel array-wide associations with WC and WHR among 15 945 African descendants using all and sex-stratified groups. We further interrogated 17 known WHR regions for African ancestry-specific variants. Results Of the 17 WHR loci, eight SNPs located in four loci were replicated in the sex-combined or sex-stratified meta-analyses. Two of these eight independently associated with WHR after conditioning on the known variant in European descendants (rs12096179 in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine mapping assessment, the putative functional region was reduced across all four loci but to varying degrees (average 40% drop in number of putative SNPs and 20% drop in genomic region). Similar to previous studies, the significant SNPs in the female stratified analysis were stronger than the significant SNPs from the sex-combined analysis. No novel associations were detected in the array-wide analyses. Conclusions Of 17 previously identified loci, four loci replicated in the African ancestry populations of

Allelic variation of the FRMD7 gene in congenital idiopathic nystagmus.

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Self, James E; Shawkat, Fatima; Malpas, Crispin T; Thomas, N Simon; Harris, Christopher M; Hodgkins, Peter R; Chen, Xiaoli; Trump, Dorothy; Lotery, Andrew J

2007-09-01

To perform a genotype-phenotype correlation study in an X-linked congenital idiopathic nystagmus pedigree (pedigree 1) and to assess the allelic variance of the FRMD7 gene in congenital idiopathic nystagmus. Subjects from pedigree 1 underwent detailed clinical examination including nystagmology. Screening of FRMD7 was undertaken in pedigree 1 and in 37 other congenital idiopathic nystagmus probands and controls. Direct sequencing confirmed sequence changes. X-inactivation studies were performed in pedigree 1. The nystagmus phenotype was extremely variable in pedigree 1. We identified 2 FRMD7 mutations. However, 80% of X-linked families and 96% of simplex cases showed no mutations. X-inactivation studies demonstrated no clear causal link between skewing and variable penetrance. We confirm profound phenotypic variation in X-linked congenital idiopathic nystagmus pedigrees. We demonstrate that other congenital nystagmus genes exist besides FRMD7. We show that the role of X inactivation in variable penetrance is unclear in congenital idiopathic nystagmus. Clinical Relevance We demonstrate that phenotypic variation of nystagmus occurs in families with FRMD7 mutations. While FRMD7 mutations may be found in some cases of X-linked congenital idiopathic nystagmus, the diagnostic yield is low. X-inactivation assays are unhelpful as a test for carrier status for this disease.

Denisovan Ancestry in East Eurasian and Native American Populations.

OpenAIRE

Stoneking, Mark; Qin, Pengfei

2015-01-01

Although initial studies suggested that Denisovan ancestry was found only in modern human populations from island Southeast Asia and Oceania, more recent studies have suggested that Denisovan ancestry may be more widespread. However, the geographic extent of Denisovan ancestry has not been determined, and moreover the relationship between the Denisovan ancestry in Oceania and that elsewhere has not been studied. Here we analyze genome-wide SNP data from 2493 individuals from 221 worldwide pop...

Genetic ancestry, social classification, and racial inequalities in blood pressure in Southeastern Puerto Rico.

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Clarence C Gravlee

2009-09-01

Full Text Available The role of race in human genetics and biomedical research is among the most contested issues in science. Much debate centers on the relative importance of genetic versus sociocultural factors in explaining racial inequalities in health. However, few studies integrate genetic and sociocultural data to test competing explanations directly.We draw on ethnographic, epidemiologic, and genetic data collected in Southeastern Puerto Rico to isolate two distinct variables for which race is often used as a proxy: genetic ancestry versus social classification. We show that color, an aspect of social classification based on the culturally defined meaning of race in Puerto Rico, better predicts blood pressure than does a genetic-based estimate of continental ancestry. We also find that incorporating sociocultural variables reveals a new and significant association between a candidate gene polymorphism for hypertension (alpha(2C adrenergic receptor deletion and blood pressure.This study addresses the recognized need to measure both genetic and sociocultural factors in research on racial inequalities in health. Our preliminary results provide the most direct evidence to date that previously reported associations between genetic ancestry and health may be attributable to sociocultural factors related to race and racism, rather than to functional genetic differences between racially defined groups. Our results also imply that including sociocultural variables in future research may improve our ability to detect significant allele-phenotype associations. Thus, measuring sociocultural factors related to race may both empower future genetic association studies and help to clarify the biological consequences of social inequalities.

Genomics Assisted Ancestry Deconvolution in Grape

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Sawler, Jason; Reisch, Bruce; Aradhya, Mallikarjuna K.; Prins, Bernard; Zhong, Gan-Yuan; Schwaninger, Heidi; Simon, Charles; Buckler, Edward; Myles, Sean

2013-01-01

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. PMID:24244717

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.

Phenotypic variance explained by local ancestry in admixed African Americans.

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Shriner, Daniel; Bentley, Amy R; Doumatey, Ayo P; Chen, Guanjie; Zhou, Jie; Adeyemo, Adebowale; Rotimi, Charles N

2015-01-01

We surveyed 26 quantitative traits and disease outcomes to understand the proportion of phenotypic variance explained by local ancestry in admixed African Americans. After inferring local ancestry as the number of African-ancestry chromosomes at hundreds of thousands of genotyped loci across all autosomes, we used a linear mixed effects model to estimate the variance explained by local ancestry in two large independent samples of unrelated African Americans. We found that local ancestry at major and polygenic effect genes can explain up to 20 and 8% of phenotypic variance, respectively. These findings provide evidence that most but not all additive genetic variance is explained by genetic markers undifferentiated by ancestry. These results also inform the proportion of health disparities due to genetic risk factors and the magnitude of error in association studies not controlling for local ancestry.

Ancestry and dental development: A geographic and genetic perspective.

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Dhamo, Brunilda; Kragt, Lea; Grgic, Olja; Vucic, Strahinja; Medina-Gomez, Carolina; Rivadeneira, Fernando; Jaddoe, Vincent W V; Wolvius, Eppo B; Ongkosuwito, Edwin M

2018-02-01

In this study, we investigated the influence of ancestry on dental development in the Generation R Study. Information on geographic ancestry was available in 3,600 children (1,810 boys and 1,790 girls, mean age 9.81 ± 0.35 years) and information about genetic ancestry was available in 2,786 children (1,387 boys and 1,399 girls, mean age 9.82 ± 0.34 years). Dental development was assessed in all children using the Demirjian method. The associations of geographic ancestry (Cape Verdean, Moroccan, Turkish, Dutch Antillean, Surinamese Creole and Surinamese Hindustani vs Dutch as the reference group) and genetic content of ancestry (European, African or Asian) with dental development was analyzed using linear regression models. In a geographic perspective of ancestry, Moroccan (β = 0.18; 95% CI: 0.07, 0.28), Turkish (β = 0.22; 95% CI: 0.12, 0.32), Dutch Antillean (β = 0.27; 95% CI: 0.12, 0.41), and Surinamese Creole (β = 0.16; 95% CI: 0.03, 0.30) preceded Dutch children in dental development. Moreover, in a genetic perspective of ancestry, a higher proportion of European ancestry was associated with decelerated dental development (β = -0.32; 95% CI: -.44, -.20). In contrast, a higher proportion of African ancestry (β = 0.29; 95% CI: 0.16, 0.43) and a higher proportion of Asian ancestry (β = 0.28; 95% CI: 0.09, 0.48) were associated with accelerated dental development. When investigating only European children, these effect estimates increased to twice as large in absolute value. Based on a geographic and genetic perspective, differences in dental development exist in a population of heterogeneous ancestry and should be considered when describing the physiological growth in children. © 2017 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.

Extensive copy number variations in admixed Indian population of African ancestry: potential involvement in adaptation.

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Narang, Ankita; Jha, Pankaj; Kumar, Dhirendra; Kutum, Rintu; Mondal, Anupam Kumar; Dash, Debasis; Mukerji, Mitali

2014-11-13

Admixture mapping has been enormously resourceful in identifying genetic variations linked to phenotypes, adaptation, and diseases. In this study through analysis of copy number variable regions (CNVRs), we report extensive restructuring in the genomes of the recently admixed African-Indian population (OG-W-IP) that inhabits a highly saline environment in Western India. The study included subjects from OG-W-IP (OG), five different Indian and three HapMap populations that were genotyped using Affymetrix version 6.0 arrays. Copy number variations (CNVs) detected using Birdsuite were used to define CNVRs. Population structure with respect to CNVRs was delineated using random forest approach. OG genomes have a surprising excess of CNVs in comparison to other studied populations. Individual ancestry proportions computed using STRUCTURE also reveals a unique genetic component in OGs. Population structure analysis with CNV genotypes indicates OG to be distant from both the African and Indian ancestral populations. Interestingly, it shows genetic proximity with respect to CNVs to only one Indian population IE-W-LP4, which also happens to reside in the same geographical region. We also observe a significant enrichment of molecular processes related to ion binding and receptor activity in genes encompassing OG-specific CNVRs. Our results suggest that retention of CNVRs from ancestral natives and de novo acquisition of CNVRs could accelerate the process of adaptation especially in an extreme environment. Additionally, this population would be enormously useful for dissecting genes and delineating the involvement of CNVs in salt adaptation. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Genetic variation associated with mammalian feeding in Culex pipiens from a West Nile virus epidemic region in Chicago, Illinois.

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Huang, Shaoming; Hamer, Gabriel L; Molaei, Goudarz; Walker, Edward D; Goldberg, Tony L; Kitron, Uriel D; Andreadis, Theodore G

2009-12-01

Mosquitoes of the Culex pipiens complex are important vectors of West Nile virus in the United States. We examined the genetic variations of Cx. pipiens mosquitoes from Chicago, Illinois that were determined to be principally ornithophilic but exhibited a relatively higher inclination for mammalian hosts including humans. Microsatellite analysis of 10 polymorphic markers was performed on 346 engorged Cx. pipiens specimens with identified avian or mammalian blood meals. Our results indicated that there were no significant differences in allelic richness, the pattern of conformity to Hardy-Weinberg equilibrium, and linkage disequilibrium, nor was there overall genetic differentiation between specimens with avian- and mammalian-derived blood meals. However, Cx. pipiens form pipiens with mammalian- (including human-) derived blood meals had significantly higher ancestry (p 0.05) and the proportion of hybrids (p > 0.05) from Cx. quinquefasciatus (population from Harris Country, Texas). No temporal genetic variation was detected in accordance with the observation that there was no shift in blood feeding from birds to mammals. The results of this study in conjunction with regional host-feeding behavior suggest that the probability of genetic ancestry from Cx. pipiens f. molestus may predispose mosquitoes to feed more readily on mammals; however, the genetic mechanisms are unknown.

Unexpected inverse correlation between Native American ancestry and Asian American variants of HPV16 in admixed Colombian cervical cancer cases.

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Lopera, Esteban A; Baena, Armando; Florez, Victor; Montiel, Jehidys; Duque, Constanza; Ramirez, Tatiana; Borrero, Mauricio; Cordoba, Carlos M; Rojas, Fredy; Pareja, Rene; Bedoya, Astrid M; Bedoya, Gabriel; Sanchez, Gloria I

2014-12-01

European (E) variants of HPV 16 are evenly distributed among world regions, meanwhile Non-European variants such as European-Asian (EAs), Asian American (AA) and African (Af) are mostly confined to Eastern Asia, The Americas and African regions respectively. Several studies have shown that genetic variation of HPV 16 is associated with the risk of cervical cancer, which also seems to be dependent on the population. This relationship between ethnicity and variants have led to the suggestion that there is co-evolution of variants with humankind. Our aim was to evaluate the relationship between the individual ancestry proportion and infection with HPV 16 variants in cervical cancer. We examined the association between ancestry and HPV 16 variants in samples of 82 cervical cancer cases from different regions of Colombia. Individual ancestry proportions (European, African and Native American) were estimated by genotyping 106 ancestry informative markers. Variants were identified by PCR amplification of the E6 gene, followed by reverse line blot hybridization (RLB) with variants specific probes. Overall European (E) and Asian American (AA) variants frequency was 66.5% and 33.5% respectively. Similar distribution was observed in cases with higher proportions of European or African ancestry. A higher Native American ancestry was significantly associated with higher frequency of E variants (median ancestry>23.6%, Age and place of birth adjusted OR: 3.55, 95% CI: 1.26-10.03, p=0.01). Even further, an inverse geographic correlation between Native American ancestry and frequency of infections with AA variants was observed (ρ=-0.825, p=0.008). Regions with higher proportion of Native American ancestry had a lower frequency of AA variants of HPV 16. This study suggests replacement of AA variants by E variants of human papillomavirus 16 in cervical cancer cases with high Native American ancestry. Copyright © 2014 Elsevier B.V. All rights reserved.

Iris pigmentation as a quantitative trait: variation in populations of European, East Asian and South Asian ancestry and association with candidate gene polymorphisms.

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Edwards, Melissa; Cha, David; Krithika, S; Johnson, Monique; Cook, Gillian; Parra, Esteban J

2016-03-01

In this study, we present a new quantitative method to measure iris colour based on high-resolution photographs. We applied this method to analyse iris colour variation in a sample of individuals of East Asian, European and South Asian ancestry. We show that measuring iris colour using the coordinates of the CIELAB colour space uncovers a significant amount of variation that is not captured using conventional categorical classifications, such as 'brown', 'blue' or 'green'. We tested the association of a selected panel of polymorphisms with iris colour in each population group. Six markers showed significant associations with iris colour in the European sample, three in the South Asian sample and two in the East Asian sample. We also observed that the marker HERC2 rs12913832, which is the main determinant of 'blue' versus 'brown' iris colour in European populations, is also significantly associated with central heterochromia in the European sample. © 2015 The Authors. Pigment Cell & Melanoma Research Published by John Wiley & Sons Ltd.

Ancestry and dental development: A geographic and genetic perspective

NARCIS (Netherlands)

B. Dhamo (Brunilda); L. Kragt (Lea); Grgic, O. (Olja); S. Vucic (Strahinja); M.C. Medina-Gomez (Carolina); Rivadeneira, F. (Fernando); V.W.V. Jaddoe (Vincent); E.B. Wolvius (Eppo); E.M. Ongkosuwito (Edwin)

2017-01-01

textabstractObjective: In this study, we investigated the influence of ancestry on dental development in the Generation R Study. Methods: Information on geographic ancestry was available in 3,600 children (1,810 boys and 1,790 girls, mean age 9.81±0.35 years) and information about genetic ancestry

Investigating relationships between ancestry, lifestyle behaviors and perceptions of heart disease and breast cancer among Canadian women with British and with South Asian ancestry.

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Curtin, Kimberley D; Berry, Tanya R; Courneya, Kerry S; McGannon, Kerry R; Norris, Colleen M; Rodgers, Wendy M; Spence, John C

2018-04-01

Ethnic minority groups including Asians in Canada have different knowledge and perceptions of heart disease and breast cancer compared with the ethnic majority group. Examine relationships between perceptions of heart disease and breast cancer, and lifestyle behaviors for Canadian women with British and with South Asian ancestry. Women with South Asian ( n = 170) and with British ( n = 373) ancestry ( M age = 33.01, SD = 12.86) reported leisure time physical activity, intended fruit and vegetable consumption, disease perceptions (ability to reduce risk, control over getting the diseases, and influence of family history), and demographic information. Mann-Whitney tests and multiple hierarchical linear regressions were used to examine the relationships between lifestyle behaviors and disease perceptions, with ancestry explored as a possible moderator. Participants with South Asian ancestry believed they had greater ability to reduce their risk and have control over getting breast cancer than participants with British ancestry. Family history influences on getting either disease was perceived as higher for women with British ancestry. Age was positively related to all three perceptions in both diseases. Intended fruit and vegetable consumption was positively related to perceptions of ability to reduce risk and control of both diseases, but was stronger for women with South Asian ancestry regarding perceptions of breast cancer. Leisure time physical activity was positively related to perceptions of control over getting heart disease for women with British ancestry. Women's disease perceptions can vary by ancestry and lifestyle behaviors. Accurate representation of diseases is essential in promoting effective preventative behaviors.

Differences in early cognitive and receptive-expressive neurodevelopment by ancestry and underlying pathways in Brazil and Argentina.

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Wehby, George L; Trujillo, Antonio J

2017-02-01

We examine disparities in early child cognitive and receptive-expressive skills by ethnic ancestry among infants aged 3-24 months from Brazil and Argentina. We employ unique data on the neurodevelopment of children who were seeking routine well-child care at a set of pediatric clinics in these countries. The sample included children who had normal birth outcomes and no major health complications, allowing us to focus on variation in neurodevelopment among children without major physical health limitations. The physicians attending the pediatric clinics were trained in administering the Bayley Infant Neurodevelopmental Screener, a standardized instrument used to screen an infant's risk of neurodevelopmental problems on various domains of abilities. We evaluate disparities in overall neurodevelopmental scores and risk for neurodevelopmental problems as well as in cognitive functioning and receptive-expressive neurodevelopment. We also examine the extent to which household demographic and socioeconomic characteristics and geographic location explain these disparities. We find large gaps in both cognitive and receptive-expressive neurodevelopment by ancestry. In Brazil, children of African ancestry have lower scores on both cognitive and receptive-expressive domains and on overall neurodevelopment than children of European ancestry. In Argentina, children of Native ancestry have lower scores on these outcomes than children of European ancestry. These gaps however are largely explained by differences in geographic location and household characteristics, highlighting the importance of policies that reduce socioeconomic and geographic disparities in social capital and economic development for eliminating ethnic disparities in infant neurodevelopment. Copyright © 2016. Published by Elsevier Inc.

Allelic diversity in an NLR gene BPH9 enables rice to combat planthopper variation.

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Zhao, Yan; Huang, Jin; Wang, Zhizheng; Jing, Shengli; Wang, Yang; Ouyang, Yidan; Cai, Baodong; Xin, Xiu-Fang; Liu, Xin; Zhang, Chunxiao; Pan, Yufang; Ma, Rui; Li, Qiaofeng; Jiang, Weihua; Zeng, Ya; Shangguan, Xinxin; Wang, Huiying; Du, Bo; Zhu, Lili; Xu, Xun; Feng, Yu-Qi; He, Sheng Yang; Chen, Rongzhi; Zhang, Qifa; He, Guangcun

2016-10-24

Brown planthopper (BPH), Nilaparvata lugens Stål, is one of the most devastating insect pests of rice (Oryza sativa L.). Currently, 30 BPH-resistance genes have been genetically defined, most of which are clustered on specific chromosome regions. Here, we describe molecular cloning and characterization of a BPH-resistance gene, BPH9, mapped on the long arm of rice chromosome 12 (12L). BPH9 encodes a rare type of nucleotide-binding and leucine-rich repeat (NLR)-containing protein that localizes to the endomembrane system and causes a cell death phenotype. BPH9 activates salicylic acid- and jasmonic acid-signaling pathways in rice plants and confers both antixenosis and antibiosis to BPH. We further demonstrated that the eight BPH-resistance genes that are clustered on chromosome 12L, including the widely used BPH1, are allelic with each other. To honor the priority in the literature, we thus designated this locus as BPH1/9 These eight genes can be classified into four allelotypes, BPH1/9-1, -2, -7, and -9 These allelotypes confer varying levels of resistance to different biotypes of BPH. The coding region of BPH1/9 shows a high level of diversity in rice germplasm. Homologous fragments of the nucleotide-binding (NB) and leucine-rich repeat (LRR) domains exist, which might have served as a repository for generating allele diversity. Our findings reveal a rice plant strategy for modifying the genetic information to gain the upper hand in the struggle against insect herbivores. Further exploration of natural allelic variation and artificial shuffling within this gene may allow breeding to be tailored to control emerging biotypes of BPH.

The effects of socioeconomic status, clinical factors, and genetic ancestry on pulmonary tuberculosis disease in northeastern Mexico.

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Bonnie N Young

Full Text Available Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs. We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic

The effects of socioeconomic status, clinical factors, and genetic ancestry on pulmonary tuberculosis disease in northeastern Mexico.

Science.gov (United States)

Young, Bonnie N; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L

2014-01-01

Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB

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.

Explicit Modeling of Ancestry Improves Polygenic Risk Scores and BLUP Prediction.

Science.gov (United States)

Chen, Chia-Yen; Han, Jiali; Hunter, David J; Kraft, Peter; Price, Alkes L

2015-09-01

Polygenic prediction using genome-wide SNPs can provide high prediction accuracy for complex traits. Here, we investigate the question of how to account for genetic ancestry when conducting polygenic prediction. We show that the accuracy of polygenic prediction in structured populations may be partly due to genetic ancestry. However, we hypothesized that explicitly modeling ancestry could improve polygenic prediction accuracy. We analyzed three GWAS of hair color (HC), tanning ability (TA), and basal cell carcinoma (BCC) in European Americans (sample size from 7,440 to 9,822) and considered two widely used polygenic prediction approaches: polygenic risk scores (PRSs) and best linear unbiased prediction (BLUP). We compared polygenic prediction without correction for ancestry to polygenic prediction with ancestry as a separate component in the model. In 10-fold cross-validation using the PRS approach, the R(2) for HC increased by 66% (0.0456-0.0755; P ancestry, which prevents ancestry effects from entering into each SNP effect and being overweighted. Surprisingly, explicitly modeling ancestry produces a similar improvement when using the BLUP approach, which fits all SNPs simultaneously in a single variance component and causes ancestry to be underweighted. We validate our findings via simulations, which show that the differences in prediction accuracy will increase in magnitude as sample sizes increase. In summary, our results show that explicitly modeling ancestry can be important in both PRS and BLUP prediction. © 2015 WILEY PERIODICALS, INC.

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

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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; Oorschot, R A H van; 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

Statistical evidence for common ancestry: Application to primates.

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Baum, David A; Ané, Cécile; Larget, Bret; Solís-Lemus, Claudia; Ho, Lam Si Tung; Boone, Peggy; Drummond, Chloe P; Bontrager, Martin; Hunter, Steven J; Saucier, William

2016-06-01

Since Darwin, biologists have come to recognize that the theory of descent from common ancestry (CA) is very well supported by diverse lines of evidence. However, while the qualitative evidence is overwhelming, we also need formal methods for quantifying the evidential support for CA over the alternative hypothesis of separate ancestry (SA). In this article, we explore a diversity of statistical methods using data from the primates. We focus on two alternatives to CA, species SA (the separate origin of each named species) and family SA (the separate origin of each family). We implemented statistical tests based on morphological, molecular, and biogeographic data and developed two new methods: one that tests for phylogenetic autocorrelation while correcting for variation due to confounding ecological traits and a method for examining whether fossil taxa have fewer derived differences than living taxa. We overwhelmingly rejected both species and family SA with infinitesimal P values. We compare these results with those from two companion papers, which also found tremendously strong support for the CA of all primates, and discuss future directions and general philosophical issues that pertain to statistical testing of historical hypotheses such as CA. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

AD-LIBS: inferring ancestry across hybrid genomes using low-coverage sequence data.

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Schaefer, Nathan K; Shapiro, Beth; Green, Richard E

2017-04-04

Inferring the ancestry of each region of admixed individuals' genomes is useful in studies ranging from disease gene mapping to speciation genetics. Current methods require high-coverage genotype data and phased reference panels, and are therefore inappropriate for many data sets. We present a software application, AD-LIBS, that uses a hidden Markov model to infer ancestry across hybrid genomes without requiring variant calling or phasing. This approach is useful for non-model organisms and in cases of low-coverage data, such as ancient DNA. We demonstrate the utility of AD-LIBS with synthetic data. We then use AD-LIBS to infer ancestry in two published data sets: European human genomes with Neanderthal ancestry and brown bear genomes with polar bear ancestry. AD-LIBS correctly infers 87-91% of ancestry in simulations and produces ancestry maps that agree with published results and global ancestry estimates in humans. In brown bears, we find more polar bear ancestry than has been published previously, using both AD-LIBS and an existing software application for local ancestry inference, HAPMIX. We validate AD-LIBS polar bear ancestry maps by recovering a geographic signal within bears that mirrors what is seen in SNP data. Finally, we demonstrate that AD-LIBS is more effective than HAPMIX at inferring ancestry when preexisting phased reference data are unavailable and genomes are sequenced to low coverage. AD-LIBS is an effective tool for ancestry inference that can be used even when few individuals are available for comparison or when genomes are sequenced to low coverage. AD-LIBS is therefore likely to be useful in studies of non-model or ancient organisms that lack large amounts of genomic DNA. AD-LIBS can therefore expand the range of studies in which admixture mapping is a viable tool.

African Ancestry Is Associated with Higher Intraocular Pressure in Latinos.

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Nannini, Drew; Torres, Mina; Chen, Yii-Der I; Taylor, Kent D; Rotter, Jerome I; Varma, Rohit; Gao, Xiaoyi

2016-01-01

Intraocular pressure (IOP) is a major risk factor, as well as the only modifiable risk factor, for glaucoma. Racial differences have been observed in IOP measurements with individuals of African descent experiencing the highest IOP when compared with other ethnic groups. The purpose of this study was to examine the relationship between genetic ancestry and IOP in Latinos. Population-based genetic association study. A total of 3541 participants recruited from the Los Angeles Latino Eye Study. Study participants were genotyped using the Illumina OmniExpress BeadChip (∼730K markers). We used STRUCTURE to estimate individual genetic ancestry. Simple and multiple linear regression, as well as quantile regression, analyses were performed to investigate the relationship between genetic ancestry and IOP. The relationship between genetic ancestry and IOP in Latinos. African ancestry was significantly associated with higher IOP in Latinos in our simple linear regression analysis (P = 0.002). After adjusting for age, gender, body mass index, systolic blood pressure, central corneal thickness, and type 2 diabetes, this association remained significant (P = 0.0005). The main association was modified by a significant interaction between African ancestry and hypertension (P = 0.037), with hypertensive individuals experiencing a greater increase in IOP with increasing African ancestry. To our knowledge, we demonstrate for the first time that African ancestry and its interaction with hypertension are associated with higher IOP in Latinos. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Detecting imbalanced expression of SNP alleles by minisequencing on microarrays

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Dahlgren Andreas

2004-10-01

Full Text Available Abstract Background Each of the human genes or transcriptional units is likely to contain single nucleotide polymorphisms that may give rise to sequence variation between individuals and tissues on the level of RNA. Based on recent studies, differential expression of the two alleles of heterozygous coding single nucleotide polymorphisms (SNPs may be frequent for human genes. Methods with high accuracy to be used in a high throughput setting are needed for systematic surveys of expressed sequence variation. In this study we evaluated two formats of multiplexed, microarray based minisequencing for quantitative detection of imbalanced expression of SNP alleles. We used a panel of ten SNPs located in five genes known to be expressed in two endothelial cell lines as our model system. Results The accuracy and sensitivity of quantitative detection of allelic imbalance was assessed for each SNP by constructing regression lines using a dilution series of mixed samples from individuals of different genotype. Accurate quantification of SNP alleles by both assay formats was evidenced for by R2 values > 0.95 for the majority of the regression lines. According to a two sample t-test, we were able to distinguish 1–9% of a minority SNP allele from a homozygous genotype, with larger variation between SNPs than between assay formats. Six of the SNPs, heterozygous in either of the two cell lines, were genotyped in RNA extracted from the endothelial cells. The coefficient of variation between the fluorescent signals from five parallel reactions was similar for cDNA and genomic DNA. The fluorescence signal intensity ratios measured in the cDNA samples were compared to those in genomic DNA to determine the relative expression levels of the two alleles of each SNP. Four of the six SNPs tested displayed a higher than 1.4-fold difference in allelic ratios between cDNA and genomic DNA. The results were verified by allele-specific oligonucleotide hybridisation and

Subtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile.

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Justo Lorenzo Bermejo

2017-05-01

Full Text Available Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26. By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1-4.3%, P = 6×10-27. Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data.

Subtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile.

Science.gov (United States)

Lorenzo Bermejo, Justo; Boekstegers, Felix; González Silos, Rosa; Marcelain, Katherine; Baez Benavides, Pablo; Barahona Ponce, Carol; Müller, Bettina; Ferreccio, Catterina; Koshiol, Jill; Fischer, Christine; Peil, Barbara; Sinsheimer, Janet; Fuentes Guajardo, Macarena; Barajas, Olga; Gonzalez-Jose, Rolando; Bedoya, Gabriel; Cátira Bortolini, Maria; Canizales-Quinteros, Samuel; Gallo, Carla; Ruiz Linares, Andres; Rothhammer, Francisco

2017-05-01

Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1-4.3%, P = 6×10-27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data.

Embryonic aneuploidy does not differ among genetic ancestry according to continental origin as determined by ancestry informative markers.

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Franasiak, Jason M; Olcha, Meir; Shastri, Shefali; Molinaro, Thomas A; Congdon, Haley; Treff, Nathan R; Scott, Richard T

2016-10-01

Is embryonic aneuploidy, as determined by comprehensive chromosome screening (CCS), related to genetic ancestry, as determined by ancestry informative markers (AIMs)? In this study, when determining continental ancestry utilizing AIMs, genetic ancestry does not have an impact on embryonic aneuploidy. Aneuploidy is one of the best-characterized barriers to ART success and little information exists regarding ethnicity and whole chromosome aneuploidy in IVF. Classifying continental ancestry utilizing genetic profiles from a selected group of single nucleotide polymorphisms, termed AIMs, can determine ancestral origin with more accuracy than self-reported data. This is a retrospective cohort study of patients undergoing their first cycle of IVF with CCS at a single center from 2008 to 2014. There were 2328 patients identified whom had undergone IVF/CCS and AIM genotyping. All patients underwent IVF/ICSI and CCS after trophectoderm biopsy. Patients' serum was genotyped using 32 custom AIMs to identify continental origin. Admixture proportions were determined using Bayesian clustering algorithms. Patients were assigned to the population (European, African, East Asian or Central/South Asian) corresponding to their greatest admixture proportion. The mean number of embryos tested was 5.3 (range = 1-40) and the mode was 1. Patients' ethnic classifications revealed European (n = 1698), African (n = 103), East Asian (n = 206) or Central/South Asian (n = 321). When controlling for age and BMI, aneuploidy rate did not differ by genetic ancestry (P = 0.28). The study type (retrospective) and the ability to classify patients by continental rather than sub-continental origin as well as the predominantly European patient mix may impact generalizability. Post hoc power calculation revealed power to detect a 16.8% difference in embryonic aneuploidy between the two smallest sample size groups. These data do not support differences in embryonic aneuploidy among various genetic

Genetic Ancestry of Hadza and Sandawe Peoples Reveals Ancient Population Structure in Africa.

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Shriner, Daniel; Tekola-Ayele, Fasil; Adeyemo, Adebowale; Rotimi, Charles N

2018-03-01

The Hadza and Sandawe populations in present-day Tanzania speak languages containing click sounds and therefore thought to be distantly related to southern African Khoisan languages. We analyzed genome-wide genotype data for individuals sampled from the Hadza and Sandawe populations in the context of a global data set of 3,528 individuals from 163 ethno-linguistic groups. We found that Hadza and Sandawe individuals share ancestry distinct from and most closely related to Omotic ancestry; share Khoisan ancestry with populations such as ≠Khomani, Karretjie, and Ju/'hoansi in southern Africa; share Niger-Congo ancestry with populations such as Yoruba from Nigeria and Luhya from Kenya, consistent with migration associated with the Bantu Expansion; and share Cushitic ancestry with Somali, multiple Ethiopian populations, the Maasai population in Kenya, and the Nama population in Namibia. We detected evidence for low levels of Arabian, Nilo-Saharan, and Pygmy ancestries in a minority of individuals. Our results indicate that west Eurasian ancestry in eastern Africa is more precisely the Arabian parent of Cushitic ancestry. Relative to the Out-of-Africa migrations, Hadza ancestry emerged early whereas Sandawe ancestry emerged late.

The Mosaic Ancestry of the Drosophila Genetic Reference Panel and the D. melanogaster Reference Genome Reveals a Network of Epistatic Fitness Interactions

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Pool, John E.

2015-01-01

North American populations of Drosophila melanogaster derive from both European and African source populations, but despite their importance for genetic research, patterns of ancestry along their genomes are largely undocumented. Here, I infer geographic ancestry along genomes of the Drosophila Genetic Reference Panel (DGRP) and the D. melanogaster reference genome, which may have implications for reference alignment, association mapping, and population genomic studies in Drosophila. Overall, the proportion of African ancestry was estimated to be 20% for the DGRP and 9% for the reference genome. Combining my estimate of admixture timing with historical records, I provide the first estimate of natural generation time for this species (approximately 15 generations per year). Ancestry levels were found to vary strikingly across the genome, with less African introgression on the X chromosome, in regions of high recombination, and at genes involved in specific processes (e.g., circadian rhythm). An important role for natural selection during the admixture process was further supported by evidence that many unlinked pairs of loci showed a deficiency of Africa–Europe allele combinations between them. Numerous epistatic fitness interactions may therefore exist between African and European genotypes, leading to ongoing selection against incompatible variants. By focusing on hubs in this network of fitness interactions, I identified a set of interacting loci that include genes with roles in sensation and neuropeptide/hormone reception. These findings suggest that admixed D. melanogaster samples could become an important study system for the genetics of early-stage isolation between populations. PMID:26354524

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

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Margrit Urbanek

Full Text Available 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.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.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.

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

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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

Ancestry and Severity of Disability: A National Study.

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Wheaton, Joe E.; Hertzfeld, Jennifer

2002-01-01

Examines effects of ancestry and severity of disability of vocational rehabilitation consumers. European Americans, individuals with higher costs, and persons who received assistive technology were more likely to be closed rehabilitated. Individuals from other ancestry groups, who were coded severely disabled, or who had been in the system for…

Outlining the Ancestry Landscape of Colombian Admixed Populations.

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Ossa, Humberto; Aquino, Juliana; Pereira, Rui; Ibarra, Adriana; Ossa, Rafael H; Pérez, Luz Adriana; Granda, Juan David; Lattig, Maria Claudia; Groot, Helena; Fagundes de Carvalho, Elizeu; Gusmão, Leonor

2016-01-01

The ancestry of the Colombian population comprises a large number of well differentiated Native communities belonging to diverse linguistic groups. In the late fifteenth century, a process of admixture was initiated with the arrival of the Europeans, and several years later, Africans also became part of the Colombian population. Therefore, the genepool of the current Colombian population results from the admixture of Native Americans, Europeans and Africans. This admixture occurred differently in each region of the country, producing a clearly stratified population. Considering the importance of population substructure in both clinical and forensic genetics, we sought to investigate and compare patterns of genetic ancestry in Colombia by studying samples from Native and non-Native populations living in its 5 continental regions: the Andes, Caribe, Amazonia, Orinoquía, and Pacific regions. For this purpose, 46 AIM-Indels were genotyped in 761 non-related individuals from current populations. Previously published genotype data from 214 Colombian Natives from five communities were used for population comparisons. Significant differences were observed between Native and non-Native populations, among non-Native populations from different regions and among Native populations from different ethnic groups. The Pacific was the region with the highest African ancestry, Amazonia harboured the highest Native ancestry and the Andean and Orinoquían regions showed the highest proportion of European ancestry. The Andean region was further sub-divided into 6 sub-regions: North East, Central West, Central East, West, South West and South East. Among these regions, the South West region showed a significantly lower European admixture than the other regions. Hardy-Weinberg equilibrium and variance values of ancestry among individuals within populations showed a potential stratification of the Pacific population.

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

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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.

Genome-wide analysis of SNPs is consistent with no domestic dog ancestry in the endangered Mexican Wolf (Canis lupus baileyi)

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Fitak, Robert R.; Rinkevich, Sarah E.; Culver, Melanie

2018-01-01

The Mexican gray wolf (Canis lupus baileyi) was historically distributed throughout the southwestern United States and northern Mexico. Extensive predator removal campaigns during the early 20th century, however, resulted in its eventual extirpation by the mid 1980s. At this time, the Mexican wolf existed only in 3 separate captive lineages (McBride, Ghost Ranch, and Aragón) descended from 3, 2, and 2 founders, respectively. These lineages were merged in 1995 to increase the available genetic variation, and Mexican wolves were reintroduced into Arizona and New Mexico in 1998. Despite the ongoing management of the Mexican wolf population, it has been suggested that a proportion of the Mexican wolf ancestry may be recently derived from hybridization with domestic dogs. In this study, we genotyped 87 Mexican wolves, including individuals from all 3 captive lineages and cross-lineage wolves, for more than 172000 single nucleotide polymorphisms. We identified levels of genetic variation consistent with the pedigree record and effects of genetic rescue. To identify the potential to detect hybridization with domestic dogs, we compared our Mexican wolf genotypes with those from studies of domestic dogs and other gray wolves. The proportion of Mexican wolf ancestry assigned to domestic dogs was only between 0.06% (SD 0.23%) and 7.8% (SD 1.0%) for global and local ancestry estimates, respectively; and was consistent with simulated levels of incomplete lineage sorting. Overall, our results suggested that Mexican wolves lack biologically significant ancestry with dogs and have useful implications for the conservation and management of this endangered wolf subspecies.

Genomic ancestry as a predictor of haemodynamic profile in heart failure.

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Bernardez-Pereira, Sabrina; Gioli-Pereira, Luciana; Marcondes-Braga, Fabiana G; Santos, Paulo Caleb Junior Lima; Spina, Joceli Mabel Rocha; Horimoto, Andréa Roseli Vançan Russo; Santos, Hadassa Campos; Bacal, Fernando; Fernandes, Fábio; Mansur, Alfredo Jose; Pietrobon, Ricardo; Krieger, José Eduardo; Mesquita, Evandro Tinoco; Pereira, Alexandre Costa

2016-01-01

The aim of this study is to assess the association between genetic ancestry, self-declared race and haemodynamic parameters in patients with chronic heart failure (HF). Observational, cross-sectional study. Eligible participants were aged between 18 and 80 years; ejection fraction was ≤50%. Patients underwent genetic analysis of ancestry informative markers, echocardiography and impedance cardiography (ICG). Race was determined by self-classification into two groups: white and non-white. Genomic ancestry was estimated using a panel of 101 348 polymorphic markers and three continental reference populations (European, African and Native American). Our study included 362 patients with HF between August 2012 and August 2014. 123 patients with HF declared themselves as white and 234 patients declared themselves as non-white. No statistically significant differences were found regarding the ICG parameters according to self-declared race. The Amerindian ancestry was positively correlated with systolic time ratio (r=0.109, pancestry. In multiple linear regression, African ancestry remained associated with the E/e' ratio, even after adjustment to risk factors. The African genetic ancestry was associated with worse parameters of diastolic function; the Amerindian ancestry correlated with a worse pattern of ventricular contractility, while self-declared colour was not helpful to infer haemodynamic profiles in HF. NTC02043431.

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

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.

An evaluation of non-metric cranial traits used to estimate ancestry in a South African sample.

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L'Abbé, E N; Van Rooyen, C; Nawrocki, S P; Becker, P J

2011-06-15

Establishing ancestry from a skeleton for forensic purposes has been shown to be difficult. The purpose of this paper is to address the application of thirteen non-metric traits to estimate ancestry in three South African groups, namely White, Black and "Coloured". In doing so, the frequency distribution of thirteen non-metric traits among South Africans are presented; the relationship of these non-metric traits with ancestry, sex, age at death are evaluated; and Kappa statistics are utilized to assess the inter and intra-rater reliability. Crania of 520 known individuals were obtained from four skeletal samples in South Africa: the Pretoria Bone Collection, the Raymond A. Dart Collection, the Kirsten Collection and the Student Bone Collection from the University of the Free State. Average age at death was 51, with an age range between 18 and 90. Thirteen commonly used non-metric traits from the face and jaw were scored; definition and illustrations were taken from Hefner, Bass and Hauser and De Stephano. Frequency distributions, ordinal regression and Cohen's Kappa statistics were performed as a means to assess population variation and repeatability. Frequency distributions were highly variable among South Africans. Twelve of the 13 variables had a statistically significant relationship with ancestry. Sex significantly affected only one variable, inter-orbital breadth, and age at death affected two (anterior nasal spine and alveolar prognathism). The interaction of ancestry and sex independently affected three variables (nasal bone contour, nasal breadth, and interorbital breadth). Seven traits had moderate to excellent repeatability, while poor scoring consistency was noted for six variables. Difficulties in repeating several of the trait scores may require either a need for refinement of the definitions, or these character states may not adequately describe the observable morphology in the population. The application of the traditional experience-based approach

allelic variation of hmw glutenin subunits of ethiopian bread wheat

African Journals Online (AJOL)

journal

High molecular weight glutenins are often effective in identifying wheat (Triticum ... There were highly significant differences between genotypes and banding ... was without deliberate selection pressure towards high Glu-1 scoring alleles ...

Accuracy Rates of Ancestry Estimation by Forensic Anthropologists Using Identified Forensic Cases.

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Thomas, Richard M; Parks, Connie L; Richard, Adam H

2017-07-01

A common task in forensic anthropology involves the estimation of the ancestry of a decedent by comparing their skeletal morphology and measurements to skeletons of individuals from known geographic groups. However, the accuracy rates of ancestry estimation methods in actual forensic casework have rarely been studied. This article uses 99 forensic cases with identified skeletal remains to develop accuracy rates for ancestry estimations conducted by forensic anthropologists. The overall rate of correct ancestry estimation from these cases is 90.9%, which is comparable to most research-derived rates and those reported by individual practitioners. Statistical tests showed no significant difference in accuracy rates depending on examiner education level or on the estimated or identified ancestry. More recent cases showed a significantly higher accuracy rate. The incorporation of metric analyses into the ancestry estimate in these cases led to a higher accuracy rate. © 2017 American Academy of Forensic Sciences.

The Mosaic Ancestry of the Drosophila Genetic Reference Panel and the D. melanogaster Reference Genome Reveals a Network of Epistatic Fitness Interactions.

Science.gov (United States)

Pool, John E

2015-12-01

North American populations of Drosophila melanogaster derive from both European and African source populations, but despite their importance for genetic research, patterns of ancestry along their genomes are largely undocumented. Here, I infer geographic ancestry along genomes of the Drosophila Genetic Reference Panel (DGRP) and the D. melanogaster reference genome, which may have implications for reference alignment, association mapping, and population genomic studies in Drosophila. Overall, the proportion of African ancestry was estimated to be 20% for the DGRP and 9% for the reference genome. Combining my estimate of admixture timing with historical records, I provide the first estimate of natural generation time for this species (approximately 15 generations per year). Ancestry levels were found to vary strikingly across the genome, with less African introgression on the X chromosome, in regions of high recombination, and at genes involved in specific processes (e.g., circadian rhythm). An important role for natural selection during the admixture process was further supported by evidence that many unlinked pairs of loci showed a deficiency of Africa-Europe allele combinations between them. Numerous epistatic fitness interactions may therefore exist between African and European genotypes, leading to ongoing selection against incompatible variants. By focusing on hubs in this network of fitness interactions, I identified a set of interacting loci that include genes with roles in sensation and neuropeptide/hormone reception. These findings suggest that admixed D. melanogaster samples could become an important study system for the genetics of early-stage isolation between populations. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Self-declared ethnicity and genomic ancestry in prostate cancer patients from Brazil.

Science.gov (United States)

Oliveira, J S; Ferreira, R S; Santos, L M; Marin, L J; Corrêa, R X; Luizon, M R; Simões, A L; Gadelha, S R; Sousa, S M B

2016-10-17

Some studies of polymorphisms in prostate cancer (PCa) analyze individuals in a uniform manner, regardless of genetic ancestry. However, PCa aggressiveness differs between subjects of African descent and those of European extraction. Thus, genetic ancestry analysis may be used to detect population stratification in case-control association studies. We genotyped 11 ancestry informative markers to estimate the contributions of African, European, and Amerindian ancestries in a case-control sample of 213 individuals from Bahia State, Northeast Brazil, including 104 PCa patients. We compared this data with self-reported ancestry and the stratification of cases by PCa aggressiveness according to Gleason score. A larger African genetic contribution (44%) was detected among cases, and a greater European contribution (61%) among controls. Self-declaration data revealed that 74% of PCa patients considered themselves non-white (black and brown), and 41.3% of controls viewed themselves as white. Our data showed a higher degree of European ancestry among fast-growing cancer cases than those of intermediate and slow development. This differs from many previous studies, in which the prevalence of African ancestry has been reported for all grades. Differences were observed between degrees of PCa aggressiveness in terms of genetic ancestry. In particular, the greater European contribution among patients with high-grade PCa indicates that a population's genetic structure can influence case-control studies. This investigation contributes to our understanding of the genetic basis of tumor aggressiveness among groups of different genetic ancestries, especially admixed populations, and has significant implications for the assessment of inter-population heterogeneity in drug treatment effects.

What Is Genetic Ancestry Testing?

Science.gov (United States)

... consumer genetic testing? What kinds of direct-to-consumer genetic tests are available? What is genetic ancestry testing? What are the benefits and risks of direct-to-consumer genetic testing? ...

Complex Ancestries of Lager-Brewing Hybrids Were Shaped by Standing Variation in the Wild Yeast Saccharomyces eubayanus.

Science.gov (United States)

Peris, David; Langdon, Quinn K; Moriarty, Ryan V; Sylvester, Kayla; Bontrager, Martin; Charron, Guillaume; Leducq, Jean-Baptiste; Landry, Christian R; Libkind, Diego; Hittinger, Chris Todd

2016-07-01

Lager-style beers constitute the vast majority of the beer market, and yet, the genetic origin of the yeast strains that brew them has been shrouded in mystery and controversy. Unlike ale-style beers, which are generally brewed with Saccharomyces cerevisiae, lagers are brewed at colder temperatures with allopolyploid hybrids of Saccharomyces eubayanus x S. cerevisiae. Since the discovery of S. eubayanus in 2011, additional strains have been isolated from South America, North America, Australasia, and Asia, but only interspecies hybrids have been isolated in Europe. Here, using genome sequence data, we examine the relationships of these wild S. eubayanus strains to each other and to domesticated lager strains. Our results support the existence of a relatively low-diversity (π = 0.00197) lineage of S. eubayanus whose distribution stretches across the Holarctic ecozone and includes wild isolates from Tibet, new wild isolates from North America, and the S. eubayanus parents of lager yeasts. This Holarctic lineage is closely related to a population with higher diversity (π = 0.00275) that has been found primarily in South America but includes some widely distributed isolates. A second diverse South American population (π = 0.00354) and two early-diverging Asian subspecies are more distantly related. We further show that no single wild strain from the Holarctic lineage is the sole closest relative of lager yeasts. Instead, different parts of the genome portray different phylogenetic signals and ancestry, likely due to outcrossing and incomplete lineage sorting. Indeed, standing genetic variation within this wild Holarctic lineage of S. eubayanus is responsible for genetic variation still segregating among modern lager-brewing hybrids. We conclude that the relationships among wild strains of S. eubayanus and their domesticated hybrids reflect complex biogeographical and genetic processes.

Enhanced Methods for Local Ancestry Assignment in Sequenced Admixed Individuals

Science.gov (United States)

Brown, Robert; Pasaniuc, Bogdan

2014-01-01

Inferring the ancestry at each locus in the genome of recently admixed individuals (e.g., Latino Americans) plays a major role in medical and population genetic inferences, ranging from finding disease-risk loci, to inferring recombination rates, to mapping missing contigs in the human genome. Although many methods for local ancestry inference have been proposed, most are designed for use with genotyping arrays and fail to make use of the full spectrum of data available from sequencing. In addition, current haplotype-based approaches are very computationally demanding, requiring large computational time for moderately large sample sizes. Here we present new methods for local ancestry inference that leverage continent-specific variants (CSVs) to attain increased performance over existing approaches in sequenced admixed genomes. A key feature of our approach is that it incorporates the admixed genomes themselves jointly with public datasets, such as 1000 Genomes, to improve the accuracy of CSV calling. We use simulations to show that our approach attains accuracy similar to widely used computationally intensive haplotype-based approaches with large decreases in runtime. Most importantly, we show that our method recovers comparable local ancestries, as the 1000 Genomes consensus local ancestry calls in the real admixed individuals from the 1000 Genomes Project. We extend our approach to account for low-coverage sequencing and show that accurate local ancestry inference can be attained at low sequencing coverage. Finally, we generalize CSVs to sub-continental population-specific variants (sCSVs) and show that in some cases it is possible to determine the sub-continental ancestry for short chromosomal segments on the basis of sCSVs. PMID:24743331

Segregating YKU80 and TLC1 alleles underlying natural variation in telomere properties in wild yeast.

Directory of Open Access Journals (Sweden)

Gianni Liti

2009-09-01

Full Text Available In yeast, as in humans, telomere length varies among individuals and is controlled by multiple loci. In a quest to define the extent of variation in telomere length, we screened 112 wild-type Saccharomyces sensu stricto isolates. We found extensive telomere length variation in S. paradoxus isolates. This phenotype correlated with their geographic origin: European strains were observed to have extremely short telomeres (400 bp. Insertions of a URA3 gene near telomeres allowed accurate analysis of individual telomere lengths and telomere position effect (TPE. Crossing the American and European strains resulted in F1 spores with a continuum of telomere lengths consistent with what would be predicted if many quantitative trait loci (QTLs were involved in length maintenance. Variation in TPE is similarly quantitative but only weakly correlated with telomere length. Genotyping F1 segregants indicated several QTLs associated with telomere length and silencing variation. These QTLs include likely candidate genes but also map to regions where there are no known genes involved in telomeric properties. We detected transgressive segregation for both phenotypes. We validated by reciprocal hemizygosity that YKU80 and TLC1 are telomere-length QTLs in the two S. paradoxus subpopulations. Furthermore, we propose that sequence divergence within the Ku heterodimer generates negative epistasis within one of the allelic combinations (American-YKU70 and European-YKU80 resulting in very short telomeres.

Segregating YKU80 and TLC1 alleles underlying natural variation in telomere properties in wild yeast.

Science.gov (United States)

Liti, Gianni; Haricharan, Svasti; Cubillos, Francisco A; Tierney, Anna L; Sharp, Sarah; Bertuch, Alison A; Parts, Leopold; Bailes, Elizabeth; Louis, Edward J

2009-09-01

In yeast, as in humans, telomere length varies among individuals and is controlled by multiple loci. In a quest to define the extent of variation in telomere length, we screened 112 wild-type Saccharomyces sensu stricto isolates. We found extensive telomere length variation in S. paradoxus isolates. This phenotype correlated with their geographic origin: European strains were observed to have extremely short telomeres (400 bp). Insertions of a URA3 gene near telomeres allowed accurate analysis of individual telomere lengths and telomere position effect (TPE). Crossing the American and European strains resulted in F1 spores with a continuum of telomere lengths consistent with what would be predicted if many quantitative trait loci (QTLs) were involved in length maintenance. Variation in TPE is similarly quantitative but only weakly correlated with telomere length. Genotyping F1 segregants indicated several QTLs associated with telomere length and silencing variation. These QTLs include likely candidate genes but also map to regions where there are no known genes involved in telomeric properties. We detected transgressive segregation for both phenotypes. We validated by reciprocal hemizygosity that YKU80 and TLC1 are telomere-length QTLs in the two S. paradoxus subpopulations. Furthermore, we propose that sequence divergence within the Ku heterodimer generates negative epistasis within one of the allelic combinations (American-YKU70 and European-YKU80) resulting in very short telomeres.

Immunization coverage among Hispanic ancestry, 2003 National Immunization Survey.

Science.gov (United States)

Darling, Natalie J; Barker, Lawrence E; Shefer, Abigail M; Chu, Susan Y

2005-12-01

The Hispanic population is increasing and heterogeneous (Hispanic refers to persons of Spanish, Hispanic, or Latino descent). The objective was to examine immunization rates among Hispanic ancestry for the 4:3:1:3:3 series (> or = 4 doses diphtheria, tetanus toxoids, and pertussis vaccine; > or = 3 doses poliovirus vaccine; > or = 1 doses measles-containing vaccine; > or = 3 doses Haemophilus influenzae type b vaccine; and > or = 3 doses hepatitis B vaccine). The National Immunization Survey measures immunization coverage among 19- to 35-month-old U.S. children. Coverage was compared from combined 2001-2003 data among Hispanics and non-Hispanic whites using t-tests, and among Hispanic ancestry using a chi-square test. Hispanics were categorized as Mexican, Mexican American, Central American, South American, Puerto Rican, Cuban, Spanish Caribbean (primarily Dominican Republic), other, and multiple ancestry. Children of Hispanic ancestry increased from 21% in 1999 to 25% in 2003. These Hispanic children were less well immunized than non-Hispanic whites (77.0%, +/-2.1% [95% confidence interval] compared to 82.5%, +/-1.1% (95% CI) > in 2003). Immunization coverage did not vary significantly among Hispanics of varying ancestries (p=0.26); however, there was substantial geographic variability. In some areas, immunization coverage among Hispanics was significantly higher than non-Hispanic whites. Hispanic children were less well immunized than non-Hispanic whites; however, coverage varied notably by geographic area. Although a chi-square test found no significant differences in coverage among Hispanic ancestries, the range of coverage, 79.2%, +/-5.1% for Cuban Americans to 72.1%, +/-2.4% for Mexican descent, may suggest a need for improved and more localized monitoring among Hispanic communities.

Effects of Amerindian Genetic Ancestry on Clinical Variables and Therapy in Patients with Rheumatoid Arthritis.

Science.gov (United States)

Sánchez, Elena; García de la Torre, Ignacio; Sacnún, Mónica; Goñi, Mario; Berbotto, Guillermo; Paira, Sergio; Musuruana, Jorge Luis; Graf, César; Alvarellos, Alejandro; Messina, Osvaldo D; Babini, Alejandra; Strusberg, Ingrid; Marcos, Juan Carlos; Scherbarth, Hugo; Spindler, Alberto; Quinteros, Ana; Toloza, Sergio; Moreno, José Luis C; Catoggio, Luis J; Tate, Guillermo; Eimon, Alicia; Citera, Gustavo; Pellet, Antonio Catalán; Nasswetter, Gustavo; Cardiel, Mario H; Miranda, Pedro; Ballesteros, Francisco; Esquivel-Valerio, Jorge A; Maradiaga-Ceceña, Marco A; Acevedo-Vásquez, Eduardo M; García, Conrado García; Tusié-Luna, Teresa; Pons-Estel, Bernardo A; Alarcón-Riquelme, Marta E

2017-12-01

To define whether Amerindian genetic ancestry correlates with clinical and therapeutic variables in admixed individuals with rheumatoid arthritis (RA) from Latin America. Patients with RA (n = 1347) and healthy controls (n = 1012) from Argentina, Mexico, Chile, and Peru were included. Samples were genotyped for the Immunochip v1 using the Illumina platform. Clinical data were obtained through interviews or the clinical history. Percentage of Amerindian ancestry was comparable between cases and controls. Morning stiffness (p ancestry after Bonferroni correction. Higher Amerindian ancestry correlated only with weight loss (p Bonferroni ancestry correlated with higher doses of azathioprine (p ancestry protects against most major clinical criteria of RA, but regarding the association of RF with increased European ancestry, age, sex, and smoking are modifiers. Ancestry also correlates with the therapeutic profiles.

Deleterious alleles in the human genome are on average younger than neutral alleles of the same frequency

NARCIS (Netherlands)

Kiezun, Adam; Pulit, Sara L.; Francioli, Laurent C.; van Dijk, Freerk; Swertz, Morris; Boomsma, Dorret I.; van Duijn, Cornelia M.; Slagboom, P. Eline; van Ommen, G. J. B.; Wijmenga, Cisca; de Bakker, Paul I. W.; Sunyaev, Shamil R.

Large-scale population sequencing studies provide a complete picture of human genetic variation within the studied populations. A key challenge is to identify, among the myriad alleles, those variants that have an effect on molecular function, phenotypes, and reproductive fitness. Most non-neutral

ALEA: a toolbox for allele-specific epigenomics analysis.

Science.gov (United States)

Younesy, Hamid; Möller, Torsten; Heravi-Moussavi, Alireza; Cheng, Jeffrey B; Costello, Joseph F; Lorincz, Matthew C; Karimi, Mohammad M; Jones, Steven J M

2014-04-15

The assessment of expression and epigenomic status using sequencing based methods provides an unprecedented opportunity to identify and correlate allelic differences with epigenomic status. We present ALEA, a computational toolbox for allele-specific epigenomics analysis, which incorporates allelic variation data within existing resources, allowing for the identification of significant associations between epigenetic modifications and specific allelic variants in human and mouse cells. ALEA provides a customizable pipeline of command line tools for allele-specific analysis of next-generation sequencing data (ChIP-seq, RNA-seq, etc.) that takes the raw sequencing data and produces separate allelic tracks ready to be viewed on genome browsers. The pipeline has been validated using human and hybrid mouse ChIP-seq and RNA-seq data. The package, test data and usage instructions are available online at http://www.bcgsc.ca/platform/bioinfo/software/alea CONTACT: : mkarimi1@interchange.ubc.ca or sjones@bcgsc.ca Supplementary information: Supplementary data are available at Bioinformatics online. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Relationship between Native American Ancestry, Body Mass Index and Diabetes Risk among Mexican-Americans.

Science.gov (United States)

Hu, Hao; Huff, Chad D; Yamamura, Yuko; Wu, Xifeng; Strom, Sara S

2015-01-01

Higher body mass index (BMI) is a well-established risk factor for type 2 diabetes, and rates of obesity and type 2 diabetes are substantially higher among Mexican-Americans relative to non-Hispanic European Americans. Mexican-Americans are genetically diverse, with a highly variable distribution of Native American, European, and African ancestries. Here, we evaluate the role of Native American ancestry on BMI and diabetes risk in a well-defined Mexican-American population. Participants were randomly selected among individuals residing in the Houston area who are enrolled in the Mexican-American Cohort study. Using a custom Illumina GoldenGate Panel, we genotyped DNA from 4,662 cohort participants for 87 Ancestry-Informative Markers. On average, the participants were of 50.2% Native American ancestry, 42.7% European ancestry and 7.1% African ancestry. Using multivariate linear regression, we found BMI and Native American ancestry were inversely correlated; individuals with ancestry were 2.5 times more likely to be severely obese compared to those with >80% Native American ancestry. Furthermore, we demonstrated an interaction between BMI and Native American ancestry in diabetes risk among women; Native American ancestry was a strong risk factor for diabetes only among overweight and obese women (OR = 1.190 for each 10% increase in Native American ancestry). This study offers new insight into the complex relationship between obesity, genetic ancestry, and their respective effects on diabetes risk. Findings from this study may improve the diabetes risk prediction among Mexican-American individuals thereby facilitating targeted prevention strategies.

An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans

NARCIS (Netherlands)

Scott, Robert A; Scott, Laura J; Mägi, Reedik; Marullo, Letizia; Gaulton, Kyle J; Kaakinen, Marika; Pervjakova, Natalia; Pers, Tune H; Johnson, Andrew D; Eicher, John D; Jackson, Anne U; Ferreira, Teresa; Lee, Yeji; Ma, Clement; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Qi, Lu; Van Zuydam, Natalie R; Mahajan, Anubha; Chen, Han; Almgren, Peter; Voight, Ben F; Grallert, Harald; Müller-Nurasyid, Martina; Ried, Janina S; Rayner, William N; Robertson, Neil; Karssen, Lennart C; van Leeuwen, Elisabeth M; Willems, Sara M; Fuchsberger, Christian; Kwan, Phoenix; Teslovich, Tanya M; Chanda, Pritam; Li, Man; Lu, Yingchang; Dina, Christian; Thuillier, Dorothee; Yengo, Loic; Jiang, Longda; Sparso, Thomas; Kestler, Hans A; Chheda, Himanshu; Eisele, Lewin; Gustafsson, Stefan; Frånberg, Mattias; Strawbridge, Rona J; Benediktsson, Rafn; Hreidarsson, Astradur B; Kong, Augustine; Sigurðsson, Gunnar; Kerrison, Nicola D; Luan, Jian'an; Liang, Liming; Meitinger, Thomas; Roden, Michael; Thorand, Barbara; Esko, Tõnu; Mihailov, Evelin; Fox, Caroline; Liu, Ching-Ti; Rybin, Denis; Isomaa, Bo; Lyssenko, Valeriya; Tuomi, Tiinamaija; Couper, David J; Pankow, James S; Grarup, Niels; Have, Christian T; Jørgensen, Marit E; Jørgensen, Torben; Linneberg, Allan; Cornelis, Marilyn C; van Dam, Rob M; Hunter, David J; Kraft, Peter; Sun, Qi; Edkins, Sarah; Owen, Katharine R; Perry, John Rb; Wood, Andrew R; Zeggini, Eleftheria; Tajes-Fernandes, Juan; Abecasis, Goncalo R; Bonnycastle, Lori L; Chines, Peter S; Stringham, Heather M; Koistinen, Heikki A; Kinnunen, Leena; Sennblad, Bengt; Mühleisen, Thomas W; Nöthen, Markus M; Pechlivanis, Sonali; Baldassarre, Damiano; Gertow, Karl; Humphries, Steve E; Tremoli, Elena; Klopp, Norman; Meyer, Julia; Steinbach, Gerald; Wennauer, Roman; Eriksson, Johan G; Mӓnnistö, Satu; Peltonen, Leena; Tikkanen, Emmi; Charpentier, Guillaume; Eury, Elodie; Lobbens, Stéphane; Gigante, Bruna; Leander, Karin; McLeod, Olga; Bottinger, Erwin P; Gottesman, Omri; Ruderfer, Douglas; Blüher, Matthias; Kovacs, Peter; Tonjes, Anke; Maruthur, Nisa M; Scapoli, Chiara; Erbel, Raimund; Jöckel, Karl-Heinz; Moebus, Susanne; de Faire, Ulf; Hamsten, Anders; Stumvoll, Michael; Deloukas, Panagiotis; Donnelly, Peter J; Frayling, Timothy M; Hattersley, Andrew T; Ripatti, Samuli; Salomaa, Veikko; Pedersen, Nancy L; Boehm, Bernhard O; Bergman, Richard N; Collins, Francis S; Mohlke, Karen L; Tuomilehto, Jaakko; Hansen, Torben; Pedersen, Oluf; Barroso, Inês; Lannfelt, Lars; Ingelsson, Erik; Lind, Lars; Lindgren, Cecilia M; Cauchi, Stephane; Froguel, Philippe; Loos, Ruth Jf; Balkau, Beverley; Boeing, Heiner; Franks, Paul W; Gurrea, Aurelio Barricarte; Palli, Domenico; van der Schouw, Yvonne T; Altshuler, David; Groop, Leif C; Langenberg, Claudia; Wareham, Nicholas J; Sijbrands, Eric; van Duijn, Cornelia M; Florez, Jose C; Meigs, James B; Boerwinkle, Eric; Gieger, Christian; Strauch, Konstantin; Metspalu, Andres; Morris, Andrew D; Palmer, Colin Na; Hu, Frank B; Thorsteinsdottir, Unnur; Stefansson, Kari; Dupuis, Josée; Morris, Andrew P; Boehnke, Michael; McCarthy, Mark I; Prokopenko, Inga

2017-01-01

To characterise type 2 diabetes (T2D) associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D cases and 132,532 controls of European ancestry after imputation using the 1000 Genomes multi-ethnic reference panel.

Relative Skeletal Maturation and Population Ancestry in Nonobese Children and Adolescents.

Science.gov (United States)

McCormack, Shana E; Chesi, Alessandra; Mitchell, Jonathan A; Roy, Sani M; Cousminer, Diana L; Kalkwarf, Heidi J; Lappe, Joan M; Gilsanz, Vicente; Oberfield, Sharon E; Shepherd, John A; Mahboubi, Soroosh; Winer, Karen K; Kelly, Andrea; Grant, Struan Fa; Zemel, Babette S

2017-01-01

More rapid skeletal maturation in African-American (AA) children is recognized and generally attributed to an increased prevalence of obesity. The objective of the present study was to evaluate the effects of population ancestry on relative skeletal maturation in healthy, non-obese children and adolescents, accounting for body composition and sexual maturation. To do this, we leveraged a multiethnic, mixed-longitudinal study with annual assessments for up to 7 years (The Bone Mineral Density in Childhood Study and its ancillary cohort) conducted at five US clinical centers. Participants included 1592 children, skeletally immature (45% females, 19% AA) who were aged 5 to 17 years at study entry. The primary outcome measure was relative skeletal maturation as assessed by hand-wrist radiograph. Additional covariates measured included anthropometrics, body composition by dual-energy X-ray absorptiometry (DXA), and Tanner stage of sexual maturation. Using mixed effects longitudinal models, without covariates, advancement in relative skeletal maturation was noted in self-reported AA girls (∼0.33 years, p ancestry groups showed independent positive associations of height, lean mass, fat mass, and puberty with relative skeletal maturation. The effect of ancestry was attenuated but persistent after accounting for covariates: for girls, 0.19 years (ancestry by self-report, p = 0.02) or 0.29 years (ancestry by admixture, p = 0.004); and for boys, 0.20 years (ancestry by self-report, p = 0.004), or 0.29 years (ancestry by admixture, p = 0.004). In summary, we conclude that advancement in relative skeletal maturation was associated with AA ancestry in healthy, non-obese children, independent of growth, body composition, and puberty. Further research into the mechanisms underlying this observation may provide insights into the regulation of skeletal maturation. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and

Case Study on Ancestry Estimation in an Alaskan Native Family: Identity and Safeguards Against Reductionism.

Science.gov (United States)

Bader, Alyssa C; Malhi, Ripan S

2015-10-01

Understanding the complexities of ancestry-related identity is a necessary component of ethically sound research related to the genetic ancestry of modern-day communities. This is especially true when working with indigenous populations, given the legal and social implications that genetic ancestry interpretations may have in these communities. This study employs a multicomponent approach to explore the intricacies of ancestry-related identity within one extended family with members who identify as Alaskan Native. The seven participants were interviewed about their own self-identity, perceptions regarding genetic ancestry estimation, and their knowledge of oral family history. Additionally, each participant consented to having his or her genetic ancestry estimated. The researchers also surveyed ancestry-related documents, such as census records, birth certificates, and Certificates of Indian Blood. These three different perspectives-oral family history and self-identity, genetic ancestry estimation, historical and legal documentation-illustrate the complex nature of ancestry-related identity within the context of indigenous and colonial interactions in North America. While estimates of genetic ancestry broadly reflected each individual's self-reported biogeographic ancestry and supported all described and historically reported biological relationships, the estimates did not always match federally recorded blood quantum values, nor did they provide any information on relationships at the tribe or clan level. Employing a multicomponent approach and engaging study participants may help to safeguard against genetic essentialism and provide a more nuanced understanding of ancestry-related identity within a larger political, legal, and historical context.

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

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...

Transposable elements generate population-specific insertional patterns and allelic variation in genes of wild emmer wheat (Triticum turgidum ssp. dicoccoides).

Science.gov (United States)

Domb, Katherine; Keidar, Danielle; Yaakov, Beery; Khasdan, Vadim; Kashkush, Khalil

2017-10-27

Natural populations of the tetraploid wild emmer wheat (genome AABB) were previously shown to demonstrate eco-geographically structured genetic and epigenetic diversity. Transposable elements (TEs) might make up a significant part of the genetic and epigenetic variation between individuals and populations because they comprise over 80% of the wild emmer wheat genome. In this study, we performed detailed analyses to assess the dynamics of transposable elements in 50 accessions of wild emmer wheat collected from 5 geographically isolated sites. The analyses included: the copy number variation of TEs among accessions in the five populations, population-unique insertional patterns, and the impact of population-unique/specific TE insertions on structure and expression of genes. We assessed the copy numbers of 12 TE families using real-time quantitative PCR, and found significant copy number variation (CNV) in the 50 wild emmer wheat accessions, in a population-specific manner. In some cases, the CNV difference reached up to 6-fold. However, the CNV was TE-specific, namely some TE families showed higher copy numbers in one or more populations, and other TE families showed lower copy numbers in the same population(s). Furthermore, we assessed the insertional patterns of 6 TE families using transposon display (TD), and observed significant population-specific insertional patterns. The polymorphism levels of TE-insertional patterns reached 92% among all wild emmer wheat accessions, in some cases. In addition, we observed population-specific/unique TE insertions, some of which were located within or close to protein-coding genes, creating allelic variations in a population-specific manner. We also showed that those genes are differentially expressed in wild emmer wheat. For the first time, this study shows that TEs proliferate in wild emmer wheat in a population-specific manner, creating new alleles of genes, which contribute to the divergent evolution of homeologous genes

A combined evidence Bayesian method for human ancestry inference applied to Afro-Colombians.

Science.gov (United States)

Rishishwar, Lavanya; Conley, Andrew B; Vidakovic, Brani; Jordan, I King

2015-12-15

Uniparental genetic markers, mitochondrial DNA (mtDNA) and Y chromosomal DNA, are widely used for the inference of human ancestry. However, the resolution of ancestral origins based on mtDNA haplotypes is limited by the fact that such haplotypes are often found to be distributed across wide geographical regions. We have addressed this issue here by combining two sources of ancestry information that have typically been considered separately: historical records regarding population origins and genetic information on mtDNA haplotypes. To combine these distinct data sources, we applied a Bayesian approach that considers historical records, in the form of prior probabilities, together with data on the geographical distribution of mtDNA haplotypes, formulated as likelihoods, to yield ancestry assignments from posterior probabilities. This combined evidence Bayesian approach to ancestry assignment was evaluated for its ability to accurately assign sub-continental African ancestral origins to Afro-Colombians based on their mtDNA haplotypes. We demonstrate that the incorporation of historical prior probabilities via this analytical framework can provide for substantially increased resolution in sub-continental African ancestry assignment for members of this population. In addition, a personalized approach to ancestry assignment that involves the tuning of priors to individual mtDNA haplotypes yields even greater resolution for individual ancestry assignment. Despite the fact that Colombia has a large population of Afro-descendants, the ancestry of this community has been understudied relative to populations with primarily European and Native American ancestry. Thus, the application of the kind of combined evidence approach developed here to the study of ancestry in the Afro-Colombian population has the potential to be impactful. The formal Bayesian analytical framework we propose for combining historical and genetic information also has the potential to be widely applied

Identifying tagging SNPs for African specific genetic variation from the African Diaspora Genome.

Science.gov (United States)

Johnston, Henry Richard; Hu, Yi-Juan; Gao, Jingjing; O'Connor, Timothy D; Abecasis, Gonçalo R; Wojcik, Genevieve L; Gignoux, Christopher R; Gourraud, Pierre-Antoine; Lizee, Antoine; Hansen, Mark; Genuario, Rob; Bullis, Dave; Lawley, Cindy; Kenny, Eimear E; Bustamante, Carlos; Beaty, Terri H; Mathias, Rasika A; Barnes, Kathleen C; Qin, Zhaohui S

2017-04-21

A primary goal of The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to develop an 'African Diaspora Power Chip' (ADPC), a genotyping array consisting of tagging SNPs, useful in comprehensively identifying African specific genetic variation. This array is designed based on the novel variation identified in 642 CAAPA samples of African ancestry with high coverage whole genome sequence data (~30× depth). This novel variation extends the pattern of variation catalogued in the 1000 Genomes and Exome Sequencing Projects to a spectrum of populations representing the wide range of West African genomic diversity. These individuals from CAAPA also comprise a large swath of the African Diaspora population and incorporate historical genetic diversity covering nearly the entire Atlantic coast of the Americas. Here we show the results of designing and producing such a microchip array. This novel array covers African specific variation far better than other commercially available arrays, and will enable better GWAS analyses for researchers with individuals of African descent in their study populations. A recent study cataloging variation in continental African populations suggests this type of African-specific genotyping array is both necessary and valuable for facilitating large-scale GWAS in populations of African ancestry.

Genetic ancestry-smoking interactions and lung function in African Americans: a cohort study.

Directory of Open Access Journals (Sweden)

Melinda C Aldrich

Full Text Available 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 African Americans participating in the Health, Aging, and Body Composition (Health ABC Study initiated in 1997. We also examined an ongoing prospective cohort initiated in 1985 of 1,223 African Americans in the Coronary Artery Disease in Young Adults (CARDIA Study. Pulmonary function and tobacco smoking exposure were measured at baseline and repeatedly over the follow-up period. Individual genetic ancestry proportions were estimated using ancestry informative markers selected to distinguish European and West African ancestry. African Americans with a high proportion of African ancestry had lower baseline forced expiratory volume in one second (FEV₁ per pack-year of smoking (-5.7 ml FEV₁/ smoking pack-year compared with smokers with lower African ancestry (-4.6 ml in FEV₁/ smoking pack-year (interaction P value  = 0.17. Longitudinal analyses revealed a suggestive interaction between smoking, and African ancestry on the rate of FEV(1 decline in Health ABC and independently replicated in CARDIA. CONCLUSIONS/SIGNIFICANCE: African American individuals with a high proportion of African ancestry are at greater risk for losing lung function while smoking.

The Genetic Ancestry of African Americans, Latinos, and European Americans across the United States

Science.gov (United States)

Bryc, Katarzyna; Durand, Eric Y.; Macpherson, J. Michael; Reich, David; Mountain, Joanna L.

2015-01-01

Over the past 500 years, North America has been the site of ongoing mixing of Native Americans, European settlers, and Africans (brought largely by the trans-Atlantic slave trade), shaping the early history of what became the United States. We studied the genetic ancestry of 5,269 self-described African Americans, 8,663 Latinos, and 148,789 European Americans who are 23andMe customers and show that the legacy of these historical interactions is visible in the genetic ancestry of present-day Americans. We document pervasive mixed ancestry and asymmetrical male and female ancestry contributions in all groups studied. We show that regional ancestry differences reflect historical events, such as early Spanish colonization, waves of immigration from many regions of Europe, and forced relocation of Native Americans within the US. This study sheds light on the fine-scale differences in ancestry within and across the United States and informs our understanding of the relationship between racial and ethnic identities and genetic ancestry. PMID:25529636

Genetic African Ancestry and Markers of Mineral Metabolism in CKD.

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Gutiérrez, Orlando M; Parsa, Afshin; Isakova, Tamara; Scialla, Julia J; Chen, Jing; Flack, John M; Nessel, Lisa C; Gupta, Jayanta; Bellovich, Keith A; Steigerwalt, Susan; Sondheimer, James H; Wright, Jackson T; Feldman, Harold I; Kusek, John W; Lash, James P; Wolf, Myles

2016-04-07

Disorders of mineral metabolism are more common in African Americans with CKD than in European Americans with CKD. Previous studies have focused on the differences in mineral metabolism by self-reported race, making it difficult to delineate the importance of environmental compared with biologic factors. In a cross-sectional analysis of 3013 participants of the Chronic Renal Insufficiency Cohort study with complete data, we compared markers of mineral metabolism (phosphorus, calcium, alkaline phosphatase, parathyroid hormone, fibroblast growth factor 23, and urine calcium and phosphorus excretion) in European Americans versus African Americans and separately, across quartiles of genetic African ancestry in African Americans (n=1490). Compared with European Americans, African Americans had higher blood concentrations of phosphorus, alkaline phosphatase, fibroblast growth factor 23, and parathyroid hormone, lower 24-hour urinary excretion of calcium and phosphorus, and lower urinary fractional excretion of calcium and phosphorus at baseline (PAfrican Americans, a higher percentage of African ancestry was associated with lower 24-hour urinary excretion of phosphorus (PtrendAfrican ancestry was significantly associated with lower 24-hour urinary phosphorus excretion (each 10% higher African ancestry was associated with 39.6 mg lower 24-hour urinary phosphorus, PAfrican ancestry was associated with an absolute 1.1% lower fractional excretion of phosphorus, P=0.01). A higher percentage of African ancestry was independently associated with lower 24-hour urinary phosphorus excretion and lower fractional excretion of phosphorus among African Americans with CKD. These findings suggest that genetic variability might contribute to racial differences in urinary phosphorus excretion in CKD. Copyright © 2016 by the American Society of Nephrology.

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

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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 (Pmyositis phenotypes together, as well as for the four clinical and autoantibody phenotypes studied separately. Imputation and regression analyses found that alleles comprising the human leukocyte antigen (HLA) 8.1 ancestral haplotype (AH8.1) 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.

Race, Genetic Ancestry and Response to Antidepressant Treatment for Major Depression

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Murphy, Eleanor; Hou, Liping; Maher, Brion S; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J

2013-01-01

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attempted to disentangle race and genetic ancestry. Here we used genome-wide single-nucleotide polymorphism (SNP) data to examine independent contributions of race and genetic ancestry to citalopram response. Secondary data analyses included 1877 STAR*D participants who completed an average of 10 weeks of citalopram treatment and provided DNA samples. Participants reported their race as White (n=1464), black (n=299) or other/mixed (n=114). Genetic ancestry was estimated by multidimensional scaling (MDS) analyses of about 500 000 SNPs. Ancestry proportions were estimated by STRUCTURE. Structural equation modeling was used to examine the direct and indirect effects of observed and latent predictors of response, defined as change in the Quick Inventory of Depressive Symptomatology (QIDS) score from baseline to exit. Socioeconomic and baseline clinical factors, race, and anxiety significantly predicted response, as previously reported. However, direct effects of race disappeared in all models that included genetic ancestry. Genetic African ancestry predicted lower treatment response in all models. Although socioeconomic and baseline clinical factors drive racial differences in antidepressant response, genetic ancestry, rather than self-reported race, explains a significant fraction of the residual differences. Larger samples would be needed to identify the specific genetic mechanisms that may be involved, but these findings underscore the importance of including more African-American patients in drug trials. PMID:23827886

Ancestry dynamics in a South American population: The impact of gene flow and preferential mating.

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Hedrick, Philip W

2017-07-01

European ancestry in many populations in Latin America at autosomal loci is often higher than that from X-linked loci indicating more European male ancestry and more Amerindian female ancestry. Generally, this has been attributed to more European male gene flow but could also result from an advantage to European mating or reproductive success. Population genetic models were developed to investigate the dynamics of gene flow and mating or reproductive success. Using estimates of autosomal and X-chromosome European ancestry, the amount of male gene flow or mating or reproductive advantage for Europeans, or those with European ancestry, was estimated. In a population from Antioquia, Colombia with an estimated 79% European autosomal ancestry and an estimated 69% European X-chromosome ancestry, about 15% male gene flow from Europe or about 20% mating or reproductive advantage of Europeans over Amerindians resulted in these levels of European ancestry in the contemporary population. Combinations of gene flow and mating advantage were nearly additive in their impact. Gene flow, mating advantage, or a combination of both factors, are consistent with observed levels of European ancestry in a Latin American population. This approach provides a general methodology to determine the levels of gene flow and mating differences that can explain the observed contemporary differences in ancestry from autosomes and X-chromosomes. © 2017 Wiley Periodicals, Inc.

HLA class II variation in the Gila River Indian Community of Arizona: alleles, haplotypes, and a high frequency epitope at the HLA-DR locus.

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Williams, R C; McAuley, J E

1992-01-01

A genetic distribution for the HLA class II loci is described for 349 "full-blooded" Pima and Tohono O'odham Indians (Pimans) in the Gila River Indian Community. A high frequency epitope in the *DRw52 family was defined by reactions with 31 alloantisera, which we have designated *DR3X6. It segregates as a codominant allele at HLA-DR with alleles *DR2, *DR4, and *DRw8, and has the highest frequency yet reported for an HLA-DR specificity, 0.735. It forms a common haplotype with *DRw52 and *DQw3 that is a valuable marker for genetic admixture and anthropological studies. Phenotype and allele frequencies, and haplotype frequencies for two and three loci, are presented. Variation at these loci is highly restricted, the mean heterozygosity for HLA-DR and HLA-DQ being 0.361. The Pimans represent a contemporary model for the Paleo-Indians who first entered North America 20,000 to 40,000 years ago.

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

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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-ancestry inferences made by mtDNA-haplogroup membership to those made by autosomal SNPs in ∼940 samples of the Human Genome Diversity Panel and recently admixed populations from the 1000 Genomes Project. Continental-ancestry proportions often varied widely among individuals sharing the same mtDNA haplogroup. For only half of mtDNA haplogroups did the highest average continental-ancestry proportion match the highest continental-ancestry proportion of a majority of individuals with that haplogroup. Prediction of an individual’s mtDNA haplogroup from his or her continental-ancestry proportions was often incorrect. Collectively, these results indicate that for most individuals in the worldwide populations sampled, mtDNA-haplogroup membership provides limited information about either continental ancestry or continental region of origin. PMID:25620206

Fitness differences due to allelic variation at Esterase-4 locus in ...

Indian Academy of Sciences (India)

KAVITA KRISHNAMOORTI

2017-08-31

Aug 31, 2017 ... Keywords. esterases; null allele; reproductive fitness; natural selection; Drosophila ananassae. .... cific substrate (1-naphthylacetate AR) and stain (fast blue. RR). On the ... transferred to fresh food vials and eggs were counted.

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

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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. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

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

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

Mitochondrial and genomic ancestry are associated with etiology of heart failure in Brazilian patients.

Science.gov (United States)

Cardena, M M S G; Ribeiro-Dos-Santos, A K; Santos, S E B; Mansur, A J; Bernardez-Pereira, S; Santos, P C J L; Pereira, A C; Fridman, C

2016-02-01

There is a high prevalence of heart failure (HF) in the general population, but it is more common in black people. We evaluated the association between genomic ancestry and mitochondrial haplogroups (mt-haplogroups) with HF etiology in 503 Brazilian patients. We elicited Mt-haplogroups by analyzing the control region of mitochondrial DNA, and genomic ancestry, by using 48 autosomal insertion-deletion ancestry informative markers. Hypertensive (28.6%, n=144) and ischemic (28.4%, n=143) etiologies of HF were the most prevalent herein. Our results showed that 233 individuals (46.3%) presented African mitochondrial (mt)-haplogroups, and the major contribution in the genomic ancestry analysis was the European ancestry (57.5% (±22.1%)). African mt-haplogroups were positively associated with a diagnosis of hypertensive cardiomyopathy (odds ratio, OR 1.55, confidence interval, CI 95% 1.04-2.44, P=0.04) when compared with European mt-haplogroups. Regarding the genomic ancestry, the African ancestry variant had higher risks (OR 7.84, 95% CI 2.81-21.91, Pancestry variant had lower risks (OR 0.14, 95% CI 0.04-5.00, Pancestry showed an OR of 4.05 (CI 95% 1.53-10.74, P=0.005), whereas African ancestry showed an OR of 0.17 (CI 95% 0.06-0.48, P=0.001) for developing ischemic etiology. In conclusion, this study supports the importance of using ancestry informative markers and mitochondrial DNA to study the genetics of complex diseases in admixed populations to improve the management, treatment and prevention of these illnesses. Therefore, the ancestry informative markers and mt-haplogroups could provide new biomarkers to be associated with HF etiologies and be used as a premise for more specific management.

A novel test for gene-ancestry interactions in genome-wide association data.

Directory of Open Access Journals (Sweden)

Joanna L Davies

Full Text Available Genome-wide association study (GWAS data on a disease are increasingly available from multiple related populations. In this scenario, meta-analyses can improve power to detect homogeneous genetic associations, but if there exist ancestry-specific effects, via interactions on genetic background or with a causal effect that co-varies with genetic background, then these will typically be obscured. To address this issue, we have developed a robust statistical method for detecting susceptibility gene-ancestry interactions in multi-cohort GWAS based on closely-related populations. We use the leading principal components of the empirical genotype matrix to cluster individuals into "ancestry groups" and then look for evidence of heterogeneous genetic associations with disease or other trait across these clusters. Robustness is improved when there are multiple cohorts, as the signal from true gene-ancestry interactions can then be distinguished from gene-collection artefacts by comparing the observed interaction effect sizes in collection groups relative to ancestry groups. When applied to colorectal cancer, we identified a missense polymorphism in iron-absorption gene CYBRD1 that associated with disease in individuals of English, but not Scottish, ancestry. The association replicated in two additional, independently-collected data sets. Our method can be used to detect associations between genetic variants and disease that have been obscured by population genetic heterogeneity. It can be readily extended to the identification of genetic interactions on other covariates such as measured environmental exposures. We envisage our methodology being of particular interest to researchers with existing GWAS data, as ancestry groups can be easily defined and thus tested for interactions.

Weight of the evidence of genetic investigations of ancestry informative markers

DEFF Research Database (Denmark)

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

2018-01-01

Ancestry-informative markers (AIMs) are markers that give information about the ancestry of individuals. They are used in forensic genetics for predicting the geographic origin of the investigated individual in crime and identification cases. In the exploration of the genogeographic origin...

Ancestry as a potential modifier of gene expression in breast tumors from Colombian women.

Science.gov (United States)

Serrano-Gómez, Silvia J; Sanabria-Salas, María Carolina; Garay, Jone; Baddoo, Melody C; Hernández-Suarez, Gustavo; Mejía, Juan Carlos; García, Oscar; Miele, Lucio; Fejerman, Laura; Zabaleta, Jovanny

2017-01-01

Hispanic/Latino populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. The molecular profile of breast cancer has been widely described in non-Hispanic Whites but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian women was Luminal B as defined by St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. We found 5 genes potentially modulated by genetic ancestry: ERBB2 (log2FC = 2.367, padjancestry (p = 0.02, B = 3.11). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value.

Dried blood spots of pooled samples for RHD gene screening in blood donors of mixed ancestry.

Science.gov (United States)

Silva-Malta, M C F; Araujo, N C Fidélis; Vieira, O V Neves; Schmidt, L Cayres; Gonçalves, P de Cassia; Martins, M Lobato

2015-10-01

In this study, we present a strategy for RHD gene screening based on real-time polymerase chain reaction (PCR) using dried blood spots of pooled samples. Molecular analysis of blood donors may be used to detect RHD variants among the presumed D-negative individuals. RHD genotyping using pooled samples is a strategy to test a large number of samples at a more reasonable cost. RHD gene detection based on real-time PCR using dried blood spots of pooled samples was standardised and used to evaluate 1550 Brazilian blood donors phenotyped as RhD-negative. Positive results were re-evaluated by retesting single samples using real-time PCR and conventional multiplex PCR to amplify five RHD-specific exons. PCR-sequence-specific primers was used to amplify RHDψ allele. We devised a strategy for RHD gene screening using dried blood spots of five pooled samples. Among 1550 serologically D-negative blood donors, 58 (3.74%) had the RHD gene. The non-functional RHDψ allele was detected in 47 samples (3.02%). The present method is a promising strategy to detect the RHD gene among presumed RhD-negative blood donors, particularly for populations with African ancestry. © 2015 British Blood Transfusion Society.

Rare coding variants associated with blood pressure variation in 15 914 individuals of African ancestry.

Science.gov (United States)

Nandakumar, Priyanka; Lee, Dongwon; Richard, Melissa A; Tekola-Ayele, Fasil; Tayo, Bamidele O; Ware, Erin; Sung, Yun J; Salako, Babatunde; Ogunniyi, Adesola; Gu, C Charles; Grove, Megan L; Fornage, Myriam; Kardia, Sharon; Rotimi, Charles; Cooper, Richard S; Morrison, Alanna C; Ehret, Georg; Chakravarti, Aravinda

2017-07-01

Hypertension is a major risk factor for all cardiovascular diseases, especially among African Americans. This study focuses on identifying specific blood pressure (BP) genes using 15 914 individuals of African ancestry from eight cohorts (Africa America Diabetes Mellitus, Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in young Adults, Genetics Network, Genetic Epidemiology Network of Arteriopathy, Howard University Family Study, Hypertension Genetic Epidemiology Network, and Loyola University Chicago Cohort) to further genetic findings in this population which has generally been underrepresented in BP studies. We genotyped and performed various single variant and gene-based exome-wide analyses on 15 914 individuals on the Illumina HumanExome Beadchip v1.0 or v1.1 to test association with SBP and DBP long-term average residuals that were adjusted for age, age-squared, sex, and BMI. We identified rare variants affecting SBP and DBP in 10 genes: AFF1, GAPDHS, SLC28A3, COL6A1, CRYBA2, KRBA1, SEL1L3, YOD1, CCDC13, and QSOX1. Prior experimental evidence for six of these 10 candidate genes supports their involvement in cardiovascular mechanisms, corroborating their potential roles in BP regulation. Although our results require replication or validation due to their low numbers of carriers, and an ethnicity-specific genotyping array may be more informative, this study, which has identified several candidate genes in this population most susceptible to hypertension, presents one of the largest African-ancestry BP studies to date and the largest including analysis of rare variants.

Allelic Variations at Four Major Maturity E Genes and Transcriptional Abundance of the E1 Gene Are Associated with Flowering Time and Maturity of Soybean Cultivars

Science.gov (United States)

Wang, Yueqiang; Chen, Xin; Ren, Haixiang; Yang, Jiayin; Cheng, Wen; Zong, Chunmei; Gu, Heping; Qiu, Hongmei; Wu, Hongyan; Zhang, Xingzheng; Cui, Tingting; Xia, Zhengjun

2014-01-01

The time to flowering and maturity are ecologically and agronomically important traits for soybean landrace and cultivar adaptation. As a typical short-day crop, long day conditions in the high-latitude regions require soybean cultivars with photoperiod insensitivity that can mature before frost. Although the molecular basis of four major E loci (E1 to E4) have been deciphered, it is not quite clear whether, or to what degree, genetic variation and the expression level of the four E genes are associated with the time to flowering and maturity of soybean cultivars. In this study, we genotyped 180 cultivars at E1 to E4 genes, meanwhile, the time to flowering and maturity of those cultivars were investigated at six geographic locations in China from 2011 to 2012 and further confirmed in 2013. The percentages of recessive alleles at E1, E2, E3 and E4 loci were 38.34%, 84.45%, 36.33%, and 7.20%, respectively. Statistical analysis showed that allelic variations at each of four loci had a significant effect on flowering time as well as maturity. We classified the 180 cultivars into eight genotypic groups based on allelic variations of the four major E loci. The genetic group of e1-nf representing dysfunctional alleles at the E1 locus flowered earliest in all the geographic locations. In contrast, cultivars in the E1E2E3E4 group originated from the southern areas flowered very late or did not flower before frost at high latitude locations. The transcriptional abundance of functional E1 gene was significantly associated with flowering time. However, the ranges of time to flowering and maturity were quite large within some genotypic groups, implying the presence of some other unknown genetic factors that are involved in control of flowering time or maturity. Known genes (e.g. E3 and E4) and other unknown factors may function, at least partially, through regulation of the expression of the E1 gene. PMID:24830458

Genomic Ancestry of North Africans Supports Back-to-Africa Migrations

Science.gov (United States)

Gravel, Simon; Wang, Wei; Brisbin, Abra; Byrnes, Jake K.; Fadhlaoui-Zid, Karima; Zalloua, Pierre A.; Moreno-Estrada, Andres; Bertranpetit, Jaume; Bustamante, Carlos D.; Comas, David

2012-01-01

North African populations are distinct from sub-Saharan Africans based on cultural, linguistic, and phenotypic attributes; however, the time and the extent of genetic divergence between populations north and south of the Sahara remain poorly understood. Here, we interrogate the multilayered history of North Africa by characterizing the effect of hypothesized migrations from the Near East, Europe, and sub-Saharan Africa on current genetic diversity. We present dense, genome-wide SNP genotyping array data (730,000 sites) from seven North African populations, spanning from Egypt to Morocco, and one Spanish population. We identify a gradient of likely autochthonous Maghrebi ancestry that increases from east to west across northern Africa; this ancestry is likely derived from “back-to-Africa” gene flow more than 12,000 years ago (ya), prior to the Holocene. The indigenous North African ancestry is more frequent in populations with historical Berber ethnicity. In most North African populations we also see substantial shared ancestry with the Near East, and to a lesser extent sub-Saharan Africa and Europe. To estimate the time of migration from sub-Saharan populations into North Africa, we implement a maximum likelihood dating method based on the distribution of migrant tracts. In order to first identify migrant tracts, we assign local ancestry to haplotypes using a novel, principal component-based analysis of three ancestral populations. We estimate that a migration of western African origin into Morocco began about 40 generations ago (approximately 1,200 ya); a migration of individuals with Nilotic ancestry into Egypt occurred about 25 generations ago (approximately 750 ya). Our genomic data reveal an extraordinarily complex history of migrations, involving at least five ancestral populations, into North Africa. PMID:22253600

Genomic ancestry of North Africans supports back-to-Africa migrations.

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Brenna M Henn

2012-01-01

Full Text Available North African populations are distinct from sub-Saharan Africans based on cultural, linguistic, and phenotypic attributes; however, the time and the extent of genetic divergence between populations north and south of the Sahara remain poorly understood. Here, we interrogate the multilayered history of North Africa by characterizing the effect of hypothesized migrations from the Near East, Europe, and sub-Saharan Africa on current genetic diversity. We present dense, genome-wide SNP genotyping array data (730,000 sites from seven North African populations, spanning from Egypt to Morocco, and one Spanish population. We identify a gradient of likely autochthonous Maghrebi ancestry that increases from east to west across northern Africa; this ancestry is likely derived from "back-to-Africa" gene flow more than 12,000 years ago (ya, prior to the Holocene. The indigenous North African ancestry is more frequent in populations with historical Berber ethnicity. In most North African populations we also see substantial shared ancestry with the Near East, and to a lesser extent sub-Saharan Africa and Europe. To estimate the time of migration from sub-Saharan populations into North Africa, we implement a maximum likelihood dating method based on the distribution of migrant tracts. In order to first identify migrant tracts, we assign local ancestry to haplotypes using a novel, principal component-based analysis of three ancestral populations. We estimate that a migration of western African origin into Morocco began about 40 generations ago (approximately 1,200 ya; a migration of individuals with Nilotic ancestry into Egypt occurred about 25 generations ago (approximately 750 ya. Our genomic data reveal an extraordinarily complex history of migrations, involving at least five ancestral populations, into North Africa.

Analysis of Latino populations from GALA and MEC studies reveals genomic loci with biased local ancestry estimation

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Pasaniuc, Bogdan; Sankararaman, Sriram; Torgerson, Dara G.; Gignoux, Christopher; Zaitlen, Noah; Eng, Celeste; Rodriguez-Cintron, William; Chapela, Rocio; Ford, Jean G.; Avila, Pedro C.; Rodriguez-Santana, Jose; Chen, Gary K.; Le Marchand, Loic; Henderson, Brian; Reich, David; Haiman, Christopher A.; Gonzàlez Burchard, Esteban; Halperin, Eran

2013-01-01

Motivation: Local ancestry analysis of genotype data from recently admixed populations (e.g. Latinos, African Americans) provides key insights into population history and disease genetics. Although methods for local ancestry inference have been extensively validated in simulations (under many unrealistic assumptions), no empirical study of local ancestry accuracy in Latinos exists to date. Hence, interpreting findings that rely on local ancestry in Latinos is challenging. Results: Here, we use 489 nuclear families from the mainland USA, Puerto Rico and Mexico in conjunction with 3204 unrelated Latinos from the Multiethnic Cohort study to provide the first empirical characterization of local ancestry inference accuracy in Latinos. Our approach for identifying errors does not rely on simulations but on the observation that local ancestry in families follows Mendelian inheritance. We measure the rate of local ancestry assignments that lead to Mendelian inconsistencies in local ancestry in trios (MILANC), which provides a lower bound on errors in the local ancestry estimates. We show that MILANC rates observed in simulations underestimate the rate observed in real data, and that MILANC varies substantially across the genome. Second, across a wide range of methods, we observe that loci with large deviations in local ancestry also show enrichment in MILANC rates. Therefore, local ancestry estimates at such loci should be interpreted with caution. Finally, we reconstruct ancestral haplotype panels to be used as reference panels in local ancestry inference and show that ancestry inference is significantly improved by incoroprating these reference panels. Availability and implementation: We provide the reconstructed reference panels together with the maps of MILANC rates as a public resource for researchers analyzing local ancestry in Latinos at http://bogdanlab.pathology.ucla.edu. Contact: bpasaniuc@mednet.ucla.edu Supplementary information: Supplementary data are

Preferential binding to Elk-1 by SLE-associated IL10 risk allele upregulates IL10 expression.

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Daisuke Sakurai

Full Text Available Immunoregulatory cytokine interleukin-10 (IL-10 is elevated in sera from patients with systemic lupus erythematosus (SLE correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA (P = 2.7×10⁻⁸, OR = 1.30, but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively, and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1 detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele

Origin and differential selection of allelic variation at TAS2R16 associated with salicin bitter taste sensitivity in Africa.

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

2014-02-01

Bitter taste perception influences human nutrition and health, and the genetic variation underlying this trait may play a role in disease susceptibility. To better understand the genetic architecture and patterns of phenotypic variability of bitter taste perception, we sequenced a 996 bp region, encompassing the coding exon of TAS2R16, a bitter taste receptor gene, in 595 individuals from 74 African populations and in 94 non-Africans from 11 populations. We also performed genotype-phenotype association analyses of threshold levels of sensitivity to salicin, a bitter anti-inflammatory compound, in 296 individuals from Central and East Africa. In addition, we characterized TAS2R16 mutants in vitro to investigate the effects of polymorphic loci identified at this locus on receptor function. Here, we report striking signatures of positive selection, including significant Fay and Wu's H statistics predominantly in East Africa, indicating strong local adaptation and greater genetic structure among African populations than expected under neutrality. Furthermore, we observed a "star-like" phylogeny for haplotypes with the derived allele at polymorphic site 516 associated with increased bitter taste perception that is consistent with a model of selection for "high-sensitivity" variation. In contrast, haplotypes carrying the "low-sensitivity" ancestral allele at site 516 showed evidence of strong purifying selection. We also demonstrated, for the first time, the functional effect of nonsynonymous variation at site 516 on salicin phenotypic variance in vivo in diverse Africans and showed that most other nonsynonymous substitutions have weak or no effect on cell surface expression in vitro, suggesting that one main polymorphism at TAS2R16 influences salicin recognition. Additionally, we detected geographic differences in levels of bitter taste perception in Africa not previously reported and infer an East African origin for high salicin sensitivity in human populations.

[Analysis of allele dropout at TH01 locus in paternity testing].

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Lai, Li; Shen, Xiao-li; Xue, Shi-jie; Hu, Jie

2013-10-01

To analyze allele dropout at TH01 locus in paternity testing in order to determine the accurate genotype. To use a two STR loci genotyping system to verify an abnormal genotype for the TH01 locus with PCR using specific primers, cloning and DNA sequencing. A rare allele at TH01 locus named 5.2, which was undetectable with PowerPlex 21 system, was detected with an Identifiler system. Genetic variations may result in rare alleles and loci loss. To avoid misjudgment, laboratories should have a variety of methods for detecting loci loss.

Applying Ancestry and Sex Computation as a Quality Control Tool in Targeted Next-Generation Sequencing.

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Mathias, Patrick C; Turner, Emily H; Scroggins, Sheena M; Salipante, Stephen J; Hoffman, Noah G; Pritchard, Colin C; Shirts, Brian H

2016-03-01

To apply techniques for ancestry and sex computation from next-generation sequencing (NGS) data as an approach to confirm sample identity and detect sample processing errors. We combined a principal component analysis method with k-nearest neighbors classification to compute the ancestry of patients undergoing NGS testing. By combining this calculation with X chromosome copy number data, we determined the sex and ancestry of patients for comparison with self-report. We also modeled the sensitivity of this technique in detecting sample processing errors. We applied this technique to 859 patient samples with reliable self-report data. Our k-nearest neighbors ancestry screen had an accuracy of 98.7% for patients reporting a single ancestry. Visual inspection of principal component plots was consistent with self-report in 99.6% of single-ancestry and mixed-ancestry patients. Our model demonstrates that approximately two-thirds of potential sample swaps could be detected in our patient population using this technique. Patient ancestry can be estimated from NGS data incidentally sequenced in targeted panels, enabling an inexpensive quality control method when coupled with patient self-report. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Education of Non-European Ancestry Immigrant Students in Suburban High Schools

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Shodavaram, Mary P.; Jones, Lisa A.; Weaver, Laurie R.; Marquez, Judith A.; Ensle, Anne L.

2009-01-01

The purpose of this study was to examine suburban high school teachers' beliefs about non-European ancestry immigrant students; more specifically, suburban teachers' beliefs regarding the impact of students' cultural backgrounds on academic performance were examined. Non-European ancestry immigrant students are those students whose ancestral…

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

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Jing, Lijun; Su, Li; Ring, Brian Z

2014-01-01

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 studied and employed.

Ethnic Background and Genetic Variation in the Evaluation of Cancer Risk: A Systematic Review

Science.gov (United States)

Jing, Lijun; Su, Li; Ring, Brian Z.

2014-01-01

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 studied and

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

The genomic ancestry, landscape genetics and invasion history of introduced mice in New Zealand.

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Veale, Andrew J; Russell, James C; King, Carolyn M

2018-01-01

The house mouse ( Mus musculus ) provides a fascinating system for studying both the genomic basis of reproductive isolation, and the patterns of human-mediated dispersal. New Zealand has a complex history of mouse invasions, and the living descendants of these invaders have genetic ancestry from all three subspecies, although most are primarily descended from M. m. domesticus . We used the GigaMUGA genotyping array (approximately 135 000 loci) to describe the genomic ancestry of 161 mice, sampled from 34 locations from across New Zealand (and one Australian city-Sydney). Of these, two populations, one in the south of the South Island, and one on Chatham Island, showed complete mitochondrial lineage capture, featuring two different lineages of M. m. castaneus mitochondrial DNA but with only M. m. domesticus nuclear ancestry detectable. Mice in the northern and southern parts of the North Island had small traces (approx. 2-3%) of M. m. castaneus nuclear ancestry, and mice in the upper South Island had approximately 7-8% M. m. musculus nuclear ancestry including some Y-chromosomal ancestry-though no detectable M. m. musculus mitochondrial ancestry. This is the most thorough genomic study of introduced populations of house mice yet conducted, and will have relevance to studies of the isolation mechanisms separating subspecies of mice.

Impact of ancestry and body size on sonographic ulnar nerve dimensions

International Nuclear Information System (INIS)

Childs, Jessie T.; Phillips, Maureen; Thoirs, Kerry A.

2012-01-01

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.

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

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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.

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

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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

2011-05-01

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 and lengths of IBD segments derived from high-density SNP or whole-genome sequence data. We used ERSA to estimate relationships from SNP genotypes in 169 individuals from three large, well-defined human pedigrees. ERSA is accurate to within one degree of relationship for 97% of first-degree through fifth-degree relatives and 80% of sixth-degree and seventh-degree relatives. We demonstrate that ERSA's statistical power approaches the maximum theoretical limit imposed by the fact that distant relatives frequently share no DNA through a common ancestor. ERSA greatly expands the range of relationships that can be estimated from genetic data and is implemented in a freely available software package.

Sex-specific allelic transmission bias suggests sexual conflict at MC1R.

Science.gov (United States)

Ducret, Valérie; Gaigher, Arnaud; Simon, Céline; Goudet, Jérôme; Roulin, Alexandre

2016-09-01

Sexual conflict arises when selection in one sex causes the displacement of the other sex from its phenotypic optimum, leading to an inevitable tension within the genome - called intralocus sexual conflict. Although the autosomal melanocortin-1-receptor gene (MC1R) can generate colour variation in sexually dichromatic species, most previous studies have not considered the possibility that MC1R may be subject to sexual conflict. In the barn owl (Tyto alba), the allele MC1RWHITE is associated with whitish plumage coloration, typical of males, and the allele MC1RRUFOUS is associated with dark rufous coloration, typical of females, although each sex can express any phenotype. Because each colour variant is adapted to specific environmental conditions, the allele MC1RWHITE may be more strongly selected in males and the allele MC1RRUFOUS in females. We therefore investigated whether MC1R genotypes are in excess or deficit in male and female fledglings compared with the expected Hardy-Weinberg proportions. Our results show an overall deficit of 7.5% in the proportion of heterozygotes in males and of 12.9% in females. In males, interannual variation in assortative pairing with respect to MC1R explained the year-specific deviations from Hardy-Weinberg proportions, whereas in females, the deficit was better explained by the interannual variation in the probability of inheriting the MC1RWHITE or MC1RRUFOUS allele. Additionally, we observed that sons inherit the MC1RRUFOUS allele from their fathers on average slightly less often than expected under the first Mendelian law. Transmission ratio distortion may be adaptive in this sexually dichromatic species if males and females are, respectively, selected to display white and rufous plumages. © 2016 John Wiley & Sons Ltd.

The M405V allele of the glutaryl-CoA dehydrogenase gene is an important marker for glutaric aciduria type I (GA-I) low excretors.

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Schillaci, Lori-Anne P; Greene, Carol L; Strovel, Erin; Rispoli-Joines, Jessica; Spector, Elaine; Woontner, Michael; Scharer, Gunter; Enns, Gregory M; Gallagher, Renata; Zinn, Arthur B; McCandless, Shawn E; Hoppel, Charles L; Goodman, Stephen I; Bedoyan, Jirair K

2016-09-01

Glutaric aciduria type I (GA-I) is an autosomal recessive organic aciduria resulting from a functional deficiency of glutaryl-CoA dehydrogenase, encoded by GCDH. Two clinically indistinguishable diagnostic subgroups of GA-I are known; low and high excretors (LEs and HEs, respectively). Early medical and dietary interventions can result in significantly better outcomes and improved quality of life for patients with GA-I. We report on nine cases of GA-I LE patients all sharing the M405V allele with two cases missed by newborn screening (NBS) using tandem mass spectrometry (MS/MS). We describe a novel case with the known pathogenic M405V variant and a novel V133L variant, and present updated and previously unreported clinical, biochemical, functional and molecular data on eight other patients all sharing the M405V allele. Three of the nine patients are of African American ancestry, with two as siblings. GCDH activity was assayed in six of the nine patients and varied from 4 to 25% of the control mean. We support the use of urine glutarylcarnitine as a biochemical marker of GA-I by demonstrating that glutarylcarnitine is efficiently cleared by the kidney (50-90%) and that plasma and urine glutarylcarnitine follow a linear relationship. We report the allele frequencies for three known GA-I LE GCDH variants (M405V, V400M and R227P) and note that both the M405V and V400M variants are significantly more common in the population of African ancestry compared to the general population. This report highlights the M405V allele as another important molecular marker in patients with the GA-I LE phenotype. Therefore, the incorporation into newborn screening of molecular screening for the M405V and V400M variants in conjunction with MS/MS could help identify asymptomatic at-risk GA-I LE patients that could potentially be missed by current NBS programs. Copyright © 2016 Elsevier Inc. All rights reserved.

Skin color variation in Orang Asli tribes of Peninsular Malaysia.

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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.

Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21

Science.gov (United States)

Adoue, Véronique; Michailidou, Kyriaki; Canisius, Sander; Lemaçon, Audrey; Droit, Arnaud; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Baynes, Caroline; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Borresen-Dale, Anne-Lise; Brand, Judith S.; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Burwinkel, Barbara; Chang-Claude, Jenny; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Eriksson, Mikael; Fasching, Peter A.; Figueroa, Jonine; Flyger, Henrik; García-Closas, Montserrat; Giles, Graham G.; Goldberg, Mark S.; González-Neira, Anna; Grenaker-Alnæs, Grethe; Guénel, Pascal; Haeberle, Lothar; Haiman, Christopher A.; Hamann, Ute; Hallberg, Emily; Hooning, Maartje J.; Hopper, John L.; Jakubowska, Anna; Jones, Michael; Kabisch, Maria; Kataja, Vesa; Lambrechts, Diether; Marchand, Loic Le; Lindblom, Annika; Lubinski, Jan; Mannermaa, Arto; Maranian, Mel; Margolin, Sara; Marme, Frederik; Milne, Roger L.; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Olswold, Curtis; Peto, Julian; Plaseska-Karanfilska, Dijana; Pylkäs, Katri; Radice, Paolo; Rudolph, Anja; Sawyer, Elinor J.; Schmidt, Marjanka K.; Shu, Xiao-Ou; Southey, Melissa C.; Swerdlow, Anthony; Tollenaar, Rob A.E.M.; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine; Van Den Ouweland, Ans M. W.; Wang, Qin; Winqvist, Robert; Investigators, kConFab/AOCS; Zheng, Wei; Benitez, Javier; Chenevix-Trench, Georgia; Dunning, Alison M.; Pharoah, Paul D. P.; Kristensen, Vessela; Hall, Per; Easton, Douglas F.; Pastinen, Tomi; Nord, Silje; Simard, Jacques

2016-01-01

There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P = 5.6x10-6). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS), encoding a BRCA1 BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ (P = 8.28x10-14), MRPS18C (P = 1.94x10-27) and FAM175A (P = 3.83x10-3), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas. PMID:27792995

Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21.

Science.gov (United States)

Hamdi, Yosr; Soucy, Penny; Adoue, Véronique; Michailidou, Kyriaki; Canisius, Sander; Lemaçon, Audrey; Droit, Arnaud; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Baynes, Caroline; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Borresen-Dale, Anne-Lise; Brand, Judith S; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Burwinkel, Barbara; Chang-Claude, Jenny; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flyger, Henrik; García-Closas, Montserrat; Giles, Graham G; Goldberg, Mark S; González-Neira, Anna; Grenaker-Alnæs, Grethe; Guénel, Pascal; Haeberle, Lothar; Haiman, Christopher A; Hamann, Ute; Hallberg, Emily; Hooning, Maartje J; Hopper, John L; Jakubowska, Anna; Jones, Michael; Kabisch, Maria; Kataja, Vesa; Lambrechts, Diether; Le Marchand, Loic; Lindblom, Annika; Lubinski, Jan; Mannermaa, Arto; Maranian, Mel; Margolin, Sara; Marme, Frederik; Milne, Roger L; Neuhausen, Susan L; Nevanlinna, Heli; Neven, Patrick; Olswold, Curtis; Peto, Julian; Plaseska-Karanfilska, Dijana; Pylkäs, Katri; Radice, Paolo; Rudolph, Anja; Sawyer, Elinor J; Schmidt, Marjanka K; Shu, Xiao-Ou; Southey, Melissa C; Swerdlow, Anthony; Tollenaar, Rob A E M; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine; Van Den Ouweland, Ans M W; Wang, Qin; Winqvist, Robert; Zheng, Wei; Benitez, Javier; Chenevix-Trench, Georgia; Dunning, Alison M; Pharoah, Paul D P; Kristensen, Vessela; Hall, Per; Easton, Douglas F; Pastinen, Tomi; Nord, Silje; Simard, Jacques

2016-12-06

There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P = 5.6x10-6). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS), encoding a BRCA1 BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ (P = 8.28x10-14), MRPS18C (P = 1.94x10-27) and FAM175A (P = 3.83x10-3), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas.

Improved Ancestry Estimation for both Genotyping and Sequencing Data using Projection Procrustes Analysis and Genotype Imputation

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Wang, Chaolong; Zhan, Xiaowei; Liang, Liming; Abecasis, Gonçalo R.; Lin, Xihong

2015-01-01

Accurate estimation of individual ancestry is important in genetic association studies, especially when a large number of samples are collected from multiple sources. However, existing approaches developed for genome-wide SNP data do not work well with modest amounts of genetic data, such as in targeted sequencing or exome chip genotyping experiments. We propose a statistical framework to estimate individual ancestry in a principal component ancestry map generated by a reference set of individuals. This framework extends and improves upon our previous method for estimating ancestry using low-coverage sequence reads (LASER 1.0) to analyze either genotyping or sequencing data. In particular, we introduce a projection Procrustes analysis approach that uses high-dimensional principal components to estimate ancestry in a low-dimensional reference space. Using extensive simulations and empirical data examples, we show that our new method (LASER 2.0), combined with genotype imputation on the reference individuals, can substantially outperform LASER 1.0 in estimating fine-scale genetic ancestry. Specifically, LASER 2.0 can accurately estimate fine-scale ancestry within Europe using either exome chip genotypes or targeted sequencing data with off-target coverage as low as 0.05×. Under the framework of LASER 2.0, we can estimate individual ancestry in a shared reference space for samples assayed at different loci or by different techniques. Therefore, our ancestry estimation method will accelerate discovery in disease association studies not only by helping model ancestry within individual studies but also by facilitating combined analysis of genetic data from multiple sources. PMID:26027497

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

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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

Replication and functional genomic analyses of the breast cancer susceptibility locus at 6q25.1 generalize its importance in women of chinese, Japanese, and European ancestry.

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Cai, Qiuyin; Wen, Wanqing; Qu, Shimian; Li, Guoliang; Egan, Kathleen M; Chen, Kexin; Deming, Sandra L; Shen, Hongbing; Shen, Chen-Yang; Gammon, Marilie D; Blot, William J; Matsuo, Keitaro; Haiman, Christopher A; Khoo, Ui Soon; Iwasaki, Motoki; Santella, Regina M; Zhang, Lina; Fair, Alecia Malin; Hu, Zhibin; Wu, Pei-Ei; Signorello, Lisa B; Titus-Ernstoff, Linda; Tajima, Kazuo; Henderson, Brian E; Chan, Kelvin Y K; Kasuga, Yoshio; Newcomb, Polly A; Zheng, Hong; Cui, Yong; Wang, Furu; Shieh, Ya-Lan; Iwata, Hiroji; Le Marchand, Loic; Chan, Sum Yin; Shrubsole, Martha J; Trentham-Dietz, Amy; Tsugane, Shoichiro; Garcia-Closas, Montserrat; Long, Jirong; Li, Chun; Shi, Jiajun; Huang, Bo; Xiang, Yong-Bing; Gao, Yu-Tang; Lu, Wei; Shu, Xiao-Ou; Zheng, Wei

2011-02-15

We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of more than 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinese women [ORs (95% CI) = 1.30 (1.22-1.38) and 1.64 (1.50-1.80) for the AG and AA genotypes, respectively, P for trend = 1.54 × 10⁻³⁰], Japanese women [ORs (95% CI) = 1.31 (1.13-1.52) and 1.37 (1.06-1.76), P for trend = 2.51 × 10⁻⁴], and European-ancestry American women [ORs (95% CI) = 1.07 (0.99-1.16) and 1.18 (1.04-1.34), P for trend = 0.0069]. No association with this SNP, however, was observed in African American women [ORs (95% CI) = 0.81 (0.63-1.06) and 0.85 (0.65-1.11) for the AG and AA genotypes, respectively, P for trend = 0.4027]. In vitro functional genomic studies identified a putative functional variant, rs6913578. This SNP is 1,440 bp downstream of rs2046210 and is in high linkage disequilibrium with rs2046210 in Chinese (r(2) = 0.91) and European-ancestry (r² = 0.83) populations, but not in Africans (r² = 0.57). SNP rs6913578 was found to be associated with breast cancer risk in Chinese and European-ancestry American women. After adjusting for rs2046210, the association of rs6913578 with breast cancer risk in African Americans approached borderline significance. Results from this large consortium study confirmed the association of rs2046210 with breast cancer risk among women of Chinese, Japanese, and European ancestry. This association may be explained in part by a putatively functional variant (rs6913578) identified in the region. ©2011 AACR.

Mutation Rate Variation is a Primary Determinant of the Distribution of Allele Frequencies in Humans.

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Arbel Harpak

2016-12-01

Full Text Available The site frequency spectrum (SFS has long been used to study demographic history and natural selection. Here, we extend this summary by examining the SFS conditional on the alleles found at the same site in other species. We refer to this extension as the "phylogenetically-conditioned SFS" or cSFS. Using recent large-sample data from the Exome Aggregation Consortium (ExAC, combined with primate genome sequences, we find that human variants that occurred independently in closely related primate lineages are at higher frequencies in humans than variants with parallel substitutions in more distant primates. We show that this effect is largely due to sites with elevated mutation rates causing significant departures from the widely-used infinite sites mutation model. Our analysis also suggests substantial variation in mutation rates even among mutations involving the same nucleotide changes. In summary, we show that variable mutation rates are key determinants of the SFS in humans.

Copy number variations and genetic admixtures in three Xinjiang ethnic minority groups.

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Lou, Haiyi; Li, Shilin; Jin, Wenfei; Fu, Ruiqing; Lu, Dongsheng; Pan, Xinwei; Zhou, Huaigu; Ping, Yuan; Jin, Li; Xu, Shuhua

2015-04-01

Xinjiang is geographically located in central Asia, and it has played an important historical role in connecting eastern Eurasian (EEA) and western Eurasian (WEA) people. However, human population genomic studies in this region have been largely underrepresented, especially with respect to studies of copy number variations (CNVs). Here we constructed the first CNV map of the three major ethnic minority groups, the Uyghur, Kazakh and Kirgiz, using Affymetrix Genome-Wide Human SNP Array 6.0. We systematically compared the properties of CNVs we identified in the three groups with the data from representatives of EEA and WEA. The analyses indicated a typical genetic admixture pattern in all three groups with ancestries from both EEA and WEA. We also identified several CNV regions showing significant deviation of allele frequency from the expected genome-wide distribution, which might be associated with population-specific phenotypes. Our study provides the first genome-wide perspective on the CNVs of three major Xinjiang ethnic minority groups and has implications for both evolutionary and medical studies.

Ethnicity, desirable responding, and self-reports of abuse: a comparison of European- and Asian-ancestry undergraduates.

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Meston, C M; Heiman, J R; Trapnell, P D; Carlin, A S

1999-02-01

One thousand fifty-two (582 non-Asian, 470 Asian) university students were assessed regarding levels of physical abuse, emotional abuse, sexual abuse, neglect, and socially desirable responding. Differences between Asian-ancestry and European-ancestry students in self-reported incidence and expression of abuse were evaluated, as was gender and the relation between self-reported abuse and socially desirable responding. Asian-ancestry men and women reported higher levels of physical abuse, emotional abuse, and neglect than did their Euro-ancestry counterparts, and Euro-ancestry women reported a higher incidence of sexual abuse than did Asian-ancestry women. Across ethnicity, men reported higher levels of physical abuse and neglect but lower levels of sexual abuse than did women. Socially desirable responding was not related to measures of abuse. Findings are discussed in terms of cultural influences on child-rearing and disciplinary practices.

A Comparative Analysis of Genetic Ancestry and Admixture in the Colombian Populations of Chocó and Medellín.

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Conley, Andrew B; Rishishwar, Lavanya; Norris, Emily T; Valderrama-Aguirre, Augusto; Mariño-Ramírez, Leonardo; Medina-Rivas, Miguel A; Jordan, I King

2017-10-05

At least 20% of Colombians identify as having African ancestry, yielding the second largest population of Afro-descendants in Latin America. To date, there have been relatively few studies focused on the genetic ancestry of Afro-Latino populations. We report a comparative analysis of the genetic ancestry of Chocó, a state located on Colombia's Pacific coast with a population that is >80% Afro-Colombian. We compared genome-wide patterns of genetic ancestry and admixture for Chocó to six other admixed American populations, with an emphasis on a Mestizo population from the nearby Colombian city of Medellín. One hundred sample donors from Chocó were genotyped across 610,545 genomic sites and compared with 94 publicly available whole genome sequences from Medellín. At the continental level, Chocó shows mostly African genetic ancestry (76%) with a nearly even split between European (13%) and Native American (11%) fractions, whereas Medellín has primarily European ancestry (75%), followed by Native American (18%) and African (7%). Sample donors from Chocó self-identify as having more African ancestry, and conversely less European and Native American ancestry, than can be genetically inferred, as opposed to what we previously found for Medellín, where individuals tend to overestimate levels of European ancestry. We developed a novel approach for subcontinental ancestry assignment, which allowed us to characterize subcontinental source populations for each of the three distinct continental ancestry fractions separately. Despite the clear differences between Chocó and Medellín at the level of continental ancestry, the two populations show overall patterns of subcontinental ancestry that are highly similar. Their African subcontinental ancestries are only slightly different, with Chocó showing more exclusive shared ancestry with the modern Yoruba (Nigerian) population, and Medellín having relatively more shared ancestry with West African populations in Sierra

Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry.

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Wen, Wanqing; Shu, Xiao-Ou; Guo, Xingyi; Cai, Qiuyin; Long, Jirong; Bolla, Manjeet K; Michailidou, Kyriaki; Dennis, Joe; Wang, Qin; Gao, Yu-Tang; Zheng, Ying; Dunning, Alison M; García-Closas, Montserrat; Brennan, Paul; Chen, Shou-Tung; Choi, Ji-Yeob; Hartman, Mikael; Ito, Hidemi; Lophatananon, Artitaya; Matsuo, Keitaro; Miao, Hui; Muir, Kenneth; Sangrajrang, Suleeporn; Shen, Chen-Yang; Teo, Soo H; Tseng, Chiu-Chen; Wu, Anna H; Yip, Cheng Har; Simard, Jacques; Pharoah, Paul D P; Hall, Per; Kang, Daehee; Xiang, Yongbing; Easton, Douglas F; Zheng, Wei

2016-12-08

Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry. We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk. We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P women in the middle quintile of the PRS, women in the top 1% group had a 2.70-fold elevated risk of breast cancer (95% CI: 2.15-3.40). The risk prediction model with the PRS had an area under the receiver operating characteristic curve of 0.606. The lifetime risk of breast cancer for Shanghai Chinese women in the lowest and highest 1% of the PRS was 1.35% and 10.06%, respectively. Approximately one-half of GWAS-identified breast cancer risk variants can be directly replicated in East Asian women. Collectively, common genetic variants are important predictors for breast cancer risk. Using common genetic variants for breast cancer could help identify women at high risk of breast cancer.

Allelic sequence variations in the hypervariable region of a T-cell receptor β chain: Correlation with restriction fragment length polymorphism in human families and populations

International Nuclear Information System (INIS)

Robinson, M.A.

1989-01-01

Direct sequence analysis of the human T-cell antigen receptor (TCR) V β1 variable gene identified a single base-pair allelic variation (C/G) located within the coding region. This change results in substitution of a histidine (CAC) for a glutamine (CAG) at position 48 of the TCR β chain, a position predicted to be in the TCR antigen binding site. The V β1 polymorphism was found by DNA sequence analysis of V β1 genes from seven unrelated individuals; V β1 genes were amplified by the polymerase chain reaction, the amplified fragments were cloned into M13 phage vectors, and sequences were determined. To determined the inheritance patterns of the V β1 substitution and to test correlation with V β1 restriction fragment length polymorphism detected with Pvu II and Taq I, allele-specific oligonucleotides were constructed and used to characterize amplified DNA samples. Seventy unrelated individuals and six families were tested for both restriction fragment length polymorphism and for the V β1 substitution. The correlation was also tested using amplified, size-selected, Pvu II- and Taq I-digested DNA samples from heterozygotes. Pvu II allele 1 (61/70) and Taq I allele 1 (66/70) were found to be correlated with the substitution giving rise to a histidine at position 48. Because there are exceptions to the correlation, the use of specific probes to characterize allelic forms of TCR variable genes will provide important tools for studies of basic TCR genetics and disease associations

An unusual occurrence of repeated single allele variation on Y-STR locus DYS458

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Pankaj Shrivastava

2016-09-01

Full Text Available Six brothers were accused of gagging and raping a woman. A single male Y-STR profile was obtained from vaginal smear swab and clothes of the victim, which did not match with the DNA profile of the accused brothers. As a reference point, the blood sample of their father (aged 87 years was also analyzed with the same kit. The Y-STR haplotype of all six brothers was found to be the same as that of their father except at locus DYS458. At this locus, while the eldest, second and fourth siblings share allele 18 with their father, a loss of one repeat (allele 17 instead of 18 is observed in the third son while fifth and sixth siblings have allele 19 representing a gain of one repeat. Thus, two changes viz. a gain (twice and loss of one repeat at this locus in one generation is both interesting and unusual.

Allelic Imbalance Is a Prevalent and Tissue-Specific Feature of the Mouse Transcriptome

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Pinter, Stefan F.; Colognori, David; Beliveau, Brian J.; Sadreyev, Ruslan I.; Payer, Bernhard; Yildirim, Eda; Wu, Chao-ting; Lee, Jeannie T.

2015-01-01

In mammals, several classes of monoallelic genes have been identified, including those subject to X-chromosome inactivation (XCI), genomic imprinting, and random monoallelic expression (RMAE). However, the extent to which these epigenetic phenomena are influenced by underlying genetic variation is unknown. Here we perform a systematic classification of allelic imbalance in mouse hybrids derived from reciprocal crosses of divergent strains. We observe that deviation from balanced biallelic expression is common, occurring in ∼20% of the mouse transcriptome in a given tissue. Allelic imbalance attributed to genotypic variation is by far the most prevalent class and typically is tissue-specific. However, some genotype-based imbalance is maintained across tissues and is associated with greater genetic variation, especially in 5′ and 3′ termini of transcripts. We further identify novel random monoallelic and imprinted genes and find that genotype can modify penetrance of parental origin even in the setting of large imprinted regions. Examination of nascent transcripts in single cells from inbred parental strains reveals that genes showing genotype-based imbalance in hybrids can also exhibit monoallelic expression in isogenic backgrounds. This surprising observation may suggest a competition between alleles and/or reflect the combined impact of cis- and trans-acting variation on expression of a given gene. Our findings provide novel insights into gene regulation and may be relevant to human genetic variation and disease. PMID:25858912

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

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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. Copyright © 2016 Elsevier B.V. All rights reserved.

ETHNOPRED: a novel machine learning method for accurate continental and sub-continental ancestry identification and population stratification correction

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2013-01-01

Background Population stratification is a systematic difference in allele frequencies between subpopulations. This can lead to spurious association findings in the case–control genome wide association studies (GWASs) used to identify single nucleotide polymorphisms (SNPs) associated with disease-linked phenotypes. Methods such as self-declared ancestry, ancestry informative markers, genomic control, structured association, and principal component analysis are used to assess and correct population stratification but each has limitations. We provide an alternative technique to address population stratification. Results We propose a novel machine learning method, ETHNOPRED, which uses the genotype and ethnicity data from the HapMap project to learn ensembles of disjoint decision trees, capable of accurately predicting an individual’s continental and sub-continental ancestry. To predict an individual’s continental ancestry, ETHNOPRED produced an ensemble of 3 decision trees involving a total of 10 SNPs, with 10-fold cross validation accuracy of 100% using HapMap II dataset. We extended this model to involve 29 disjoint decision trees over 149 SNPs, and showed that this ensemble has an accuracy of ≥ 99.9%, even if some of those 149 SNP values were missing. On an independent dataset, predominantly of Caucasian origin, our continental classifier showed 96.8% accuracy and improved genomic control’s λ from 1.22 to 1.11. We next used the HapMap III dataset to learn classifiers to distinguish European subpopulations (North-Western vs. Southern), East Asian subpopulations (Chinese vs. Japanese), African subpopulations (Eastern vs. Western), North American subpopulations (European vs. Chinese vs. African vs. Mexican vs. Indian), and Kenyan subpopulations (Luhya vs. Maasai). In these cases, ETHNOPRED produced ensembles of 3, 39, 21, 11, and 25 disjoint decision trees, respectively involving 31, 502, 526, 242 and 271 SNPs, with 10-fold cross validation accuracy of

A rare FANCA gene variation as a breast cancer susceptibility allele in an Iranian population.

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Abbasi, Sakineh; Rasouli, Mina

2017-06-01

Fanconi Anemia (FA) is an autosomal recessive syndrome characterized by congenital abnormalities, progressive bone marrow failure and Fanconi anemia complementation group A (FANCA) is also a potential breast and ovarian cancer susceptibility gene. A novel allele with tandem duplication of 13 base pair sequence in promoter region was identified. To investigate whether the 13 base pair sequence of tandem duplication in promoter region of the FANCA gene is of high penetrance in patients with breast cancer and to determine if the presence of the duplicated allele was associated with an altered risk of breast cancer, the present study screened DNA in blood samples from 304 breast cancer patients and 295 normal individuals as controls. The duplication allele had a frequency of 35.4 and 21.2% in patients with breast cancer and normal controls, respectively. There was a significant increase in the frequency of the duplication allele in patients with familial breast cancer compared with controls (45.1%, P=0.001). Furthermore, the estimated risk of breast cancer in individuals with a homozygote [odds ratio (OR), 4.093; 95% confidence intervals (CI), 1.957‑8.561] or heterozygote duplicated genotype (OR, 3.315; 95% CI, 1.996‑5.506) was higher compared with the corresponding normal homozygote genotype. In conclusion, the present study indicated that the higher the frequency of the duplicated allele, the higher the risk of breast cancer. To the best of our knowledge, the present study is the first to report FANCA gene duplication in patients with breast cancer.

Worldwide Patterns of Ancestry, Divergence, and Admixture in Domesticated Cattle

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Decker, Jared E.; McKay, Stephanie D.; Rolf, Megan M.; Kim, JaeWoo; Molina Alcalá, Antonio; Sonstegard, Tad S.; Hanotte, Olivier; Götherström, Anders; Seabury, Christopher M.; Praharani, Lisa; Babar, Masroor Ellahi; Correia de Almeida Regitano, Luciana; Yildiz, Mehmet Ali; Heaton, Michael P.; Liu, Wan-Sheng; Lei, Chu-Zhao; Reecy, James M.; Saif-Ur-Rehman, Muhammad; Schnabel, Robert D.; Taylor, Jeremy F.

2014-01-01

The domestication and development of cattle has considerably impacted human societies, but the histories of cattle breeds and populations have been poorly understood especially for African, Asian, and American breeds. Using genotypes from 43,043 autosomal single nucleotide polymorphism markers scored in 1,543 animals, we evaluate the population structure of 134 domesticated bovid breeds. Regardless of the analytical method or sample subset, the three major groups of Asian indicine, Eurasian taurine, and African taurine were consistently observed. Patterns of geographic dispersal resulting from co-migration with humans and exportation are recognizable in phylogenetic networks. All analytical methods reveal patterns of hybridization which occurred after divergence. Using 19 breeds, we map the cline of indicine introgression into Africa. We infer that African taurine possess a large portion of wild African auroch ancestry, causing their divergence from Eurasian taurine. We detect exportation patterns in Asia and identify a cline of Eurasian taurine/indicine hybridization in Asia. We also identify the influence of species other than Bos taurus taurus and B. t. indicus in the formation of Asian breeds. We detect the pronounced influence of Shorthorn cattle in the formation of European breeds. Iberian and Italian cattle possess introgression from African taurine. American Criollo cattle originate from Iberia, and not directly from Africa with African ancestry inherited via Iberian ancestors. Indicine introgression into American cattle occurred in the Americas, and not Europe. We argue that cattle migration, movement and trading followed by admixture have been important forces in shaping modern bovine genomic variation. PMID:24675901

Genomic ancestry and education level independently influence abdominal fat distributions in a Brazilian admixed population.

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França, Giovanny Vinícius Araújo de; De Lucia Rolfe, Emanuella; Horta, Bernardo Lessa; Gigante, Denise Petrucci; Yudkin, John S; Ong, Ken K; Victora, Cesar Gomes

2017-01-01

We aimed to identify the independent associations of genomic ancestry and education level with abdominal fat distributions in the 1982 Pelotas birth cohort study, Brazil. In 2,890 participants (1,409 men and 1,481 women), genomic ancestry was assessed using genotype data on 370,539 genome-wide variants to quantify ancestral proportions in each individual. Years of completed education was used to indicate socio-economic position. Visceral fat depth and subcutaneous abdominal fat thickness were measured by ultrasound at age 29-31y; these measures were adjusted for BMI to indicate abdominal fat distributions. Linear regression models were performed, separately by sex. Admixture was observed between European (median proportion 85.3), African (6.6), and Native American (6.3) ancestries, with a strong inverse correlation between the African and European ancestry scores (ρ = -0.93; pabdominal fat distributions in men (both P = 0.001), and inversely associated with subcutaneous abdominal fat distribution in women (p = 0.009). Independent of genomic ancestry, higher education level was associated with lower visceral fat, but higher subcutaneous fat, in both men and women (all pabdominal fat distribution in adults. African ancestry appeared to lower abdominal fat distributions, particularly in men.

Associations between Common Variants in Iron-Related Genes with Haematological Traits in Populations of African Ancestry.

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Gichohi-Wainaina, Wanjiku N; Tanaka, Toshiko; Towers, G Wayne; Verhoef, Hans; Veenemans, Jacobien; Talsma, Elise F; Harryvan, Jan; Boekschoten, Mark V; Feskens, Edith J; Melse-Boonstra, Alida

2016-01-01

Large genome-wide association (GWA) studies of European ancestry individuals have identified multiple genetic variants influencing iron status. Studies on the generalizability of these associations to African ancestry populations have been limited. These studies are important given interethnic differences in iron status and the disproportionate burden of iron deficiency among African ancestry populations. We tested the associations of 20 previously identified iron status-associated single nucleotide polymorphisms (SNPs) in 628 Kenyans, 609 Tanzanians, 608 South Africans and 228 African Americans. In each study, we examined the associations present between 20 SNPs with ferritin and haemoglobin, adjusting for age, sex and CRP levels. In the meta analysis including all 4 African ancestry cohorts, we replicated previously reported associations with lowered haemoglobin concentrations for rs2413450 (β = -0.19, P = 0.02) and rs4820268 (β = -0.16, P = 0.04) in TMPRSS6. An association with increased ferritin concentrations was also confirmed for rs1867504 in TF (β = 1.04, P = ancestry individuals. While there is now evidence for the associations of a number of genetic variants with iron status in both European and African ancestry populations, the considerable lack of concordance highlights the importance of continued ancestry-specific studies to elucidate the genetic underpinnings of iron status in ethnically diverse populations.

The genomic ancestry, landscape genetics and invasion history of introduced mice in New Zealand

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Russell, James C.; King, Carolyn M.

2018-01-01

The house mouse (Mus musculus) provides a fascinating system for studying both the genomic basis of reproductive isolation, and the patterns of human-mediated dispersal. New Zealand has a complex history of mouse invasions, and the living descendants of these invaders have genetic ancestry from all three subspecies, although most are primarily descended from M. m. domesticus. We used the GigaMUGA genotyping array (approximately 135 000 loci) to describe the genomic ancestry of 161 mice, sampled from 34 locations from across New Zealand (and one Australian city—Sydney). Of these, two populations, one in the south of the South Island, and one on Chatham Island, showed complete mitochondrial lineage capture, featuring two different lineages of M. m. castaneus mitochondrial DNA but with only M. m. domesticus nuclear ancestry detectable. Mice in the northern and southern parts of the North Island had small traces (approx. 2–3%) of M. m. castaneus nuclear ancestry, and mice in the upper South Island had approximately 7–8% M. m. musculus nuclear ancestry including some Y-chromosomal ancestry—though no detectable M. m. musculus mitochondrial ancestry. This is the most thorough genomic study of introduced populations of house mice yet conducted, and will have relevance to studies of the isolation mechanisms separating subspecies of mice. PMID:29410804

The genomic ancestry of individuals from different geographical regions of Brazil is more uniform than expected.

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Sérgio D J Pena

2011-02-01

Full Text Available Based on pre-DNA racial/color methodology, clinical and pharmacological trials have traditionally considered the different geographical regions of Brazil as being very heterogeneous. We wished to ascertain how such diversity of regional color categories correlated with ancestry. Using a panel of 40 validated ancestry-informative insertion-deletion DNA polymorphisms we estimated individually the European, African and Amerindian ancestry components of 934 self-categorized White, Brown or Black Brazilians from the four most populous regions of the Country. We unraveled great ancestral diversity between and within the different regions. Especially, color categories in the northern part of Brazil diverged significantly in their ancestry proportions from their counterparts in the southern part of the Country, indicating that diverse regional semantics were being used in the self-classification as White, Brown or Black. To circumvent these regional subjective differences in color perception, we estimated the general ancestry proportions of each of the four regions in a form independent of color considerations. For that, we multiplied the proportions of a given ancestry in a given color category by the official census information about the proportion of that color category in the specific region, to arrive at a "total ancestry" estimate. Once such a calculation was performed, there emerged a much higher level of uniformity than previously expected. In all regions studied, the European ancestry was predominant, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of six million Europeans to Brazil in the 19th and 20th centuries--a phenomenon described and intended as the "whitening of Brazil"--is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. These findings, of both clinical and sociological importance for Brazil

Evaluating genetic ancestry and self-reported ethnicity in the context of carrier screening.

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Shraga, Roman; Yarnall, Sarah; Elango, Sonya; Manoharan, Arun; Rodriguez, Sally Ann; Bristow, Sara L; Kumar, Neha; Niknazar, Mohammad; Hoffman, David; Ghadir, Shahin; Vassena, Rita; Chen, Serena H; Hershlag, Avner; Grifo, Jamie; Puig, Oscar

2017-11-28

Current professional society guidelines recommend genetic carrier screening be offered on the basis of ethnicity, or when using expanded carrier screening panels, they recommend to compute residual risk based on ethnicity. We investigated the reliability of self-reported ethnicity in 9138 subjects referred to carrier screening. Self-reported ethnicity gathered from test requisition forms and during post-test genetic counseling, and genetic ancestry predicted by a statistical model, were compared for concordance. We identified several discrepancies between the two sources of self-reported ethnicity and genetic ancestry. Only 30.3% of individuals who indicated Mediterranean ancestry during consultation self-reported this on requisition forms. Additionally, the proportion of individuals who reported Southeast Asian but were estimated to have a different genetic ancestry was found to depend on the source of self-report. Finally, individuals who reported Latin American demonstrated a high degree of ancestral admixture. As a result, carrier rates and residual risks provided for patient decision-making are impacted if using self-reported ethnicity. Our analysis highlights the unreliability of ethnicity classification based on patient self-reports. We recommend the routine use of pan-ethnic carrier screening panels in reproductive medicine. Furthermore, the use of an ancestry model would allow better estimation of carrier rates and residual risks.

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

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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

Divergent Patterns of Mitochondrial and Nuclear Ancestry Are Associated with the Risk for Preterm Birth.

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Crawford, Nicholas; Prendergast, D'Arcy; Oehlert, John W; Shaw, Gary M; Stevenson, David K; Rappaport, Nadav; Sirota, Marina; Tishkoff, Sarah A; Sondheimer, Neal

2018-03-01

To examine linkages between mitochondrial genetics and preterm birth by assessing the risk for preterm birth associated with the inheritance of nuclear haplotypes that are ancestrally distinct from mitochondrial haplogroup. Genome-wide genotyping studies of cohorts of preterm and term individuals were evaluated. We determined the mitochondrial haplogroup and nuclear ancestry for individuals and developed a scoring for the degree to which mitochondrial ancestry is divergent from nuclear ancestry. Infants with higher degrees of divergent mitochondrial ancestry were at increased risk for preterm birth (0.124 for preterm vs 0.105 for term infants; Pancestry correlated with earlier delivery within the primary study population, but this finding was not replicated in secondary cohorts born preterm. Individuals with divergent patterns of mitochondrial and nuclear ancestry are at increased risk for preterm birth. These findings may in part explain the higher rates of preterm birth in African Americans and in individuals with a matrilineal family history of preterm birth. Copyright © 2017 Elsevier Inc. All rights reserved.

Accuracy of administratively-assigned ancestry for diverse populations in an electronic medical record-linked biobank.

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Jacob B Hall

Full Text Available Recently, the development of biobanks linked to electronic medical records has presented new opportunities for genetic and epidemiological research. Studies based on these resources, however, present unique challenges, including the accurate assignment of individual-level population ancestry. In this work we examine the accuracy of administratively-assigned race in diverse populations by comparing assigned races to genetically-defined ancestry estimates. Using 220 ancestry informative markers, we generated principal components for patients in our dataset, which were used to cluster patients into groups based on genetic ancestry. Consistent with other studies, we find a strong overall agreement (Kappa  = 0.872 between genetic ancestry and assigned race, with higher rates of agreement for African-descent and European-descent assignments, and reduced agreement for Hispanic, East Asian-descent, and South Asian-descent assignments. These results suggest caution when selecting study samples of non-African and non-European backgrounds when administratively-assigned race from biobanks is used.

Association between common variation at the FTO locus and changes in body mass index from infancy to late childhood: the complex nature of genetic association through growth and development.

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Ulla Sovio

2011-02-01

Full Text Available An age-dependent association between variation at the FTO locus and BMI in children has been suggested. We meta-analyzed associations between the FTO locus (rs9939609 and BMI in samples, aged from early infancy to 13 years, from 8 cohorts of European ancestry. We found a positive association between additional minor (A alleles and BMI from 5.5 years onwards, but an inverse association below age 2.5 years. Modelling median BMI curves for each genotype using the LMS method, we found that carriers of minor alleles showed lower BMI in infancy, earlier adiposity rebound (AR, and higher BMI later in childhood. Differences by allele were consistent with two independent processes: earlier AR equivalent to accelerating developmental age by 2.37% (95% CI 1.87, 2.87, p = 10(-20 per A allele and a positive age by genotype interaction such that BMI increased faster with age (p = 10(-23. We also fitted a linear mixed effects model to relate genotype to the BMI curve inflection points adiposity peak (AP in infancy and AR. Carriage of two minor alleles at rs9939609 was associated with lower BMI at AP (-0.40% (95% CI: -0.74, -0.06, p = 0.02, higher BMI at AR (0.93% (95% CI: 0.22, 1.64, p = 0.01, and earlier AR (-4.72% (-5.81, -3.63, p = 10(-17, supporting cross-sectional results. Overall, we confirm the expected association between variation at rs9939609 and BMI in childhood, but only after an inverse association between the same variant and BMI in infancy. Patterns are consistent with a shift on the developmental scale, which is reflected in association with the timing of AR rather than just a global increase in BMI. Results provide important information about longitudinal gene effects and about the role of FTO in adiposity. The associated shifts in developmental timing have clinical importance with respect to known relationships between AR and both later-life BMI and metabolic disease risk.

Plasminogen alleles influence susceptibility to invasive aspergillosis.

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Aimee K Zaas

2008-06-01

Full Text Available Invasive aspergillosis (IA is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855 correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn was also identified in the human homolog (PLG; Gene ID 5340. An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection.

Genetic Ancestry and Asthma and Rhinitis Occurrence in Hispanic Children: Findings from the Southern California Children's Health Study.

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Muhammad T Salam

Full Text Available Asthma and rhinitis are common childhood health conditions. Being an understudied and rapidly growing population in the US, Hispanic children have a varying risk for these conditions that may result from sociocultural (including acculturative factors, exposure and genetic diversities. Hispanic populations have varying contributions from European, Amerindian and African ancestries. While previous literature separately reported associations between genetic ancestry and acculturation factors with asthma, whether Amerindian ancestry and acculturative factors have independent associations with development of early-life asthma and rhinitis in Hispanic children remains unknown. We hypothesized that genetic ancestry is an important determinant of early-life asthma and rhinitis occurrence in Hispanic children independent of sociodemographic, acculturation and environmental factors.Subjects were Hispanic children (5-7 years who participated in the southern California Children's Health Study. Data from birth certificates and questionnaire provided information on acculturation, sociodemographic and environmental factors. Genetic ancestries (Amerindian, European, African and Asian were estimated based on 233 ancestry informative markers. Asthma was defined by parental report of doctor-diagnosed asthma. Rhinitis was defined by parental report of a history of chronic sneezing or runny or blocked nose without a cold or flu. Sample sizes were 1,719 and 1,788 for investigating the role of genetic ancestry on asthma and rhinitis, respectively.Children had major contributions from Amerindian and European ancestries. After accounting for potential confounders, per 25% increase in Amerindian ancestry was associated with 17.6% (95% confidence interval [CI]: 0.74-0.99 and 13.6% (95% CI: 0.79-0.98 lower odds of asthma and rhinitis, respectively. Acculturation was not associated with either outcome.Earlier work documented that Hispanic children with significant

Evaluation of the Precision ID Ancestry Panel for crime case work

DEFF Research Database (Denmark)

Pereira, Vania; Mogensen, Helle S; Børsting, Claus

2017-01-01

The application of massive parallel sequencing (MPS) methodologies in forensic genetics is promising and it is gradually being implemented in forensic genetic case work. One of the major advantages of these technologies is that several traditional electrophoresis assays can be combined into one...... single MPS assay. This reduces both the amount of sample used and the time of the investigations. This study assessed the utility of the Precision ID Ancestry Panel (Thermo Fisher Scientific, Waltham, USA) in forensic genetics. This assay was developed for the Ion Torrent PGM™ System and genotypes 165...... ancestry informative SNPs. The performance of the assay and the accompanying software solution for ancestry inference was assessed by typing 142 Danes and 98 Somalis. Locus balance, heterozygote balance, and noise levels were calculated and future analysis criteria for crime case work were estimated...

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

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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

Degree of European Genetic Ancestry is Associated with Serum Vitamin D Levelsin African Americans.

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Haddad, Stephen A; Ruiz-Narváez, Edward A; Cozier, Yvette C; Gerlovin, Hanna; Rosenberg, Lynn; Palmer, Julie R

2018-01-30

Circulating levels of vitamin D are generally lower in African Americans compared to U.S. whites, and one prior analysis in a small number of African Americans suggested that, within this population, vitamin D levels may be related to the degree of genetic admixture. We assessed the association of percent European ancestry with serum vitamin D levels in 2183 African American women from the Black Women's Health Study in 2013-2015, whose DNA had been genotyped for ancestry informative markers. ADMIXMAP software was used to estimate percent European versus African ancestry in each individual. In linear regression analyses with adjustment for genotype batch, age, body mass index, supplemental vitamin D use, UVB flux in state of residence, and season of blood draw, each 10% increase in European ancestry was associated with a 0.672 ng/mL increase in serum vitamin D concentration (95% confidence interval 0.173, 1.170). The association was statistically significant only among women who were not taking vitamin D supplements (beta coefficient for 10% increase in European ancestry 0.855, 95% confidence interval 0.139, 1.571). Among African Americans, use of vitamin D supplementation may help to reduce vitamin D deficiency due to genetic ancestry. © The Author(s) 2018. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Associations among ancestry, geography and breast cancer incidence, mortality, and survival in Trinidad and Tobago.

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Warner, Wayne A; Morrison, Robert L; Lee, Tammy Y; Williams, Tanisha M; Ramnarine, Shelina; Roach, Veronica; Slovacek, Simeon; Maharaj, Ravi; Bascombe, Nigel; Bondy, Melissa L; Ellis, Matthew J; Toriola, Adetunji T; Roach, Allana; Llanos, Adana A M

2015-11-01

Breast cancer (BC) is the most common newly diagnosed cancer among women in Trinidad and Tobago (TT) and BC mortality rates are among the highest in the world. Globally, racial/ethnic trends in BC incidence, mortality and survival have been reported. However, such investigations have not been conducted in TT, which has been noted for its rich diversity. In this study, we investigated associations among ancestry, geography and BC incidence, mortality and survival in TT. Data on 3767 incident BC cases, reported to the National Cancer Registry of TT, from 1995 to 2007, were analyzed in this study. Women of African ancestry had significantly higher BC incidence and mortality rates ( 66.96; 30.82 per 100,000) compared to women of East Indian ( 41.04, MORTALITY: 14.19 per 100,000) or mixed ancestry ( 36.72, MORTALITY: 13.80 per 100,000). Geographically, women residing in the North West Regional Health Authority (RHA) catchment area followed by the North Central RHA exhibited the highest incidence and mortality rates. Notable ancestral differences in survival were also observed. Women of East Indian and mixed ancestry experienced significantly longer survival than those of African ancestry. Differences in survival by geography were not observed. In TT, ancestry and geographical residence seem to be strong predictors of BC incidence and mortality rates. Additionally, disparities in survival by ancestry were found. These data should be considered in the design and implementation of strategies to reduce BC incidence and mortality rates in TT. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Tracing the genomic ancestry of Peruvians reveals a major legacy of pre-Columbian ancestors.

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Sandoval, Jose R; Salazar-Granara, Alberto; Acosta, Oscar; Castillo-Herrera, Wilder; Fujita, Ricardo; Pena, Sergio D J; Santos, Fabricio R

2013-09-01

In order to investigate the underlying genetic structure and genomic ancestry proportions of Peruvian subpopulations, we analyzed 551 human samples of 25 localities from the Andean, Amazonian, and Coastal regions of Peru with a set of 40 ancestry informative insertion-deletion polymorphisms. Using genotypes of reference populations from different continents for comparison, our analysis indicated that populations from all 25 Peruvian locations had predominantly Amerindian genetic ancestry. Among populations from the Titicaca Lake islands of Taquile, Amantani, Anapia, and Uros, and the Yanque locality from the southern Peruvian Andes, there was no significant proportion of non-autochthonous genomes, indicating that their genetic background is effectively derived from the first settlers of South America. However, the Andean populations from San Marcos, Cajamarca, Characato and Chogo, and coastal populations from Lambayeque and Lima displayed a low but significant European ancestry proportion. Furthermore, Amazonian localities of Pucallpa, Lamas, Chachapoyas, and Andean localities of Ayacucho and Huancayo displayed intermediate levels of non-autochthonous ancestry, mostly from Europe. These results are in close agreement with the documented history of post-Columbian immigrations in Peru and with several reports suggesting a larger effective size of indigenous inhabitants during the formation of the current country's population.

Allelic variation at the rpv1 locus controls partial resistance to Plum pox virus infection in Arabidopsis thaliana.

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Poque, S; Pagny, G; Ouibrahim, L; Chague, A; Eyquard, J-P; Caballero, M; Candresse, T; Caranta, C; Mariette, S; Decroocq, V

2015-06-25

Sharka is caused by Plum pox virus (PPV) in stone fruit trees. In orchards, the virus is transmitted by aphids and by grafting. In Arabidopsis, PPV is transferred by mechanical inoculation, by biolistics and by agroinoculation with infectious cDNA clones. Partial resistance to PPV has been observed in the Cvi-1 and Col-0 Arabidopsis accessions and is characterized by a tendency to escape systemic infection. Indeed, only one third of the plants are infected following inoculation, in comparison with the susceptible Ler accession. Genetic analysis showed this partial resistance to be monogenic or digenic depending on the allelic configuration and recessive. It is detected when inoculating mechanically but is overcome when using biolistic or agroinoculation. A genome-wide association analysis was performed using multiparental lines and 147 Arabidopsis accessions. It identified a major genomic region, rpv1. Fine mapping led to the positioning of rpv1 to a 200 kb interval on the long arm of chromosome 1. A candidate gene approach identified the chloroplast phosphoglycerate kinase (cPGK2) as a potential gene underlying the resistance. A virus-induced gene silencing strategy was used to knock-down cPGK2 expression, resulting in drastically reduced PPV accumulation. These results indicate that rpv1 resistance to PPV carried by the Cvi-1 and Col-0 accessions is linked to allelic variations at the Arabidopsis cPGK2 locus, leading to incomplete, compatible interaction with the virus.

African ancestry is associated with facial melasma in women: a cross-sectional study.

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D'Elia, Maria Paula Barbieri; Brandão, Marcela Calixto; de Andrade Ramos, Bruna Ribeiro; da Silva, Márcia Guimarães; Miot, Luciane Donida Bartoli; Dos Santos, Sidney Emanuel Batista; Miot, Hélio Amante

2017-02-17

Melasma is a chronic acquired focal hypermelanosis affecting photoexposed areas, especially for women during fertile age. Several factors contribute to its development: sun exposure, sex steroids, medicines, and family history. Melanic pigmentation pathway discloses several SNPs in different populations. Here, we evaluated the association between genetic ancestry and facial melasma. A cross-sectional study involving women with melasma and an age-matched control group from outpatients at FMB-Unesp, Botucatu-SP, Brazil was performed. DNA was extracted from oral mucosa swabs and ancestry determined by studying 61 INDELs. The genetic ancestry components were adjusted by other known risk factors by multiple logistic regression. We evaluated 119 women with facial melasma and 119 controls. Mean age was 39 ± 9 years. Mean age at beginning of disease was 27 ± 8 years. Pregnancy (40%), sun exposure (37%), and hormonal oral contraception (22%) were the most frequently reported melasma triggers. All subjects presented admixed ancestry, African and European genetic contributions were significantly different between cases and controls (respectively 10% vs 6%; 77% vs 82%; p ancestry (OR = 1.04; 95% CI 1.01 to 1.07), first generation family history (OR = 3.04; 95% CI 1.56 to 5.94), low education level (OR = 4.04; 95% CI 1.56 to 5.94), and use of antidepressants by individuals with affected family members (OR = 6.15; 95% CI 1.13 to 33.37) were associated with melasma, independently of other known risk factors. Facial melasma was independently associated with African ancestry in a highly admixed population.

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

International Nuclear Information System (INIS)

Zapparoli, Giada V; Jorissen, Robert N; Hewitt, Chelsee A; McBean, Michelle; Westerman, David A; Dobrovic, Alexander

2013-01-01

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

Genetic variation in alcohol metabolizing enzymes among Inuit and its relation to drinking patterns

DEFF Research Database (Denmark)

Bjerregaard, Peter; Mikkelsen, Stine Schou; Becker, Ulrik

2014-01-01

BACKGROUND: Variation in genes involved in alcohol metabolism is associated with drinking patterns worldwide. We compared variation in these genes among the Inuit with published results from the general population of Denmark and, due to the Asian ancestry of the Inuit, with Han Chinese. We analyzed...

Use of the LUS in sequence allele designations to facilitate probabilistic genotyping of NGS-based STR typing results.

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Just, Rebecca S; Irwin, Jodi A

2018-05-01

Some of the expected advantages of next generation sequencing (NGS) for short tandem repeat (STR) typing include enhanced mixture detection and genotype resolution via sequence variation among non-homologous alleles of the same length. However, at the same time that NGS methods for forensic DNA typing have advanced in recent years, many caseworking laboratories have implemented or are transitioning to probabilistic genotyping to assist the interpretation of complex autosomal STR typing results. Current probabilistic software programs are designed for length-based data, and were not intended to accommodate sequence strings as the product input. Yet to leverage the benefits of NGS for enhanced genotyping and mixture deconvolution, the sequence variation among same-length products must be utilized in some form. Here, we propose use of the longest uninterrupted stretch (LUS) in allele designations as a simple method to represent sequence variation within the STR repeat regions and facilitate - in the nearterm - probabilistic interpretation of NGS-based typing results. An examination of published population data indicated that a reference LUS region is straightforward to define for most autosomal STR loci, and that using repeat unit plus LUS length as the allele designator can represent greater than 80% of the alleles detected by sequencing. A proof of concept study performed using a freely available probabilistic software demonstrated that the LUS length can be used in allele designations when a program does not require alleles to be integers, and that utilizing sequence information improves interpretation of both single-source and mixed contributor STR typing results as compared to using repeat unit information alone. The LUS concept for allele designation maintains the repeat-based allele nomenclature that will permit backward compatibility to extant STR databases, and the LUS lengths themselves will be concordant regardless of the NGS assay or analysis tools

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.

Extensive Variation in Chromatin States Across Humans

KAUST Repository

Kasowski, M.; Kyriazopoulou-Panagiotopoulou, S.; Grubert, F.; Zaugg, J. B.; Kundaje, A.; Liu, Y.; Boyle, A. P.; Zhang, Q. C.; Zakharia, F.; Spacek, D. V.; Li, J.; Xie, D.; Olarerin-George, A.; Steinmetz, L. M.; Hogenesch, J. B.; Kellis, M.; Batzoglou, S.; Snyder, M.

2013-01-01

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.

Genome-wide linkage scan for primary open angle glaucoma: influences of ancestry and age at diagnosis.

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Kristy R Crooks

Full Text Available Primary open-angle glaucoma (POAG is the most common form of glaucoma and one of the leading causes of vision loss worldwide. The genetic etiology of POAG is complex and poorly understood. The purpose of this work is to identify genomic regions of interest linked to POAG. This study is the largest genetic linkage study of POAG performed to date: genomic DNA samples from 786 subjects (538 Caucasian ancestry, 248 African ancestry were genotyped using either the Illumina GoldenGate Linkage 4 Panel or the Illumina Infinium Human Linkage-12 Panel. A total of 5233 SNPs was analyzed in 134 multiplex POAG families (89 Caucasian ancestry, 45 African ancestry. Parametric and non-parametric linkage analyses were performed on the overall dataset and within race-specific datasets (Caucasian ancestry and African ancestry. Ordered subset analysis was used to stratify the data on the basis of age of glaucoma diagnosis. Novel linkage regions were identified on chromosomes 1 and 20, and two previously described loci-GLC1D on chromosome 8 and GLC1I on chromosome 15--were replicated. These data will prove valuable in the context of interpreting results from genome-wide association studies for POAG.

Ancestry Analysis in the 11-M Madrid Bomb Attack Investigation

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

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 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 results

Genetic variation in alcohol metabolizing enzymes among Inuit and its relation to drinking patterns.

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Bjerregaard, Peter; Mikkelsen, Stine Schou; Becker, Ulrik; Hansen, Torben; Tolstrup, Janne S

2014-11-01

Variation in genes involved in alcohol metabolism is associated with drinking patterns worldwide. We compared variation in these genes among the Inuit with published results from the general population of Denmark and, due to the Asian ancestry of the Inuit, with Han Chinese. We analyzed the association between gene variations and drinking patterns among the Inuit. We genotyped 4162 Inuit participants from two population health surveys. Information on drinking patterns was available for 3560. Seven single nucleotide polymorphisms (SNPs) were examined: ADH1B arg48his, ADH1C ile350val, ADH1C arg272gln, ALDH2 glu504lys, ALDH2 5'-UTR A-357G, ALDH1B1 ala86val and ALDH1B1 arg107leu. The allele distribution differed significantly between Inuit and the general population of Denmark. A protective effect on heavy drinking was found for the TT genotype of the ALDH1B1 arg107leu SNP (OR=0.59; 95% CI 0.37-0.92), present in 3% of pure Inuit and 37% of Danes. The ADH1C GG genotype was associated with heavy drinking and a positive CAGE test (OR 1.34; 95% CI 1.05-1.72). It was present in 27% of Inuit and 18% of Danes. The Asian genotype pattern with a high frequency of the ADH1B A allele and an ALDH2 gene coding for an inactive enzyme was not present in Greenland. ADH1C and ALDH1B1 arg107leu SNPs play a role in the shaping of drinking patterns among the Inuit in Greenland. A low frequency of the ALDH1B1 arg107leu TT genotype compared with the general population in Denmark deserves further study. This genotype was protective of heavy drinking among the Inuit. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Race/ethnicity, genetic ancestry, and breast cancer-related lymphedema in the Pathways Study.

Science.gov (United States)

Kwan, Marilyn L; Yao, Song; Lee, Valerie S; Roh, Janise M; Zhu, Qianqian; Ergas, Isaac J; Liu, Qian; Zhang, Yali; Kutner, Susan E; Quesenberry, Charles P; Ambrosone, Christine B; Kushi, Lawrence H

2016-08-01

Breast cancer-related lymphedema (BCRL) is a serious chronic condition after breast cancer (BC) surgery and treatment. It is unclear if BCRL risk varies by race/ethnicity. In a multiethnic prospective cohort study of 2953 BC patients, we examined the association of self-reported BCRL status with self-reported race/ethnicity and estimated genetic ancestry. Hazard ratios (HR) and 95 % confidence intervals (CI) were calculated by multivariable Cox proportional hazards models, with follow-up starting 6 months post-BC diagnosis. Estimates were further stratified by body mass index (BMI). By 48 months of follow-up, 342 (11.6 %) women reported having BCRL. Younger age at BC diagnosis, higher BMI at baseline, and lower physical activity were associated with greater BCRL risk. African American (AA) women had a 2-fold increased risk of BCRL compared with White women (HR = 2.04; 95 % CI 1.35-3.08). African genetic ancestry was also associated with an increased risk (HR = 2.50; 95 % CI 1.43, 4.36). Both risks were attenuated but remained elevated after adjusting for known risk factors and became more pronounced when restricted to the nonobese women (adjusted HR = 2.31 for AA and HR = 3.70 for African ancestry, both p ancestry data, with a potential ancestry-obesity interaction.

African Ancestry Influences CCR5 –2459G>A Genotype-Associated Virologic Success of Highly Active Antiretroviral Therapy

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Cheruvu, Vinay K.; Igo, Robert P.; Jurevic, Richard J.; Serre, David; Zimmerman, Peter A.; Rodriguez, Benigno; Mehlotra, Rajeev K.

2014-01-01

Introduction In a North American, HIV-positive, highly active antiretroviral therapy (HAART)-treated, adherent cohort of self-identified white and black patients, we previously observed that chemokine (C-C motif) receptor 5 (CCR5) –2459G>A genotype had a strong association with time to achieve virologic success (TVLS) in black but not in white patients. Methods Using 128 genome-wide ancestry informative markers, we performed a quantitative assessment of ancestry in these patients (n = 310) to determine (1) whether CCR5 –2459G>A genotype is still associated with TVLS of HAART when ancestry, not self-identified race, is considered and (2) whether this association is influenced by varying African ancestry. Results We found that the interaction between CCR5 –2459G>A genotype and African ancestry (≤0.125 vs. ≥0.425 and A genotype and TVLS was stronger in patients with African ancestry ≥0.71 than in patients with African ancestry ≥0.452, in both Kaplan-Meier (log-rank P = 0.039 and 0.057, respectively, for AA, GA, and GG) and Cox proportional hazards regression (relative hazard for GG compared with AA 2.59 [95% CI, 1.27–5.22; P = 0.01] and 2.26 [95% CI, 1.18–4.32; P = 0.01], respectively) analyses. Conclusions We observed that the association between CCR5 –2459G>A genotype and TVLS of HAART increased with stronger African ancestry. Understanding the genomic mechanisms by which African ancestry influences this association is critical, and requires further studies. PMID:24714069

Allele-specific gene expression in a wild nonhuman primate population

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Tung, J.; Akinyi, M. Y.; Mutura, S.; Altmann, J.; Wray, G. A.; Alberts, S. C.

2015-01-01

Natural populations hold enormous potential for evolutionary genetic studies, especially when phenotypic, genetic and environmental data are all available on the same individuals. However, untangling the genotype-phenotype relationship in natural populations remains a major challenge. Here, we describe results of an investigation of one class of phenotype, allele-specific gene expression (ASGE), in the well-studied natural population of baboons of the Amboseli basin, Kenya. ASGE measurements identify cases in which one allele of a gene is overexpressed relative to the alternative allele of the same gene, within individuals, thus providing a control for background genetic and environmental effects. Here, we characterize the incidence of ASGE in the Amboseli baboon population, focusing on the genetic and environmental contributions to ASGE in a set of eleven genes involved in immunity and defence. Within this set, we identify evidence for common ASGE in four genes. We also present examples of two relationships between cis-regulatory genetic variants and the ASGE phenotype. Finally, we identify one case in which this relationship is influenced by a novel gene-environment interaction. Specifically, the dominance rank of an individual’s mother during its early life (an aspect of that individual’s social environment) influences the expression of the gene CCL5 via an interaction with cis-regulatory genetic variation. These results illustrate how environmental and ecological data can be integrated into evolutionary genetic studies of functional variation in natural populations. They also highlight the potential importance of early life environmental variation in shaping the genetic architecture of complex traits in wild mammals. PMID:21226779

Delimiting Allelic Imbalance of TYMS by Allele-Specific Analysis.

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Balboa-Beltrán, Emilia; Cruz, Raquel; Carracedo, Angel; Barros, Francisco

2015-07-01

Allelic imbalance of thymidylate synthase (TYMS) is attributed to polymorphisms in the 5'- and 3'-untranslated region (UTR). These polymorphisms have been related to the risk of suffering different cancers, for example leukemia, breast or gastric cancer, and response to different drugs, among which are methotrexate glutamates, stavudine, and specifically 5-fluorouracil (5-FU), as TYMS is its direct target. A vast literature has been published in relation to 5-FU, even suggesting the sole use of these polymorphisms to effectively manage 5-FU dosage. Estimates of the extent to which these polymorphisms influence in TYMS expression have in the past been based on functional analysis by luciferase assays and quantification of TYMS mRNA, but both these studies, as the association studies with cancer risk or with toxicity or response to 5-FU, are very contradictory. Regarding functional assays, the artificial genetic environment created in luciferase assay and the problems derived from quantitative polymerase chain reactions (qPCRs), for example the use of a reference gene, may have distorted the results. To avoid these sources of interference, we have analyzed the allelic imbalance of TYMS by allelic-specific analysis in peripheral blood mononuclear cells (PBMCs) from patients.Allelic imbalance in PBMCs, taken from 40 patients with suspected myeloproliferative haematological diseases, was determined by fluorescent fragment analysis (for the 3'-UTR polymorphism), Sanger sequencing and allelic-specific qPCR in multiplex (for the 5'-UTR polymorphisms).For neither the 3'- nor the 5'-UTR polymorphisms did the observed allelic imbalance exceed 1.5 fold. None of the TYMS polymorphisms is statistically associated with allelic imbalance.The results acquired allow us to deny the previously established assertion of an influence of 2 to 4 fold of the rs45445694 and rs2853542 polymorphisms in the expression of TYMS and narrow its allelic imbalance to 1.5 fold, in our population

RFMix: A Discriminative Modeling Approach for Rapid and Robust Local-Ancestry Inference

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Maples, Brian K.; Gravel, Simon; Kenny, Eimear E.; Bustamante, Carlos D.

2013-01-01

Local-ancestry inference is an important step in the genetic analysis of fully sequenced human genomes. Current methods can only detect continental-level ancestry (i.e., European versus African versus Asian) accurately even when using millions of markers. Here, we present RFMix, a powerful discriminative modeling approach that is faster (∼30×) and more accurate than existing methods. We accomplish this by using a conditional random field parameterized by random forests trained on reference panels. RFMix is capable of learning from the admixed samples themselves to boost performance and autocorrect phasing errors. RFMix shows high sensitivity and specificity in simulated Hispanics/Latinos and African Americans and admixed Europeans, Africans, and Asians. Finally, we demonstrate that African Americans in HapMap contain modest (but nonzero) levels of Native American ancestry (∼0.4%). PMID:23910464

Accurate Local-Ancestry Inference in Exome-Sequenced Admixed Individuals via Off-Target Sequence Reads

Science.gov (United States)

Hu, Youna; Willer, Cristen; Zhan, Xiaowei; Kang, Hyun Min; Abecasis, Gonçalo R.

2013-01-01

Estimates of the ancestry of specific chromosomal regions in admixed individuals are useful for studies of human evolutionary history and for genetic association studies. Previously, this ancestry inference relied on high-quality genotypes from genome-wide association study (GWAS) arrays. These high-quality genotypes are not always available when samples are exome sequenced, and exome sequencing is the strategy of choice for many ongoing genetic studies. Here we show that off-target reads generated during exome-sequencing experiments can be combined with on-target reads to accurately estimate the ancestry of each chromosomal segment in an admixed individual. To reconstruct local ancestry, our method SEQMIX models aligned bases directly instead of relying on hard genotype calls. We evaluate the accuracy of our method through simulations and analysis of samples sequenced by the 1000 Genomes Project and the NHLBI Grand Opportunity Exome Sequencing Project. In African Americans, we show that local-ancestry estimates derived by our method are very similar to those derived with Illumina’s Omni 2.5M genotyping array and much improved in relation to estimates that use only exome genotypes and ignore off-target sequencing reads. Software implementing this method, SEQMIX, can be applied to analysis of human population history or used for genetic association studies in admixed individuals. PMID:24210252

Rare Mutations of Peroxisome Proliferator-Activated Receptor Gamma: Frequencies and Relationship with Insulin Resistance and Diabetes Risk in the Mixed Ancestry Population from South Africa

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Z. Vergotine

2014-01-01

Full Text Available Background. Genetic variants in the nuclear transcription receptor, PPARG, are associated with cardiometabolic traits, but reports remain conflicting. We determined the frequency and the clinical relevance of PPARG SNPs in an African mixed ancestry population. Methods. In a cross-sectional study, 820 participants were genotyped for rs1800571, rs72551362, rs72551363, rs72551364, and rs3856806, using allele-specific TaqMan technology. The homeostatic model assessment of insulin (HOMA-IR, β-cells function (HOMA-B%, fasting insulin resistance index (FIRI, and the quantitative insulin-sensitivity check index (QUICKI were calculated. Results. No sequence variants were found except for the rs3856806. The frequency of the PPARG-His447His variant was 23.8% in the overall population group, with no difference by diabetes status (P=0.215. The His447His allele T was associated with none of the markers of insulin resistance overall and by diabetes status. In models adjusted for 2-hour insulin, the T allele was associated with lower prevalent diabetes risk (odds ratio 0.56 (95% CI 0.31–0.95. Conclusion. Our study confirms the almost zero occurrences of known rare PPARG SNPs and has shown for the first time in an African population that one of the common SNPs, His447His, may be protective against type 2 diabetes.

Palate Shape and Depth: A Shape-Matching and Machine Learning Method for Estimating Ancestry from Human Skeletal Remains.

Science.gov (United States)

Maier, Christopher A; Zhang, Kang; Manhein, Mary H; Li, Xin

2015-09-01

In the past, assessing ancestry relied on the naked eye and observer experience; however, replicability has become an important aspect of such analysis through the application of metric techniques. This study examines palate shape and assesses ancestry quantitatively using a 3D digitizer and shape-matching and machine learning methods. Palate curves and depths were recorded, processed, and tested for 376 individuals. Palate shape was an accurate indicator of ancestry in 58% of cases. Cluster analysis revealed that the parabolic, hyperbolic, and elliptical shapes are discrete from one another. Preliminary results indicate that palate depth in Hispanic individuals is greatest. Palate shape appears to be a useful indicator of ancestry, particularly when assessed by a computer. However, these data suggest that palate shape is not useful for assessing ancestry in Hispanic individuals. Although ancestry may be determined from palate shape, the use of multiple features is recommended and more reliable. © 2015 American Academy of Forensic Sciences.

Gun Violence, African Ancestry, and Asthma: A Case-Control Study in Puerto Rican Children.

Science.gov (United States)

Rosas-Salazar, Christian; Han, Yueh-Ying; Brehm, John M; Forno, Erick; Acosta-Pérez, Edna; Cloutier, Michelle M; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C

2016-06-01

Exposure to gun violence and African ancestry have been separately associated with increased risk of asthma in Puerto Rican children. The objective of this study was to examine whether African ancestry and gun violence interact on asthma and total IgE in school-aged Puerto Rican children. This is a case-control study of 747 Puerto Rican children aged 9 to 14 years living in San Juan, Puerto Rico (n = 472), and Hartford, Connecticut (n = 275). Exposure to gun violence was defined as the child's report of hearing gunshots more than once, and the percentage of African ancestry was estimated using genome-wide genotypic data. Asthma was defined as parental report of physician-diagnosed asthma and wheeze in the previous year. Serum total IgE (IU/mL) was measured in study participants. Multivariate logistic and linear regressions were used for the analysis of asthma and total IgE, respectively. In multivariate analyses, there was a significant interaction between exposure to gun violence and African ancestry on asthma (P = .001) and serum total IgE (P = .04). Among children exposed to gun violence, each quartile increase in the percentage of African ancestry was associated with approximately 45% higher odds of asthma (95% CI, 1.15-1.84; P = .002) and an approximately 19% increment in total IgE (95% , 0.60-40.65, P = .04). In contrast, there was no significant association between African ancestry and asthma or total IgE in children not exposed to gun violence. Our results suggest that exposure to gun violence modifies the estimated effect of African ancestry on asthma and atopy in Puerto Rican children. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Genomic ancestry, self-reported "color" and quantitative measures of skin pigmentation in Brazilian admixed siblings.

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Tailce K M Leite

Full Text Available A current concern in genetic epidemiology studies in admixed populations is that population stratification can lead to spurious results. The Brazilian census classifies individuals according to self-reported "color", but several studies have demonstrated that stratifying according to "color" is not a useful strategy to control for population structure, due to the dissociation between self-reported "color" and genomic ancestry. We report the results of a study in a group of Brazilian siblings in which we measured skin pigmentation using a reflectometer, and estimated genomic ancestry using 21 Ancestry Informative Markers (AIMs. Self-reported "color", according to the Brazilian census, was also available for each participant. This made it possible to evaluate the relationship between self-reported "color" and skin pigmentation, self-reported "color" and genomic ancestry, and skin pigmentation and genomic ancestry. We observed that, although there were significant differences between the three "color" groups in genomic ancestry and skin pigmentation, there was considerable dispersion within each group and substantial overlap between groups. We also saw that there was no good agreement between the "color" categories reported by each member of the sibling pair: 30 out of 86 sibling pairs reported different "color", and in some cases, the sibling reporting the darker "color" category had lighter skin pigmentation. Socioeconomic status was significantly associated with self-reported "color" and genomic ancestry in this sample. This and other studies show that subjective classifications based on self-reported "color", such as the one that is used in the Brazilian census, are inadequate to describe the population structure present in recently admixed populations. Finally, we observed that one of the AIMs included in the panel (rs1426654, which is located in the known pigmentation gene SLC24A5, was strongly associated with skin pigmentation in this sample.

Genomic ancestry, self-reported "color" and quantitative measures of skin pigmentation in Brazilian admixed siblings.

Science.gov (United States)

Leite, Tailce K M; Fonseca, Rômulo M C; de França, Nanci M; Parra, Esteban J; Pereira, Rinaldo W

2011-01-01

A current concern in genetic epidemiology studies in admixed populations is that population stratification can lead to spurious results. The Brazilian census classifies individuals according to self-reported "color", but several studies have demonstrated that stratifying according to "color" is not a useful strategy to control for population structure, due to the dissociation between self-reported "color" and genomic ancestry. We report the results of a study in a group of Brazilian siblings in which we measured skin pigmentation using a reflectometer, and estimated genomic ancestry using 21 Ancestry Informative Markers (AIMs). Self-reported "color", according to the Brazilian census, was also available for each participant. This made it possible to evaluate the relationship between self-reported "color" and skin pigmentation, self-reported "color" and genomic ancestry, and skin pigmentation and genomic ancestry. We observed that, although there were significant differences between the three "color" groups in genomic ancestry and skin pigmentation, there was considerable dispersion within each group and substantial overlap between groups. We also saw that there was no good agreement between the "color" categories reported by each member of the sibling pair: 30 out of 86 sibling pairs reported different "color", and in some cases, the sibling reporting the darker "color" category had lighter skin pigmentation. Socioeconomic status was significantly associated with self-reported "color" and genomic ancestry in this sample. This and other studies show that subjective classifications based on self-reported "color", such as the one that is used in the Brazilian census, are inadequate to describe the population structure present in recently admixed populations. Finally, we observed that one of the AIMs included in the panel (rs1426654), which is located in the known pigmentation gene SLC24A5, was strongly associated with skin pigmentation in this sample.

Analysis of the genetic ancestry of patients with oral clefts from South American admixed populations.

Science.gov (United States)

Vieira-Machado, Camilla D; de Carvalho, Flavia M; Santana da Silva, Luiz C; Dos Santos, Sidney E; Martins, Claudia; Poletta, Fernando A; Mereb, Juan C; Vieira, Alexandre R; Castilla, Eduardo E; Orioli, Iêda M

2016-08-01

Increased susceptibility to cleft lip, with or without cleft palate (CL±P) has been observed in South America, as related to Amerindian ancestry, using epidemiological data, uniparental markers, and blood groups. In this study, it was evaluated whether this increased risk remains when Amerindian ancestry is estimated using autosomal markers and considered in the predictive model. Ancestry was estimated through genotyping 62 insertion and deletion (INDEL) markers in sample sets of patients with CL±P, patients with cleft palate (CP), and controls, from Patagonia in southern Argentina and Belém in northern Brazil. The Amerindian ancestry in patients from Patagonia with CL±P was greater than in controls although it did not reach statistical significance. The European ancestry in patients with CL±P from Belém and in patients with CP from Belém and Patagonia was higher than in controls and statistically significant for patients with CP who were from Belém. This high contribution of European genetic ancestry among patients with CP who were from Belém has not been previously observed in American populations. Our results do not corroborate the currently accepted risks for CL±P and CP estimated by epidemiological studies in the North American populations and probably reflect the higher admixture found in South American ethnic groups when compared with the same ethnic groups from the North American populations. © 2016 Eur J Oral Sci.

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

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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.

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

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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

Race, Ethnicity and Ancestry in Unrelated Transplant Matching for the National Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with Genetics.

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Jill A Hollenbach

Full Text Available We conducted a nationwide study comparing self-identification to genetic ancestry classifications in a large cohort (n = 1752 from the National Marrow Donor Program. We sought to determine how various measures of self-identification intersect with genetic ancestry, with the aim of improving matching algorithms for unrelated bone marrow transplant. Multiple dimensions of self-identification, including race/ethnicity and geographic ancestry were compared to classifications based on ancestry informative markers (AIMs, and the human leukocyte antigen (HLA genes, which are required for transplant matching. Nearly 20% of responses were inconsistent between reporting race/ethnicity versus geographic ancestry. Despite strong concordance between AIMs and HLA, no measure of self-identification shows complete correspondence with genetic ancestry. In certain cases geographic ancestry reporting matches genetic ancestry not reflected in race/ethnicity identification, but in other cases geographic ancestries show little correspondence to genetic measures, with important differences by gender. However, when respondents assign ancestry to grandparents, we observe sub-groups of individuals with well- defined genetic ancestries, including important differences in HLA frequencies, with implications for transplant matching. While we advocate for tailored questioning to improve accuracy of ancestry ascertainment, collection of donor grandparents' information will improve the chances of finding matches for many patients, particularly for mixed-ancestry individuals.

Race, Ethnicity and Ancestry in Unrelated Transplant Matching for the National Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with Genetics

Science.gov (United States)

Hollenbach, Jill A.; Saperstein, Aliya; Albrecht, Mark; Vierra-Green, Cynthia; Parham, Peter; Norman, Paul J.; Maiers, Martin

2015-01-01

We conducted a nationwide study comparing self-identification to genetic ancestry classifications in a large cohort (n = 1752) from the National Marrow Donor Program. We sought to determine how various measures of self-identification intersect with genetic ancestry, with the aim of improving matching algorithms for unrelated bone marrow transplant. Multiple dimensions of self-identification, including race/ethnicity and geographic ancestry were compared to classifications based on ancestry informative markers (AIMs), and the human leukocyte antigen (HLA) genes, which are required for transplant matching. Nearly 20% of responses were inconsistent between reporting race/ethnicity versus geographic ancestry. Despite strong concordance between AIMs and HLA, no measure of self-identification shows complete correspondence with genetic ancestry. In certain cases geographic ancestry reporting matches genetic ancestry not reflected in race/ethnicity identification, but in other cases geographic ancestries show little correspondence to genetic measures, with important differences by gender. However, when respondents assign ancestry to grandparents, we observe sub-groups of individuals with well- defined genetic ancestries, including important differences in HLA frequencies, with implications for transplant matching. While we advocate for tailored questioning to improve accuracy of ancestry ascertainment, collection of donor grandparents’ information will improve the chances of finding matches for many patients, particularly for mixed-ancestry individuals. PMID:26287376

DRD4 dopamine receptor allelic diversity in various primate species

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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.

Prevalence of IFNL3 gene polymorphism among blood donors and its relation to genomic profile of ancestry in Brazil.

Science.gov (United States)

Rizzo, Silvia Renata Cornelio Parolin; Gazito, Diana; Pott-Junior, Henrique; Latini, Flavia Roche Moreira; Castelo, Adauto

The recent development of interferon-free regimens based on direct-acting antivirals for the treatment of chronic hepatitis C virus infection has benefited many but not all patients. Some patients still experience treatment failure, possibly attributed to unknown host and viral factors, such as IFNL3 gene polymorphism. The present study assessed the prevalence of rs12979860-CC, rs12979860-CT, and rs12979860-TT genotypes of the IFNL3 gene, and its relationship with ancestry informative markers in 949 adult Brazilian healthy blood donors. Race was analyzed using ancestry informative markers as a surrogate for ancestry. IFNL3 gene was genotyped using the ABI TaqMan single nucleotide polymorphisms genotyping assays. The overall frequency of rs12979860-CC genotype was 36.9%. The contribution of African ancestry was significantly higher among donors from the northeast region in relation to southeast donors, whereas the influence of European ancestry was significantly higher in southeast donors. Donors with rs12979860-CC and rs12979860-CT genotypes had similar ancestry background. The contribution of African ancestry was higher among rs12979860-TT genotype donors in comparison to both rs12979860-CC and rs12979860-CT genotypes. The prevalence of rs12979860-CC genotype is similar to that found in the US, despite the Brazilian ancestry informative markers admixture. However, in terms of ancestry, rs12979860-CT genotype was much closer to rs12979860-CC individuals than to rs12979860-TT. Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Assessment of the myostatin Q204X allele using an allelic discrimination assay

OpenAIRE

Sifuentes-Rincón,Ana M.; Puentes-Montiel,Herlinda E.; Moreno-Medina,Víctor R.; Rosa-Reyna,Xóchitl F. de la

2006-01-01

An allelic discrimination assay was designed and used to determine the genotypic and allelic frequencies of the myostatin (MSTN) gene Q204X allele from two Mexican Full-French herds. The assay is a simple high throughput genotyping method that could be applied to investigate the effect of the Q204X allele on the Charolais breed.

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…

Evaluating self-declared ancestry of U.S. Americans with autosomal, Y-chromosomal and mitochondrial DNA

NARCIS (Netherlands)

O. Lao Grueso (Oscar); P.M. Vallone (Peter); M.D. Coble (Michael); T.M. Diegoli (Toni); M. van Oven (Mannis); K. van der Gaag (Kristiaan); J. Pijpe (Jeroen); P. de Knijff (Peter); M.H. Kayser (Manfred)

2010-01-01

textabstractThe current U.S. population represents an amalgam of individuals originating mainly from four continental regions (Africa, Europe, Asia and America). To study the genetic ancestry and compare with self-declared ancestry we have analyzed paternally, maternally and bi-parentally inherited

QTL detection and elite alleles mining for stigma traits in Oryza sativa by association mapping

Directory of Open Access Journals (Sweden)

Xiaojing Dang

2016-08-01

Full Text Available Stigma traits are very important for hybrid seed production in Oryza sativa, which is a self-pollinated crop; however, the genetic mechanism controlling the traits is poorly understood. In this study, we investigated the phenotypic data of 227 accessions across two years and assessed their genotypic variation with 249 simple sequence repeat (SSR markers. By combining phenotypic and genotypic data, a genome-wide association (GWA map was generated. Large phenotypic variations in stigma length (STL, stigma brush-shaped part length (SBPL and stigma non-brush-shaped part length (SNBPL were found. Significant positive correlations were identified among stigma traits. In total, 2,072 alleles were detected among 227 accessions, with an average of 8.3 alleles per SSR locus. GWA mapping detected 6 quantitative trait loci (QTLs for the STL, 2 QTLs for the SBPL and 7 QTLs for the SNBPL. Eleven, 5, and 12 elite alleles were found for the STL, SBPL and SNBPL, respectively. Optimal cross designs were predicted for improving the target traits. The detected genetic variation in stigma traits and QTLs provides helpful information for cloning candidate STL genes and breeding rice cultivars with longer STLs in the future.

Allele frequencies of human platelet antigens in Banjar, Bugis, Champa, Jawa and Kelantan Malays in Peninsular Malaysia.

Science.gov (United States)

Wan Syafawati, W U; Norhalifah, H K; Zefarina, Z; Zafarina, Z; Panneerchelvam, S; Norazmi, M N; Chambers, G K; Edinur, H A

2015-10-01

The major aims of this study are to characterise and compile allelic data of human platelet antigen (HPA)-1 to -6 and -15 systems in five Malay sub-ethnic groups in Peninsular Malaysia. HPAs are polymorphic glycoproteins expressed on the surface of platelet membranes and are genetically differentiated across ethnogeographically unrelated populations. Blood samples were obtained with informed consent from 192 volunteers: Banjar (n = 30), Bugis (n = 37), Champa (n = 51), Jawa (n = 39) and Kelantan (n = 35). Genotyping was done using polymerase chain reaction-sequence specific primer method. In general, frequencies of HPAs in the Malay sub-ethnic groups are more similar to those in Asian populations compared with other more distinct populations such as Indians, Australian Aborigines and Europeans. This study provides the first HPA datasets for the selected Malay sub-ethnic groups. Subsequent analyses including previously reported HPA data of Malays, Chinese and Indians revealed details of the genetic relationships and ancestry of various sub-populations in Peninsular Malaysia. Furthermore, the comprehensive HPA allele frequency information from Peninsular Malaysia provided in this report has potential applications for future study of diseases, estimating risks associated with HPA alloimmunization and for developing an efficient HPA-typed donor recruitment strategy. © 2015 British Blood Transfusion Society.

Genetic dissection of the Drosophila melanogaster female head transcriptome reveals widespread allelic heterogeneity.

Science.gov (United States)

King, Elizabeth G; Sanderson, Brian J; McNeil, Casey L; Long, Anthony D; Macdonald, Stuart J

2014-05-01

Modern genetic mapping is plagued by the "missing heritability" problem, which refers to the discordance between the estimated heritabilities of quantitative traits and the variance accounted for by mapped causative variants. One major potential explanation for the missing heritability is allelic heterogeneity, in which there are multiple causative variants at each causative gene with only a fraction having been identified. The majority of genome-wide association studies (GWAS) implicitly assume that a single SNP can explain all the variance for a causative locus. However, if allelic heterogeneity is prevalent, a substantial amount of genetic variance will remain unexplained. In this paper, we take a haplotype-based mapping approach and quantify the number of alleles segregating at each locus using a large set of 7922 eQTL contributing to regulatory variation in the Drosophila melanogaster female head. Not only does this study provide a comprehensive eQTL map for a major community genetic resource, the Drosophila Synthetic Population Resource, but it also provides a direct test of the allelic heterogeneity hypothesis. We find that 95% of cis-eQTLs and 78% of trans-eQTLs are due to multiple alleles, demonstrating that allelic heterogeneity is widespread in Drosophila eQTL. Allelic heterogeneity likely contributes significantly to the missing heritability problem common in GWAS studies.

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

Directory of Open Access Journals (Sweden)

Pathik D Wadhwa

Full Text Available 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.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.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.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.

Impaired cognitive flexibility during sleep deprivation among carriers of the Brain Derived Neurotrophic Factor (BDNF) Val66Met allele.

Science.gov (United States)

Grant, Leilah K; Cain, Sean W; Chang, Anne-Marie; Saxena, Richa; Czeisler, Charles A; Anderson, Clare

2018-02-15

Accumulating evidence points to a genetic contribution to explain inter-individual vulnerability to sleep deprivation. A functional polymorphism in the BDNF gene, which causes a valine (Val) to methionine (Met) amino acid substitution at Codon 66, has been associated with cognitive impairment, particularly in populations with impaired frontal functioning. We hypothesised that sleep deprivation, which affects frontal function, may lead to cognitive dysfunction in Met allele carriers. To examine this, we investigated, in different BDNF genotypes, the effects of sleep deprivation on cognitive flexibility, as measured by response inhibition using the Stroop Color Naming Task. Thirty healthy, adults of European ancestry, including 12 heterozygous Met allele carriers and 18 Val/Val homozygotes, underwent 30-h of extended wakefulness under constant routine conditions. A computerised Stroop task was administered every 2h. Error rate and reaction times increased with time awake for all individuals. Participants with the Val/Met genotype made more errors on incongruent trials after 20h awake. While Val/Met participants also took significantly longer to respond when inhibiting a prepotent response irrespective of time awake, this was particularly evident during the biological night. Our study shows that carriers of the BDNF Met allele are more vulnerable to the impact of prolonged wakefulness and the biological night on a critical component of executive function, as measured by response inhibition on the Stroop task. Copyright © 2017 Elsevier B.V. All rights reserved.

A minimum set of ancestry informative markers for determining admixture proportions in a mixed American population: the Brazilian set.

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Santos, Hadassa C; Horimoto, Andréa V R; Tarazona-Santos, Eduardo; Rodrigues-Soares, Fernanda; Barreto, Mauricio L; Horta, Bernardo L; Lima-Costa, Maria F; Gouveia, Mateus H; Machado, Moara; Silva, Thiago M; Sanches, José M; Esteban, Nubia; Magalhaes, Wagner C S; Rodrigues, Maíra R; Kehdy, Fernanda S G; Pereira, Alexandre C

2016-05-01

The Brazilian population is considered to be highly admixed. The main contributing ancestral populations were European and African, with Amerindians contributing to a lesser extent. The aims of this study were to provide a resource for determining and quantifying individual continental ancestry using the smallest number of SNPs possible, thus allowing for a cost- and time-efficient strategy for genomic ancestry determination. We identified and validated a minimum set of 192 ancestry informative markers (AIMs) for the genetic ancestry determination of Brazilian populations. These markers were selected on the basis of their distribution throughout the human genome, and their capacity of being genotyped on widely available commercial platforms. We analyzed genotyping data from 6487 individuals belonging to three Brazilian cohorts. Estimates of individual admixture using this 192 AIM panels were highly correlated with estimates using ~370 000 genome-wide SNPs: 91%, 92%, and 74% of, respectively, African, European, and Native American ancestry components. Besides that, 192 AIMs are well distributed among populations from these ancestral continents, allowing greater freedom in future studies with this panel regarding the choice of reference populations. We also observed that genetic ancestry inferred by AIMs provides similar association results to the one obtained using ancestry inferred by genomic data (370 K SNPs) in a simple regression model with rs1426654, related to skin pigmentation, genotypes as dependent variable. In conclusion, these markers can be used to identify and accurately quantify ancestry of Latin Americans or US Hispanics/Latino individuals, in particular in the context of fine-mapping strategies that require the quantification of continental ancestry in thousands of individuals.

A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor–negative breast cancer

Science.gov (United States)

Haiman, Christopher A; Chen, Gary K; Vachon, Celine M; Canzian, Federico; Dunning, Alison; Millikan, Robert C; Wang, Xianshu; Ademuyiwa, Foluso; Ahmed, Shahana; Ambrosone, Christine B; Baglietto, Laura; Balleine, Rosemary; Bandera, Elisa V; Beckmann, Matthias W; Berg, Christine D; Bernstein, Leslie; Blomqvist, Carl; Blot, William J; Brauch, Hiltrud; Buring, Julie E; Carey, Lisa A; Carpenter, Jane E; Chang-Claude, Jenny; Chanock, Stephen J; Chasman, Daniel I; Clarke, Christine L; Cox, Angela; Cross, Simon S; Deming, Sandra L; Diasio, Robert B; Dimopoulos, Athanasios M; Driver, W Ryan; Dünnebier, Thomas; Durcan, Lorraine; Eccles, Diana; Edlund, Christopher K; Ekici, Arif B; Fasching, Peter A; Feigelson, Heather S; Flesch-Janys, Dieter; Fostira, Florentia; Försti, Asta; Fountzilas, George; Gerty, Susan M; Giles, Graham G; Godwin, Andrew K; Goodfellow, Paul; Graham, Nikki; Greco, Dario; Hamann, Ute; Hankinson, Susan E; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Holbrook, Andrea; Hoover, Robert N; Hu, Jennifer J; Hunter, David J; Ingles, Sue A; Irwanto, Astrid; Ivanovich, Jennifer; John, Esther M; Johnson, Nicola; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Ko, Yon-Dschun; Kolonel, Laurence N; Konstantopoulou, Irene; Kosma, Veli-Matti; Kulkarni, Swati; Lambrechts, Diether; Lee, Adam M; Le Marchand, Loïc; Lesnick, Timothy; Liu, Jianjun; Lindstrom, Sara; Mannermaa, Arto; Margolin, Sara; Martin, Nicholas G; Miron, Penelope; Montgomery, Grant W; Nevanlinna, Heli; Nickels, Stephan; Nyante, Sarah; Olswold, Curtis; Palmer, Julie; Pathak, Harsh; Pectasides, Dimitrios; Perou, Charles M; Peto, Julian; Pharoah, Paul D P; Pooler, Loreall C; Press, Michael F; Pylkäs, Katri; Rebbeck, Timothy R; Rodriguez-Gil, Jorge L; Rosenberg, Lynn; Ross, Eric; Rüdiger, Thomas; Silva, Isabel dos Santos; Sawyer, Elinor; Schmidt, Marjanka K; Schulz-Wendtland, Rüdiger; Schumacher, Fredrick; Severi, Gianluca; Sheng, Xin; Signorello, Lisa B; Sinn, Hans-Peter; Stevens, Kristen N; Southey, Melissa C; Tapper, William J; Tomlinson, Ian; Hogervorst, Frans B L; Wauters, Els; Weaver, JoEllen; Wildiers, Hans; Winqvist, Robert; Van Den Berg, David; Wan, Peggy; Xia, Lucy Y; Yannoukakos, Drakoulis; Zheng, Wei; Ziegler, Regina G; Siddiq, Afshan; Slager, Susan L; Stram, Daniel O; Easton, Douglas; Kraft, Peter; Henderson, Brian E; Couch, Fergus J

2012-01-01

Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10−10). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10−9), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10−9). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations. PMID:22037553

A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer.

Science.gov (United States)

Haiman, Christopher A; Chen, Gary K; Vachon, Celine M; Canzian, Federico; Dunning, Alison; Millikan, Robert C; Wang, Xianshu; Ademuyiwa, Foluso; Ahmed, Shahana; Ambrosone, Christine B; Baglietto, Laura; Balleine, Rosemary; Bandera, Elisa V; Beckmann, Matthias W; Berg, Christine D; Bernstein, Leslie; Blomqvist, Carl; Blot, William J; Brauch, Hiltrud; Buring, Julie E; Carey, Lisa A; Carpenter, Jane E; Chang-Claude, Jenny; Chanock, Stephen J; Chasman, Daniel I; Clarke, Christine L; Cox, Angela; Cross, Simon S; Deming, Sandra L; Diasio, Robert B; Dimopoulos, Athanasios M; Driver, W Ryan; Dünnebier, Thomas; Durcan, Lorraine; Eccles, Diana; Edlund, Christopher K; Ekici, Arif B; Fasching, Peter A; Feigelson, Heather S; Flesch-Janys, Dieter; Fostira, Florentia; Försti, Asta; Fountzilas, George; Gerty, Susan M; Giles, Graham G; Godwin, Andrew K; Goodfellow, Paul; Graham, Nikki; Greco, Dario; Hamann, Ute; Hankinson, Susan E; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Holbrook, Andrea; Hoover, Robert N; Hu, Jennifer J; Hunter, David J; Ingles, Sue A; Irwanto, Astrid; Ivanovich, Jennifer; John, Esther M; Johnson, Nicola; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Ko, Yon-Dschun; Kolonel, Laurence N; Konstantopoulou, Irene; Kosma, Veli-Matti; Kulkarni, Swati; Lambrechts, Diether; Lee, Adam M; Marchand, Loïc Le; Lesnick, Timothy; Liu, Jianjun; Lindstrom, Sara; Mannermaa, Arto; Margolin, Sara; Martin, Nicholas G; Miron, Penelope; Montgomery, Grant W; Nevanlinna, Heli; Nickels, Stephan; Nyante, Sarah; Olswold, Curtis; Palmer, Julie; Pathak, Harsh; Pectasides, Dimitrios; Perou, Charles M; Peto, Julian; Pharoah, Paul D P; Pooler, Loreall C; Press, Michael F; Pylkäs, Katri; Rebbeck, Timothy R; Rodriguez-Gil, Jorge L; Rosenberg, Lynn; Ross, Eric; Rüdiger, Thomas; Silva, Isabel dos Santos; Sawyer, Elinor; Schmidt, Marjanka K; Schulz-Wendtland, Rüdiger; Schumacher, Fredrick; Severi, Gianluca; Sheng, Xin; Signorello, Lisa B; Sinn, Hans-Peter; Stevens, Kristen N; Southey, Melissa C; Tapper, William J; Tomlinson, Ian; Hogervorst, Frans B L; Wauters, Els; Weaver, JoEllen; Wildiers, Hans; Winqvist, Robert; Van Den Berg, David; Wan, Peggy; Xia, Lucy Y; Yannoukakos, Drakoulis; Zheng, Wei; Ziegler, Regina G; Siddiq, Afshan; Slager, Susan L; Stram, Daniel O; Easton, Douglas; Kraft, Peter; Henderson, Brian E; Couch, Fergus J

2011-10-30

Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.

Mutation intolerant genes and targets of FMRP are enriched for nonsynonymous alleles in schizophrenia.

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Leonenko, Ganna; Richards, Alexander L; Walters, James T; Pocklington, Andrew; Chambert, Kimberly; Al Eissa, Mariam M; Sharp, Sally I; O'Brien, Niamh L; Curtis, David; Bass, Nicholas J; McQuillin, Andrew; Hultman, Christina; Moran, Jennifer L; McCarroll, Steven A; Sklar, Pamela; Neale, Benjamin M; Holmans, Peter A; Owen, Michael J; Sullivan, Patrick F; O'Donovan, Michael C

2017-10-01

Risk of schizophrenia is conferred by alleles occurring across the full spectrum of frequencies from common SNPs of weak effect through to ultra rare alleles, some of which may be moderately to highly penetrant. Previous studies have suggested that some of the risk of schizophrenia is attributable to uncommon alleles represented on Illumina exome arrays. Here, we present the largest study of exomic variation in schizophrenia to date, using samples from the United Kingdom and Sweden (10,011 schizophrenia cases and 13,791 controls). Single variants, genes, and gene sets were analyzed for association with schizophrenia. No single variant or gene reached genome-wide significance. Among candidate gene sets, we found significant enrichment for rare alleles (minor allele frequency [MAF] schizophrenia by excluding a role for uncommon exomic variants (0.01 ≤ MAF ≥ 0.001) that confer a relatively large effect (odds ratio [OR] > 4). We also show risk alleles within this frequency range exist, but confer smaller effects and should be identified by larger studies. © 2017 Wiley Periodicals, Inc.

Association of breast cancer risk with genetic variants showing differential allelic expression

DEFF Research Database (Denmark)

Hamdi, Yosr; Soucy, Penny; Adoue, Véronique

2016-01-01

There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional...

QuASAR: quantitative allele-specific analysis of reads.

Science.gov (United States)

Harvey, Chris T; Moyerbrailean, Gregory A; Davis, Gordon O; Wen, Xiaoquan; Luca, Francesca; Pique-Regi, Roger

2015-04-15

Expression quantitative trait loci (eQTL) studies have discovered thousands of genetic variants that regulate gene expression, enabling a better understanding of the functional role of non-coding sequences. However, eQTL studies are costly, requiring large sample sizes and genome-wide genotyping of each sample. In contrast, analysis of allele-specific expression (ASE) is becoming a popular approach to detect the effect of genetic variation on gene expression, even within a single individual. This is typically achieved by counting the number of RNA-seq reads matching each allele at heterozygous sites and testing the null hypothesis of a 1:1 allelic ratio. In principle, when genotype information is not readily available, it could be inferred from the RNA-seq reads directly. However, there are currently no existing methods that jointly infer genotypes and conduct ASE inference, while considering uncertainty in the genotype calls. We present QuASAR, quantitative allele-specific analysis of reads, a novel statistical learning method for jointly detecting heterozygous genotypes and inferring ASE. The proposed ASE inference step takes into consideration the uncertainty in the genotype calls, while including parameters that model base-call errors in sequencing and allelic over-dispersion. We validated our method with experimental data for which high-quality genotypes are available. Results for an additional dataset with multiple replicates at different sequencing depths demonstrate that QuASAR is a powerful tool for ASE analysis when genotypes are not available. http://github.com/piquelab/QuASAR. fluca@wayne.edu or rpique@wayne.edu Supplementary Material is available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Ecological interactions and the fitness effect of water-use efficiency: Competition and drought alter the impact of natural MPK12 alleles in Arabidopsis.

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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. © 2016 John Wiley & Sons Ltd/CNRS.

African genetic ancestry interacts with body mass index to modify risk for uterine fibroids.

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Giri, Ayush; Edwards, Todd L; Hartmann, Katherine E; Torstenson, Eric S; Wellons, Melissa; Schreiner, Pamela J; Velez Edwards, Digna R

2017-07-01

Race, specifically African ancestry, and obesity are important risk factors for uterine fibroids, and likely interact to provide the right conditions for fibroid growth. However, existing studies largely focus on the main-effects rather than their interaction. Here, we firstly provide evidence for interaction between categories of body mass index (BMI) and reported-race in relation to uterine fibroids. We then investigate whether the association between inferred local European ancestry and fibroid risk is modified by BMI in African American (AA) women in the Vanderbilt University Medical Center bio-repository (BioVU) (539 cases and 794 controls) and the Coronary Artery Risk Development in Young Adults study (CARDIA, 264 cases and 173 controls). We used multiple logistic regression to evaluate interactions between local European ancestry and BMI in relation to fibroid risk, then performed fixed effects meta-analysis. Statistical significance threshold for local-ancestry and BMI interactions was empirically estimated with 10,000 permutations (p-value = 1.18x10-4). Admixture mapping detected an association between European ancestry and fibroid risk which was modified by BMI (continuous-interaction p-value = 3.75x10-5) around ADTRP (chromosome 6p24); the strongest association was found in the obese category (ancestry odds ratio (AOR) = 0.51, p-value = 2.23x10-5). Evaluation of interaction between genotyped/imputed variants and BMI in this targeted region suggested race-specific interaction, present in AAs only; strongest evidence was found for insertion/deletion variant (6:11946435), again in the obese category (OR = 1.66, p-value = 1.72x10-6). We found nominal evidence for interaction between local ancestry and BMI at a previously reported region in chromosome 2q31-32, which includes COL5A2, and TFPI, an immediate downstream target of ADTRP. Interactions between BMI and SNPs (single nucleotide polymorphisms) found in this region in AA women were also detected in an

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

Science.gov (United States)

Lima-Costa, M Fernanda; Macinko, James; Mambrini, Juliana Vaz de Mello; Peixoto, Sérgio Viana; Pereira, Alexandre Costa; Tarazona-Santos, Eduardo; Ribeiro, Antonio Luiz Pinho

2016-05-01

The influence of genetic ancestry on Trypanosoma cruzi infection and Chagas disease outcomes is unknown. 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. 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.

Genomic Ancestry, Self-Reported “Color” and Quantitative Measures of Skin Pigmentation in Brazilian Admixed Siblings

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Leite, Tailce K. M.; Fonseca, Rômulo M. C.; de França, Nanci M.; Parra, Esteban J.; Pereira, Rinaldo W.

2011-01-01

A current concern in genetic epidemiology studies in admixed populations is that population stratification can lead to spurious results. The Brazilian census classifies individuals according to self-reported “color”, but several studies have demonstrated that stratifying according to “color” is not a useful strategy to control for population structure, due to the dissociation between self-reported “color” and genomic ancestry. We report the results of a study in a group of Brazilian siblings in which we measured skin pigmentation using a reflectometer, and estimated genomic ancestry using 21 Ancestry Informative Markers (AIMs). Self-reported “color”, according to the Brazilian census, was also available for each participant. This made it possible to evaluate the relationship between self-reported “color” and skin pigmentation, self-reported “color” and genomic ancestry, and skin pigmentation and genomic ancestry. We observed that, although there were significant differences between the three “color” groups in genomic ancestry and skin pigmentation, there was considerable dispersion within each group and substantial overlap between groups. We also saw that there was no good agreement between the “color” categories reported by each member of the sibling pair: 30 out of 86 sibling pairs reported different “color”, and in some cases, the sibling reporting the darker “color” category had lighter skin pigmentation. Socioeconomic status was significantly associated with self-reported “color” and genomic ancestry in this sample. This and other studies show that subjective classifications based on self-reported “color”, such as the one that is used in the Brazilian census, are inadequate to describe the population structure present in recently admixed populations. Finally, we observed that one of the AIMs included in the panel (rs1426654), which is located in the known pigmentation gene SLC24A5, was strongly associated with

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.

What role does African ancestry play in how hypertensive patients respond to certain antihypertensive drug therapy?

Science.gov (United States)

Seedat, Yackoob K; Brewster, Lizzy M

2014-02-01

This article is a summary of the response of the four commonly used antihypertensive agents in African ancestry patients. They are thiazide like diuretics or indapamide, calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers, and β-adrenergic blockers (ARB). Response was superior in African ancestry patients on a thiazide like diuretic or indapamide and CCB, while the response to β-adrenergic blockers and ACEI are attenuated. Available data are very limited but self-defined ancestry seems to be the best predictor of individual responses to antihypertensive drugs. Knowledge of the factors like economic and social consideration affect the lower rate of detection, treatment and control of hypertension in the African ancestry population of the USA. For regions in which health care resources are particularly scarce, investment in population-based primary prevention strategies may yield the largest benefit.

Identification of the sequence variations of 15 autosomal STR loci in a Chinese population.

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Chen, Wenjing; Cheng, Jianding; Ou, Xueling; Chen, Yong; Tong, Dayue; Sun, Hongyu

2014-01-01

DNA sequence variation including base(s) changes and insertion or deletion in the primer binding region may cause a null allele and, if this changes the length of the amplified fragment out of the allelic ladder, off-ladder (OL) alleles may be detected. In order to provide accurate and reliable DNA evidence for forensic DNA analysis, it is essential to clarify sequence variations in prevalently used STR loci. Suspected null alleles and OL alleles of PlowerPlex16® System from 21,934 unrelated Chinese individuals were verified by alternative systems and sequenced. A total of 17 cases with null alleles were identified, including 12 kinds of point mutations in 16 cases and a 19-base deletion in one case. The total frequency of null alleles was 7.751 × 10(-4). Eight hundred and forty-four OL alleles classified as being of 97 different kinds were observed at 15 STR loci of the PowerPlex®16 system except vWA. All the frequencies of OL alleles were under 0.01. Null alleles should be confirmed by alternative primers and OL alleles should be named appropriately. Particular attention should be paid to sequence variation, since incorrect designation could lead to false conclusions.

Uniparental ancestry markers in Chilean populations

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Camilla Dutra Vieira-Machado

Full Text Available Abstract The presence of Native Americans, Europeans, and Africans has led to the development of a multi-ethnic, admixed population in Chile. This study aimed to contribute to the characterization of the uniparental genetic structure of three Chilean regions. Newborns from seven hospitals in Independencia, Providencia, Santiago, Curicó, Cauquenes, Valdívia, and Puerto Montt communes, belonging to the Chilean regions of Santiago, Maule, and Los Lagos, were studied. The presence of Native American mitochondrial DNA (mtDNA haplogroups and two markers present in the non-recombinant region of the Y chromosome, DYS199 and DYS287, indicative of Native American and African ancestry, respectively, was determined. A high Native American matrilineal contribution and a low Native American and African patrilineal contributions were found in all three studied regions. As previously found in Chilean admixed populations, the Native American matrilineal contribution was lower in Santiago than in the other studied regions. However, there was an unexpectedly higher contribution of Native American ancestry in one of the studied communes in Santiago, probably due to the high rate of immigration from other regions of the country. The population genetic sub-structure we detected in Santiago using few uniparental markers requires further confirmation, owing to possible stratification for autosomal and X-chromosome markers.

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

Global pharmacogenomics: distribution of CYP3A5 polymorphisms and phenotypes in the Brazilian population.

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Guilherme Suarez-Kurtz

Full Text Available The influence of self-reported "race/color", geographical origin and genetic ancestry on the distribution of three functional CYP3A5 polymorphisms, their imputed haplotypes and inferred phenotypes was examined in 909 healthy, adult Brazilians, self-identified as White, Brown or Black ("race/color" categories of the Brazilian census. The cohort was genotyped for CYP3A5*3 (rs776746, CYP3A5*6 (rs10264272 and CYP3A5*7 (rs41303343, CYP3A5 haplotypes were imputed and CYP3A5 metabolizer phenotypes were inferred according to the number of defective CYP3A5 alleles. Estimates of the individual proportions of Amerindian, African and European ancestry were available for the entire cohort. Multinomial log-linear regression models were applied to infer the statistical association between the distribution of CYP3A5 alleles, haplotypes and phenotypes (response variables, and self-reported Color, geographical region and ancestry (explanatory variables. We found that Color per se or in combination with geographical region associates significantly with the distribution of CYP3A5 variant alleles and CYP3A5 metabolizer phenotypes, whereas geographical region per se influences the frequency distribution of CYP3A5 variant alleles. The odds of having the default CYP3A5*3 allele and the poor metabolizer phenotype increases continuously with the increase of European ancestry and decrease of African ancestry. The opposite trend is observed in relation to CYP3A5*6, CYP3A5*7, the default CYP3A5*1 allele, and both the extensive and intermediate phenotypes. No significant effect of Amerindian ancestry on the distribution of CYP3A5 alleles or phenotypes was observed. In conclusion, this study strongly supports the notion that the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of pharmacogenomic studies, and dealt with as a continuous variable, rather than proportioned in arbitrary categories that do not capture the

Genome-wide association study of pigmentary traits (skin and iris color in individuals of East Asian ancestry

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Lida Rawofi

2017-11-01

Full Text Available Background Currently, there is limited knowledge about the genetics underlying pigmentary traits in East Asian populations. Here, we report the results of the first genome-wide association study of pigmentary traits (skin and iris color in individuals of East Asian ancestry. Methods We obtained quantitative skin pigmentation measures (M-index in the inner upper arm of the participants using a portable reflectometer (N = 305. Quantitative measures of iris color (expressed as L*, a* and b* CIELab coordinates were extracted from high-resolution iris pictures (N = 342. We also measured the color differences between the pupillary and ciliary regions of the iris (e.g., iris heterochromia. DNA samples were genotyped with Illumina’s Infinium Multi-Ethnic Global Array (MEGA and imputed using the 1000 Genomes Phase 3 samples as reference haplotypes. Results For skin pigmentation, we did not observe any genome-wide significant signal. We followed-up in three independent Chinese samples the lead SNPs of five regions showing multiple common markers (minor allele frequency ≥ 5% with good imputation scores and suggestive evidence of association (p-values < 10−5. One of these markers, rs2373391, which is located in an intron of the ZNF804B gene on chromosome 7, was replicated in one of the Chinese samples (p = 0.003. For iris color, we observed genome-wide signals in the OCA2 region on chromosome 15. This signal is driven by the non-synonymous rs1800414 variant, which explains 11.9%, 10.4% and 6% of the variation observed in the b*, a* and L* coordinates in our sample, respectively. However, the OCA2 region was not associated with iris heterochromia. Discussion Additional genome-wide association studies in East Asian samples will be necessary to further disentangle the genetic architecture of pigmentary traits in East Asian populations.

Ancestry, Plasmodium cynomolgi prevalence and rhesus macaque admixture in cynomolgus macaques (Macaca fascicularis) bred for export in Chinese breeding farms.

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Zhang, Xinjun; Meng, Yuhuan; Houghton, Paul; Liu, Mingyu; Kanthaswamy, Sreetharan; Oldt, Robert; Ng, Jillian; Trask, Jessica Satkoski; Huang, Ren; Singh, Balbir; Du, Hongli; Smith, David Glenn

2017-04-01

Most cynomolgus macaques (Macaca fascicularis) used in the United States as animal models are imported from Chinese breeding farms without documented ancestry. Cynomolgus macaques with varying rhesus macaque ancestry proportions may exhibit differences, such as susceptibility to malaria, that affect their suitability as a research model. DNA of 400 cynomolgus macaques from 10 Chinese breeding farms was genotyped to characterize their regional origin and rhesus ancestry proportion. A nested PCR assay was used to detect Plasmodium cynomolgi infection in sampled individuals. All populations exhibited high levels of genetic heterogeneity and low levels of inbreeding and genetic subdivision. Almost all individuals exhibited an Indochinese origin and a rhesus ancestry proportion of 5%-48%. The incidence of P. cynomolgi infection in cynomolgus macaques is strongly associated with proportion of rhesus ancestry. The varying amount of rhesus ancestry in cynomolgus macaques underscores the importance of monitoring their genetic similarity in malaria research. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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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.

Lack of adaptation from standing genetic variation despite the presence of putatively adaptive alleles in introduced sweet vernal grass (Anthoxanthum odoratum).

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Gould, B; Geber, M

2016-01-01

Population genetic theory predicts that the availability of appropriate standing genetic variation should facilitate rapid evolution when species are introduced to new environments. However, few tests of rapid evolution have been paired with empirical surveys for the presence of previously identified adaptive genetic variants in natural populations. In this study, we examined local adaptation to soil Al toxicity in the introduced range of sweet vernal grass (Anthoxanthum odoratum), and we genotyped populations for the presence of Al tolerance alleles previously identified at the long-term ecological Park Grass Experiment (PGE, Harpenden, UK) in the species native range. We found that markers associated with Al tolerance at the PGE were present at appreciable frequency in introduced populations. Despite this, there was no strong evidence of local adaptation to soil Al toxicity among populations. Populations demonstrated significantly different intrinsic root growth rates in the absence of Al. This suggests that selection on correlated root growth traits may constrain the ability of populations to evolve significantly different root growth responses to Al. Our results demonstrate that genotype-phenotype associations may differ substantially between the native and introduced parts of a species range and that adaptive alleles from a native species range may not necessarily promote phenotypic differentiation in the introduced range. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Deducing the pathogenic contribution of recessive ABCA4 alleles in an outbred population.

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Schindler, Emily I; Nylen, Erik L; Ko, Audrey C; Affatigato, Louisa M; Heggen, Andrew C; Wang, Kai; Sheffield, Val C; Stone, Edwin M

2010-10-01

Accurate prediction of the pathogenic effects of specific genotypes is important for the design and execution of clinical trials as well as for meaningful counseling of individual patients. However, for many autosomal recessive diseases, it can be difficult to deduce the relative pathogenic contribution of individual alleles because relatively few affected individuals share the same two disease-causing variations. In this study, we used multiple regression analysis to estimate the pathogenicity of specific alleles of ABCA4 in patients with retinal phenotypes ranging from Stargardt disease to retinitis pigmentosa. This analysis revealed quantitative allelic effects on two aspects of the visual phenotype, visual acuity (P disease and will also aid in the optimal selection of subjects for clinical trials of new therapies.

Genetic dissection of the Drosophila melanogaster female head transcriptome reveals widespread allelic heterogeneity.

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Elizabeth G King

2014-05-01

Full Text Available Modern genetic mapping is plagued by the "missing heritability" problem, which refers to the discordance between the estimated heritabilities of quantitative traits and the variance accounted for by mapped causative variants. One major potential explanation for the missing heritability is allelic heterogeneity, in which there are multiple causative variants at each causative gene with only a fraction having been identified. The majority of genome-wide association studies (GWAS implicitly assume that a single SNP can explain all the variance for a causative locus. However, if allelic heterogeneity is prevalent, a substantial amount of genetic variance will remain unexplained. In this paper, we take a haplotype-based mapping approach and quantify the number of alleles segregating at each locus using a large set of 7922 eQTL contributing to regulatory variation in the Drosophila melanogaster female head. Not only does this study provide a comprehensive eQTL map for a major community genetic resource, the Drosophila Synthetic Population Resource, but it also provides a direct test of the allelic heterogeneity hypothesis. We find that 95% of cis-eQTLs and 78% of trans-eQTLs are due to multiple alleles, demonstrating that allelic heterogeneity is widespread in Drosophila eQTL. Allelic heterogeneity likely contributes significantly to the missing heritability problem common in GWAS studies.

Allele coding in genomic evaluation

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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

Tailoring Nutritional Advice for Mexicans Based on Prevalence Profiles of Diet-Related Adaptive Gene Polymorphisms

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Claudia Ojeda-Granados

2017-11-01

Full Text Available Diet-related adaptive gene (DRAG polymorphisms identified in specific populations are associated with chronic disorders in carriers of the adaptive alleles due to changes in dietary and lifestyle patterns in recent times. Mexico’s population is comprised of Amerindians (AM and Mestizos who have variable AM, European (EUR and African genetic ancestry and an increased risk of nutrition-related chronic diseases. Nutritional advice based on the Mexican genome and the traditional food culture is needed to develop preventive and therapeutic strategies. Therefore, we aimed to provide a prevalence profile of several DRAG polymorphisms in the Mexican population, including Central West (CW Mexico subpopulations. Geographic heat maps were built using ArcGIS10 (Esri, Redlands, CA, USA software, based on the published data of the MTHFR C677T (rs1801133, ABCA1 Arg230Cys (rs9282541, APOE T388C (rs429358/C526T (rs7412, LCT C-13910T (rs4988235 polymorphisms and AMY1 copy number variation (CNV. Also, new data obtained by allelic discrimination-real-time polymerase chain reaction (RT-PCR assays for the MTHFR, ABCA1, and APOE polymorphisms as well as the AMY1 CNV in the CW Mexico subpopulations with different proportions of AM and EUR ancestry were included. In the CW region, the highest frequency of the MTHFR 677T, ABCA1 230C and APOE ε4 adaptive alleles was observed in the AM groups, followed by Mestizos with intermediate AM ancestry. The LCT-13910T allele frequency was highest in Mestizos-EUR but extremely low in AM, while the AMY1 diploid copy number was 6.82 ± 3.3 copies. Overall, the heat maps showed a heterogeneous distribution of the DRAG polymorphisms, in which the AM groups revealed the highest frequencies of the adaptive alleles followed by Mestizos. Given these genetic differences, genome-based nutritional advice should be tailored in a regionalized and individualized manner according to the available foods and Mexican traditional food culture that

Massively parallel sequencing of 165 ancestry informative SNPs in two Chinese Tibetan-Burmese minority ethnicities.

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Wang, Zheng; He, Guanglin; Luo, Tao; Zhao, Xueying; Liu, Jing; Wang, Mengge; Zhou, Di; Chen, Xu; Li, Chengtao; Hou, Yiping

2018-05-01

The Tibeto-Burman language, one subfamily of the Sino-Tibetan languages, is spoken by over 60 million people all over East Asia. Yet the ethnic origin and genetic architecture of Tibeto-Burman speaking populations remain largely unexplored. In the present study, 169 Chinese individuals from Tibeto-Burman speaking populations (two ethnic groups: Tibetan and Yi) in four different geographic regions in western China were analyzed using the Precision ID Ancestry Panel (165 AISNPs) and the Ion PGM System. The performance and corresponding forensic statistical parameters of this AISNPs panel were investigated. Comprehensive population genetic comparisons (143 populations based on Kidd' SNPs, 92 populations on the basis of Seldin' SNPs and 31 populations based on the Precision ID Ancestry Panel) and ancestry inference were further performed. Sequencing performance demonstrated that the Precision ID Ancestry Panel is effective and robust. Forensic characteristics suggested that this panel not only can be used for ancestry estimation of Tibeto-Burman populations but also for individual identification. Tibetan and Yi shared a common genetic ancestry origin but experienced the complex history of gene flow, local adaptation, and isolation, and constructed the specific genetic landscape of human genetic diversity of Highlander and Lowlander populations. Tibetan-Burman populations and other East Asian populations showed sufficient genetic difference and could be distinguished into three distinct groups. Furthermore, analysis of population structure revealed that significant genetic difference was existed inter-continent populations and strong genetic affinity was observed within-continent populations. Additional population-specific AISNPs and a relatively more comprehensive database with sufficient reference population data remain necessary to get better-scale resolution within a geographically proximate populations in East Asia. Copyright © 2018 Elsevier B.V. All rights

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

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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.

Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.

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Guillaume Lettre

2011-02-01

Full Text Available Coronary heart disease (CHD is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C, hypertension, smoking, and type-2 diabetes in individuals of African ancestry, we performed a genome-wide association study (GWAS in 8,090 African Americans from five population-based cohorts. We replicated 17 loci previously associated with CHD or its risk factors in Caucasians. For five of these regions (CHD: CDKN2A/CDKN2B; HDL-C: FADS1-3, PLTP, LPL, and ABCA1, we could leverage the distinct linkage disequilibrium (LD patterns in African Americans to identify DNA polymorphisms more strongly associated with the phenotypes than the previously reported index SNPs found in Caucasian populations. We also developed a new approach for association testing in admixed populations that uses allelic and local ancestry variation. Using this method, we discovered several loci that would have been missed using the basic allelic and global ancestry information only. Our conclusions suggest that no major loci uniquely explain the high prevalence of CHD in African Americans. Our project has developed resources and methods that address both admixture- and SNP-association to maximize power for genetic discovery in even larger African-American consortia.

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

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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

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

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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.

Differential distribution and association of FTO rs9939609 gene polymorphism with obesity: A cross-sectional study among two tribal populations of India with East-Asian ancestry.

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Ningombam, Somorjit Singh; Chhungi, Varhlun; Newmei, Masan Kambo; Rajkumari, Sunanda; Devi, Naorem Kiranmala; Mondal, Prakash Ranjan; Saraswathy, Kallur Nava

2018-03-20

The fat mass and obesity associated (FTO) rs9939609 gene polymorphism is most widely studied in terms of obesity in various populations. Recently, the prevalence of obesity has been reported to be very high among the North-Eastern State of India. The major aim of the present study is to understand the extent of FTO rs9939609 gene polymorphism and its association with obesity among the two North-East Indian tribal populations with similar East Asian ancestry. Somatometric data and fasting blood sample were collected from 521 tribal individuals (258 Liangmai and 263 Mizo) of Manipur after obtaining written informed consent. Genotyping of FTO rs9939609 single nucleotide polymorphism (SNP) was done using restriction fragment length polymorphism method for PCR-amplified fragments. Both the presently studied populations were not following Hardy-Weinberg law. The prevalence of obesity and minor allele frequency of FTO rs9939609 polymorphism was found to be significantly higher among the Mizo tribe compared to that of Liangmai. The selected polymorphism was found to be significantly associated with obesity (BMI) only among the Liangmai tribe (Odds ratio-3.0; 95% CI-1.4, 6.4; p-0.003), after adjusting for age and occupation. Age-cohort wise distribution and absolute fitness analysis indicated the lower fitness of minor allele in the higher age group among the Liangmai tribe. To the best of the author's knowledge this is the first study, associating FTO rs9939609 gene polymorphism and obesity in the North-eastern Indian tribal populations with East-Asian ancestry. This study revealed the FTO rs9939609 polymorphism is observed to be associated with obesity only among the Liangmai tribe not among the Mizo tribe. The differential distribution and association observed in the two selected tribes, inhabited in a similar geographical region, could be attributed to differences in their migratory histories in terms of both route and time of settlement. Copyright © 2018 Elsevier B

Association of substance use disorders with childhood trauma but not African genetic heritage in an African American cohort.

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Ducci, Francesca; Roy, Alec; Shen, Pei-Hong; Yuan, Qiaoping; Yuan, Nicole P; Hodgkinson, Colin A; Goldman, Lynn R; Goldman, David

2009-09-01

Genetic variation influences differential vulnerability to addiction within populations. However, it remains unclear whether differences in frequencies of vulnerability alleles contribute to disparities between populations and to what extent ancestry correlates with differential exposure to environmental risk factors, including poverty and trauma. The authors used 186 ancestry-informative markers to measure African ancestry in 407 addicts and 457 comparison subjects self-identified as African Americans. The reference group was 1,051 individuals from the Human Genome Diversity Cell Line Panel, which includes 51 diverse populations representing most worldwide genetic diversity. African Americans varied in degrees of African, European, Middle Eastern, and Central Asian genetic heritage. The overall level of African ancestry was actually smaller among cocaine, opiate, and alcohol addicts (proportion=0.76-0.78) than nonaddicted African American comparison subjects (proportion=0.81). African ancestry was associated with living in impoverished neighborhoods, a factor previously associated with risk. There was no association between African ancestry and exposure to childhood abuse or neglect, a factor that strongly predicted all types of addictions. These results suggest that African genetic heritage does not increase the likelihood of genetic risk for addictions. They highlight the complex interrelation between genetic ancestry and social, economic, and environmental conditions and the strong relation of those factors to addiction. Studies of epidemiological samples characterized for genetic ancestry and social, psychological, demographic, economic, cultural, and historical factors are needed to better disentangle the effects of genetic and environmental factors underlying interpopulation differences in vulnerability to addiction and other health disparities.

Amerindian (but not African or European) ancestry is significantly associated with diurnal preference within an admixed Brazilian population.

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Egan, Kieren J; Campos Santos, Hadassa; Beijamini, Felipe; Duarte, Núbia E; Horimoto, Andréa R V R; Taporoski, Tâmara P; Vallada, Homero; Negrão, André B; Krieger, José E; Pedrazzoli, Mário; Knutson, Kristen L; Pereira, Alexandre C; von Schantz, Malcolm

2017-01-01

Significant questions remain unanswered regarding the genetic versus environmental contributions to racial/ethnic differences in sleep and circadian rhythms. We addressed this question by investigating the association between diurnal preference, using the morningness-eveningness questionnaire (MEQ), and genetic ancestry within the Baependi Heart Study cohort, a highly admixed Brazilian population based in a rural town. Analysis was performed using measures of ancestry, using the Admixture program, and MEQ from 1,453 individuals. We found an association between the degree of Amerindian (but not European of African) ancestry and morningness, equating to 0.16 units for each additional percent of Amerindian ancestry, after adjustment for age, sex, education, and residential zone. To our knowledge, this is the first published report identifying an association between genetic ancestry and MEQ, and above all, the first one based on ancestral contributions within individuals living in the same community. This previously unknown ancestral dimension of diurnal preference suggests a stratification between racial/ethnic groups in an as yet unknown number of genetic polymorphisms.

Allele-specific cytokine responses at the HLA-C locus, implications for psoriasis

Science.gov (United States)

Hundhausen, Christian; Bertoni, Anna; Mak, Rose K; Botti, Elisabetta; Di Meglio, Paola; Clop, Alex; Laggner, Ute; Chimenti, Sergio; Hayday, Adrian C; Barker, Jonathan N; Trembath, Richard C; Capon, Francesca; Nestle, Frank O

2011-01-01

Psoriasis is an inflammatory skin disorder that is inherited as a complex trait. Genetic studies have repeatedly highlighted HLA-C as the major determinant for psoriasis susceptibility, with the Cw*0602 allele conferring significant disease risk in a wide-range of populations. Despite the potential importance of HLA-C variation in psoriasis, either via an effect on peptide presentation or immuno-inhibitory activity, allele-specific expression patterns have not been investigated. Here, we used reporter assays to characterize two regulatory variants, which virtually abolished the response to TNF-α (rs2524094) and IFN-γ (rs10657191) in HLA-Cw*0602 and a cluster of related alleles. We validated these findings through the analysis of HLA-Cw*0602 expression in primary keratinocytes treated with TNF-α and IFN-γ. Finally, we showed that HLA-Cw*0602 transcripts are not increased in psoriatic skin lesions, despite highly elevated TNF-α levels. Thus, our findings demonstrate the presence of allele-specific differences in HLA-C expression and indicate that HLA-Cw*0602 is unresponsive to up-regulation by key pro-inflammatory cytokines in psoriasis. These data pave the way for functional studies into the pathogenic role of the major psoriasis susceptibility allele. PMID:22113476

Allele-specific cytokine responses at the HLA-C locus: implications for psoriasis.

Science.gov (United States)

Hundhausen, Christian; Bertoni, Anna; Mak, Rose K; Botti, Elisabetta; Di Meglio, Paola; Clop, Alex; Laggner, Ute; Chimenti, Sergio; Hayday, Adrian C; Barker, Jonathan N; Trembath, Richard C; Capon, Francesca; Nestle, Frank O

2012-03-01

Psoriasis is an inflammatory skin disorder that is inherited as a complex trait. Genetic studies have repeatedly highlighted HLA-C as the major determinant for psoriasis susceptibility, with the Cw*0602 allele conferring significant disease risk in a wide range of populations. Despite the potential importance of HLA-C variation in psoriasis, either via an effect on peptide presentation or immuno-inhibitory activity, allele-specific expression patterns have not been investigated. Here, we used reporter assays to characterize two regulatory variants, which virtually abolished the response to tumor necrosis factor (TNF)-α (rs2524094) and IFN-γ (rs10657191) in HLA-Cw*0602 and a cluster of related alleles. We validated these findings through the analysis of HLA-Cw*0602 expression in primary keratinocytes treated with TNF-α and IFN-γ. Finally, we showed that HLA-Cw*0602 transcripts are not increased in psoriatic skin lesions, despite highly elevated TNF-α levels. Thus, our findings demonstrate the presence of allele-specific differences in HLA-C expression and indicate that HLA-Cw*0602 is unresponsive to upregulation by key proinflammatory cytokines in psoriasis. These data pave the way for functional studies into the pathogenic role of the major psoriasis susceptibility allele.

Genetic variants demonstrating flip-flop phenomenon and breast cancer risk prediction among women of African ancestry.

Science.gov (United States)

Wang, Shengfeng; Qian, Frank; Zheng, Yonglan; Ogundiran, Temidayo; Ojengbede, Oladosu; Zheng, Wei; Blot, William; Nathanson, Katherine L; Hennis, Anselm; Nemesure, Barbara; Ambs, Stefan; Olopade, Olufunmilayo I; Huo, Dezheng

2018-04-01

Few studies have evaluated the performance of existing breast cancer risk prediction models among women of African ancestry. In replication studies of genetic variants, a change in direction of the risk association is a common phenomenon. Termed flip-flop, it means that a variant is risk factor in one population but protective in another, affecting the performance of risk prediction models. We used data from the genome-wide association study (GWAS) of breast cancer in the African diaspora (The Root consortium), which included 3686 participants of African ancestry from Nigeria, USA, and Barbados. Polygenic risk scores (PRSs) were constructed from the published odds ratios (ORs) of four sets of susceptibility loci for breast cancer. Discrimination capacity was measured using the area under the receiver operating characteristic curve (AUC). Flip-flop phenomenon was observed among 30~40% of variants across studies. Using the 34 variants with consistent directionality among previous studies, we constructed a PRS with AUC of 0.531 (95% confidence interval [CI]: 0.512-0.550), which is similar to the PRS using 93 variants and ORs from European ancestry populations (AUC = 0.525, 95% CI: 0.506-0.544). Additionally, we found the 34-variant PRS has good discriminative accuracy in women with family history of breast cancer (AUC = 0.586, 95% CI: 0.532-0.640). We found that PRS based on variants identified from prior GWASs conducted in women of European and Asian ancestries did not provide a comparable degree of risk stratification for women of African ancestry. Further large-scale fine-mapping studies in African ancestry populations are desirable to discover population-specific genetic risk variants.

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

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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. © 2016 American Academy of Forensic Sciences.

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

Directory of Open Access Journals (Sweden)

Sergio eTofanelli

2014-11-01

Full Text Available 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.

Measurement Uncertainty in Racial and Ethnic Identification among Adolescents of Mixed Ancestry: A Latent Variable Approach

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Tracy, Allison J.; Erkut, Sumru; Porche, Michelle V.; Kim, Jo; Charmaraman, Linda; Grossman, Jennifer M.; Ceder, Ineke; Garcia, Heidie Vazquez

2010-01-01

In this article, we operationalize identification of mixed racial and ethnic ancestry among adolescents as a latent variable to (a) account for measurement uncertainty, and (b) compare alternative wording formats for racial and ethnic self-categorization in surveys. Two latent variable models were fit to multiple mixed-ancestry indicator data from…

Assessing the risk for suicide in schizophrenia according to migration, ethnicity and geographical ancestry.

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Hettige, Nuwan C; Bani-Fatemi, Ali; Kennedy, James L; De Luca, Vincenzo

2017-02-09

Suicide is a leading cause of mortality among those afflicted by schizophrenia. Previous studies demonstrated that the stressors associated with immigration may lead to an onset of schizophrenia and suicide separately in susceptible individuals. However, no studies have shown whether immigration may lead to suicidal behaviour for individuals with schizophrenia. Our study proposes that an individual's geographical ancestry, ethnicity or migration status may be predictive of suicide risk in schizophrenia. In a sample of 276 participants with schizophrenia spectrum disorders, we conducted cross-sectional assessments to collect clinical information. Self-identified ethnicity and suicide history were collected through self-report questionnaires and interview-based scales. Ancestry was identified using 292 genetic markers from HapMap. Migrants were classified as those who immigrated to Canada during their lifetime. Using a regression analysis, we tested whether a history of migration, ethnicity or geographical ancestry were predictive of a history of suicide attempts. Our analysis failed to demonstrate a significant relationship between suicide history and migration, ethnicity or ancestry. However, ethnicity appears to be significantly associated with the number of psychiatric hospitalizations in our sample. Ethnicity and migration history are not predictive of previous suicide attempts. Ethnicity may be an important demographic factor affecting access to mental health resources and frequency of hospitalizations.

[Phenotypic effects of puroindoline gene alleles of bread wheat].

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Chebotar, S V; Kurakina, K O; Khokhlov, O M; Chebotar, H O; Syvolap, Iu M

2012-01-01

85 winter bread wheat varieties and lines that have been developed mostly in Ukraine were analyzed with NIR for parameters of hardness and protein content. The hardness data were compared with the data of puroindoline gene alleles analysis done earlier and the published data. Significant variation of parameters of hardness was revealed when there was low polymorphism of puroindoline genes indicating the presence of additional genes that influence the hardness parameters.

Considering the significance of ancestry through the prism of mixed-race identity.

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Tashiro, Cathy J

2002-12-01

People of mixed ancestry promise to be a significant percentage of the population of the United States in the 21st century. This article describes a qualitative study of 20 older mixed-race adults of African-American-white and Asian-American-white ancestries and focuses on how the participants construct identity. Using grounded theory methodology, racial identity did not emerge as a singular, distinct entity in this study, and five dimensions of racial identity were observed. Significant differences in patterns of identity dimensions were noted for the two mixed groups. Implications for nursing practice are discussed.

A Hidden Markov Model Approach for Simultaneously Estimating Local Ancestry and Admixture Time Using Next Generation Sequence Data in Samples of Arbitrary Ploidy.

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Corbett-Detig, Russell; Nielsen, Rasmus

2017-01-01

Admixture-the mixing of genomes from divergent populations-is increasingly appreciated as a central process in evolution. To characterize and quantify patterns of admixture across the genome, a number of methods have been developed for local ancestry inference. However, existing approaches have a number of shortcomings. First, all local ancestry inference methods require some prior assumption about the expected ancestry tract lengths. Second, existing methods generally require genotypes, which is not feasible to obtain for many next-generation sequencing projects. Third, many methods assume samples are diploid, however a wide variety of sequencing applications will fail to meet this assumption. To address these issues, we introduce a novel hidden Markov model for estimating local ancestry that models the read pileup data, rather than genotypes, is generalized to arbitrary ploidy, and can estimate the time since admixture during local ancestry inference. We demonstrate that our method can simultaneously estimate the time since admixture and local ancestry with good accuracy, and that it performs well on samples of high ploidy-i.e. 100 or more chromosomes. As this method is very general, we expect it will be useful for local ancestry inference in a wider variety of populations than what previously has been possible. We then applied our method to pooled sequencing data derived from populations of Drosophila melanogaster on an ancestry cline on the east coast of North America. We find that regions of local recombination rates are negatively correlated with the proportion of African ancestry, suggesting that selection against foreign ancestry is the least efficient in low recombination regions. Finally we show that clinal outlier loci are enriched for genes associated with gene regulatory functions, consistent with a role of regulatory evolution in ecological adaptation of admixed D. melanogaster populations. Our results illustrate the potential of local ancestry

SSR allelic diversity changes in 480 European bread wheat varieties released from 1840 to 2000.

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Roussel, V; Leisova, L; Exbrayat, F; Stehno, Z; Balfourier, F

2005-06-01

A sample of 480 bread wheat varieties originating from 15 European geographical areas and released from 1840 to 2000 were analysed with a set of 39 microsatellite markers. The total number of alleles ranged from 4 to 40, with an average of 16.4 alleles per locus. When seven successive periods of release were considered, the total number of alleles was quite stable until the 1960s, from which time it regularly decreased. Clustering analysis on Nei's distance matrix between these seven temporal groups showed a clear separation between groups of varieties registered before and after 1970. Analysis of qualitative variation over time in allelic composition of the accessions indicated that, on average, the more recent the European varieties, the more similar they were to each other. However, European accessions appear to be more differentiated as a function of their geographical origin than of their registration period. On average, western European countries (France, The Netherlands, Great Britain, Belgium) displayed a lower number of alleles than southeastern European countries (former Yugoslavia, Greece, Bulgaria, Romania, Hungary) and than the Mediterranean area (Italy, Spain and Portugal), which had a higher number. A hierarchical tree on Nei's distance matrix between the 15 geographical groups of accessions exhibited clear opposition between the geographical areas north and south of the arc formed by the Alps and the Carpathian mountains. These results suggest that diversity in European wheat accessions is not randomly distributed but can be explained both by temporal and geographical variation trends linked to breeding practices and agriculture policies in different countries.

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

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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

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

Science.gov (United States)

Shtir, Corina J; Marjoram, Paul; Azen, Stanley; Conti, David V; Le Marchand, Loic; Haiman, Christopher A; Varma, Rohit

2009-11-10

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. 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. 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 it will be important to assess this heterogeneity

Studying the Genetics of Complex Disease With Ancestry-Specific Human Phenotype Networks: The Case of Type 2 Diabetes in East Asian Populations.

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Qiu, Jingya; Moore, Jason H; Darabos, Christian

2016-05-01

Genome-wide association studies (GWAS) have led to the discovery of over 200 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes mellitus (T2DM). Additionally, East Asians develop T2DM at a higher rate, younger age, and lower body mass index than their European ancestry counterparts. The reason behind this occurrence remains elusive. With comprehensive searches through the National Human Genome Research Institute (NHGRI) GWAS catalog literature, we compiled a database of 2,800 ancestry-specific SNPs associated with T2DM and 70 other related traits. Manual data extraction was necessary because the GWAS catalog reports statistics such as odds ratio and P-value, but does not consistently include ancestry information. Currently, many statistics are derived by combining initial and replication samples from study populations of mixed ancestry. Analysis of all-inclusive data can be misleading, as not all SNPs are transferable across diverse populations. We used ancestry data to construct ancestry-specific human phenotype networks (HPN) centered on T2DM. Quantitative and visual analysis of network models reveal the genetic disparities between ancestry groups. Of the 27 phenotypes in the East Asian HPN, six phenotypes were unique to the network, revealing the underlying ancestry-specific nature of some SNPs associated with T2DM. We studied the relationship between T2DM and five phenotypes unique to the East Asian HPN to generate new interaction hypotheses in a clinical context. The genetic differences found in our ancestry-specific HPNs suggest different pathways are involved in the pathogenesis of T2DM among different populations. Our study underlines the importance of ancestry in the development of T2DM and its implications in pharmocogenetics and personalized medicine. © 2016 The Authors. *Genetic Epidemiology Published by Wiley Periodicals, Inc.

Surname-inferred Andean ancestry is associated with child stature and limb lengths at high altitude in Peru, but not at sea level.

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Pomeroy, Emma; Wells, Jonathan C K; Stanojevic, Sanja; Miranda, J Jaime; Moore, Lorna G; Cole, Tim J; Stock, Jay T

2015-01-01

Native Andean ancestry gives partial protection from reduced birthweight at high altitude in the Andes compared with European ancestry. Whether Andean ancestry is also associated with body proportions and greater postnatal body size at altitude is unknown. Therefore, we tested whether a greater proportion of Andean ancestry is associated with stature and body proportions among Peruvian children at high and low altitude. Height, head circumference, head-trunk height, upper and lower limb lengths, and tibia, ulna, hand and foot lengths, were measured in 133 highland and 169 lowland children aged 6 months to 8.5 years. For highland and lowland groups separately, age-sex-adjusted anthropometry z scores were regressed on the number of indigenous parental surnames as a proxy for Andean ancestry, adjusting for potential confounders (maternal age and education, parity, altitude [highlands only]). Among highland children, greater Andean ancestry was negatively associated with stature and tibia, ulna, and lower limb lengths, independent of negative associations with greater altitude for these measurements. Relationships were strongest for tibia length: each additional Andean surname or 1,000 m increase at altitude among highland children was associated with 0.18 and 0.65 z score decreases in tibia length, respectively. Anthropometry was not significantly associated with ancestry among lowland children. Greater Andean ancestry is associated with shorter stature and limb measurements at high but not low altitude. Gene-environment interactions between high altitude and Andean ancestry may exacerbate the trade-off between chest dimensions and stature that was proposed previously, though we could not test this directly. © 2015 Wiley Periodicals, Inc.

A matching-allele model explains host resistance to parasites.

Science.gov (United States)

Luijckx, Pepijn; Fienberg, Harris; Duneau, David; Ebert, Dieter

2013-06-17

The maintenance of genetic variation and sex despite its costs has long puzzled biologists. A popular idea, the Red Queen Theory, is that under rapid antagonistic coevolution between hosts and their parasites, the formation of new rare host genotypes through sex can be advantageous as it creates host genotypes to which the prevailing parasite is not adapted. For host-parasite coevolution to lead to an ongoing advantage for rare genotypes, parasites should infect specific host genotypes and hosts should resist specific parasite genotypes. The most prominent genetics capturing such specificity are matching-allele models (MAMs), which have the key feature that resistance for two parasite genotypes can reverse by switching one allele at one host locus. Despite the lack of empirical support, MAMs have played a central role in the theoretical development of antagonistic coevolution, local adaptation, speciation, and sexual selection. Using genetic crosses, we show that resistance of the crustacean Daphnia magna against the parasitic bacterium Pasteuria ramosa follows a MAM. Simulation results show that the observed genetics can explain the maintenance of genetic variation and contribute to the maintenance of sex in the facultatively sexual host as predicted by the Red Queen Theory. Copyright © 2013 Elsevier Ltd. All rights reserved.

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...

A microsatellite study for determination of allelic variation of Kurdish population-Kurdistan region-Iraq

Science.gov (United States)

Murad, Media J.; Amin, Bushra K.

2017-09-01

The purpose of this study was detecting genetic variations for the Kurdish population in Kurdistan region-Iraq, using fifteen autosomal STR loci. Buccal swabs were collected and depositing on Nucleic Card (Copan, Italia Spa) from 302 healthy unrelated Iraqi Kurds in five provinces of Kurdistan region-Iraq. Fifteen autosomal STR loci are D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, FGA and Amelogenin included in the AmpFlSTR Identifiler® Direct PCR Amplification Kit (Applied Biosystems, Foster City, CA, USA). No significant departure from Hardy Weinberg Equilibrium (HWE) expectations were observed in 10 from 15 STR loci analyzed (a 5% significance level was taken). The exceptions were the CSF1PO, D3S1358, D13S317, D16S539 and D2S1338 loci. Statistical parameters of forensic efficiencies were estimated for the loci, based on allelic frequencies. The mean of observed heterozygosity, expected heterozygosity and PIC values across the 15 loci were 0.762, 0.797 and 0.768 respectively, indicating high gene diversity. The combined probability of exclusion, power of discrimination, probability of matching value for all the 15 STR loci were 0.9999968; 0.9999999 and 4.966×10-17, respectively. These parameters indicated the importance of the loci for forensic genetic purposes and paternity testing.

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

Science.gov (United States)

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; Yu Mok, Zuan; 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; Ann Rozario, Michelle; 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

2016-01-01

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 × 10−21). 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

Elucidating the genetic architecture of reproductive ageing in the Japanese population.

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Horikoshi, Momoko; Day, Felix R; Akiyama, Masato; Hirata, Makoto; Kamatani, Yoichiro; Matsuda, Koichi; Ishigaki, Kazuyoshi; Kanai, Masahiro; Wright, Hollis; Toro, Carlos A; Ojeda, Sergio R; Lomniczi, Alejandro; Kubo, Michiaki; Ong, Ken K; Perry, John R B

2018-05-17

Population studies elucidating the genetic architecture of reproductive ageing have been largely limited to European ancestries, restricting the generalizability of the findings and overlooking possible key genes poorly captured by common European genetic variation. Here, we report 26 loci (all P Japanese ancestry). Highlighted genes for menopause include GNRH1, which supports a primary, rather than passive, role for hypothalamic-pituitary GnRH signalling in the timing of menopause. For puberty timing, we demonstrate an aetiological role for receptor-like protein tyrosine phosphatases by combining evidence across population genetics and pre- and peri-pubertal changes in hypothalamic gene expression in rodent and primate models. Furthermore, our findings demonstrate widespread differences in allele frequencies and effect estimates between Japanese and European associated variants, highlighting the benefits and challenges of large-scale trans-ethnic approaches.

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.

Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations.

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Pompei, Fiorenza; Ciminelli, Bianca Maria; Bombieri, Cristina; Ciccacci, Cinzia; Koudova, Monika; Giorgi, Silvia; Belpinati, Francesca; Begnini, Angela; Cerny, Milos; Des Georges, Marie; Claustres, Mireille; Ferec, Claude; Macek, Milan; Modiano, Guido; Pignatti, Pier Franco

2006-01-01

An average of about 1700 CFTR (cystic fibrosis transmembrane conductance regulator) alleles from normal individuals from different European populations were extensively screened for DNA sequence variation. A total of 80 variants were observed: 61 coding SNSs (results already published), 13 noncoding SNSs, three STRs, two short deletions, and one nucleotide insertion. Eight DNA variants were classified as non-CF causing due to their high frequency of occurrence. Through this survey the CFTR has become the most exhaustively studied gene for its coding sequence variability and, though to a lesser extent, for its noncoding sequence variability as well. Interestingly, most variation was associated with the M470 allele, while the V470 allele showed an 'extended haplotype homozygosity' (EHH). These findings make us suggest a role for selection acting either on the M470V itself or through an hitchhiking mechanism involving a second site. The possible ancient origin of the V allele in an 'out of Africa' time frame is discussed.

Energy homeostasis genes and breast cancer risk: The influence of ancestry, body size, and menopausal status, the breast cancer health disparities study.

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Slattery, Martha L; Lundgreen, Abbie; Hines, Lisa; Wolff, Roger K; Torres-Mejia, Gabriella; Baumgartner, Kathy N; John, Esther M

2015-12-01

Obesity and breast cancer risk is multifaceted and genes associated with energy homeostasis may modify this relationship. We evaluated 10 genes that have been associated with obesity and energy homeostasis to determine their association with breast cancer risk in Hispanic/Native American (2111 cases, 2597 controls) and non-Hispanic white (1481 cases, 1585 controls) women. Cholecystokinin (CCK) rs747455 and proopiomelanocortin (POMC) rs6713532 and rs7565877 (for low Indigenous American (IA) ancestry); CCK rs8192472 and neuropeptide Y (NYP) rs16141 and rs14129 (intermediate IA ancestry); and leptin receptor (LEPR) rs11585329 (high IA ancestry) were strongly associated with multiple indicators of body size. There were no significant associations with breast cancer risk between genes and SNPs overall. However, LEPR was significantly associated with breast cancer risk among women with low IA ancestry (PARTP=0.024); POMC was significantly associated with breast cancer risk among women with intermediate (PARTP=0.015) and high (PARTP=0.012) IA ancestry. The overall pathway was statistically significant for pre-menopausal women with low IA ancestry (PARTP=0.05), as was cocaine and amphetamine regulated transcript protein (CARTPT) (PARTP=0.014) and ghrelin (GHRL) (PARTP=0.007). POMC was significantly associated with breast cancer risk among post-menopausal women with higher IA ancestry (PARTP=0.005). Three SNPs in LEPR (rs6704167, rs17412175, and rs7626141), and adiponectin (ADIPOQ); rs822391) showed significant 4-way interactions (GxExMenopausexAncestry) for multiple indicators of body size among pre-menopausal women. Energy homeostasis genes were associated with breast cancer risk; menopausal status, body size, and genetic ancestry influenced this relationship. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fanconi anaemia in South African patients with Afrikaner ancestry ...

African Journals Online (AJOL)

Background. Fanconi anaemia (FA) is a rare genetic disorder of impaired DNA repair that results in physical and haematological consequences in affected individuals. In South Africa (SA), individuals with Afrikaner ancestry are at an increased risk of inheriting disease-causing FA mutations, owing to the three common ...

Allelic variations at the haploid TBX1 locus do not influence the cardiac phenotype in cases of 22q11 microdeletion.

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Voelckel, Marie-Antoinette; Girardot, Lydie; Giusiano, Bernard; Levy, Nicolas; Philip, Nicole

2004-01-01

Microdeletion at the 22q11 locus is characterised by a high clinical variability. Congenital heart defects (CHD) are the most life-threatening manifestations of the syndrome and affect approximately 50% of patients carrying the deleted chromosome 22. The causes of this phenotype variability remain unknown although several hypotheses have been raised. It has been suggested that allelic variations at the haploid locus could modify the phenotypic expression. Regarding this hypothesis, TBX1 was thought to be a major candidate to the cardiac phenotype or its severity in patients carrying the 22q11 microdeletion. A mutational screening was performed in this gene, in a series of 39 deleted patients, with and without CHD. The results indicate that mutations in TBX1 are not likely to be involved in the cardiac phenotype observed in del22q11 patients.

Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer.

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Huo, Dezheng; Feng, Ye; Haddad, Stephen; Zheng, Yonglan; Yao, Song; Han, Yoo-Jeong; Ogundiran, Temidayo O; Adebamowo, Clement; Ojengbede, Oladosu; Falusi, Adeyinka G; Zheng, Wei; Blot, William; Cai, Qiuyin; Signorello, Lisa; John, Esther M; Bernstein, Leslie; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah; Bandera, Elisa V; Ingles, Sue A; Press, Michael F; Deming, Sandra L; Rodriguez-Gil, Jorge L; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy R; Ruiz-Narváez, Edward A; Sucheston-Campbell, Lara E; Bensen, Jeannette T; Simon, Michael S; Hennis, Anselm; Nemesure, Barbara; Leske, M Cristina; Ambs, Stefan; Chen, Lin S; Qian, Frank; Gamazon, Eric R; Lunetta, Kathryn L; Cox, Nancy J; Chanock, Stephen J; Kolonel, Laurence N; Olshan, Andrew F; Ambrosone, Christine B; Olopade, Olufunmilayo I; Palmer, Julie R; Haiman, Christopher A

2016-11-01

Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina’s HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5 Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P = 1.8 × 10 − 8). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR = 1.30; P = 2.4 × 10 − 10) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR = 1.34; P = 2.2 × 10 − 8) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.

Crinoid ancestry without blastozoans

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Thomas E. Guensburg

2016-06-01

Full Text Available At present, a debate in the paleontologic literature focuses on whether or not the immediate ancestry of the Crinoidea lies in an unidentified member of the Blastozoa, which includes eocrinoids and an assemblage known variously as the “cystoids”. Those proposing to derive crinoids from within the blastozoans have recently argued for homologies in the construction of the oral region of certain derived taxa from both groups. An opposing viewpoint, outlined here, finds evidence that aside from plesiomorphies, proposed similarities are superficial and homoplastic. We suggest these superficialities represent convergent adaptive strategies. Earliest crinoids express ambulacral traits unlike any blastozoan but that are expressed in the only other pentaradial echinoderms with a known record early enough to be considered in the context of crinoid origins, edrioasteroids and edrioasteroid-like stem echinoderms.

PLCL1 rs7595412 variation is not associated with hip bone size variation in postmenopausal Danish women

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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.

Allele-dependent differences in quorum-sensing dynamics result in variant expression of virulence genes in Staphylococcus aureus.

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Geisinger, Edward; Chen, John; Novick, Richard P

2012-06-01

Agr is an autoinducing, quorum-sensing system that functions in many Gram-positive species and is best characterized in the pathogen Staphylococcus aureus, in which it is a global regulator of virulence gene expression. Allelic variations in the agr genes have resulted in the emergence of four quorum-sensing specificity groups in S. aureus, which correlate with different strain pathotypes. The basis for these predilections is unclear but is hypothesized to involve the phenomenon of quorum-sensing interference between strains of different agr groups, which may drive S. aureus strain isolation and divergence. Whether properties intrinsic to each agr allele directly influence virulence phenotypes within S. aureus is unknown. In this study, we examined group-specific differences in agr autoinduction and virulence gene regulation by utilizing congenic strains, each harboring a unique S. aureus agr allele, enabling a dissection of agr locus-dependent versus genotype-dependent effects on quorum-sensing dynamics and virulence factor production. Employing a reporter fusion to the principal agr promoter, P3, we observed allele-dependent differences in the timing and magnitude of agr activation. These differences were mediated by polymorphisms within the agrBDCA genes and translated to significant variations in the expression of a key transcriptional regulator, Rot, and of several important exoproteins and surface factors involved in pathogenesis. This work uncovers the contribution of divergent quorum-sensing alleles to variant expression of virulence determinants within a bacterial species.

Genome-Wide Association Analysis Reveals Genetic Heterogeneity of Sjögren's Syndrome According to Ancestry.

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Taylor, Kimberly E; Wong, Quenna; Levine, David M; McHugh, Caitlin; Laurie, Cathy; Doheny, Kimberly; Lam, Mi Y; Baer, Alan N; Challacombe, Stephen; Lanfranchi, Hector; Schiødt, Morten; Srinivasan, M; Umehara, Hisanori; Vivino, Frederick B; Zhao, Yan; Shiboski, Stephen C; Daniels, Troy E; Greenspan, John S; Shiboski, Caroline H; Criswell, Lindsey A

2017-06-01

The Sjögren's International Collaborative Clinical Alliance (SICCA) is an international data registry and biorepository derived from a multisite observational study of participants in whom genotyping was performed on the Omni2.5M platform and who had undergone deep phenotyping using common protocol-directed methods. The aim of this study was to examine the genetic etiology of Sjögren's syndrome (SS) across ancestry and disease subsets. We performed genome-wide association study analyses using SICCA subjects and external controls obtained from dbGaP data sets, one using all participants (1,405 cases, 1,622 SICCA controls, and 3,125 external controls), one using European participants (585, 966, and 580, respectively), and one using Asian participants (460, 224, and 901, respectively) with ancestry adjustments via principal components analyses. We also investigated whether subphenotype distributions differ by ethnicity, and whether this contributes to the heterogeneity of genetic associations. We observed significant associations in established regions of the major histocompatibility complex (MHC), IRF5, and STAT4 (P = 3 × 10 -42 , P = 3 × 10 -14 , and P = 9 × 10 -10 , respectively), and several novel suggestive regions (those with 2 or more associations at P ancestry (P = 4 × 10 -15 and P = 4 × 10 -5 , respectively), but that subphenotype differences did not explain most of the ancestry differences in genetic associations. Genetic associations with SS differ markedly according to ancestry; however, this is not explained by differences in subphenotypes. © 2017, The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

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 O.

2002-01-01

/GCA, MBL variant alleles were associated with signs of increased inflammatory activity and clinical signs of arteritic manifestations. This was not found for HLA-DR4 alleles. These findings indicate that HLA-DR4 and MBL are contributing to the pathophysiology of GCA at different levels in the disease...... alleles in controls, patients with PMR only, and patients with GCA was 37, 32, and 53% (p = 0.01), respectively. HLA-DRB1*04 was found in 47% of patients with PMR only and in 54% of patients with GCA, which differed significantly from the 35% found in controls (p = 0.01). HLA-DR4 alleles were...... not associated with any clinical phenotypes of PMR/GCA, whereas MBL variant alleles were associated with cranial arteritis, high erythrocyte sedimentation rate, and low B-hemoglobin. CONCLUSION: We found MBL variant alleles and HLA-DR4 alleles to be weak susceptibility markers for GCA. In patients with PMR...

Allelic barley MLA immune receptors recognize sequence-unrelated avirulence effectors of the powdery mildew pathogen.

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Lu, Xunli; Kracher, Barbara; Saur, Isabel M L; Bauer, Saskia; Ellwood, Simon R; Wise, Roger; Yaeno, Takashi; Maekawa, Takaki; Schulze-Lefert, Paul

2016-10-18

Disease-resistance genes encoding intracellular nucleotide-binding domain and leucine-rich repeat proteins (NLRs) are key components of the plant innate immune system and typically detect the presence of isolate-specific avirulence (AVR) effectors from pathogens. NLR genes define the fastest-evolving gene family of flowering plants and are often arranged in gene clusters containing multiple paralogs, contributing to copy number and allele-specific NLR variation within a host species. Barley mildew resistance locus a (Mla) has been subject to extensive functional diversification, resulting in allelic resistance specificities each recognizing a cognate, but largely unidentified, AVR a gene of the powdery mildew fungus, Blumeria graminis f. sp. hordei (Bgh). We applied a transcriptome-wide association study among 17 Bgh isolates containing different AVR a genes and identified AVR a1 and AVR a13 , encoding candidate-secreted effectors recognized by Mla1 and Mla13 alleles, respectively. Transient expression of the effector genes in barley leaves or protoplasts was sufficient to trigger Mla1 or Mla13 allele-specific cell death, a hallmark of NLR receptor-mediated immunity. AVR a1 and AVR a13 are phylogenetically unrelated, demonstrating that certain allelic MLA receptors evolved to recognize sequence-unrelated effectors. They are ancient effectors because corresponding loci are present in wheat powdery mildew. AVR A1 recognition by barley MLA1 is retained in transgenic Arabidopsis, indicating that AVR A1 directly binds MLA1 or that its recognition involves an evolutionarily conserved host target of AVR A1 Furthermore, analysis of transcriptome-wide sequence variation among the Bgh isolates provides evidence for Bgh population structure that is partially linked to geographic isolation.

Parasites and parallel divergence of the number of individual MHC alleles between sympatric three-spined stickleback Gasterosteus aculeatus morphs in Iceland.

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Natsopoulou, M E; Pálsson, S; Ólafsdóttir, G Á

2012-10-01

Two pairs of sympatric three-spined stickleback Gasterosteus aculeatus morphs and two single morph populations inhabiting mud and lava or rocky benthic habitats in four Icelandic lakes were screened for parasites and genotyped for MHC class IIB diversity. Parasitic infection differed consistently between G. aculeatus from different benthic habitats. Gasterosteus aculeatus from the lava or rocky habitats were more heavily infected in all lakes. A parallel pattern was also found in individual MHC allelic variation with lava G. aculeatus morphs exhibiting lower levels of variation than the mud morphs. Evidence for selective divergence in MHC allele number is ambiguous but supported by two findings in addition to the parallel pattern observed. MHC allele diversity was not consistent with diversity reported at neutral markers (microsatellites) and in Þingvallavatn the most common number of alleles in each morph was associated with lower infection levels. In the Þingvallavatn lava morph, lower infection levels by the two most common parasites, Schistocephalus solidus and Diplostomum baeri, were associated with different MHC allele numbers. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

Association of primary biliary cirrhosis with the allele HLA-DPB1*0301 in a German population.

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Mella, J G; Roschmann, E; Maier, K P; Volk, B A

1995-02-01

The major histocompatibility complex class II alleles at the HLA-DPB1 locus were investigated in 32 German Caucasoid patients with primary biliary cirrhosis (PBC) and compared with those from 47 normal control patients using molecular genotyping techniques. The second exon of the HLA-DPB1 gene was amplified by polymerase chain reaction (PCR) and hybridized with 25 sequence-specific oligonucleotides (SSOs) to assign the HLA-DPB1 alleles on the basis of known sequence variations, according to the protocols of the Eleventh International Histocompatibility Workshop. A strong association of PBC was found with the allele HLA-DPB1*0301. The allele HLA DPB1*0301 was present in 50% (16 of 32) of the patients with PBC compared with 13% (6 of 47) of normal controls (P corrected < .015), whereas the other HLA-DPB1 alleles showed no significant differences in both groups. The relative risk (RR) estimate for the allele HLA-DPB1*0301 was 6.8 (95% confidence limits: 2.27 to 20.57). In summary, this study clearly demonstrates an association of PBC with the HLA-DPB1*0301 allele in German Caucasoids and may add new data to the immunogenetic background of PBC, suggesting a contribution of the HLA-DPB1 gene to the genetic susceptibility of the disease.

Multiple loci associated with renal function in African Americans.

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Daniel Shriner

Full Text Available The incidence of chronic kidney disease varies by ethnic group in the USA, with African Americans displaying a two-fold higher rate than European Americans. One of the two defining variables underlying staging of chronic kidney disease is the glomerular filtration rate. Meta-analysis in individuals of European ancestry has identified 23 genetic loci associated with the estimated glomerular filtration rate (eGFR. We conducted a follow-up study of these 23 genetic loci using a population-based sample of 1,018 unrelated admixed African Americans. We included in our follow-up study two variants in APOL1 associated with end-stage kidney disease discovered by admixture mapping in admixed African Americans. To address confounding due to admixture, we estimated local ancestry at each marker and global ancestry. We performed regression analysis stratified by local ancestry and combined the resulting regression estimates across ancestry strata using an inverse variance-weighted fixed effects model. We found that 11 of the 24 loci were significantly associated with eGFR in our sample. The effect size estimates were not significantly different between the subgroups of individuals with two copies of African ancestry vs. two copies of European ancestry for any of the 11 loci. In contrast, allele frequencies were significantly different at 10 of the 11 loci. Collectively, the 11 loci, including four secondary signals revealed by conditional analyses, explained 14.2% of the phenotypic variance in eGFR, in contrast to the 1.4% explained by the 24 loci in individuals of European ancestry. Our findings provide insight into the genetic basis of variation in renal function among admixed African Americans.

Bonobos fall within the genomic variation of chimpanzees.

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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.

A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure

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Timothy M. Frayling

2018-04-01

Full Text Available Summary: Fibroblast growth factor 21 (FGF21 is a hormone that has insulin-sensitizing properties. Some trials of FGF21 analogs show weight loss and lipid-lowering effects. Recent studies have shown that a common allele in the FGF21 gene alters the balance of macronutrients consumed, but there was little evidence of an effect on metabolic traits. We studied a common FGF21 allele (A:rs838133 in 451,099 people from the UK Biobank study, aiming to use the human allele to inform potential adverse and beneficial effects of targeting FGF21. We replicated the association between the A allele and higher percentage carbohydrate intake. We then showed that this allele is more strongly associated with higher blood pressure and waist-hip ratio, despite an association with lower total body-fat percentage, than it is with BMI or type 2 diabetes. These human phenotypes of variation in the FGF21 gene will inform research into FGF21’s mechanisms and therapeutic potential. : Drugs targeting the hormone FGF21 may have beneficial health effects. Variations in human DNA in the FGF21 gene provide an indication of what those effects may be. Here, we show that variation in the FGF21 gene is associated with higher blood pressure and altered body shape, despite lower total body-fat percentage. Keywords: FGF21, BMI, waist-hip ratio, blood pressure, body fat, allele, genetic variant, UK Biobank

HLA-DQA1 and HLA-DQB1 allele diversity and its extended haplotypes in Madeira Island (Portugal).

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Spínola, H; Lemos, A; Couto, A R; Parreira, B; Soares, M; Dutra, I; Bruges-Armas, J; Brehm, A

2017-02-01

This study shows, for the first time, high-resolution allele frequencies of HLA-DQA1 loci in Madeira Island (Portugal) and allows us to better understand and refine present knowledge on DQB1 variation, with the identification of several alleles not previously reported in this population. Estimates on haplotype profile, involving HLA-A, HLA-B, HLA-DRB1, HLA-DQA1 and HLA-DQB1, are also reported. © 2016 John Wiley & Sons Ltd.

Identification of Low Molecular Weight Glutenin Alleles by Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) in Common Wheat (Triticum aestivum L.)

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Islam, Shahidul; Applebee, Marie; Appels, Rudi; Yan, Yueming; Ma, Wujun

2015-01-01

Low molecular weight glutenin subunits (LMW-GS) play an important role in determining dough properties and breadmaking quality. However, resolution of the currently used methodologies for analyzing LMW-GS is rather low which prevents an efficient use of genetic variations associated with these alleles in wheat breeding. The aim of the current study is to evaluate and develop a rapid, simple, and accurate method to differentiate LMW-GS alleles using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A set of standard single LMW-GS allele lines as well as a suite of well documented wheat cultivars were collected from France, CIMMYT, and Canada. Method development and optimization were focused on protein extraction procedures and MALDI-TOF instrument settings to generate reproducible diagnostic spectrum peak profiles for each of the known wheat LMW-GS allele. Results revealed a total of 48 unique allele combinations among the studied genotypes. Characteristic MALDI-TOF peak patterns were obtained for 17 common LMW-GS alleles, including 5 (b, a or c, d, e, f), 7 (a, b, c, d or i, f, g, h) and 5 (a, b, c, d, f) patterns or alleles for the Glu-A3, Glu-B3, and Glu-D3 loci, respectively. In addition, some reproducible MALDI-TOF peak patterns were also obtained that did not match with any known alleles. The results demonstrated a high resolution and throughput nature of MALDI-TOF technology in analyzing LMW-GS alleles, which is suitable for application in wheat breeding programs in processing a large number of wheat lines with high accuracy in limited time. It also suggested that the variation of LMW-GS alleles is more abundant than what has been defined by the current nomenclature system that is mainly based on SDS-PAGE system. The MALDI-TOF technology is useful to differentiate these variations. An international joint effort may be needed to assign allele symbols to these newly identified alleles and determine their effects on end

Genome-wide association study meta-analysis of European and Asian-ancestry samples identifies three novel loci associated with bipolar disorder.

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Chen, D T; Jiang, X; Akula, N; Shugart, Y Y; Wendland, J R; Steele, C J M; Kassem, L; Park, J-H; Chatterjee, N; Jamain, S; Cheng, A; Leboyer, M; Muglia, P; Schulze, T G; Cichon, S; Nöthen, M M; Rietschel, M; McMahon, F J; Farmer, A; McGuffin, P; Craig, I; Lewis, C; Hosang, G; Cohen-Woods, S; Vincent, J B; Kennedy, J L; Strauss, J

2013-02-01

Meta-analyses of bipolar disorder (BD) genome-wide association studies (GWAS) have identified several genome-wide significant signals in European-ancestry samples, but so far account for little of the inherited risk. We performed a meta-analysis of ∼750,000 high-quality genetic markers on a combined sample of ∼14,000 subjects of European and Asian-ancestry (phase I). The most significant findings were further tested in an extended sample of ∼17,700 cases and controls (phase II). The results suggest novel association findings near the genes TRANK1 (LBA1), LMAN2L and PTGFR. In phase I, the most significant single nucleotide polymorphism (SNP), rs9834970 near TRANK1, was significant at the P=2.4 × 10(-11) level, with no heterogeneity. Supportive evidence for prior association findings near ANK3 and a locus on chromosome 3p21.1 was also observed. The phase II results were similar, although the heterogeneity test became significant for several SNPs. On the basis of these results and other established risk loci, we used the method developed by Park et al. to estimate the number, and the effect size distribution, of BD risk loci that could still be found by GWAS methods. We estimate that >63,000 case-control samples would be needed to identify the ∼105 BD risk loci discoverable by GWAS, and that these will together explain <6% of the inherited risk. These results support previous GWAS findings and identify three new candidate genes for BD. Further studies are needed to replicate these findings and may potentially lead to identification of functional variants. Sample size will remain a limiting factor in the discovery of common alleles associated with BD.

Mutation rate heterogeneity and the generation of allele diversity at the human minisatellite MS205 (D16S309).

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May, C A; Jeffreys, A J; Armour, J A

1996-11-01

Many tandemly repeated minisatellite loci display extreme levels of length variation as a consequence of high rates of spontaneous germline mutation altering repeat copy number. Direct screening for new allele lengths by small-pool PCR has shown that instability at the human minisatellite locus MS205 (D16S309) is largely germline specific and usually results in the gain or loss of just a few repeat units. Structural analysis of the order of variant repeats has shown that these events occur preferentially at one end of the tandem array and can result in complex rearrangements including the inter-allelic transfer of repeat units. In contrast, putative mutants recovered from somatic DNA occur at a substantially lower rate and are simple and non-polar in nature. Germline mutation rates vary considerably between alleles, consistent with regulation occurring in cis. Although examination of DNA sequence polymorphisms immediately flanking the minisatellite reveals no definitive associations with germline mutation rate variation, differences in rate may be paralleled by changes in mutation spectrum. These findings help to explain the diversity of MS205 allele structures in modern humans and suggest a common mutation pathway with some other minisatellites.

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...... 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...

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

NARCIS (Netherlands)

Shahin, A.; Smulders, M.J.M.; Tuyl, van J.M.; Arens, P.F.P.; Bakker, F.T.

2014-01-01

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

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......-out using the results of all STR loci in the case sample as reference. The methodology of logistic regression is appropriate for this analysis, and we demonstrate how to incorporate this in a forensic genetic framework....

Allele frequencies of AVPR1A and MAOA in the Afrikaner population

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J. Christoff Erasmus

2015-07-01

Full Text Available The Afrikaner population was founded mainly by European immigrants that arrived in South Africa from 1652. However, female slaves from Asia and Africa and local KhoeSan women may have contributed as much as 7% to this population’s genes. We quantified variation at two tandem repeats to see if this historical founder effect and/or admixture could be detected. The two loci were chosen because they are in the promoters of genes of neurotransmitters that are known to be correlated with social behaviour. Specifically, arginine vasopressin receptor 1A’s (AVPR1A RS3 locus has been shown to correlate with age of sexual onset and happiness in monogamous relationships while the tandem repeat in the promoter of the monoamine oxidase A (MAOA gene correlates with reactive aggression. The Afrikaner population contained more AVPR1A RS3 alleles than other Caucasoid populations, potentially reflecting a history of admixture. Even though Afrikaners have one of the lowest recorded non-paternity rates in the world, the population did not differ at AVPR1A RS3 locus form other European populations, suggesting a non-genetic explanation, presumably religion, for the low non-paternity rate. By comparing population allele-frequency spectra it was found that different studies have confused AVPR1A RS3 alleles and we make some suggestions to rectify these mistakes in future studies. While MAOA allele frequencies differed between racial groups, the Afrikaner population showed no evidence of admixture. In fact, Afrikaners had more 4-repeat alleles than other populations of European origin, not fewer. The 4-repeat allele may have been selected for during colonisation.

An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans

DEFF Research Database (Denmark)

Scott, Robert A; Scott, Laura J; Mägi, Reedik

2017-01-01

To characterise type 2 diabetes (T2D) associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D cases and 132,532 controls of European ancestry after imputation using the 1000 Genomes multi-ethnic reference panel. Promi...... secretion, and in adipocytes, monocytes and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology....

The DRD4 exon III VNTR, bupropion, and associations with prospective abstinence.

Science.gov (United States)

Bergen, Andrew W; Javitz, Harold S; Su, Li; He, Yungang; Conti, David V; Benowitz, Neal L; Tyndale, Rachel F; Lerman, Caryn; Swan, Gary E

2013-07-01

DRD4 Exon III Variable Number of Tandem Repeat (VNTR) variation was found to interact with bupropion to influence prospective smoking abstinence, in a recently published longitudinal analyses of N = 331 individuals from a randomized double-blind placebo-controlled trial of bupropion and intensive cognitive-behavioral mood management therapy. We used univariate, multivariate, and longitudinal logistic regression to evaluate gene, treatment, time, and interaction effects on point prevalence and continuous abstinence at end of treatment, 6 months, and 12 months, respectively, in N = 416 European ancestry participants in a double-blind pharmacogenetic efficacy trial randomizing participants to active or placebo bupropion. Participants received 10 weeks of pharmacotherapy and 7 sessions of behavioral therapy, with a target quit date 2 weeks after initiating both therapies. VNTR genotypes were coded with the long allele dominant resulting in 4 analysis categories. Covariates included demographics, dependence measures, depressive symptoms, and genetic ancestry. We also performed genotype-stratified secondary analyses. We observed significant effects of time in longitudinal analyses of both abstinence outcomes, of treatment in individuals with VNTR long allele genotypes for both abstinence outcomes, and of covariates in some analyses. We observed non-significantly larger differences in active versus placebo effect sizes in individuals with VNTR long allele genotypes than in individuals without the VNTR long allele, in the directions previously reported. VNTR by treatment interaction differences between these and previous analyses may be attributable to insufficient size of the replication sample. Analyses of multiple randomized clinical trials will enable identification and validation of factors mediating treatment response.

Differentiation of African components of ancestry to stratify groups in a case-control study of a Brazilian urban population.

Science.gov (United States)

Silbiger, Vivian N; Hirata, Mario H; Luchessi, Andre D; Genvigir, Fabiana D V; Cerda, Alvaro; Rodrigues, Alice C; Willrich, Maria A V; Arazi, Simone S; Dorea, Egidio L; Bernik, Marcia M S; Faludi, Andre A; Bertolami, Marcelo C; Santos, Carla; Carracedo, Angel; Salas, Antonio; Freire, Ana; Lareu, Maria Victoria; Phillips, Christopher; Porras-Hurtado, Liliana; Fondevila, Manuel; Hirata, Rosario D C

2012-06-01

Balancing the subject composition of case and control groups to create homogenous ancestries between each group is essential for medical association studies. We explored the applicability of single-tube 34-plex ancestry informative markers (AIM) single nucleotide polymorphisms (SNPs) to estimate the African Component of Ancestry (ACA) to design a future case-control association study of a Brazilian urban sample. One hundred eighty individuals (107 case group; 73 control group) self-described as white, brown-intermediate or black were selected. The proportions of the relative contribution of a variable number of ancestral population components were similar between case and control groups. Moreover, the case and control groups demonstrated similar distributions for ACA 0.50 categories. Notably a high number of outlier values (23 samples) were observed among individuals with ACA population. This can be achieved using a straight forward multiplexed AIM-SNPs assay of highly discriminatory ancestry markers.

A simple and optimal ancestry labeling scheme for trees

DEFF Research Database (Denmark)

Dahlgaard, Søren; Knudsen, Mathias Bæk Tejs; Rotbart, Noy Galil

2015-01-01

We present a lg n + 2 lg lg n + 3 ancestry labeling scheme for trees. The problem was first presented by Kannan et al. [STOC 88’] along with a simple 2 lg n solution. Motivated by applications to XML files, the label size was improved incrementally over the course of more than 20 years by a series...

Global phylogeography of the avian malaria pathogen Plasmodium relictum based on MSP1 allelic diversity

Science.gov (United States)

Hellgren, Olof; Atkinson, Carter T.; Bensch, Staffan; Albayrak, Tamer; Dimitrov, Dimitar; Ewen, John G.; Kim, Kyeong Soon; Lima, Marcos R.; Martin, Lynn; Palinauskas, Vaidas; Ricklefs, Robert; Sehgal, Ravinder N. M.; Gediminas, Valkiunas; Tsuda, Yoshio; Marzal, Alfonso

2015-01-01

Knowing the genetic variation that occurs in pathogen populations and how it is distributed across geographical areas is essential to understand parasite epidemiology, local patterns of virulence, and evolution of host-resistance. In addition, it is important to identify populations of pathogens that are evolutionarily independent and thus ‘free’ to adapt to hosts and environments. Here, we investigated genetic variation in the globally distributed, highly invasive avian malaria parasite Plasmodium relictum, which has several distinctive mitochondrial haplotyps (cyt b lineages, SGS1, GRW11 and GRW4). The phylogeography of P. relictum was accessed using the highly variable nuclear gene merozoite surface protein 1 (MSP1), a gene linked to the invasion biology of the parasite. We show that the lineage GRW4 is evolutionarily independent of GRW11 and SGS1 whereas GRW11 and SGS1 share MSP1 alleles and thus suggesting the presence of two distinct species (GRW4 versus SGS1 and GRW11). Further, there were significant differences in the global distribution of MSP1 alleles with differences between GRW4 alleles in the New and the Old World. For SGS1, a lineage formerly believed to have both tropical and temperate transmission, there were clear differences in MSP1 alleles transmitted in tropical Africa compared to the temperate regions of Europe and Asia. Further, we highlight the occurrence of multiple MSP1 alleles in GRW4 isolates from the Hawaiian Islands, where the parasite has contributed to declines and extinctions of endemic forest birds since it was introduced. This study stresses the importance of multiple independent loci for understanding patterns of transmission and evolutionary independence across avian malaria parasites.

Assessing Patterns of Admixture and Ancestry in Canadian Honey Bees

Science.gov (United States)

Canada has a large beekeeping industry comprised of 8483 beekeepers managing 672094 23 colonies. Canadian honey bees, like all honey bees in the New World, originate from centuries of importation of predominately European honey bees, but their precise ancestry remains unknown. There have been no i...

Patterns of ancestry, signatures of natural selection, and genetic association with stature in Western African pygmies.

Directory of Open Access Journals (Sweden)

Joseph P Jarvis

Full Text Available African Pygmy groups show a distinctive pattern of phenotypic variation, including short stature, which is thought to reflect past adaptation to a tropical environment. Here, we analyze Illumina 1M SNP array data in three Western Pygmy populations from Cameroon and three neighboring Bantu-speaking agricultural populations with whom they have admixed. We infer genome-wide ancestry, scan for signals of positive selection, and perform targeted genetic association with measured height variation. We identify multiple regions throughout the genome that may have played a role in adaptive evolution, many of which contain loci with roles in growth hormone, insulin, and insulin-like growth factor signaling pathways, as well as immunity and neuroendocrine signaling involved in reproduction and metabolism. The most striking results are found on chromosome 3, which harbors a cluster of selection and association signals between approximately 45 and 60 Mb. This region also includes the positional candidate genes DOCK3, which is known to be associated with height variation in Europeans, and CISH, a negative regulator of cytokine signaling known to inhibit growth hormone-stimulated STAT5 signaling. Finally, pathway analysis for genes near the strongest signals of association with height indicates enrichment for loci involved in insulin and insulin-like growth factor signaling.

Effect of ancestry on interleukin-10 haplotypes in chronic periodontitis.

Science.gov (United States)

Lopes, Camile de Barros; Barroso, Regina Fatima Feio; Burbano, Rommel Mario Rodrigues; Garcia, Patricia Aleixo; Pinto, Pablo Diego do Carmo; Santos, Ney Pereira Carneiro Dos; Santos, Sidney Emanuel Batista; Ribeiro-Dos-Santos, Andrea Kely Campos

2017-06-01

Chronic periodontitis is caused by an inflammatory reaction of the periodontal tissues and alveolar bone. This inflammation is caused by periodontopathic bacteria located in the subgingival biofilm, resulting in inflammatory reactions that may lead to loss of attachment. This tissue destruction is a consequence of host immune and inflammatory responses to specific periodontal pathogens and their metabolic products. Cytokines modulate the immune response, altering its efficiency in the competition against pathogens and increasing periodontal susceptibility. This study investigated genetic polymorphisms in Interleukin 10 (A-1082G, C-819T and C-592A) in 205 individuals from an admixed Brazilian population. A significantly increased risk of developing chronic periodontitis was observed in individuals with low IL-10 production and Amerindian ancestry. These results suggest that the polymorphisms A-1082G, C-819T, and C-592A, which are associated with ancestry, are involved in the susceptibility to the development of chronic periodontitis in an admixed northern Brazilian population.

Genetic Bio-Ancestry and Social Construction of Racial Classification in Social Surveys in the Contemporary United States

Science.gov (United States)

Guo, Guang; Fu, Yilan; Lee, Hedwig; Cai, Tianji; Harris, Kathleen Mullan; Li, Yi

2013-01-01

Self-reported race is generally considered the basis for racial classification in social surveys, including the U.S. census. Drawing on recent advances in human molecular genetics and social science perspectives of socially constructed race, our study takes into account both genetic bio-ancestry and social context in understanding racial classification. This article accomplishes two objectives. First, our research establishes geographic genetic bio-ancestry as a component of racial classification. Second, it shows how social forces trump biology in racial classification and/or how social context interacts with bio-ancestry in shaping racial classification. The findings were replicated in two racially and ethnically diverse data sets: the College Roommate Study (N = 2,065) and the National Longitudinal Study of Adolescent Health (N = 2,281). PMID:24019100

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

Science.gov (United States)

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, Guanji; 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; 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.; Freedman, Barry I.; Gillanders, Elizabeth M.; Gottesman, Omri; Guo, Xiuqing; Haritunians, Talin; Harris, Tamara; Harris, Curtis C.; Hennis, Anselm JM; 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.; Velez Edwards, Digna R.; 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, Michèle 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.; Zhu, Xiaofeng; Zonderman, Alan B.; Kooperberg, Charles; Papanicolaou, George; Henderson, Brian E.; Reiner, Alex P.; Hirschhorn, Joel N.; Loos, Ruth JF; 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 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 with data from the Giant consortium (MIR148A/NFE2L3, rs10261878, p=1.2×10−10). We also found suggestive evidence of an association at a third locus at 6q16 in the African ancestry sample (KLHL32, rs974417, p=6.9×10−8). Thirty-two of the 36 previously established BMI variants displayed directionally consistent effect estimates in our GWAS (binomial p=9.7×10−7), of which five reached genome-wide significance. These findings provide strong support for shared BMI loci across populations as well as for the utility of studying ancestrally diverse populations. PMID:23583978

Forensic Applicability of Femur Subtrochanteric Shape to Ancestry Assessment in Thai and White American Males.

Science.gov (United States)

Tallman, Sean D; Winburn, Allysha P

2015-09-01

Ancestry assessment from the postcranial skeleton presents a significant challenge to forensic anthropologists. However, metric dimensions of the femur subtrochanteric region are believed to distinguish between individuals of Asian and non-Asian descent. This study tests the discriminatory power of subtrochanteric shape using modern samples of 128 Thai and 77 White American males. Results indicate that the samples' platymeric index distributions are significantly different (p≤0.001), with the Thai platymeric index range generally lower and the White American range generally higher. While the application of ancestry assessment methods developed from Native American subtrochanteric data results in low correct classification rates for the Thai sample (50.8-57.8%), adapting these methods to the current samples leads to better classification. The Thai data may be more useful in forensic analysis than previously published subtrochanteric data derived from Native American samples. Adapting methods to include appropriate geographic and contemporaneous populations increases the accuracy of femur subtrochanteric ancestry methods. © 2015 American Academy of Forensic Sciences.

The paternal ancestry of Uttarakhand does not imitate the classical caste system of India.

Science.gov (United States)

Negi, Neetu; Tamang, Rakesh; Pande, Veena; Sharma, Amrita; Shah, Anish; Reddy, Alla G; Vishnupriya, Satti; Singh, Lalji; Chaubey, Gyaneshwer; Thangaraj, Kumarasamy

2016-02-01

Although, there have been rigorous research on the Indian caste system by several disciplines, it is still one of the most controversial socioscientific topic. Previous genetic studies on the subcontinent have supported a classical hierarchal sharing of genetic component by various castes of India. In the present study, we have used high-resolution mtDNA and Y chromosomal markers to characterize the genetic structuring of the Uttarakhand populations in the context of neighboring regions. Furthermore, we have tested whether the genetic structuring of caste populations at different social levels of this region, follow the classical chaturvarna system. Interestingly, we found that this region showed a high level of variation for East Eurasian ancestry in both maternal and paternal lines of descent. Moreover, the intrapopulation comparison showed a high level of heterogeneity, likely because of different caste hierarchy, interpolated on asymmetric admixture of populations inhabiting on both sides of the Himalayas.

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

2014-12-12

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.

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

Isles ancestry. In the present study we used 122 new and 19 previously published hypervariable region I sequences of the mitochondrial control region to analyse the genetic diversity of the Faroese population and compare it with other populations in the North Atlantic region. The analyses suggested...... that the Faroese mtDNA pool has been affected by genetic drift, and is among the most homogenous and isolated in the North Atlantic region. This will have implications for attempts to locate genes for complex disorders. To obtain estimates of Scandinavian vs British Isles ancestry proportions, we applied...... a 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...

Effect of Glu-B3 Allelic Variation on Sodium Dodecyl Sulfate Sedimentation Volume in Common Wheat (Triticum aestivum L.

Directory of Open Access Journals (Sweden)

Hongqi Si

2013-01-01

Full Text Available Sodium dodecyl sulfate (SDS sedimentation volume has long been used to characterize wheat flours and meals with the aim of predicting processing and end-product qualities. In order to survey the influence of low-molecular-weight glutenin subunits (LMW-GSs at Glu-B3 locus on wheat SDS sedimentation volume, a total of 283 wheat (Triticum aestivum L. varieties including landraces and improved and introduced cultivars were analyzed using 10 allele-specific PCR markers at the Glu-B3 locus. The highest allele frequency observed in the tested varieties was Glu-B3i with 21.9% in all varieties, 21.1% in landraces, 25.5% in improved cultivars, and 12% in introduced cultivars. Glu-B3 locus represented 8.6% of the variance in wheat SDS sedimentation volume, and Glu-B3b, Glu-B3g, and Glu-B3h significantly heightened the SDS sedimentation volume, but Glu-B3a, Glu-B3c, and Glu-B3j significantly lowered the SDS sedimentation volume. For the bread-making quality, the most desirable alleles Glu-B3b and Glu-B3g become more and more popular and the least desirable alleles Glu-B3a and Glu-B3c got less and less in modern improved cultivars, suggesting that wheat grain quality in China has been significantly improved through breeding effort.

Significant others and the importance of ancestry for Czech national identity

Czech Academy of Sciences Publication Activity Database

Plecitá, Klára

(2018) ISSN 1460-8944 R&D Projects: GA MŠk(CZ) LG12023 Institutional support: RVO:68378025 Keywords : national identity * ancestry * immigration Subject RIV: AO - Sociology, Demography OBOR OECD: Sociology http://www.tandfonline.com/doi/full/10.1080/14608944.2017.1362378

A panel of 130 autosomal single-nucleotide polymorphisms for ancestry assignment in five Asian populations and in Caucasians.

Science.gov (United States)

Hwa, Hsiao-Lin; Lin, Chih-Peng; Huang, Tsun-Ying; Kuo, Po-Hsiu; Hsieh, Wei-Hsin; Lin, Chun-Yen; Yin, Hsiang-I; Tseng, Li-Hui; Lee, James Chun-I

2017-06-01

Ancestry informative single-nucleotide polymorphism (AISNP) panels for differentiating between East and Southeast Asian populations are scarce. This study aimed to identify AISNPs for ancestry assignment of five East and Southeast Asian populations, and Caucasians. We analyzed 145 autosomal SNPs of the 627 DNA samples from individuals of six populations (234 Taiwanese Han, 91 Filipinos, 79 Indonesians, 60 Thais, 71 Vietnamese, and 92 Caucasians) using arrays. The multiple logistic regression model and a multi-tier approach were used for ancestry classification. We observed that 130 AISNPs were effective for classifying the ethnic origins with fair accuracy. Among the 130 AISNPs, 122 were useful for stratification between these five Asian populations and 64 were effective for differentiating between Caucasians and these Asian populations. For differentiation between Caucasians and Asians, an accuracy rate of 100% was achieved in these 627 subjects with 50 optimal AISNPs among the 64 effective SNPs. For classification of the five Asian populations, the accuracy rates of ancestry inference using 20 to 57 SNPs for each of the two Asian populations ranged from 74.1% to 100%. Another 14 degraded DNA samples with incomplete profiling were analyzed, and the ancestry of 12 (85.7%) of those subjects was accurately assigned. We developed a 130-AISNP panel for ethnic origin differentiation between the five East and Southeast Asian populations and Caucasians. This AISNP set may be helpful for individual ancestral assignment of these populations in forensic casework.

Evaluation of inflammation-related genes polymorphisms in Mexican with Alzheimer’s disease: a pilot study

Directory of Open Access Journals (Sweden)

Danira eToral-Rios

2015-05-01

Full Text Available Amyloid peptide is able to promote the activation of microglia and astrocytes in Alzheimer’s disease (AD, and this stimulates the production of pro-inflammatory cytokines. Inflammation contributes to the process of neurodegeneration and therefore is a key factor in the development of AD. Some of the most important proteins involved in AD inflammation are: clusterin (CLU, complement receptor 1 (CR1, C reactive protein (CRP, tumor necrosis factor α (TNF- α, the interleukins 1α (IL - 1α, 6 (IL-6, 10 (IL-10 and cyclooxygenase 2 (COX-2. In particular, COX-2 is encoded by the prostaglandin-endoperoxide synthase 2 gene (PTGS2. Since variations in the genes that encode these proteins may modify gene expression or function, it is important to investigate whether these variations may change the developing AD. The aim of this study was to determine whether the presence of polymorphisms in the genes encoding the aforementioned proteins is associated Mexican patients with AD. Fourteen polymorphisms were genotyped in 96 subjects with AD and the differences in allele, genotype and haplotype frequencies were analyzed. Additionally, an ancestry analysis was conducted to exclude differences in genetic ancestry among groups as a confounding factor in the study. Significant differences in frequencies between AD and controls were found for the SNP rs20417 within the PTGS2 gene. Ancestry analysis revealed no significant differences in the ancestry of the compared groups, and the association was significant even after adjustment for ancestry and correction for multiple testing, which strengthens the validity of the results. We conclude that this polymorphism plays an important role in the development of the AD pathology and further studies are required, including their proteins.

Genetic ancestry in relation to the metabolic response to a US versus traditional Mexican diet: a randomized crossover feeding trial among women of Mexican descent.

Science.gov (United States)

Santiago-Torres, M; De Dieu Tapsoba, J; Kratz, M; Lampe, J W; Breymeyer, K L; Levy, L; Song, X; Villaseñor, A; Wang, C-Y; Fejerman, L; Neuhouser, M L; Carlson, C S

2017-03-01

Certain populations with a large proportion of indigenous American (IA) genetic ancestry may be evolutionarily adapted to traditional diets high in legumes and complex carbohydrates, and may have a detrimental metabolic response to US diets high in refined carbohydrates and added sugars. We tested whether IA ancestry modified the metabolic response to a US versus traditional Mexican diet in a controlled dietary intervention. First and second generation Mexican immigrant women (n=53) completed a randomized crossover feeding trial testing the effects of a US versus traditional Mexican diet. The metabolic response to the diets was measured by fasting serum concentrations of glucose, insulin, insulin-like growth factor-1 (IGF-1), IGF-binding protein-3 (IGFBP-3), adiponectin, C-reactive protein, interleukin-6 and computed homeostasis model assessment for insulin resistance (HOMA IR ). Blood collected at baseline was used for genotyping, and estimation of African, European and IA ancestries with the use of 214 ancestry informative markers. The genetic ancestral background was 56% IA, 38% European and 6% African. Women in the highest IA ancestry tertile (>62%) were shorter in height, less educated and less acculturated to the US lifestyle, and tended to have higher waist-to-hip ratio compared with women in the middle and lowest IA ancestry tertiles, respectively. Compared with the US diet, the traditional Mexican diet tended to reduce glucose, insulin, IGF-1, IGFBP-3 and HOMA IR among women in the middle IA ancestry group (IA ancestry ⩽45-62%), whereas having no effect on biomarkers related to inflammation. We observed modest interactions between IA ancestry and the metabolic response to a US versus traditional Mexican diet among Mexican immigrant women.

Genetic variation of the angiotensin-converting enzyme gene: increased frequency of the insertion allele in Koreans.

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Hong, S H; Kang, B Y; Park, W H; Kim, J Q; Lee, C C

1997-01-01

In view of the clinical importance of angiotensin-converting enzyme (ACE) as a major marker for cardiovascular diseases, we investigated insertion/deletion (I/D) polymorphism of the ACE gene in Koreans. Genotype frequencies were examined by polymerase chain reaction in 171 patients with coronary artery disease (CAD) and 120 healthy subjects. Allele frequencies of ACE polymorphism in Koreans were not significantly different between patient and control groups. In addition, association between ACE genotypes and the number of stenosed coronary arteries was not detected. ACE genotypes in the CAD group were not associated with body mass index and plasma lipid levels. Thus, our results suggest that, at least in Koreans, I/D polymorphism of the gene is unlikely to be a useful marker for CAD subjects. However, the I allele frequency of Koreans (0.58) was higher than that of Caucasian populations (0.47) but lower than that of Samoan (0.91) and Yanomami (0.85) populations. Here, we discuss the clinical and ethnic importance of ACE polymorphism.

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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Population-genetic nature of copy number variations in the human genome.

Science.gov (United States)

Kato, Mamoru; Kawaguchi, Takahisa; Ishikawa, Shumpei; Umeda, Takayoshi; Nakamichi, Reiichiro; Shapero, Michael H; Jones, Keith W; Nakamura, Yusuke; Aburatani, Hiroyuki; Tsunoda, Tatsuhiko

2010-03-01

Copy number variations (CNVs) are universal genetic variations, and their association with disease has been increasingly recognized. We designed high-density microarrays for CNVs, and detected 3000-4000 CNVs (4-6% of the genomic sequence) per population that included CNVs previously missed because of smaller sizes and residing in segmental duplications. The patterns of CNVs across individuals were surprisingly simple at the kilo-base scale, suggesting the applicability of a simple genetic analysis for these genetic loci. We utilized the probabilistic theory to determine integer copy numbers of CNVs and employed a recently developed phasing tool to estimate the population frequencies of integer copy number alleles and CNV-SNP haplotypes. The results showed a tendency toward a lower frequency of CNV alleles and that most of our CNVs were explained only by zero-, one- and two-copy alleles. Using the estimated population frequencies, we found several CNV regions with exceptionally high population differentiation. Investigation of CNV-SNP linkage disequilibrium (LD) for 500-900 bi- and multi-allelic CNVs per population revealed that previous conflicting reports on bi-allelic LD were unexpectedly consistent and explained by an LD increase correlated with deletion-allele frequencies. Typically, the bi-allelic LD was lower than SNP-SNP LD, whereas the multi-allelic LD was somewhat stronger than the bi-allelic LD. After further investigation of tag SNPs for CNVs, we conclude that the customary tagging strategy for disease association studies can be applicable for common deletion CNVs, but direct interrogation is needed for other types of CNVs.

Abnormal segregation of alleles in CEPH pedigree DNAs arising from allele loss in lymphoblastoid DNA.

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Royle, N J; Armour, J A; Crosier, M; Jeffreys, A J

1993-01-01

Somatic events that result in the reduction to hemi- or homozygosity at all loci affected by the event have been identified in lymphoblastoid DNA from mothers of two CEPH families. Using suitably informative probes, the allele deficiencies were detected by the abnormal transmission of alleles from grandparents to grandchildren, with the apparent absence of the alleles from the parent. Undetected somatic deficiencies in family DNAs could result in misscoring of recombination events and consequently introduce errors into linkage analysis.

European Population Genetic Substructure: Further Definition of Ancestry Informative Markers for Distinguishing Among Diverse European Ethnic Groups

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Tian, Chao; Kosoy, Roman; Nassir, Rami; Lee, Annette; Villoslada, Pablo; Klareskog, Lars; Hammarström, Lennart; Garchon, Henri-Jean; Pulver, Ann E.; Ransom, Michael; Gregersen, Peter K.; Seldin, Michael F.

2009-01-01

The definition of European population genetic substructure and its application to understanding complex phenotypes is becoming increasingly important. In the current study using over 4000 subjects genotyped for 300 thousand SNPs we provide further insight into relationships among European population groups and identify sets of SNP ancestry informative markers (AIMs) for application in genetic studies. In general, the graphical description of these principal components analyses (PCA) of diverse European subjects showed a strong correspondence to the geographical relationships of specific countries or regions of origin. Clearer separation of different ethnic and regional populations was observed when northern and southern European groups were considered separately and the PCA results were influenced by the inclusion or exclusion of different self-identified population groups including Ashkenazi Jewish, Sardinian and Orcadian ethnic groups. SNP AIM sets were identified that could distinguish the regional and ethnic population groups. Moreover, the studies demonstrated that most allele frequency differences between different European groups could be effectively controlled in analyses using these AIM sets. The European substructure AIMs should be widely applicable to ongoing studies to confirm and delineate specific disease susceptibility candidate regions without the necessity to perform additional genome-wide SNP studies in additional subject sets. PMID:19707526

Polymorphic genes of major effect: consequences for variation, selection and evolution in Arabidopsis thaliana.

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Stinchcombe, John R; Weinig, Cynthia; Heath, Katy D; Brock, Marcus T; Schmitt, Johanna

2009-07-01

The importance of genes of major effect for evolutionary trajectories within and among natural populations has long been the subject of intense debate. For example, if allelic variation at a major-effect locus fundamentally alters the structure of quantitative trait variation, then fixation of a single locus can have rapid and profound effects on the rate or direction of subsequent evolutionary change. Using an Arabidopsis thaliana RIL mapping population, we compare G-matrix structure between lines possessing different alleles at ERECTA, a locus known to affect ecologically relevant variation in plant architecture. We find that the allele present at ERECTA significantly alters G-matrix structure-in particular the genetic correlations between branch number and flowering time traits-and may also modulate the strength of natural selection on these traits. Despite these differences, however, when we extend our analysis to determine how evolution might differ depending on the ERECTA allele, we find that predicted responses to selection are similar. To compare responses to selection between allele classes, we developed a resampling strategy that incorporates uncertainty in estimates of selection that can also be used for statistical comparisons of G matrices.

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

Ancestry and Language in the United States: November 1979. Current Population Reports, Special Studies. Series P-23. No. 116.

Science.gov (United States)

Levin, Michael J.; Sweet, Nancy S.

Information on the ancestry, languages, and literacy of the U.S. population based on data collected by the Bureau of the Census in 1979 is reported. Items surveyed include ancestry, country of birth of the individual and parents, citizenship, year of immigration, native language, language spoken in the home, ability to speak English, and ability…

Haemoglobin A1c as a screening tool for type 2 diabetes and prediabetes in populations of Swedish and Middle-East ancestry.

Science.gov (United States)

Hellgren, Margareta; Hjörleifsdottir Steiner, Kristin; Bennet, Louise

2017-08-01

To explore and compare sensitivity and specificity for HbA1c ≥48mmol/mol as a predictor for type 2 diabetes mellitus (T2DM) in two populations with different ethnicity and to examine the predictive value of two levels of HbA1c (≥42mmol/mol, ≥39mmol/mol) for prediabetes in these populations. Four cohorts were examined with an oral glucose tolerance test. (1) The MEDIM Study (n=1991 individuals of Swedish and Iraqi ancestry); (2) The Skaraborg Project (n=1327 individuals of Swedish ancestry); (3) The 4-D study (n=424 individuals of Swedish, Iraqi and Turkish ancestry); (4) The Flemingsberg study (n=212 participants of Turkish ancestry). HbA1c ≥48mmol/mol had a sensitivity for T2DM of 31% and 25% respectively in individuals of Middle-East and Swedish ancestry. The positive and negative predictive value was high in both populations (70.3, 96.4 and 96.2, 97.6 respectively). Using HbA1c ≥42mmol/mol and ≥39mmol/mol as a predictor for prediabetes gave a sensitivity of 17% and 36% in individuals of Middle-East and 15% and 34% in individuals of Swedish ancestry. Even if HbA1c ≥48mmol/mol is a valuable diagnostic tool, it is a blunt and insensitive tool for screening and would exclude most people with T2DM, independent of ancestry and age. HbA1c is an inefficient way to detect individuals with prediabetes. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Class II HLA interactions modulate genetic risk for multiple sclerosis

Science.gov (United States)

Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D’Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen; McVean, Gil

2016-01-01

Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles. PMID:26343388

Genetic Ancestry Is not Associated with Breast Cancer Recurrence or Survival in U.S. Latina Women Enrolled in the Kaiser Permanente Pathways Study.

Science.gov (United States)

Engmann, Natalie J; Ergas, Isaac J; Yao, Song; Kwan, Marilyn L; Roh, Janise M; Ambrosone, Christine B; Kushi, Lawrence H; Fejerman, Laura

2017-09-01

Background: The U.S. Hispanic/Latino population is heterogeneous both socioculturally and by the proportion of European, Indigenous American, and African ancestry of the regions from which individuals originate. A previous study reported that genetic ancestry was associated with breast cancer survival among Latinas, independent of sociodemographic and tumor characteristics, suggesting that a genetic factor associated with ancestry may affect breast cancer survival. Methods: We evaluated the association of genetic ancestry with breast cancer outcomes among 506 Latina women with invasive breast cancer in the Pathways Study, a cohort study within Kaiser Permanente, an integrated health care delivery system. Proportional hazards models were used to assess the effect of ancestry on breast cancer recurrence (53 events), breast cancer-specific mortality (31 events) and all-cause mortality (54 events), with a mean follow-up time of 6 years. Results: Indigenous American ancestry was not associated with breast cancer recurrence [HR = 1.00 per 10% increase; 95% confidence interval (CI), 0.86-1.16], breast cancer mortality (HR = 0.95; 95% CI, 0.77-1.17), or all-cause mortality (HR = 0.93; 95% CI, 0.80-1.08). Adjustment for sociodemographic variables, tumor characteristics, and treatment did not alter the associations. Conclusions: Our results suggest that previously reported differences in breast cancer survival by genetic ancestry may be overcome by improving health care access and/or quality. Impact: Improving health care access and quality may reduce breast cancer disparities among U.S. Latinas. Cancer Epidemiol Biomarkers Prev; 26(9); 1466-9. ©2017 AACR . ©2017 American Association for Cancer Research.

Allelic variation at the 8q23.3 colorectal cancer risk locus functions as a cis-acting regulator of EIF3H.

Directory of Open Access Journals (Sweden)

Alan M Pittman

2010-09-01

Full Text Available Common genetic variation at human 8q23.3 is significantly associated with colorectal cancer (CRC risk. To elucidate the basis of this association we compared the frequency of common variants at 8q23.3 in 1,964 CRC cases and 2,081 healthy controls. Reporter gene studies showed that the single nucleotide polymorphism rs16888589 acts as an allele-specific transcriptional repressor. Chromosome conformation capture (3C analysis demonstrated that the genomic region harboring rs16888589 interacts with the promoter of gene for eukaryotic translation initiation factor 3, subunit H (EIF3H. We show that increased expression of EIF3H gene increases CRC growth and invasiveness thereby providing a biological mechanism for the 8q23.3 association. These data provide evidence for a functional basis for the non-coding risk variant rs16888589 at 8q23.3 and provides novel insight into the etiological basis of CRC.

OSBPL10, RXRA and lipid metabolism confer African-ancestry protection against dengue haemorrhagic fever in admixed Cubans.

Directory of Open Access Journals (Sweden)

Beatriz Sierra

2017-02-01

Full Text Available Ethnic groups can display differential genetic susceptibility to infectious diseases. The arthropod-born viral dengue disease is one such disease, with empirical and limited genetic evidence showing that African ancestry may be protective against the haemorrhagic phenotype. Global ancestry analysis based on high-throughput genotyping in admixed populations can be used to test this hypothesis, while admixture mapping can map candidate protective genes. A Cuban dengue fever cohort was genotyped using a 2.5 million SNP chip. Global ancestry was ascertained through ADMIXTURE and used in a fine-matched corrected association study, while local ancestry was inferred by the RFMix algorithm. The expression of candidate genes was evaluated by RT-PCR in a Cuban dengue patient cohort and gene set enrichment analysis was performed in a Thai dengue transcriptome. OSBPL10 and RXRA candidate genes were identified, with most significant SNPs placed in inferred weak enhancers, promoters and lncRNAs. OSBPL10 had significantly lower expression in Africans than Europeans, while for RXRA several SNPs may differentially regulate its transcription between Africans and Europeans. Their expression was confirmed to change through dengue disease progression in Cuban patients and to vary with disease severity in a Thai transcriptome dataset. These genes interact in the LXR/RXR activation pathway that integrates lipid metabolism and immune functions, being a key player in dengue virus entrance into cells, its replication therein and in cytokine production. Knockdown of OSBPL10 expression in THP-1 cells by two shRNAs followed by DENV2 infection tests led to a significant reduction in DENV replication, being a direct functional proof that the lower OSBPL10 expression profile in Africans protects this ancestry against dengue disease.

Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives.

Science.gov (United States)

Brutsaert, Tom D; Parra, Esteban J; Shriver, Mark D; Gamboa, Alfredo; Rivera-Ch, Maria; León-Velarde, Fabiola

2005-07-01

Andean high-altitude (HA) natives have a low (blunted) hypoxic ventilatory response (HVR), lower effective alveolar ventilation, and lower ventilation (VE) at rest and during exercise compared with acclimatized newcomers to HA. Despite blunted chemosensitivity and hypoventilation, Andeans maintain comparable arterial O(2) saturation (Sa(O(2))). This study was designed to evaluate the influence of ancestry on these trait differences. At sea level, we measured the HVR in both acute (HVR-A) and sustained (HVR-S) hypoxia in a sample of 32 male Peruvians of mainly Quechua and Spanish origins who were born and raised at sea level. We also measured resting and exercise VE after 10-12 h of exposure to altitude at 4,338 m. Native American ancestry proportion (NAAP) was assessed for each individual using a panel of 80 ancestry-informative molecular markers (AIMs). NAAP was inversely related to HVR-S after 10 min of isocapnic hypoxia (r = -0.36, P = 0.04) but was not associated with HVR-A. In addition, NAAP was inversely related to exercise VE (r = -0.50, P = 0.005) and ventilatory equivalent (VE/Vo(2), r = -0.51, P = 0.004) measured at 4,338 m. Thus Quechua ancestry may partly explain the well-known blunted HVR (10, 35, 36, 57, 62) at least to sustained hypoxia, and the relative exercise hypoventilation at altitude of Andeans compared with European controls. Lower HVR-S and exercise VE could reflect improved gas exchange and/or attenuated chemoreflex sensitivity with increasing NAAP. On the basis of these ancestry associations and on the fact that developmental effects were completely controlled by study design, we suggest both a genetic basis and an evolutionary origin for these traits in Quechua.

Genetic variation in caribou and reindeer (Rangifer tarandus).

Science.gov (United States)

Cronin, M A; Patton, J C; Balmysheva, N; MacNeil, M D

2003-02-01

Genetic variation at seven microsatellite DNA loci was quantified in 19 herds of wild caribou and domestic reindeer (Rangifer tarandus) from North America, Scandinavia and Russia. There is an average of 2.0-6.6 alleles per locus and observed individual heterozygosity of 0.33-0.50 in most herds. A herd on Svalbard Island, Scandinavia, is an exception, with relatively few alleles and low heterozygosity. The Central Arctic, Western Arctic and Porcupine River caribou herds in Alaska have similar allele frequencies and comprise one breeding population. Domestic reindeer in Alaska originated from transplants from Siberia, Russia, more than 100 years ago. Reindeer in Alaska and Siberia have different allele frequencies at several loci, but a relatively low level of genetic differentiation. Wild caribou and domestic reindeer in Alaska have significantly different allele frequencies at the seven loci, indicating that gene flow between reindeer and caribou in Alaska has been limited.

PGG.Population: a database for understanding the genomic diversity and genetic ancestry of human populations.

Science.gov (United States)

Zhang, Chao; Gao, Yang; Liu, Jiaojiao; Xue, Zhe; Lu, Yan; Deng, Lian; Tian, Lei; Feng, Qidi; Xu, Shuhua

2018-01-04

There are a growing number of studies focusing on delineating genetic variations that are associated with complex human traits and diseases due to recent advances in next-generation sequencing technologies. However, identifying and prioritizing disease-associated causal variants relies on understanding the distribution of genetic variations within and among populations. The PGG.Population database documents 7122 genomes representing 356 global populations from 107 countries and provides essential information for researchers to understand human genomic diversity and genetic ancestry. These data and information can facilitate the design of research studies and the interpretation of results of both evolutionary and medical studies involving human populations. The database is carefully maintained and constantly updated when new data are available. We included miscellaneous functions and a user-friendly graphical interface for visualization of genomic diversity, population relationships (genetic affinity), ancestral makeup, footprints of natural selection, and population history etc. Moreover, PGG.Population provides a useful feature for users to analyze data and visualize results in a dynamic style via online illustration. The long-term ambition of the PGG.Population, together with the joint efforts from other researchers who contribute their data to our database, is to create a comprehensive depository of geographic and ethnic variation of human genome, as well as a platform bringing influence on future practitioners of medicine and clinical investigators. PGG.Population is available at https://www.pggpopulation.org. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Identification of internal variation in the pseudoautosomal VNTR DXYS17, with nonrandom distribution of the alleles on the X and the Y chromosomes

Energy Technology Data Exchange (ETDEWEB)

Decorte, R.; Wu, R.; Marynen, P.; Cassiman, J.J.

1994-03-01

The PCR technique was used to analyze the DXYS17 locus in the pseudoautosomal region of the X and the Y chromosomes. Analysis on an automated DNA sequencer allowed for sensitive and highly accurate typing of 16 different alleles with a size between 480 and 1,100 bp. Two DXYS17 alleles migrated with the same size on agarose or denaturing polyacrylamide gels but with different mobilities on nondenaturing polyacrylamide gels. Sequence analysis showed that, while an identical number of repeats were present in both alleles, differences in the composition of the units were observed. The origin of these differences was found in the 28- and 33-bp units, which only had a specific repeat pattern at the 5' and 3' ends of the region. The genotype distribution for DXYS17 in a Caucasian population did not deviate from the values expected under Hardy-Weinberg equilibrium. However, the frequency of one allele and one genotype was significantly different between males and females. Segregation analysis showed that this difference was the result of a nonrandom distribution of certain alleles on the sex chromosomes in males. 31 refs., 4 figs., 2 tabs.

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

NARCIS (Netherlands)

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

2015-01-01

textabstractWe 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

Genetic structure, diversity, and allelic richness in composite collection and reference set in chickpea (Cicer arietinum L.

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Gowda Cholenahalli LL

2008-10-01

Full Text Available Abstract Background Plant genetic resources (PGR are the basic raw materials for future genetic progress and an insurance against unforeseen threats to agricultural production. An extensive characterization of PGR provides an opportunity to dissect structure, mine allelic variations, and identify diverse accessions for crop improvement. The Generation Challenge Program http://www.generationcp.org conceptualized the development of "composite collections" and extraction of "reference sets" from these for more efficient tapping of global crop-related genetic resources. In this study, we report the genetic structure, diversity and allelic richness in a composite collection of chickpea using SSR markers, and formation of a reference set of 300 accessions. Results The 48 SSR markers detected 1683 alleles in 2915 accessions, of which, 935 were considered rare, 720 common and 28 most frequent. The alleles per locus ranged from 14 to 67, averaged 35, and the polymorphic information content was from 0.467 to 0.974, averaged 0.854. Marker polymorphism varied between groups of accessions in the composite collection and reference set. A number of group-specific alleles were detected: 104 in Kabuli, 297 in desi, and 69 in wild Cicer; 114 each in Mediterranean and West Asia (WA, 117 in South and South East Asia (SSEA, and 10 in African region accessions. Desi and kabuli shared 436 alleles, while wild Cicer shared 17 and 16 alleles with desi and kabuli, respectively. The accessions from SSEA and WA shared 74 alleles, while those from Mediterranean 38 and 33 alleles with WA and SSEA, respectively. Desi chickpea contained a higher proportion of rare alleles (53% than kabuli (46%, while wild Cicer accessions were devoid of rare alleles. A genotype-based reference set captured 1315 (78% of the 1683 composite collection alleles of which 463 were rare, 826 common, and 26 the most frequent alleles. The neighbour-joining tree diagram of this reference set represents

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

the 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...

Fanconi Anaemia in South African Patients with Afrikaner Ancestry

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C Feben

2017-10-01

Full Text Available Background. Fanconi anaemia (FA is a rare genetic disorder of impaired DNA repair that results in physical and haematological consequences in affected individuals. In South Africa (SA, individuals with Afrikaner ancestry are at an increased risk of inheriting disease-causing FA mutations, owing to the three common FANCA (FA, complementation group A founder mutations present in this population subgroup. Objectives. To describe the physical phenotype of SA patients with FANCA mutations for the purpose of recommending appropriate care for affected individuals. Methods. A structured clinical examination and file-based review were used to evaluate the physical phenotype of 7 patients with compound heterozygous and homozygous FANCA founder mutations, and 1 patient with confirmed FANCA complementation analysis. Descriptive statistical analysis was used to determine the frequency of physical anomalies in Afrikaner patients and to compare the described phenotype to other FA cohorts, including a previously clinically characterised black SA FA cohort. Results. An earlier age of diagnosis of FA in Afrikaner patients, a high frequency of somatic anomalies and a higher-than-expected incidence of the VACTERL/H phenotype were noted. Conclusions. Based on our findings, recommendations for the care of FA patients with Afrikaner ancestry are made, including renal ultrasound evaluation at diagnosis and hearing screening

Ultraconserved words point to deep language ancestry across Eurasia.

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Pagel, Mark; Atkinson, Quentin D; S Calude, Andreea; Meade, Andrew

2013-05-21

The search for ever deeper relationships among the World's languages is bedeviled by the fact that most words evolve too rapidly to preserve evidence of their ancestry beyond 5,000 to 9,000 y. On the other hand, quantitative modeling indicates that some "ultraconserved" words exist that might be used to find evidence for deep linguistic relationships beyond that time barrier. Here we use a statistical model, which takes into account the frequency with which words are used in common everyday speech, to predict the existence of a set of such highly conserved words among seven language families of Eurasia postulated to form a linguistic superfamily that evolved from a common ancestor around 15,000 y ago. We derive a dated phylogenetic tree of this proposed superfamily with a time-depth of ~14,450 y, implying that some frequently used words have been retained in related forms since the end of the last ice age. Words used more than once per 1,000 in everyday speech were 7- to 10-times more likely to show deep ancestry on this tree. Our results suggest a remarkable fidelity in the transmission of some words and give theoretical justification to the search for features of language that might be preserved across wide spans of time and geography.

Estimated allele substitution effects underlying genomic evaluation models depend on the scaling of allele counts

NARCIS (Netherlands)

Bouwman, Aniek C.; Hayes, Ben J.; Calus, Mario P.L.

2017-01-01

Background: Genomic evaluation is used to predict direct genomic values (DGV) for selection candidates in breeding programs, but also to estimate allele substitution effects (ASE) of single nucleotide polymorphisms (SNPs). Scaling of allele counts influences the estimated ASE, because scaling of

An abbreviated SNP panel for ancestry assignment of honeybees (Apis mellifera)

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This paper examines whether an abbreviated panel of 37 single nucleotide polymorphisms (SNPs) has the same power as a larger and more expensive panel of 95 SNPs to assign ancestry of honeybees (Apis mellifera) to three ancestral lineages. We selected 37 SNPs from the original 95 SNP panel using alle...

Does ancestry influence health-related quality of life in type 1 diabetes patients? A nationwide study in Brazil.

Science.gov (United States)

Santos, Deborah Conte; Pizarro, Marcela Haas; Barros, Bianca S V; de Melo, Laura G Nunes; Porto, Luis Cristovão; Silva, Dayse A; Gomes, Marilia Brito

2018-04-01

The aim of the present study was to evaluate the relationship between self-reported color/race and genomic ancestry with HRQoL of patients with type 1 diabetes in a highly admixed population. This was a nationwide, cross-sectional study conducted with 1760 patients with type 1 diabetes from 2011 to 2014 at public clinics in all five Brazilian geographical regions. Information on HRQoL was obtained from two self-completed questionnaires: Short Form-6 Dimensions (SF-6D) and EuroQol-5 Dimensions (EQ-5D) with a visual analogue scale (EQ-VAS). Genomic ancestry was assessed using a Multiplex PCR methodology. Utility scores generated from the questionnaires were analyzed with multivariate logistic regression models. We included 1698 patients. Those patients who self-reported as black had lower EQ-VAS scores compared to the patients who self-reported as white (67.46 ± 18.45; 72.37 ± 16.44, respectively, p = 0.02). In a linear regression model, each 1% increase in African ancestry resulted in a 9.5 point decrease in EQ-VAS score (p ancestry remained associated with lower EQ-VAS scores. A higher level of African ancestry implicates on lower quality of life even after adjustments for sociodemographic and diabetes-related data. Gender, physical activity and diabetes-related microvascular complications were strongly associated with low HRQoL in all three questionnaires used. This fact highlights the importance of social aspects when assessing quality of life, as well as the need for regular practice of physical activity and prevention of chronic complications to improve patients' quality of life.

Novel procedure for genotyping of the human serotonin transporter gene-linked polymorphic region (5-HTTLPR)--a region with a high level of allele diversity

DEFF Research Database (Denmark)

Rasmussen, Henrik B; Werge, Thomas M

2007-01-01

determination. After having developed a 5-HTTLPR genotyping assay, we examined all samples of DNA in two separate rounds of analyses and found complete agreement between the results from these two rounds. CONCLUSION: On the basis of simultaneous analysis of tandem repeat size variation and variation of single......BACKGROUND: The serotonin transporter, the target of a group of antidepressant drugs, is involved in the regulation of the availability and reuptake of serotonin. A variable number of tandem repeats in the promoter region of the serotonin transporter gene, designated 5-HTTLPR, affects...... for detailed genotyping of 5-HTTLPR based upon simultaneous analysis of tandem repeat size variation and single nucleotide variations. METHODS: We elaborated a list of all known 5-HTTLPR alleles to provide an overview of the allele repertoire at this polymorphic locus. Fragments of 5-HTTLPR were PCR...

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...

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

NARCIS (Netherlands)

Kato, Norihiro; Loh, Marie; Takeuchi, Fumihiko; Verweij, Niek; Wang, Xu; Zhang, Weihua; Kelly, Tanika N.; Saleheen, Danish; Lehne, Benjamin; Leach, Irene Mateo; 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, Tonu; 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; Alves, Alexessander Da Silva Couto; Das, Shikta; Dorajoo, Rajkumar; Hopewell, Jemma C.; Kim, Yun Kyoung; Koivula, Robert W.; Luan, Jian'an; Lyytikainen, 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, Ines; 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.; Katsuy, 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; Mueller-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; Sparso, 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, Vaino; Ueshima, Hirotsugu; Uitterlinden, Andre 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; Jorgensen, Torben; Jukema, J. Wouter; Kahonen, Mika; Kajio, Hiroshi; Kivimaki, Mika; Lee, Jong-Young; Lehtimaki, Terho; Linneberg, Allan; Miki, Tetsuro; Pedersen, Oluf; Samani, Nilesh J.; Sorensen, 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; Maerz, 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.

2015-01-01

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 x 10(-11) to 5.0 x

Typing of two Middle Eastern populations with the Precision ID Ancestry Panel

DEFF Research Database (Denmark)

Truelsen, Ditte Mikkelsen; Farzad, Maryam Sharafi; Mogensen, Helle Smidt

2017-01-01

, Turkish and Iranian individuals were SNP typed with Massively Parallel Sequencing with the Precision ID Ancestry Panel (Thermo Fisher Scientific) to assess whether it was possible to differentiate geographically proximate populations in the Middle East using this kit. Analyses showed that it were...

Inter- and intra-individual variation in allele-specific DNA methylation and gene expression in children conceived using assisted reproductive technology.

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Nahid Turan

2010-07-01

Full Text Available Epidemiological studies have reported a higher incidence of rare disorders involving imprinted genes among children conceived using assisted reproductive technology (ART, suggesting that ART procedures may be disruptive to imprinted gene methylation patterns. We examined intra- and inter-individual variation in DNA methylation at the differentially methylated regions (DMRs of the IGF2/H19 and IGF2R loci in a population of children conceived in vitro or in vivo. We found substantial variation in allele-specific methylation at both loci in both groups. Aberrant methylation of the maternal IGF2/H19 DMR was more common in the in vitro group, and the overall variance was also significantly greater in the in vitro group. We estimated the number of trophoblast stem cells in each group based on approximation of the variance of the binomial distribution of IGF2/H19 methylation ratios, as well as the distribution of X chromosome inactivation scores in placenta. Both of these independent measures indicated that placentas of the in vitro group were derived from fewer stem cells than the in vivo conceived group. Both IGF2 and H19 mRNAs were significantly lower in placenta from the in vitro group. Although average birth weight was lower in the in vitro group, we found no correlation between birth weight and IGF2 or IGF2R transcript levels or the ratio of IGF2/IGF2R transcript levels. Our results show that in vitro conception is associated with aberrant methylation patterns at the IGF2/H19 locus. However, very little of the inter- or intra-individual variation in H19 or IGF2 mRNA levels can be explained by differences in maternal DMR DNA methylation, in contrast to the expectations of current transcriptional imprinting models. Extraembryonic tissues of embryos cultured in vitro appear to be derived from fewer trophoblast stem cells. It is possible that this developmental difference has an effect on placental and fetal growth.

HLA-DQ genetic risk gradient for type 1 diabetes and celiac disease in north-western Mexico

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M.E. Mejía-León

2015-04-01

Conclusion: The Sonoran population has a distinctive HLA-DQ allele distribution due to its ancestry. The HLA-DQ8 combinations with DQ2 or one of its alleles conferred the highest risk for both diseases and T1D and CD frequently appear together.

On universal common ancestry, sequence similarity, and phylogenetic structure: the sins of P-values and the virtues of Bayesian evidence

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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

The COMT Val158 allele is associated with impaired delayed-match-to-sample performance in ADHD

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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.

Computation of ancestry scores with mixed families and unrelated individuals.

Science.gov (United States)

Zhou, Yi-Hui; Marron, James S; Wright, Fred A

2018-03-01

The issue of robustness to family relationships in computing genotype ancestry scores such as eigenvector projections has received increased attention in genetic association, and is particularly challenging when sets of both unrelated individuals and closely related family members are included. The current standard is to compute loadings (left singular vectors) using unrelated individuals and to compute projected scores for remaining family members. However, projected ancestry scores from this approach suffer from shrinkage toward zero. We consider two main novel strategies: (i) matrix substitution based on decomposition of a target family-orthogonalized covariance matrix, and (ii) using family-averaged data to obtain loadings. We illustrate the performance via simulations, including resampling from 1000 Genomes Project data, and analysis of a cystic fibrosis dataset. The matrix substitution approach has similar performance to the current standard, but is simple and uses only a genotype covariance matrix, while the family-average method shows superior performance. Our approaches are accompanied by novel ancillary approaches that provide considerable insight, including individual-specific eigenvalue scree plots. © 2017 The Authors. Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society.

TaGW2-6A allelic variation contributes to grain size possibly by regulating the expression of cytokinins and starch-related genes in wheat.

Science.gov (United States)

Geng, Juan; Li, Liqun; Lv, Qian; Zhao, Yi; Liu, Yan; Zhang, Li; Li, Xuejun

2017-12-01

Functional allelic variants of TaGW2 - 6A produce large grains, possibly via changes in endosperm cells and dry matter by regulating the expression of cytokinins and starch-related genes via the ubiquitin-proteasome system. In wheat, TaGW2-6A coding region allelic variants are closely related to the grain width and weight, but how this region affects grain development has not been fully elucidated; thus, we explored its influence on grain development based mainly on histological and grain filling analyses. We found that the insertion type (NIL31) TaGW2-6A allelic variants exhibited increases in cell numbers and cell size, thereby resulting in a larger (wider) grain size with an accelerated grain milk filling rate, and increases in grain width and weight. We also found that cytokinin (CK) synthesis genes and key starch biosynthesis enzyme AGPase genes were significantly upregulated in the TaGW2-6A allelic variants, while CK degradation genes and starch biosynthesis-negative regulators were downregulated in the TaGW2-6A allelic variants, which was consistent with the changes in cells and grain filling. Thus, we speculate that TaGW2-6A allelic variants are linked with CK signaling, but they also influence the accumulation of starch by regulating the expression of related genes via the ubiquitin-proteasome system to control the grain size and grain weight.

ACTN3 allele frequency in humans covaries with global latitudinal gradient.

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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.

Identification of the Rare, Four Repeat Allele of IL-4 Intron-3 VNTR Polymorphism in Indian Populations.

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Verma, Henu Kumar; Jha, Aditya Nath; Khodiar, Prafulla Kumar; Patra, Pradeep Kumar; Bhaskar, Lakkakula Venkata Kameswara Subrahmanya

2016-06-01

Cytokines are cell signaling molecules which upon release by cells facilitate the recruitment of immune-modulatory cells towards the sites of inflammation. Genetic variations in cytokine genes are shown to regulate their production and affect the risk of infectious as well as autoimmune diseases. Intron-3 of interleukin-4 gene (IL-4) harbors 70-bp variable number of tandem repeats (VNTR) that may alter the expression level of IL-4 gene. To determine the distribution of IL-4 70-bp VNTR polymorphism in seven genetically heterogeneous populations of Chhattisgarh, India and their comparison with the finding of other Indian and world populations. A total of 371 healthy unrelated individuals from 5 caste and 2 tribal populations were included in the present study. The IL-4 70-bp VNTR genotyping was carried out using PCR and electrophoresis. Overall, 3 alleles of IL-4 70-bp VNTR (a2, a3 and a4) were detected. The results demonstrated the variability of the IL-4 70-bp VNTR polymorphism in Chhattisgarh populations. Allele a3 was the most common allele at the 70-bp VNTR locus in all populations followed by a2 allele. This study reports the presence four repeat allele a4 at a low frequency in the majority of the Chhattisgarh populations studied. Further, the frequency of the minor allele (a2) in Chhattisgarh populations showed similarity with the frequencies of European populations but not with the East Asian populations where the a2 allele is a major allele. Our study provides a baseline for future research into the role of the IL-4 locus in diseases linked to inflammation in Indian populations.

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

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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.

The Rh allele frequencies in Gaza city in Palestine

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Skaik Younis

2011-01-01

Full Text Available Background: The Rh blood group system is the second most clinically significant blood group system. It includes 49 antigens, but only five (D, C, E, c and e are the most routinely identified due to their unique relation to hemolytic disease of the newborn (HDN and transfusion reactions. Frequency of the Rh alleles showed variation, with regard to race and ethnic. Objectives: The purpose of the study was to document the Rh alleles′ frequencies amongst males (M and females (F in Gaza city in Palestine. Materials and Methods: Two hundred and thirty-two blood samples (110 M and 122 F were tested against monoclonal IgM anti-C,anti-c, anti-E, anti-e and a blend of monoclonal/polyclonal IgM/IgG anti-D. The expected Rh phenotypes were calculated using gene counting method. Results: The most frequent Rh antigen in the total sample was e, while the least frequent was E.The order of the combined Rh allele frequencies in both M and F was CDe > cDe > cde > CdE > cDE > Cde > CDE. A significant difference was reported between M and F regarding the phenotypic frequencies (P < 0.05. However, no significance (P > 0.05 was reported with reference to the observed and expected Rh phenotypic frequencies in either M or F students. Conclusion: It was concluded that the Rh antigens, alleles and phenotypes in Gaza city have unique frequencies, which may be of importance to the Blood Transfusion Center in Gaza city and anthropology.

FINDbase: A worldwide database for genetic variation allele frequencies updated

NARCIS (Netherlands)

M. Georgitsi (Marianthi); E. Viennas (Emmanouil); D.I. Antoniou (Dimitris I.); V. Gkantouna (Vassiliki); S. van Baal (Sjozef); E.F. Petricoin (Emanuel F.); K. Poulas (Konstantinos); G. Tzimas (Giannis); G.P. Patrinos (George)

2011-01-01

textabstractFrequency of INherited Disorders database (FIND base; http://www.findbase. org) records frequencies of causative genetic variations worldwide. Database records include the population and ethnic group or geographical region, the disorder name and the related gene, accompanied by links to

Lumbee Native American ancestry and the incidence of aggressive histologic subtypes of endometrial cancer

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Chelsea Zhang

2015-08-01

Conclusion: In this retrospective cohort analysis, Lumbee Native American ancestry was not a significant independent predictor of rates of high-risk histological subtypes of endometrial cancer or poor survival outcomes.

Large variations in ocular dimensions in a multiethnic population with similar genetic background.

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Niu, Zhiqiang; Li, Jun; Zhong, Hua; Yuan, Zhonghua; Zhou, Hua; Zhang, Yang; Yuan, Yuansheng; Chen, Qin; Pan, Chen-Wei

2016-03-07

We aimed to describe the ethnic variations in ocular dimensions among three ethnic groups with similar genetic ancestry from mainland of China. We included 2119 ethnic Bai, 2202 ethnic Yi and 2183 ethnic Han adults aged 50 years or older in the study. Ocular dimensions including axial length (AL), anterior chamber depth (ACD), vitreous chamber depth (VCD) and lens thickness (LT) were measured using A-scan ultrasonography. Bai Chinese had longer ALs (P variations in LTs. Diabetes was associated with shallower ACDs and this association was stronger in Bai Chinese compared with Yi or Han Chinese (P for interaction = 0.02). Thicker lenses were associated with younger age (P = 0.04), male gender (P variations in cultures and lifestyles.

Allelic heterogeneity and genetic modifier loci contribute to clinical variation in males with X-linked retinitis pigmentosa due to RPGR mutations.

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Abigail T Fahim

Full Text Available Mutations in RPGR account for over 70% of X-linked retinitis pigmentosa (XlRP, characterized by retinal degeneration and eventual blindness. The clinical consequences of RPGR mutations are highly varied, even among individuals with the same mutation: males demonstrate a wide range of clinical severity, and female carriers may or may not be affected. This study describes the phenotypic diversity in a cohort of 98 affected males from 56 families with RPGR mutations, and demonstrates the contribution of genetic factors (i.e., allelic heterogeneity and genetic modifiers to this diversity. Patients were categorized as grade 1 (mild, 2 (moderate or 3 (severe according to specific clinical criteria. Patient DNAs were genotyped for coding SNPs in 4 candidate modifier genes with products known to interact with RPGR protein: RPGRIP1, RPGRIP1L, CEP290, and IQCB1. Family-based association testing was performed using PLINK. A wide range of clinical severity was observed both between and within families. Patients with mutations in exons 1-14 were more severely affected than those with ORF15 mutations, and patients with predicted null alleles were more severely affected than those predicted to make RPGR protein. Two SNPs showed association with severe disease: the minor allele (N of I393N in IQCB1 (p = 0.044 and the common allele (R of R744Q in RPGRIP1L (p = 0.049. These data demonstrate that allelic heterogeneity contributes to phenotypic diversity in XlRP and suggest that this may depend on the presence or absence of RPGR protein. In addition, common variants in 2 proteins known to interact with RPGR are associated with severe disease in this cohort.

Allelic Diversity and Geographical Distribution of the Gene Encoding Plasmodium falciparum Merozoite Surface Protein-3 in Thailand.

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Sawaswong, Vorthon; Simpalipan, Phumin; Siripoon, Napaporn; Harnyuttanakorn, Pongchai; Pattaradilokrat, Sittiporn

2015-04-01

Merozoite surface proteins (MSPs) of malaria parasites play critical roles during the erythrocyte invasion and so are potential candidates for malaria vaccine development. However, because MSPs are often under strong immune selection, they can exhibit extensive genetic diversity. The gene encoding the merozoite surface protein-3 (MSP-3) of Plasmodium falciparum displays 2 allelic types, K1 and 3D7. In Thailand, the allelic frequency of the P. falciparum msp-3 gene was evaluated in a single P. falciparum population in Tak at the Thailand and Myanmar border. However, no study has yet looked at the extent of genetic diversity of the msp-3 gene in P. falciparum populations in other localities. Here, we genotyped the msp-3 alleles of 63 P. falciparum samples collected from 5 geographical populations along the borders of Thailand with 3 neighboring countries (Myanmar, Laos, and Cambodia). Our study indicated that the K1 and 3D7 alleles coexisted, but at different proportions in different Thai P. falciparum populations. K1 was more prevalent in populations at the Thailand-Myanmar and Thailand-Cambodia borders, whilst 3D7 was more prevalent at the Thailand-Laos border. Global analysis of the msp-3 allele frequencies revealed that proportions of K1 and 3D7 alleles of msp-3 also varied in different continents, suggesting the divergence of malaria parasite populations. In conclusion, the variation in the msp-3 allelic patterns of P. falciparum in Thailand provides fundamental knowledge for inferring the P. falciparum population structure and for the best design of msp-3 based malaria vaccines.

Stress-related methylation of the catechol-O-methyltransferase Val 158 allele predicts human prefrontal cognition and activity.

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Ursini, Gianluca; Bollati, Valentina; Fazio, Leonardo; Porcelli, Annamaria; Iacovelli, Luisa; Catalani, Assia; Sinibaldi, Lorenzo; Gelao, Barbara; Romano, Raffaella; Rampino, Antonio; Taurisano, Paolo; Mancini, Marina; Di Giorgio, Annabella; Popolizio, Teresa; Baccarelli, Andrea; De Blasi, Antonio; Blasi, Giuseppe; Bertolino, Alessandro

2011-05-04

DNA methylation at CpG dinucleotides is associated with gene silencing, stress, and memory. The catechol-O-methyltransferase (COMT) Val(158) allele in rs4680 is associated with differential enzyme activity, stress responsivity, and prefrontal activity during working memory (WM), and it creates a CpG dinucleotide. We report that methylation of the Val(158) allele measured from peripheral blood mononuclear cells (PBMCs) of Val/Val humans is associated negatively with lifetime stress and positively with WM performance; it interacts with stress to modulate prefrontal activity during WM, such that greater stress and lower methylation are related to reduced cortical efficiency; and it is inversely related to mRNA expression and protein levels, potentially explaining the in vivo effects. Finally, methylation of COMT in prefrontal cortex and that in PBMCs of rats are correlated. The relationship of methylation of the COMT Val(158) allele with stress, gene expression, WM performance, and related brain activity suggests that stress-related methylation is associated with silencing of the gene, which partially compensates the physiological role of the high-activity Val allele in prefrontal cognition and activity. Moreover, these results demonstrate how stress-related DNA methylation of specific functional alleles impacts directly on human brain physiology beyond sequence variation.

Genomic Ancestry, Self-Rated Health and Its Association with Mortality in an Admixed Population: 10 Year Follow-Up of the Bambui-Epigen (Brazil) Cohort Study of Ageing.

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Lima-Costa, M Fernanda; Macinko, James; Mambrini, Juliana Vaz de Melo; Cesar, Cibele C; Peixoto, Sérgio V; Magalhães, Wagner C S; Horta, Bernardo L; Barreto, Mauricio; Castro-Costa, Erico; Firmo, Josélia O A; Proietti, Fernando A; Leal, Thiago Peixoto; Rodrigues, Maira R; Pereira, Alexandre; Tarazona-Santos, Eduardo

2015-01-01

Self-rated health (SRH) has strong predictive value for mortality in different contexts and cultures, but there is inconsistent evidence on ethnoracial disparities in SRH in Latin America, possibly due to the complexity surrounding ethnoracial self-classification. We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual genomic proportions of African, European and Native American ancestry, and ethnoracial self-classification, with baseline and 10-year SRH trajectories in 1,311 community dwelling older Brazilians. We also examined whether genomic ancestry and ethnoracial self-classification affect the predictive value of SRH for subsequent mortality. European ancestry predominated among participants, followed by African and Native American (median = 84.0%, 9.6% and 5.3%, respectively); the prevalence of Non-White (Mixed and Black) was 39.8%. Persons at higher levels of African and Native American genomic ancestry, and those self-identified as Non-White, were more likely to report poor health than other groups, even after controlling for socioeconomic conditions and an array of self-reported and objective physical health measures. Increased risks for mortality associated with worse SRH trajectories were strong and remarkably similar (hazard ratio ~3) across all genomic ancestry and ethno-racial groups. Our results demonstrated for the first time that higher levels of African and Native American genomic ancestry--and the inverse for European ancestry--were strongly correlated with worse SRH in a Latin American admixed population. Both genomic ancestry and ethnoracial self-classification did not modify the strong association between baseline SRH or SRH trajectory, and subsequent mortality.

"Do You Know Your Language?" How Teachers of Punjabi and Chinese Ancestries Construct Their Family Languages in Their Personal and Professional Lives.

Science.gov (United States)

Beynon, June; Ilieva, Roumiana; Dichupa, Marela; Hirji, Shemina

2003-01-01

Focuses on how teachers of minority ancestries construct and represent their family language identities. Drawing on poststructural, postcolonial and sociocultural theory on culture, identity, and language, examined the complex nature of linguistic identities of 25 teachers of Chinese and 20 teachers of Punjabi ancestries. (Author/VWL)

Biogeographical ancestry is associated with socioenvironmental conditions and infections in a Latin American urban population

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Thiago Magalhães da Silva

2018-04-01

Full Text Available Racial inequalities are observed for different diseases and are mainly caused by differences in socioeconomic status between ethnoracial groups. Genetic factors have also been implicated, and recently, several studies have investigated the association between biogeographical ancestry (BGA and complex diseases. However, the role of BGA as a proxy for non-genetic health determinants has been little investigated. Similarly, studies comparing the association of BGA and self-reported skin colour with these determinants are scarce. Here, we report the association of BGA and self-reported skin colour with socioenvironmental conditions and infections. We studied 1246 children living in a Brazilian urban poor area. The BGA was estimated using 370,539 genome-wide autosomal markers. Standardised questionnaires were administered to the children’s guardians to evaluate socioenvironmental conditions. Infection (or pathogen exposure was defined by the presence of positive serologic test results for IgG to seven pathogens (Toxocara spp, Toxoplasma gondii, Helicobacter pylori, and hepatitis A, herpes simplex, herpes zoster and Epstein-Barr viruses and the presence of intestinal helminth eggs in stool samples (Ascaris lumbricoides and Trichiuris trichiura. African ancestry was negatively associated with maternal education and household income and positively associated with infections and variables, indicating poorer housing and living conditions. The self-reported skin colour was associated with infections only. In stratified analyses, the proportion of African ancestry was associated with most of the outcomes investigated, particularly among admixed individuals. In conclusion, BGA was associated with socioenvironmental conditions and infections even in a low-income and highly admixed population, capturing differences that self-reported skin colour miss. Importantly, our findings suggest caution in interpreting significant associations between BGA and diseases

Killer Immunoglobulin-Like Receptor Allele Determination Using Next-Generation Sequencing Technology

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Bercelin Maniangou

2017-05-01

Full Text Available The impact of natural killer (NK cell alloreactivity on hematopoietic stem cell transplantation (HSCT outcome is still debated due to the complexity of graft parameters, HLA class I environment, the nature of killer cell immunoglobulin-like receptor (KIR/KIR ligand genetic combinations studied, and KIR+ NK cell repertoire size. KIR genes are known to be polymorphic in terms of gene content, copy number variation, and number of alleles. These allelic polymorphisms may impact both the phenotype and function of KIR+ NK cells. We, therefore, speculate that polymorphisms may alter donor KIR+ NK cell phenotype/function thus modulating post-HSCT KIR+ NK cell alloreactivity. To investigate KIR allele polymorphisms of all KIR genes, we developed a next-generation sequencing (NGS technology on a MiSeq platform. To ensure the reliability and specificity of our method, genomic DNA from well-characterized cell lines were used; high-resolution KIR typing results obtained were then compared to those previously reported. Two different bioinformatic pipelines were used allowing the attribution of sequencing reads to specific KIR genes and the assignment of KIR alleles for each KIR gene. Our results demonstrated successful long-range KIR gene amplifications of all reference samples using intergenic KIR primers. The alignment of reads to the human genome reference (hg19 using BiRD pipeline or visualization of data using Profiler software demonstrated that all KIR genes were completely sequenced with a sufficient read depth (mean 317× for all loci and a high percentage of mapping (mean 93% for all loci. Comparison of high-resolution KIR typing obtained to those published data using exome capture resulted in a reported concordance rate of 95% for centromeric and telomeric KIR genes. Overall, our results suggest that NGS can be used to investigate the broad KIR allelic polymorphism. Hence, these data improve our knowledge, not only on KIR+ NK cell alloreactivity in

Natural selection interacts with recombination to shape the evolution of hybrid genomes.

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Schumer, Molly; Xu, Chenling; Powell, Daniel L; Durvasula, Arun; Skov, Laurits; Holland, Chris; Blazier, John C; Sankararaman, Sriram; Andolfatto, Peter; Rosenthal, Gil G; Przeworski, Molly

2018-05-11

To investigate the consequences of hybridization between species, we studied three replicate hybrid populations that formed naturally between two swordtail fish species, estimating their fine-scale genetic map and inferring ancestry along the genomes of 690 individuals. In all three populations, ancestry from the "minor" parental species is more common in regions of high recombination and where there is linkage to fewer putative targets of selection. The same patterns are apparent in a reanalysis of human and archaic admixture. These results support models in which ancestry from the minor parental species is more likely to persist when rapidly uncoupled from alleles that are deleterious in hybrids. Our analyses further indicate that selection on swordtail hybrids stems predominantly from deleterious combinations of epistatically interacting alleles. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Analysis of nucleotide diversity among alleles of the major bacterial blight resistance gene Xa27 in cultivars of rice (Oryza sativa) and its wild relatives.

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Bimolata, Waikhom; Kumar, Anirudh; Sundaram, Raman Meenakshi; Laha, Gouri Shankar; Qureshi, Insaf Ahmed; Reddy, Gajjala Ashok; Ghazi, Irfan Ahmad

2013-08-01

Xa27 is one of the important R-genes, effective against bacterial blight disease of rice caused by Xanthomonas oryzae pv. oryzae (Xoo). Using natural population of Oryza, we analyzed the sequence variation in the functionally important domains of Xa27 across the Oryza species. DNA sequences of Xa27 alleles from 27 rice accessions revealed higher nucleotide diversity among the reported R-genes of rice. Sequence polymorphism analysis revealed synonymous and non-synonymous mutations in addition to a number of InDels in non-coding regions of the gene. High sequence variation was observed in the promoter region including the 5'UTR with 'π' value 0.00916 and 'θ w ' = 0.01785. Comparative analysis of the identified Xa27 alleles with that of IRBB27 and IR24 indicated the operation of both positive selection (Ka/Ks > 1) and neutral selection (Ka/Ks ≈ 0). The genetic distances of alleles of the gene from Oryza nivara were nearer to IRBB27 as compared to IR24. We also found the presence of conserved and null UPT (upregulated by transcriptional activator) box in the isolated alleles. Considerable amino acid polymorphism was localized in the trans-membrane domain for which the functional significance is yet to be elucidated. However, the absence of functional UPT box in all the alleles except IRBB27 suggests the maintenance of single resistant allele throughout the natural population.

Transferrin variation and evolution of Canadian barren-ground caribou

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Knut H. Røed

1990-09-01

Full Text Available Blood samples were obtained from 95 barren-ground caribou (Rangifer tarandus groenlandicus of the Beverly herd in Northwest Territories, Canada. Polyacrylamid gel electrophoresis was used to score for genetic variation in the locus coding for transferrin. The pattern of allele frequency distribution are compared with previously reported values of Eurasian tundra reindeer (R.t. tarandus, Alaska caribou (R.t. granti, Peary caribou (R.t. pearyi, and Svalbard reindeer (R.t. platyrhynchus. In the Beverly herd a total of 21 different transferrin alleles were detected. The amount of genetic variation was higher in the Canadian barren-ground caribou than what has been detected in other subspecies of reindeer/caribou. Highly gene-tical differences in the allele frequencies were detected between the Canadian barren-ground caribou and the other subspecies. The genetic identity analyses indicates approximately the same amount of genetic differentiation when the Canadian barren-ground caribou are compared with Alaska caribou as with the Peary caribou. The allele frequency pattern could be explained by a possible origin of the Canadian barren-ground caribou from an ancestral population which was genetical influenced by animals surviving the We-ichselian glaciation in refugia both in high Arctic, in Beringia, and south of the ice sheet.

A non-synonymous single-nucleotide polymorphism in the gene encoding Toll-like Receptor 3 (TLR3) is associated with sero-negative Rheumatoid Arthritis (RA) in a Danish population

DEFF Research Database (Denmark)

Laska, Magdalena Janina; Hansen, Bettina; Troldborg, Anne

2014-01-01

BACKGROUND: It has been suggested that polymorphisms in Toll-like Receptors (TLRs) are associated with Rheumatoid Arthritis (RA), but the implicated alleles have differed between studies. The aim of this investigation was to explore whether polymorphisms of TLR genes are associated with RA...... according to IgM rheumatoid factor (RF) and anti-cyclic citrinullated peptide (CCP) status suggested a significant association of sero-negative RA with the rs3775291 A allele and disease activity in this subset. CONCLUSION: These observations on a RA population of Danish ancestry suggest that variations...... in the TLR3 locus may be implicated in the pathogenesis of sero-negative RA. Since this TLR3 SNP has previously been associated with systemic lupus erythematous (SLE), the present findings support the notion that TLR3 genetic variants may represent a common risk factor in different chronic inflammatory...

TIMP2 gene polymorphism as a potential tool to infer Brazilian population origin

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da Silva RA

2013-12-01

Full Text Available Rodrigo Augusto da Silva,1 André Luis Shinohara,2 Denise Carleto Andia,1 Ariadne Letra,3 Regina Célia Peres,1 Ana Paula de Souza11Department of Morphology, Piracicaba Dental School, State University of Campinas, 2Oral Biology Program, Bauru Dental School, State University of São Paulo, São Paulo, Brazil; 3Department of Endodontics and Center for Craniofacial Research, School of Dentistry, University of Texas Health Science Center, Houston, TX, USAAbstract: Single nucleotide polymorphisms are genome variations that can be used as population-specific markers to infer genetic background and population origin. The Brazilian population is highly admixed due to immigration from several other populations. In particular, the state of São Paulo is recognized for the presence of Japanese individuals who seem likely to have contributed to a substantial proportion of ancestry in the modern Brazilian population. In the present study, we analyzed allele and genotype frequencies and associations of the –418G>C (rs8179090 single nucleotide polymorphism in the TIMP2 gene promoter in Brazilian and Japanese subjects, as well as in Japanese descendants from southeastern Brazil. The allele and genotype frequency analyses among groups demonstrated statistical significance (PC single nucleotide polymorphism of the TIMP2 gene, have a high probability of being Japanese or Japanese descendants. In addition to other genetic polymorphisms, the −418G>C TIMP2 polymorphism could be a population marker to assist in predicting Japanese ancestry, both in Japanese individuals and in admixed populations.Keywords: Brazilian, Japanese, polymorphism, allele, TIMP2

Genomic ancestry and the social pathways leading to major depression in adulthood: the mediating effect of socioeconomic position and discrimination.

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Loret de Mola, Christian; Hartwig, Fernando Pires; Gonçalves, Helen; Quevedo, Luciana de Avila; Pinheiro, Ricardo; Gigante, Denise Petrucci; Motta, Janaína Vieira Dos Santos; Pereira, Alexandre C; Barros, Fernando C; Horta, Bernardo Lessa

2016-09-05

Evidence suggests that there is an association between ethnicity/skin color and depression; however, many contextual and individual variables, like sense of discrimination and socioeconomic position (SEP), might influence the direction of this association. We assessed the association between African ancestry and major depression among young adults that have been followed-up since birth in a Southern Brazilian city, and the mediating effect of SEP and discrimination. In 1982, all hospital deliveries in Pelotas (Southern Brazil) were identified; liveborns were examined and their mothers interviewed (n = 5914). In 2012-13, at 30 years of age, we used the Mini International Neuropsychiatric Interview (MINI) for major depression diagnosis. In addition, DNA samples were genotyped for approximately 2.5 million single nucleotide polymorphisms (SNPs) using Illumina (CA, USA) HumanOmni2.5-8v1 array. Genomic ancestry estimation was based on approximately 370 000 single nucleotide polymorphisms (SNPs) mutually available for the Pelotas cohort and selected samples (used as reference panels) of the HapMap and Human Genome Diversity (HGDP). We estimated prevalence ratios (PR) using Poisson regression models and evaluated the association between percentage of African ancestry and major depression. We used G-computation for mediation analysis. At 30 years, 3576 individuals were evaluated for major depression (prevalence = 7.9 %). Only individuals in the highest SEP, who had a percentage of African ancestry between >5-30 % and >30 % had a prevalence of major depression 2.16 (PR = 2.16 95 % CI [1.05-4.45]) and 2.74 (PR = 2.74 95 % CI [1.06-7.06]) times higher, than those with 5 % or less, respectively. Among these subjects, sense of discrimination by skin color, captured 84 % of the association between African ancestry and major depression. SEP is an important effect modifier of the positive association between African ancestry and major depression. In addition

Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation.

Science.gov (United States)

Horikoshi, Momoko; Mӓgi, Reedik; van de Bunt, Martijn; Surakka, Ida; Sarin, Antti-Pekka; Mahajan, Anubha; Marullo, Letizia; Thorleifsson, Gudmar; Hӓgg, Sara; Hottenga, Jouke-Jan; Ladenvall, Claes; Ried, Janina S; Winkler, Thomas W; Willems, Sara M; Pervjakova, Natalia; Esko, Tõnu; Beekman, Marian; Nelson, Christopher P; Willenborg, Christina; Wiltshire, Steven; Ferreira, Teresa; Fernandez, Juan; Gaulton, Kyle J; Steinthorsdottir, Valgerdur; Hamsten, Anders; Magnusson, Patrik K E; Willemsen, Gonneke; Milaneschi, Yuri; Robertson, Neil R; Groves, Christopher J; Bennett, Amanda J; Lehtimӓki, Terho; Viikari, Jorma S; Rung, Johan; Lyssenko, Valeriya; Perola, Markus; Heid, Iris M; Herder, Christian; Grallert, Harald; Müller-Nurasyid, Martina; Roden, Michael; Hypponen, Elina; Isaacs, Aaron; van Leeuwen, Elisabeth M; Karssen, Lennart C; Mihailov, Evelin; Houwing-Duistermaat, Jeanine J; de Craen, Anton J M; Deelen, Joris; Havulinna, Aki S; Blades, Matthew; Hengstenberg, Christian; Erdmann, Jeanette; Schunkert, Heribert; Kaprio, Jaakko; Tobin, Martin D; Samani, Nilesh J; Lind, Lars; Salomaa, Veikko; Lindgren, Cecilia M; Slagboom, P Eline; Metspalu, Andres; van Duijn, Cornelia M; Eriksson, Johan G; Peters, Annette; Gieger, Christian; Jula, Antti; Groop, Leif; Raitakari, Olli T; Power, Chris; Penninx, Brenda W J H; de Geus, Eco; Smit, Johannes H; Boomsma, Dorret I; Pedersen, Nancy L; Ingelsson, Erik; Thorsteinsdottir, Unnur; Stefansson, Kari; Ripatti, Samuli; Prokopenko, Inga; McCarthy, Mark I; Morris, Andrew P

2015-07-01

Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry. We identified two loci for body mass index (BMI) at genome-wide significance, and two for fasting glucose (FG), none of which has been previously reported in larger meta-analysis efforts to combine GWAS of European ancestry. Through conditional analysis, we also detected multiple distinct signals of association mapping to established loci for waist-hip ratio adjusted for BMI (RSPO3) and FG (GCK and G6PC2). The index variant for one association signal at the G6PC2 locus is a low-frequency coding allele, H177Y, which has recently been demonstrated to have a functional role in glucose regulation. Fine-mapping analyses revealed that the non-coding variants most likely to drive association signals at established and novel loci were enriched for overlap with enhancer elements, which for FG mapped to promoter and transcription factor binding sites in pancreatic islets, in particular. Our study demonstrates that 1000G imputation and genetic fine-mapping of common and low-frequency variant association signals at GWAS loci, integrated with genomic annotation in relevant tissues, can provide insight into the functional and regulatory mechanisms through which their effects on glycaemic and obesity-related traits are mediated.

Association Analysis of FOXO3 Longevity Variants With Blood Pressure and Essential Hypertension.