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Sample records for human haplotype map

  1. [Human genomic project and human genomic haplotype map project: opportunitiy, challenge and strategy in stomatology].

    Science.gov (United States)

    Wu, Rui-qing; Zeng, Xin; Wang, Zhi

    2010-08-01

    The human genomic project and the international HapMap project were designed to create a genome-wide database of patterns of human genetic variation, with the expectation that these patterns would be useful for genetic association studies of common diseases, thus lead to molecular diagnosis and personnel therapy. The article briefly reviewed the creation, target and achievement of those two projects. Furthermore, the authors have given four suggestions in facing to the opportunities and challenges brought by the two projects, including cultivation improvement of elites, cross binding of multi-subjects, strengthening construction of research base and initiation of natural key scientific project.

  2. Mapping Haplotype-haplotype Interactions with Adaptive LASSO

    Directory of Open Access Journals (Sweden)

    Li Ming

    2010-08-01

    Full Text Available Abstract Background The genetic etiology of complex diseases in human has been commonly viewed as a complex process involving both genetic and environmental factors functioning in a complicated manner. Quite often the interactions among genetic variants play major roles in determining the susceptibility of an individual to a particular disease. Statistical methods for modeling interactions underlying complex diseases between single genetic variants (e.g. single nucleotide polymorphisms or SNPs have been extensively studied. Recently, haplotype-based analysis has gained its popularity among genetic association studies. When multiple sequence or haplotype interactions are involved in determining an individual's susceptibility to a disease, it presents daunting challenges in statistical modeling and testing of the interaction effects, largely due to the complicated higher order epistatic complexity. Results In this article, we propose a new strategy in modeling haplotype-haplotype interactions under the penalized logistic regression framework with adaptive L1-penalty. We consider interactions of sequence variants between haplotype blocks. The adaptive L1-penalty allows simultaneous effect estimation and variable selection in a single model. We propose a new parameter estimation method which estimates and selects parameters by the modified Gauss-Seidel method nested within the EM algorithm. Simulation studies show that it has low false positive rate and reasonable power in detecting haplotype interactions. The method is applied to test haplotype interactions involved in mother and offspring genome in a small for gestational age (SGA neonates data set, and significant interactions between different genomes are detected. Conclusions As demonstrated by the simulation studies and real data analysis, the approach developed provides an efficient tool for the modeling and testing of haplotype interactions. The implementation of the method in R codes can be

  3. Mapping haplotype-haplotype interactions with adaptive LASSO.

    Science.gov (United States)

    Li, Ming; Romero, Roberto; Fu, Wenjiang J; Cui, Yuehua

    2010-08-27

    The genetic etiology of complex diseases in human has been commonly viewed as a complex process involving both genetic and environmental factors functioning in a complicated manner. Quite often the interactions among genetic variants play major roles in determining the susceptibility of an individual to a particular disease. Statistical methods for modeling interactions underlying complex diseases between single genetic variants (e.g. single nucleotide polymorphisms or SNPs) have been extensively studied. Recently, haplotype-based analysis has gained its popularity among genetic association studies. When multiple sequence or haplotype interactions are involved in determining an individual's susceptibility to a disease, it presents daunting challenges in statistical modeling and testing of the interaction effects, largely due to the complicated higher order epistatic complexity. In this article, we propose a new strategy in modeling haplotype-haplotype interactions under the penalized logistic regression framework with adaptive L1-penalty. We consider interactions of sequence variants between haplotype blocks. The adaptive L1-penalty allows simultaneous effect estimation and variable selection in a single model. We propose a new parameter estimation method which estimates and selects parameters by the modified Gauss-Seidel method nested within the EM algorithm. Simulation studies show that it has low false positive rate and reasonable power in detecting haplotype interactions. The method is applied to test haplotype interactions involved in mother and offspring genome in a small for gestational age (SGA) neonates data set, and significant interactions between different genomes are detected. As demonstrated by the simulation studies and real data analysis, the approach developed provides an efficient tool for the modeling and testing of haplotype interactions. The implementation of the method in R codes can be freely downloaded from http://www.stt.msu.edu/~cui/software.html.

  4. SNP haplotype mapping in a small ALS family.

    Directory of Open Access Journals (Sweden)

    Katherine A Dick Krueger

    Full Text Available The identification of genes for monogenic disorders has proven to be highly effective for understanding disease mechanisms, pathways and gene function in humans. Nevertheless, while thousands of Mendelian disorders have not yet been mapped there has been a trend away from studying single-gene disorders. In part, this is due to the fact that many of the remaining single-gene families are not large enough to map the disease locus to a single site in the genome. New tools and approaches are needed to allow researchers to effectively tap into this genetic gold-mine. Towards this goal, we have used haploid cell lines to experimentally validate the use of high-density single nucleotide polymorphism (SNP arrays to define genome-wide haplotypes and candidate regions, using a small amyotrophic lateral sclerosis (ALS family as a prototype. Specifically, we used haploid-cell lines to determine if high-density SNP arrays accurately predict haplotypes across entire chromosomes and show that haplotype information significantly enhances the genetic information in small families. Panels of haploid-cell lines were generated and a 5 centimorgan (cM short tandem repeat polymorphism (STRP genome scan was performed. Experimentally derived haplotypes for entire chromosomes were used to directly identify regions of the genome identical-by-descent in 5 affected individuals. Comparisons between experimentally determined and in silico haplotypes predicted from SNP arrays demonstrate that SNP analysis of diploid DNA accurately predicted chromosomal haplotypes. These methods precisely identified 12 candidate intervals, which are shared by all 5 affected individuals. Our study illustrates how genetic information can be maximized using readily available tools as a first step in mapping single-gene disorders in small families.

  5. How well do HapMap haplotypes identify common haplotypes of genes? A comparison with haplotypes of 334 genes resequenced in the environmental genome project.

    Science.gov (United States)

    Taylor, Jack A; Xu, Zong-Li; Kaplan, Norman L; Morris, Richard W

    2006-01-01

    One of the goals of the International HapMap Project is the identification of common haplotypes in genes. However, HapMap uses an incomplete catalogue of single nucleotide polymorphisms (SNPs) and might miss some common haplotypes. We examined this issue using data from the Environmental Genome Project (EGP) which resequenced 335 genes in 90 people, and thus, has a nearly complete catalogue of gene SNPs. The EGP identified a total of 45,243 SNPs, of which 10,780 were common SNPs (minor allele frequency >or=0.1). Using EGP common SNP genotype data, we identified 1,459 haplotypes with frequency >or=0.05 and we use these as "benchmark" haplotypes. HapMap release 16 had genotype information for 1,573 of 10,780 (15%) EGP common SNPs. Using these SNPs, we identified common HapMap haplotypes (frequency >or=0.05) in each of the four HapMap ethnic groups. To compare common HapMap haplotypes to EGP benchmark haplotypes, we collapsed benchmark haplotypes to the set of 1,573 SNPs. Ninety-eight percent of the collapsed benchmark haplotypes could be found as common HapMap haplotypes in one or more of the four HapMap ethnic groups. However, collapsing benchmark haplotypes to the set of SNPs available in HapMap resulted in a loss of haplotype information: 545 of 1,459 (37%) benchmark haplotypes were uniquely identified, and only 25% of genes had all their benchmark haplotypes uniquely identified. We resampled the EGP data to examine the effect of increasing the number of HapMap SNPs to 5 million, and estimate that approximately 40% of common SNPs in genes will be sampled and that half of the genes will have sufficient SNPs to identify all common haplotypes. This inability to distinguish common haplotypes of genes may result in loss of power when examining haplotype-disease association.

  6. The international human genome haplotype map project%国际人类基因组单体型图计划

    Institute of Scientific and Technical Information of China (English)

    曾长青

    2004-01-01

    人类基因组单体型图(Haplotypemap,以下简称HapMap)计划是与不久前完成的基因组测序计划相当的又一多国参与的重大国际合作项目,也是人类基因组研究领域的第2个重大战略目标。其目的是在通过测序了解了遗传基本信息的基础上,进一步确立世界上主要族群基因组的遗传变异图谱。这一计划的主要

  7. Rapid haplotype reconstruction in predigrees with dense marker maps

    NARCIS (Netherlands)

    Windig, J.J.; Meuwissen, T.H.E.

    2004-01-01

    Reconstruction of marker phases is not straightforward when parents are untyped. In these cases information from other relatives has to be used. In dense marker maps, however, the space of possible haplotype configurations tends to be too large for procedures such as Monte Carlo Markov chains (MCMC)

  8. Haplotype mapping of a diploid non-meiotic organism using existing and induced aneuploidies.

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    Melanie Legrand

    2008-01-01

    Full Text Available Haplotype maps (HapMaps reveal underlying sequence variation and facilitate the study of recombination and genetic diversity. In general, HapMaps are produced by analysis of Single-Nucleotide Polymorphism (SNP segregation in large numbers of meiotic progeny. Candida albicans, the most common human fungal pathogen, is an obligate diploid that does not appear to undergo meiosis. Thus, standard methods for haplotype mapping cannot be used. We exploited naturally occurring aneuploid strains to determine the haplotypes of the eight chromosome pairs in the C. albicans laboratory strain SC5314 and in a clinical isolate. Comparison of the maps revealed that the clinical strain had undergone a significant amount of genome rearrangement, consisting primarily of crossover or gene conversion recombination events. SNP map haplotyping revealed that insertion and activation of the UAU1 cassette in essential and non-essential genes can result in whole chromosome aneuploidy. UAU1 is often used to construct homozygous deletions of targeted genes in C. albicans; the exact mechanism (trisomy followed by chromosome loss versus gene conversion has not been determined. UAU1 insertion into the essential ORC1 gene resulted in a large proportion of trisomic strains, while gene conversion events predominated when UAU1 was inserted into the non-essential LRO1 gene. Therefore, induced aneuploidies can be used to generate HapMaps, which are essential for analyzing genome alterations and mitotic recombination events in this clonal organism.

  9. De novo assembly of a haplotype-resolved human genome.

    Science.gov (United States)

    Cao, Hongzhi; Wu, Honglong; Luo, Ruibang; Huang, Shujia; Sun, Yuhui; Tong, Xin; Xie, Yinlong; Liu, Binghang; Yang, Hailong; Zheng, Hancheng; Li, Jian; Li, Bo; Wang, Yu; Yang, Fang; Sun, Peng; Liu, Siyang; Gao, Peng; Huang, Haodong; Sun, Jing; Chen, Dan; He, Guangzhu; Huang, Weihua; Huang, Zheng; Li, Yue; Tellier, Laurent C A M; Liu, Xiao; Feng, Qiang; Xu, Xun; Zhang, Xiuqing; Bolund, Lars; Krogh, Anders; Kristiansen, Karsten; Drmanac, Radoje; Drmanac, Snezana; Nielsen, Rasmus; Li, Songgang; Wang, Jian; Yang, Huanming; Li, Yingrui; Wong, Gane Ka-Shu; Wang, Jun

    2015-06-01

    The human genome is diploid, and knowledge of the variants on each chromosome is important for the interpretation of genomic information. Here we report the assembly of a haplotype-resolved diploid genome without using a reference genome. Our pipeline relies on fosmid pooling together with whole-genome shotgun strategies, based solely on next-generation sequencing and hierarchical assembly methods. We applied our sequencing method to the genome of an Asian individual and generated a 5.15-Gb assembled genome with a haplotype N50 of 484 kb. Our analysis identified previously undetected indels and 7.49 Mb of novel coding sequences that could not be aligned to the human reference genome, which include at least six predicted genes. This haplotype-resolved genome represents the most complete de novo human genome assembly to date. Application of our approach to identify individual haplotype differences should aid in translating genotypes to phenotypes for the development of personalized medicine.

  10. De novo assembly of a haplotype-resolved human genome

    DEFF Research Database (Denmark)

    Cao, Hongzhi; Wu, Honglong; Luo, Ruibang

    2015-01-01

    The human genome is diploid, and knowledge of the variants on each chromosome is important for the interpretation of genomic information. Here we report the assembly of a haplotype-resolved diploid genome without using a reference genome. Our pipeline relies on fosmid pooling together with whole-genome...... of novel coding sequences that could not be aligned to the human reference genome, which include at least six predicted genes. This haplotype-resolved genome represents the most complete de novo human genome assembly to date. Application of our approach to identify individual haplotype differences should...... shotgun strategies, based solely on next-generation sequencing and hierarchical assembly methods. We applied our sequencing method to the genome of an Asian individual and generated a 5.15-Gb assembled genome with a haplotype N50 of 484 kb. Our analysis identified previously undetected indels and 7.49 Mb...

  11. Effects of the number of markers per haplotype and clustering of haplotypes on the accuracy of QTL mapping and prediction of genomic breeding values

    NARCIS (Netherlands)

    Calus, M.P.L.; Meuwissen, T.H.E.; Windig, J.J.; Knol, E.F.; Schrooten, C.; Vereijken, A.L.J.; Veerkamp, R.F.

    2009-01-01

    The aim of this paper was to compare the effect of haplotype definition on the precision of QTL-mapping and on the accuracy of predicted genomic breeding values. In a multiple QTL model using identity-by-descent (IBD) probabilities between haplotypes, various haplotype definitions were tested i.e. i

  12. Haplotype map of sickle cell anemia in Tunisia.

    Science.gov (United States)

    Moumni, Imen; Ben Mustapha, Maha; Sassi, Sarra; Zorai, Amine; Ben Mansour, Ikbel; Douzi, Kais; Chouachi, Dorra; Mellouli, Fethi; Bejaoui, Mohamed; Abbes, Salem

    2014-01-01

    β-Globin haplotypes are important to establish the ethnic origin and predict the clinical development of sickle cell disease patients (SCD). To determine the chromosomal background of β (S) Tunisian sickle cell patients, in this first study in Tunisia, we have explored four polymorphic regions of β-globin cluster on chromosome 11. It is the 5' region of β-LCR-HS2 site, the intervening sequence II (IVSII) region of two fetal ((G)γ and (A)γ) genes and the 5' region of β-globin gene. The results reveal a high molecular diversity of a microsatellite configuration describing the sequences haplotypes. The linkage disequilibrium analysis showed various haplotype combinations giving 22 "extended haplotypes". These results confirm the utility of the β-globin haplotypes for population studies and contribute to knowledge of the Tunisian gene pool, as well as establishing the role of genetic markers in physiopathology of SCD.

  13. Mapping of HLA- DQ haplotypes in a group of Danish patients with celiac disease

    DEFF Research Database (Denmark)

    Lund, Flemming; Hermansen, Mette N; Pedersen, Merete F

    2015-01-01

    BACKGROUND: A cost-effective identification of HLA- DQ risk haplotypes using the single nucleotide polymorphism (SNP) technique has recently been applied in the diagnosis of celiac disease (CD) in four European populations. The objective of the study was to map risk HLA- DQ haplotypes in a group...

  14. Integrating haplotype-specific linkage maps in tetraploid species using SNP markers

    NARCIS (Netherlands)

    Bourke, Peter M.; Voorrips, Roeland E.; Kranenburg, Twan; Jansen, Hans; Visser, Richard G.F.; Maliepaard, Chris

    2016-01-01

    Key message: Linkage mapping can help unravel the complexities of polyploid genomes. Here, we integrate haplotype-specific linkage maps in autotetraploid potato and explore the possibilities for mapping in other polyploid species.Abstract: High-density linkage mapping in autopolyploid species has

  15. In Vivo Characterization of Human APOA5 Haplotypes

    Energy Technology Data Exchange (ETDEWEB)

    Ahituv, Nadav; Akiyama, Jennifer; Chapman-Helleboid, Audrey; Fruchart, Jamila; Pennacchio, Len A.

    2006-10-01

    Increased plasma triglycerides concentrations are an independent risk factor for cardiovascular disease. Numerous studies support a reproducible genetic association between two minor haplotypes in the human apolipoprotein A5 gene (APOA5) and increased plasma triglyceride concentrations. We thus sought to investigate the effect of these minor haplotypes (APOA5*2 and APOA5*3) on ApoAV plasma levels through the precise insertion of single-copy intact APOA5 haplotypes at a targeted location in the mouse genome. While we found no difference in the amount of human plasma ApoAV in mice containing the common APOA5*1 and minor APOA5*2 haplotype, the introduction of the single APOA5*3 defining allele (19W) resulted in 3-fold lower ApoAV plasma levels consistent with existing genetic association studies. These results indicate that S19W polymorphism is likely to be functional and explain the strong association of this variant with plasma triglycerides supporting the value of sensitive in vivo assays to define the functional nature of human haplotypes.

  16. Haplotype Map of Sickle Cell Anemia in Tunisia

    Directory of Open Access Journals (Sweden)

    Imen Moumni

    2014-01-01

    Full Text Available β-Globin haplotypes are important to establish the ethnic origin and predict the clinical development of sickle cell disease patients (SCD. To determine the chromosomal background of βS Tunisian sickle cell patients, in this first study in Tunisia, we have explored four polymorphic regions of β-globin cluster on chromosome 11. It is the 5′ region of β-LCR-HS2 site, the intervening sequence II (IVSII region of two fetal (γG and γA genes and the 5′ region of β-globin gene. The results reveal a high molecular diversity of a microsatellite configuration describing the sequences haplotypes. The linkage disequilibrium analysis showed various haplotype combinations giving 22 “extended haplotypes”. These results confirm the utility of the β-globin haplotypes for population studies and contribute to knowledge of the Tunisian gene pool, as well as establishing the role of genetic markers in physiopathology of SCD.

  17. Transgenic mice with -6A haplotype of the human angiotensinogen gene have increased blood pressure compared with -6G haplotype.

    Science.gov (United States)

    Jain, Sudhir; Tillinger, Andrej; Mopidevi, Brahmaraju; Pandey, Varunkumar G; Chauhan, Chetankumar K; Fiering, Steven N; Warming, Soren; Kumar, Ashok

    2010-12-24

    Hypertension is a serious risk factor for cardiovascular disease, and the angiotensinogen (AGT) gene locus is associated with human essential hypertension. The human AGT (hAGT) gene has an A/G polymorphism at -6, and the -6A allele is associated with increased blood pressure. However, transgenic mice containing 1.2 kb of the promoter with -6A of the hAGT gene show neither increased plasma AGT level nor increased blood pressure compared with -6G. We have found that the hAGT gene has three additional SNPs (A/G at -1670, C/G at -1562, and T/G at -1561). Variants -1670A, -1562C, and -1561T almost always occur with -6A, and variants -1670G, -1562G, and -1561G almost always occur with -6G. Therefore, the hAGT gene may be subdivided into either -6A or -6G haplotypes. We show that these polymorphisms affect the binding of HNF-1α and glucocorticoid receptor to the promoter, and a reporter construct containing a 1.8-kb hAGT gene promoter with -6A haplotype has 4-fold increased glucocorticoid-induced promoter activity as compared with -6G haplotype. In order to understand the physiological significance of these haplotypes in an in vivo situation, we have generated double transgenic mice containing either the -6A or -6G haplotype of the hAGT gene and the human renin gene. Our ChIP assay shows that HNF-1α and glucocorticoid receptor have stronger affinity for the chromatin obtained from the liver of transgenic mice containing -6A haplotype. Our studies also show that transgenic mice containing -6A haplotype have increased plasma AGT level and increased blood pressure as compared with -6G haplotype. Our studies explain the molecular mechanism involved in association of the -6A allele of the hAGT gene with hypertension.

  18. Singapore Genome Variation Project: a haplotype map of three Southeast Asian populations.

    Science.gov (United States)

    Teo, Yik-Ying; Sim, Xueling; Ong, Rick T H; Tan, Adrian K S; Chen, Jieming; Tantoso, Erwin; Small, Kerrin S; Ku, Chee-Seng; Lee, Edmund J D; Seielstad, Mark; Chia, Kee-Seng

    2009-11-01

    The Singapore Genome Variation Project (SGVP) provides a publicly available resource of 1.6 million single nucleotide polymorphisms (SNPs) genotyped in 268 individuals from the Chinese, Malay, and Indian population groups in Southeast Asia. This online database catalogs information and summaries on genotype and phased haplotype data, including allele frequencies, assessment of linkage disequilibrium (LD), and recombination rates in a format similar to the International HapMap Project. Here, we introduce this resource and describe the analysis of human genomic variation upon agglomerating data from the HapMap and the Human Genome Diversity Project, providing useful insights into the population structure of the three major population groups in Asia. In addition, this resource also surveyed across the genome for variation in regional patterns of LD between the HapMap and SGVP populations, and for signatures of positive natural selection using two well-established metrics: iHS and XP-EHH. The raw and processed genetic data, together with all population genetic summaries, are publicly available for download and browsing through a web browser modeled with the Generic Genome Browser.

  19. Haplotype Map of Sickle Cell Anemia in Tunisia

    OpenAIRE

    Imen Moumni; Maha Ben Mustapha; Sarra Sassi; Amine Zorai; Ikbel Ben Mansour; Kais Douzi; Dorra Chouachi; Fethi Mellouli; Mohamed Bejaoui; Salem Abbes

    2014-01-01

    International audience; β-Globin haplotypes are important to establish the ethnic origin and predict the clinical development of sickle cell disease patients (SCD). To determine the chromosomal background of β (S) Tunisian sickle cell patients, in this first study in Tunisia, we have explored four polymorphic regions of β-globin cluster on chromosome 11. It is the 5' region of β-LCR-HS2 site, the intervening sequence II (IVSII) region of two fetal ((G)γ and (A)γ) genes and the 5' region of β-...

  20. Genome-wide mapping of IBD segments in an Ashkenazi PD cohort identifies associated haplotypes.

    Science.gov (United States)

    Vacic, Vladimir; Ozelius, Laurie J; Clark, Lorraine N; Bar-Shira, Anat; Gana-Weisz, Mali; Gurevich, Tanya; Gusev, Alexander; Kedmi, Merav; Kenny, Eimear E; Liu, Xinmin; Mejia-Santana, Helen; Mirelman, Anat; Raymond, Deborah; Saunders-Pullman, Rachel; Desnick, Robert J; Atzmon, Gil; Burns, Edward R; Ostrer, Harry; Hakonarson, Hakon; Bergman, Aviv; Barzilai, Nir; Darvasi, Ariel; Peter, Inga; Guha, Saurav; Lencz, Todd; Giladi, Nir; Marder, Karen; Pe'er, Itsik; Bressman, Susan B; Orr-Urtreger, Avi

    2014-09-01

    The recent series of large genome-wide association studies in European and Japanese cohorts established that Parkinson disease (PD) has a substantial genetic component. To further investigate the genetic landscape of PD, we performed a genome-wide scan in the largest to date Ashkenazi Jewish cohort of 1130 Parkinson patients and 2611 pooled controls. Motivated by the reduced disease allele heterogeneity and a high degree of identical-by-descent (IBD) haplotype sharing in this founder population, we conducted a haplotype association study based on mapping of shared IBD segments. We observed significant haplotype association signals at three previously implicated Parkinson loci: LRRK2 (OR = 12.05, P = 1.23 × 10(-56)), MAPT (OR = 0.62, P = 1.78 × 10(-11)) and GBA (multiple distinct haplotypes, OR > 8.28, P = 1.13 × 10(-11) and OR = 2.50, P = 1.22 × 10(-9)). In addition, we identified a novel association signal on chr2q14.3 coming from a rare haplotype (OR = 22.58, P = 1.21 × 10(-10)) and replicated it in a secondary cohort of 306 Ashkenazi PD cases and 2583 controls. Our results highlight the power of our haplotype association method, particularly useful in studies of founder populations, and reaffirm the benefits of studying complex diseases in Ashkenazi Jewish cohorts.

  1. Effects of the number of markers per haplotype and clustering of haplotypes on the accuracy of QTL mapping and prediction of genomic breeding values

    Directory of Open Access Journals (Sweden)

    Schrooten Chris

    2009-01-01

    Full Text Available Abstract The aim of this paper was to compare the effect of haplotype definition on the precision of QTL-mapping and on the accuracy of predicted genomic breeding values. In a multiple QTL model using identity-by-descent (IBD probabilities between haplotypes, various haplotype definitions were tested i.e. including 2, 6, 12 or 20 marker alleles and clustering base haplotypes related with an IBD probability of > 0.55, 0.75 or 0.95. Simulated data contained 1100 animals with known genotypes and phenotypes and 1000 animals with known genotypes and unknown phenotypes. Genomes comprising 3 Morgan were simulated and contained 74 polymorphic QTL and 383 polymorphic SNP markers with an average r2 value of 0.14 between adjacent markers. The total number of haplotypes decreased up to 50% when the window size was increased from two to 20 markers and decreased by at least 50% when haplotypes related with an IBD probability of > 0.55 instead of > 0.95 were clustered. An intermediate window size led to more precise QTL mapping. Window size and clustering had a limited effect on the accuracy of predicted total breeding values, ranging from 0.79 to 0.81. Our conclusion is that different optimal window sizes should be used in QTL-mapping versus genome-wide breeding value prediction.

  2. Effects of the number of markers per haplotype and clustering of haplotypes on the accuracy of QTL mapping and prediction of genomic breeding values.

    Science.gov (United States)

    Calus, Mario P L; Meuwissen, Theo H E; Windig, Jack J; Knol, Egbert F; Schrooten, Chris; Vereijken, Addie L J; Veerkamp, Roel F

    2009-01-15

    The aim of this paper was to compare the effect of haplotype definition on the precision of QTL-mapping and on the accuracy of predicted genomic breeding values. In a multiple QTL model using identity-by-descent (IBD) probabilities between haplotypes, various haplotype definitions were tested i.e. including 2, 6, 12 or 20 marker alleles and clustering base haplotypes related with an IBD probability of > 0.55, 0.75 or 0.95. Simulated data contained 1100 animals with known genotypes and phenotypes and 1000 animals with known genotypes and unknown phenotypes. Genomes comprising 3 Morgan were simulated and contained 74 polymorphic QTL and 383 polymorphic SNP markers with an average r2 value of 0.14 between adjacent markers. The total number of haplotypes decreased up to 50% when the window size was increased from two to 20 markers and decreased by at least 50% when haplotypes related with an IBD probability of > 0.55 instead of > 0.95 were clustered. An intermediate window size led to more precise QTL mapping. Window size and clustering had a limited effect on the accuracy of predicted total breeding values, ranging from 0.79 to 0.81. Our conclusion is that different optimal window sizes should be used in QTL-mapping versus genome-wide breeding value prediction.

  3. Strategies for haplotype-based association mapping in complex pedigreed populations

    DEFF Research Database (Denmark)

    Boleckova, J; Christensen, Ole Fredslund; Sørensen, Peter

    2012-01-01

    , 4, 6, 10 and 20. The simulated data resembled the Danish Holstein cattle pedigree representing a complex relationship structure and QTL effects of different sizes were simulated. We observed that the random haplotype models had high power and very low type I error rates (after Bonferroni correction...... effects in association mapping models are applicable to data from other species with similar pedigree structure...

  4. HIV-1 Vif adaptation to human APOBEC3H haplotypes.

    Science.gov (United States)

    Ooms, Marcel; Brayton, Bonnie; Letko, Michael; Maio, Susan M; Pilcher, Christopher D; Hecht, Frederick M; Barbour, Jason D; Simon, Viviana

    2013-10-16

    Several human APOBEC3 deaminases can inhibit HIV-1 replication in vitro. HIV-1 Vif counteracts this restriction by targeting APOBEC3 for proteasomal degradation. Human APOBEC3H (A3H) is highly polymorphic, with natural variants differing considerably in anti-HIV-1 activity in vitro. To examine HIV-1 adaptation to variation in A3H activity in a natural infection context, we determined the A3H haplotypes and Vif sequences from 76 recently infected HIV-1 patients. We detected A3H-specific Vif changes suggesting viral adaptation. The patient-derived Vif sequences were used to engineer viruses that specifically differed in their ability to counteract A3H. Replication of these Vif-variant viruses in primary T cells naturally expressing active or inactive A3H haplotypes showed that endogenously expressed A3H restricts HIV-1 replication. Proviral DNA from A3H-restricted viruses showed high levels of G-to-A mutations in an A3H-specific GA dinucleotide context. Taken together, our data validate A3H expressed at endogenous levels as a bona fide HIV-1 restriction factor.

  5. Human Mind Maps

    Science.gov (United States)

    Glass, Tom

    2016-01-01

    When students generate mind maps, or concept maps, the maps are usually on paper, computer screens, or a blackboard. Human Mind Maps require few resources and little preparation. The main requirements are space where students can move around and a little creativity and imagination. Mind maps can be used for a variety of purposes, and Human Mind…

  6. Updated listing of haplotypes at the human phenylalanine hydroxylase (PAH) locus

    Energy Technology Data Exchange (ETDEWEB)

    Eisensmith, R.C.; Woo, S.L.C. (Baylor College of Medicine, Houston, TX (United States))

    1992-12-01

    Analysis of mutant PAH chromosomes has identified approximately 60 different single-base substitutions and deletions within the PAH locus. Nearly all of these molecular lesions are in strong linkage disequilibrium with specific RFLP haplotypes in different ethnic populations. Thus, haplotype analysis is not only useful for diagnostic purposes but is proving to be a valuable tool in population genetic studies of the origin and spread of phenylketonuria alleles in human populations. PCR-based methods have been developed to detect six of the eight polymorphic restriction sites used for determination of RFLP haplotypes at the PAH locus. A table of the proposed expanded haplotypes is given.

  7. Improved haplotype analysis of human myelin basic protein short tandem repeat loci.

    Science.gov (United States)

    Watanabe, G; Umetsu, K; Yuasa, I; Suzuki, T

    2000-06-01

    We report an improved haplotype analysis of the human myelin basic protein gene (MBP) short tandem repeat (STR) polymorphism. The polymorphic G-->A transition and 2 conventional STR polymorphisms, MBPA and MBPB, were simultaneously determined by an amplified product length polymorphism technique. After the MBPC fragments containing MBPA and MBPB were amplified, the linkage of these 2 STR loci was determined by a second amplification, using polymerase chain reaction (PCR) technique, of the isolated MBPC fragments. The present haplotype analysis dispensed with family studies for the haplotyping of MBPA and MBPB. Polymorphisms of the MBP loci studied in German and Japanese populations showed a high genomic variation. Haplotype analysis of the MBP loci showed distinct differences between the German and the Japanese populations. Consequently, haplotype analysis of the MBP loci promises to be useful in forensic identification and paternity testing.

  8. Mapping the genetic diversity of HLA haplotypes in the Japanese populations.

    Science.gov (United States)

    Saw, Woei-Yuh; Liu, Xuanyao; Khor, Chiea-Chuen; Takeuchi, Fumihiko; Katsuya, Tomohiro; Kimura, Ryosuke; Nabika, Toru; Ohkubo, Takayoshi; Tabara, Yasuharu; Yamamoto, Ken; Yokota, Mitsuhiro; Teo, Yik-Ying; Kato, Norihiro

    2015-12-09

    Japan has often been viewed as an Asian country that possesses a genetically homogenous community. The basis for partitioning the country into prefectures has largely been geographical, although cultural and linguistic differences still exist between some of the districts/prefectures, especially between Okinawa and the mainland prefectures. The Major Histocompatibility Complex (MHC) region has consistently emerged as the most polymorphic region in the human genome, harbouring numerous biologically important variants; nevertheless the presence of population-specific long haplotypes hinders the imputation of SNPs and classical HLA alleles. Here, we examined the extent of genetic variation at the MHC between eight Japanese populations sampled from Okinawa, and six other prefectures located in or close to the mainland of Japan, specifically focusing at the haplotypes observed within each population, and what the impact of any variation has on imputation. Our results indicated that Okinawa was genetically farther to the mainland Japanese than were Gujarati Indians from Tamil Indians, while the mainland Japanese from six prefectures were more homogeneous than between northern and southern Han Chinese. The distribution of haplotypes across Japan was similar, although imputation was most accurate for Okinawa and several mainland prefectures when population-specific panels were used as reference.

  9. An Extensive Analysis of Y-Chromosomal Microsatellite Haplotypes in Globally Dispersed Human Populations

    Science.gov (United States)

    Kayser, Manfred; Krawczak, Michael; Excoffier, Laurent; Dieltjes, Patrick; Corach, Daniel; Pascali, Vincente; Gehrig, Christian; Bernini, Luigi F.; Jespersen, Jørgen; Bakker, Egbert; Roewer, Lutz; de Knijff, Peter

    2001-01-01

    The genetic variance at seven Y-chromosomal microsatellite loci (or short tandem repeats [STRs]) was studied among 986 male individuals from 20 globally dispersed human populations. A total of 598 different haplotypes were observed, of which 437 (73.1%) were each found in a single male only. Population-specific haplotype-diversity values were .86–.99. Analyses of haplotype diversity and population-specific haplotypes revealed marked population-structure differences between more-isolated indigenous populations (e.g., Central African Pygmies or Greenland Inuit) and more-admixed populations (e.g., Europeans or Surinamese). Furthermore, male individuals from isolated indigenous populations shared haplotypes mainly with male individuals from their own population. By analysis of molecular variance, we found that 76.8% of the total genetic variance present among these male individuals could be attributed to genetic differences between male individuals who were members of the same population. Haplotype sharing between populations, ΦST statistics, and phylogenetic analysis identified close genetic affinities among European populations and among New Guinean populations. Our data illustrate that Y-chromosomal STR haplotypes are an ideal tool for the study of the genetic affinities between groups of male subjects and for detection of population structure. PMID:11254455

  10. Low enzymatic activity haplotypes of the human catechol-O-methyltransferase gene: enrichment for marker SNPs.

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    Andrea G Nackley

    Full Text Available Catechol-O-methyltransferase (COMT is an enzyme that plays a key role in the modulation of catechol-dependent functions such as cognition, cardiovascular function, and pain processing. Three common haplotypes of the human COMT gene, divergent in two synonymous and one nonsynonymous (val(158met position, designated as low (LPS, average (APS, and high pain sensitive (HPS, are associated with experimental pain sensitivity and risk of developing chronic musculoskeletal pain conditions. APS and HPS haplotypes produce significant functional effects, coding for 3- and 20-fold reductions in COMT enzymatic activity, respectively. In the present study, we investigated whether additional minor single nucleotide polymorphisms (SNPs, accruing in 1 to 5% of the population, situated in the COMT transcript region contribute to haplotype-dependent enzymatic activity. Computer analysis of COMT ESTs showed that one synonymous minor SNP (rs769224 is linked to the APS haplotype and three minor SNPs (two synonymous: rs6267, rs740602 and one nonsynonymous: rs8192488 are linked to the HPS haplotype. Results from in silico and in vitro experiments revealed that inclusion of allelic variants of these minor SNPs in APS or HPS haplotypes did not modify COMT function at the level of mRNA folding, RNA transcription, protein translation, or enzymatic activity. These data suggest that neutral variants are carried with APS and HPS haplotypes, while the high activity LPS haplotype displays less linked variation. Thus, both minor synonymous and nonsynonymous SNPs in the coding region are markers of functional APS and HPS haplotypes rather than independent contributors to COMT activity.

  11. Combining haplotypers

    CERN Document Server

    Kääriäinen, Matti; Lappalainen, Sampsa; Mielikäinen, Taneli

    2007-01-01

    Statistically resolving the underlying haplotype pair for a genotype measurement is an important intermediate step in gene mapping studies, and has received much attention recently. Consequently, a variety of methods for this problem have been developed. Different methods employ different statistical models, and thus implicitly encode different assumptions about the nature of the underlying haplotype structure. Depending on the population sample in question, their relative performance can vary greatly, and it is unclear which method to choose for a particular sample. Instead of choosing a single method, we explore combining predictions returned by different methods in a principled way, and thereby circumvent the problem of method selection. We propose several techniques for combining haplotype reconstructions and analyze their computational properties. In an experimental study on real-world haplotype data we show that such techniques can provide more accurate and robust reconstructions, and are useful for out...

  12. Two independent apolipoprotein a5 Haplotypes influence human plasma triglyceride levels

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Olivier, Michael; Hubacek, Jaroslav A.; Krauss, Ronald M.; Rubin, Edward M.; Cohen, Jonathan C.

    2002-09-16

    The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in {approx}16 percent of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n 1/4 419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12 percent of Caucasians, 14 percent of African-Americans and 28 percent of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25 50 percent of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.

  13. Structural forms of the human amylase locus and their relationships to SNPs, haplotypes and obesity.

    Science.gov (United States)

    Usher, Christina L; Handsaker, Robert E; Esko, Tõnu; Tuke, Marcus A; Weedon, Michael N; Hastie, Alex R; Cao, Han; Moon, Jennifer E; Kashin, Seva; Fuchsberger, Christian; Metspalu, Andres; Pato, Carlos N; Pato, Michele T; McCarthy, Mark I; Boehnke, Michael; Altshuler, David M; Frayling, Timothy M; Hirschhorn, Joel N; McCarroll, Steven A

    2015-08-01

    Hundreds of genes reside in structurally complex, poorly understood regions of the human genome. One such region contains the three amylase genes (AMY2B, AMY2A and AMY1) responsible for digesting starch into sugar. Copy number of AMY1 is reported to be the largest genomic influence on obesity, although genome-wide association studies for obesity have found this locus unremarkable. Using whole-genome sequence analysis, droplet digital PCR and genome mapping, we identified eight common structural haplotypes of the amylase locus that suggest its mutational history. We found that the AMY1 copy number in an individual's genome is generally even (rather than odd) and partially correlates with nearby SNPs, which do not associate with body mass index (BMI). We measured amylase gene copy number in 1,000 obese or lean Estonians and in 2 other cohorts totaling ∼3,500 individuals. We had 99% power to detect the lower bound of the reported effects on BMI, yet found no association.

  14. Transgenic Mice with −6A Haplotype of the Human Angiotensinogen Gene Have Increased Blood Pressure Compared with −6G Haplotype*

    Science.gov (United States)

    Jain, Sudhir; Tillinger, Andrej; Mopidevi, Brahmaraju; Pandey, Varunkumar G.; Chauhan, Chetankumar K.; Fiering, Steven N.; Warming, Soren; Kumar, Ashok

    2010-01-01

    Hypertension is a serious risk factor for cardiovascular disease, and the angiotensinogen (AGT) gene locus is associated with human essential hypertension. The human AGT (hAGT) gene has an A/G polymorphism at −6, and the −6A allele is associated with increased blood pressure. However, transgenic mice containing 1.2 kb of the promoter with −6A of the hAGT gene show neither increased plasma AGT level nor increased blood pressure compared with −6G. We have found that the hAGT gene has three additional SNPs (A/G at −1670, C/G at −1562, and T/G at −1561). Variants −1670A, −1562C, and −1561T almost always occur with −6A, and variants −1670G, −1562G, and −1561G almost always occur with −6G. Therefore, the hAGT gene may be subdivided into either −6A or −6G haplotypes. We show that these polymorphisms affect the binding of HNF-1α and glucocorticoid receptor to the promoter, and a reporter construct containing a 1.8-kb hAGT gene promoter with −6A haplotype has 4-fold increased glucocorticoid-induced promoter activity as compared with −6G haplotype. In order to understand the physiological significance of these haplotypes in an in vivo situation, we have generated double transgenic mice containing either the −6A or −6G haplotype of the hAGT gene and the human renin gene. Our ChIP assay shows that HNF-1α and glucocorticoid receptor have stronger affinity for the chromatin obtained from the liver of transgenic mice containing −6A haplotype. Our studies also show that transgenic mice containing −6A haplotype have increased plasma AGT level and increased blood pressure as compared with −6G haplotype. Our studies explain the molecular mechanism involved in association of the −6A allele of the hAGT gene with hypertension. PMID:20978123

  15. Linkage disequilibrium blocks, haplotype structure, and htSNPs of human CYP7A1 gene

    Directory of Open Access Journals (Sweden)

    Wan Yu-Jui

    2006-05-01

    Full Text Available Abstract Background Cholesterol 7-alpha-hydroxylase (CYP7A1 is the rate limiting enzyme for converting cholesterol into bile acids. Genetic variations in the CYP7A1 gene have been associated with metabolic disorders of cholesterol and bile acids, including hypercholesterolemia, hypertriglyceridemia, arteriosclerosis, and gallstone disease. Current genetic studies are focused mainly on analysis of a single nucleotide polymorphism (SNP at A-278C in the promoter region of the CYP7A1 gene. Here we report a genetic approach for an extensive analysis on linkage disequilibrium (LD blocks and haplotype structures of the entire CYP7A1 gene and its surrounding sequences in Africans, Caucasians, Asians, Mexican-Americans, and African-Americans. Result The LD patterns and haplotype blocks of CYP7A1 gene were defined in Africans, Caucasians, and Asians using genotyping data downloaded from the HapMap database to select a set of haplotype-tagging SNPs (htSNP. A low cost, microarray-based platform on thin-film biosensor chips was then developed for high-throughput genotyping to study transferability of the HapMap htSNPs to Mexican-American and African-American populations. Comparative LD patterns and haplotype block structure was defined across all test populations. Conclusion A constant genetic structure in CYP7A1 gene and its surrounding sequences was found that may lead to a better design for association studies of genetic variations in CYP7A1 gene with cholesterol and bile acid metabolism.

  16. Characterisation of the genomic architecture of human chromosome 17q and evaluation of different methods for haplotype block definition

    Directory of Open Access Journals (Sweden)

    Ollier William

    2005-04-01

    Full Text Available Abstract Background The selection of markers in association studies can be informed through the use of haplotype blocks. Recent reports have determined the genomic architecture of chromosomal segments through different haplotype block definitions based on linkage disequilibrium (LD measures or haplotype diversity criteria. The relative applicability of distinct block definitions to association studies, however, remains unclear. We compared different block definitions in 6.1 Mb of chromosome 17q in 189 unrelated healthy individuals. Using 137 single nucleotide polymorphisms (SNPs, at a median spacing of 15.5 kb, we constructed haplotype block maps using published methods and additional methods we have developed. Haplotype tagging SNPs (htSNPs were identified for each map. Results Blocks were found to be shorter and coverage of the region limited with methods based on LD measures, compared to the method based on haplotype diversity. Although the distribution of blocks was highly variable, the number of SNPs that needed to be typed in order to capture the maximum number of haplotypes was consistent. Conclusion For the marker spacing used in this study, choice of block definition is not important when used as an initial screen of the region to identify htSNPs. However, choice of block definition has consequences for the downstream interpretation of association study results.

  17. Characterisation of the genomic architecture of human chromosome 17q and evaluation of different methods for haplotype block definition.

    Science.gov (United States)

    Zeggini, Eleftheria; Barton, Anne; Eyre, Stephen; Ward, Daniel; Ollier, William; Worthington, Jane; John, Sally

    2005-04-25

    The selection of markers in association studies can be informed through the use of haplotype blocks. Recent reports have determined the genomic architecture of chromosomal segments through different haplotype block definitions based on linkage disequilibrium (LD) measures or haplotype diversity criteria. The relative applicability of distinct block definitions to association studies, however, remains unclear. We compared different block definitions in 6.1 Mb of chromosome 17q in 189 unrelated healthy individuals. Using 137 single nucleotide polymorphisms (SNPs), at a median spacing of 15.5 kb, we constructed haplotype block maps using published methods and additional methods we have developed. Haplotype tagging SNPs (htSNPs) were identified for each map. Blocks were found to be shorter and coverage of the region limited with methods based on LD measures, compared to the method based on haplotype diversity. Although the distribution of blocks was highly variable, the number of SNPs that needed to be typed in order to capture the maximum number of haplotypes was consistent. For the marker spacing used in this study, choice of block definition is not important when used as an initial screen of the region to identify htSNPs. However, choice of block definition has consequences for the downstream interpretation of association study results.

  18. Haplotype block structure is conserved across mammals.

    Directory of Open Access Journals (Sweden)

    Victor Guryev

    2006-07-01

    Full Text Available Genetic variation in genomes is organized in haplotype blocks, and species-specific block structure is defined by differential contribution of population history effects in combination with mutation and recombination events. Haplotype maps characterize the common patterns of linkage disequilibrium in populations and have important applications in the design and interpretation of genetic experiments. Although evolutionary processes are known to drive the selection of individual polymorphisms, their effect on haplotype block structure dynamics has not been shown. Here, we present a high-resolution haplotype map for a 5-megabase genomic region in the rat and compare it with the orthologous human and mouse segments. Although the size and fine structure of haplotype blocks are species dependent, there is a significant interspecies overlap in structure and a tendency for blocks to encompass complete genes. Extending these findings to the complete human genome using haplotype map phase I data reveals that linkage disequilibrium values are significantly higher for equally spaced positions in genic regions, including promoters, as compared to intergenic regions, indicating that a selective mechanism exists to maintain combinations of alleles within potentially interacting coding and regulatory regions. Although this characteristic may complicate the identification of causal polymorphisms underlying phenotypic traits, conservation of haplotype structure may be employed for the identification and characterization of functionally important genomic regions.

  19. Nasopharyngeal Carcinoma (NPC Related Human Leukocyte Antigen (HLA Haplotype Sharing among Southern East Asian Population

    Directory of Open Access Journals (Sweden)

    Rika Yuliwulandari

    2017-02-01

    Full Text Available Abstract The human leukocyte antigens (HLAs play important roles in the immune systems to response to various pathogens and disease among individuals. The aim of this study was analyze the HLA allele and haplotype frequencies of Southern East Asian population that show high incidence of nasopharyngeal carcinoma (NPC to evaluate the shared HLA haplotype contribution to NPC susceptibility among the population and analyses the genetic affinities between the population. We collect information of HLA haplotype from our previous study, other published paper, and HLA database in 19 population during 2005 to 2015. Haplotype frequencies were estimated using the maximum likelihood method based on an expectation maximization algorithm with ARLEQUIN v.2.0 software. We also calculated the genetic distance among 19 Southern East Asians based on HLA allele frequency using modified Cavalli-Sforza (DA distance method. Then, a phylogenetic tree was constructed using DISPAN software and principal component analysis (PCA was performed using XLSTAT-PRO software. A33-B58-DR3 haplotype, tightly linked to NPC, was commonly observed in all populations, supporting the high incidence of NPC in the populations. In addition, A2-B46 haplotype also associated with NPC, was also commonly found in several population that may also have a role in the disease development. The conclusion is the HLA haplotype sharing has an important role than the HLA allele sharing. The A33-B58-DR3 haplotype and A2-B46-DR9 haplotype in this study could be related to NPC in the Southern East Asian populations. The observed haplotype needs to be tested in the real patients to confirm the assumption. Abstrak Human leukocyte antigens (HLAs berperan penting dalam sistem imun untuk merespons berbagai patogen dan penyakit di antara individu yang berbeda. Tujuan penelitian ini menganalisis frekuensi alel dan haplotipe HLA populasi Southern East Asia yang menunjukkan insidensi yang tinggi terhadap

  20. Y-chromosome haplotype distribution in Han Chinese populations and modern human origin in East Asians

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    We investigated the distribution of Y-chromosome haplotype using 19 Y-SNPs in Han Chinese populations from 22 provinces of China. Our data indicate distinctive patterns of Y chromosome between southern and northern Han Chinese populations. The southern populations are much more polymorphic than northern populations. The latter has only a subset of the southern haplotypes. This result confirms the genetic difference observed between southern and northern ethnic populations in East Asia. It supports the hypothesis that the first settlement of modern hu-mans of African origin occurred in the southern part of East Asia during the last Ice Age, and a northward migration led to the peopling of northern China.

  1. Most parsimonious haplotype allele sharing determination

    Directory of Open Access Journals (Sweden)

    Xu Jiaofen

    2009-04-01

    Full Text Available Abstract Background The "common disease – common variant" hypothesis and genome-wide association studies have achieved numerous successes in the last three years, particularly in genetic mapping in human diseases. Nevertheless, the power of the association study methods are still low, in particular on quantitative traits, and the description of the full allelic spectrum is deemed still far from reach. Given increasing density of single nucleotide polymorphisms available and suggested by the block-like structure of the human genome, a popular and prosperous strategy is to use haplotypes to try to capture the correlation structure of SNPs in regions of little recombination. The key to the success of this strategy is thus the ability to unambiguously determine the haplotype allele sharing status among the members. The association studies based on haplotype sharing status would have significantly reduced degrees of freedom and be able to capture the combined effects of tightly linked causal variants. Results For pedigree genotype datasets of medium density of SNPs, we present two methods for haplotype allele sharing status determination among the pedigree members. Extensive simulation study showed that both methods performed nearly perfectly on breakpoint discovery, mutation haplotype allele discovery, and shared chromosomal region discovery. Conclusion For pedigree genotype datasets, the haplotype allele sharing status among the members can be deterministically, efficiently, and accurately determined, even for very small pedigrees. Given their excellent performance, the presented haplotype allele sharing status determination programs can be useful in many downstream applications including haplotype based association studies.

  2. Genetic analysis of completely sequenced disease-associated MHC haplotypes identifies shuffling of segments in recent human history.

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    James A Traherne

    2006-01-01

    Full Text Available The major histocompatibility complex (MHC is recognised as one of the most important genetic regions in relation to common human disease. Advancement in identification of MHC genes that confer susceptibility to disease requires greater knowledge of sequence variation across the complex. Highly duplicated and polymorphic regions of the human genome such as the MHC are, however, somewhat refractory to some whole-genome analysis methods. To address this issue, we are employing a bacterial artificial chromosome (BAC cloning strategy to sequence entire MHC haplotypes from consanguineous cell lines as part of the MHC Haplotype Project. Here we present 4.25 Mb of the human haplotype QBL (HLA-A26-B18-Cw5-DR3-DQ2 and compare it with the MHC reference haplotype and with a second haplotype, COX (HLA-A1-B8-Cw7-DR3-DQ2, that shares the same HLA-DRB1, -DQA1, and -DQB1 alleles. We have defined the complete gene, splice variant, and sequence variation contents of all three haplotypes, comprising over 259 annotated loci and over 20,000 single nucleotide polymorphisms (SNPs. Certain coding sequences vary significantly between different haplotypes, making them candidates for functional and disease-association studies. Analysis of the two DR3 haplotypes allowed delineation of the shared sequence between two HLA class II-related haplotypes differing in disease associations and the identification of at least one of the sites that mediated the original recombination event. The levels of variation across the MHC were similar to those seen for other HLA-disparate haplotypes, except for a 158-kb segment that contained the HLA-DRB1, -DQA1, and -DQB1 genes and showed very limited polymorphism compatible with identity-by-descent and relatively recent common ancestry (<3,400 generations. These results indicate that the differential disease associations of these two DR3 haplotypes are due to sequence variation outside this central 158-kb segment, and that shuffling of

  3. Mapping the human genome

    Energy Technology Data Exchange (ETDEWEB)

    Cantor, Charles R.

    1989-06-01

    The following pages aim to lay a foundation for understanding the excitement surrounding the ''human genome project,'' as well as to convey a flavor of the ongoing efforts and plans at the Human Genome Center at the Lawrence Berkeley Laboratory. Our own work, of course, is only part of a broad international effort that will dramatically enhance our understanding of human molecular genetics before the end of this century. In this country, the bulk of the effort will be carried out under the auspices of the Department of Energy and the National Institutes of Health, but significant contributions have already been made both by nonprofit private foundations and by private corporation. The respective roles of the DOE and the NIH are being coordinated by an inter-agency committee, the aims of which are to emphasize the strengths of each agency, to facilitate cooperation, and to avoid unnecessary duplication of effort. The NIH, for example, will continue its crucial work in medical genetics and in mapping the genomes of nonhuman species. The DOE, on the other hand, has unique experience in managing large projects, and its national laboratories are repositories of expertise in physics, engineering, and computer science, as well as the life sciences. The tools and techniques the project will ultimately rely on are thus likely to be developed in multidisciplinary efforts at laboratories like LBL. Accordingly, we at LBL take great pride in this enterprise -- an enterprise that will eventually transform our understanding of ourselves.

  4. Convergent myotonic dystrophy (DM) haplotypes on 19q13.3: Potential inconsistencies in human disease gene localization

    Energy Technology Data Exchange (ETDEWEB)

    Tsilfidis, C. [Eye Research Institute of Canada, Toronto (Canada); Whiting, E.J. [Univ. of Ottawa (Canada); Korneluk, R.G. [Univ. of Ottawa (Canada)]|[Childrens Hospital of Eastern Ontario, Ottawa (Canada)

    1994-09-01

    Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease which has been shown to be caused by an unstable trinucleotide repeat located on chromosome 19q. We have conducted extensive haplotype analysis on 103 DM chromosome using thirteen 19q13.3 loci identifying 18 RFLPs, spanning a physical distance of 1.3 Mb containing the myotonic dystrophy gene. Three major haplotypes, H1, H2 and H3, comprising 45.6% of the DM chromosomes, were observed in our population. The later two haplotypes, observed exclusively on DM chromosomes of French Canadian origin, contain a 500 kb core region that is identical. The low frequency of this core on normal chromosomes (0.8%) is consistent with a mapping of the DM gene within this region. However, the DM mutation is found 160 kb distal to the point of divergence between these two haplotypes. In contrast, the 450 kb shared by haplotypes H1 and H2 contain the DM mutation. Further, analysis of the DM region using a polymorphic microsatellite GJ-VSSM2 located 15 kb telomeric to the DM gene revealed strong allelic association of allele V on DM chromosomes (present on 6% of normal and 88.2% of DM chromosomes). The fact that allele V was found on all DM chromosomes with the three major haplotypes is indicative of their common origin and includes the two French Canadian haplotypes which share a region proximal to the DM mutation. This analysis indicates that convergent haplotypes, in the absence of a more extensive linkage disequilibrium analysis, may lead to a spurious disease gene localization.

  5. Y-chromosome haplotype distribution in Han Chinese populations and modern human origin in East Asians

    Institute of Scientific and Technical Information of China (English)

    KE; Yuehai

    2001-01-01

    using denaturing high performance liquid chromatography (DHPLC), Current Protocols in Human Genetics, Supplement, 1998, 19(7): 10.1-7.10.12.[17]Underhill, P. A., Jin, L., Zemans, R. et al., A pre-Columbian human Y chromosome-specific transition and its implications for human evolution, Proc. Natl. Acad. Sci., 1996, USA 93: 196-200.[18]Underhill, P. A., Jin, L., Lin, A. A. et al., Detection of numerous Y chromosome biallelic polymorphisms by denaturing high-performance liquid chromatography, Genome Research, 1997, 7: 996-1005.[19]Vollrath, D. S., Vollrath, D., Foote, S. et al.,The human Y chromosome: A 43-interval map based on naturally occurring deletions, Science,1992, 258: 52-59.[20]Underhill, P. A., Jin, L., Lin, A. A. et al., An African origin of human Y-chromosomes, Program and Abstract, 1997 An-nual Meeting of The American Society of Human Genetics, Am. J. Hum. Genet, 1997, 61(supplement): A18.[21]Kayser, M., Caglia, A., Corach, D. et al., Evaluation of Y-chromosomal STRs: a multicenter study, Int. J. Legal Med., 1997, 110: 125-133.[22]Su, B., Xiao, J. H., Underhill, P. et al., Y-chromosome evidence for a northward migration of modern humans into eastern Asia during the last ice age, Am. J. Hum. Genet., 1999, 6: 1718-1724.[23]Ballinger, S. W., Schurr, T. G., Torroni, A. et al., Southeast Asian mitochondrial DNA analysis reveals genetic continuity of ancient mongoloid migrations, Genetics, 1992, 130: 139-152.[24]Heyer, E., Puymirat, J., Dieltjes, P. et al., Estimating Y chromosome specific microsatellite mutation frequencies using deep rooting pedigrees, Human Molecular Genetics,1997, 6: 799-803.[25]Bianchi, N. O., Catanesi, C. I., Bailliet, G. et al., Characterization of ancestral and derived Y-chromosomal haplotypes of New World native populations, Am. J. Hum. Genet., 1998, 63: 1862-1871.[26]Turner, II C. G., Shifting continuity: modern human origin, in The Origin and Past of Modern Humans as Viewed From DNA (eds. Brenner

  6. How to deal with Haplotype data: An Extension to the Conceptual Schema of the Human Genome

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    José Fabián Reyes Román

    2016-12-01

    Full Text Available The goal of this work is to describe the advantages of the application of Conceptual Modeling (CM in complex domains, such as genomics. Nowadays, the study and comprehension of the human genome is a major challenge due to its high level of complexity. The constant evolution in the genomic domain contributes to the generation of ever larger amounts of new data, which means that if we do not manage it correctly data quality could be compromised (i.e., problems related with heterogeneity and inconsistent data. In this paper, we propose the use of a Conceptual Schema of the Human Genome (CSHG, designed to understand and improve our ontological commitment to the domain and also extend (enrich this schema with the integration of a novel concept: Haplotypes. Our focus is on improving the understanding of the relationship between genotype and phenotype, since new findings show that this question is more complex than was originally thought. Here we present the first steps in our data management approach with haplotypes (variations, frequencies and populations and discuss the database evolution to support this data. Each new version in our conceptual schema (CS introduces changes to the underlying database structure that has essential and practical implications for better understanding and managing the relevant information. A solution based on conceptual models gives a clear definition of the domain with direct implications in the medical field (Precision Medicine, in which Genomic Information Systems (GeIS play a very important role.

  7. Compound haplotypes at Xp11.23 and human population growth in Eurasia.

    Science.gov (United States)

    Alonso, S; Armour, J A L

    2004-09-01

    To investigate patterns of diversity and the evolutionary history of Eurasians, we have sequenced a 2.8 kb region at Xp11.23 in a sample of African and Eurasian chromosomes. This region is in a long intron of CLCN5 and is immediately flanked by a highly variable minisatellite, DXS255, and a human-specific Ta0 LINE. Compared to Africans, Eurasians showed a marked reduction in sequence diversity. The main Euro-Asiatic haplotype seems to be the ancestral haplotype for the whole sample. Coalescent simulations, including recombination and exponential growth, indicate a median length of strong linkage disequilibrium, up to approximately 9 kb for this area. The Ka/Ks ratio between the coding sequence of human CLCN5 and its mouse orthologue is much less than 1. This implies that the region sequenced is unlikely to be under the strong influence of positive selective processes on CLCN5, mutations in which have been associated with disorders such as Dent's disease. In contrast, a scenario based on a population bottleneck and exponential growth seems a more likely explanation for the reduced diversity observed in Eurasians. Coalescent analysis and linked minisatellite diversity (which reaches a gene diversity value greater than 98% in Eurasians) suggest an estimated age of origin of the Euro-Asiatic diversity compatible with a recent out-of-Africa model for colonization of Eurasia by modern Homo sapiens.

  8. Mapping the human protein interactome

    Institute of Scientific and Technical Information of China (English)

    Daniel Figeys

    2008-01-01

    Interactions are the essence of all biomolecules because they cannot fulfill their roles without interacting with other molecules. Hence, mapping the interactions of biomolecules can be useful for understanding their roles and functions. Furthermore, the development of molecular based systems biology requires an understanding of the biomolecular interactions. In recent years, the mapping of protein-protein interactions in different species has been reported, but few reports have focused on the large-scale mapping of protein-protein interactions in human. Here, we review the developments in protein interaction mapping and we discuss issues and strategies for the mapping of the human protein interactome.

  9. Genetic Mapping in Human Disease

    OpenAIRE

    Altshuler, David; Daly, Mark J; Lander, Eric S.

    2008-01-01

    Genetic mapping provides a powerful approach to identify genes and biological processes underlying any trait influenced by inheritance, including human diseases. We discuss the intellectual foundations of genetic mapping of Mendelian and complex traits in humans, examine lessons emerging from linkage analysis of Mendelian diseases and genome-wide association studies of common diseases, and discuss questions and challenges that lie ahead.

  10. A haplotype of human angiotensinogen gene containing -217A increases blood pressure in transgenic mice compared with -217G.

    Science.gov (United States)

    Jain, Sudhir; Vinukonda, Govindaiah; Fiering, Steven N; Kumar, Ashok

    2008-12-01

    The human angiotensinogen (hAGT) gene contains an A/G polymorphism at -217, and frequency of -217A allele is increased in African-American hypertensive patients. The hAGT gene has seven polymorphic sites in the 1.2-kb region of its promoter, and variant -217A almost always occurs with -532T, -793A, and -1074T, whereas variant -217G almost always occurs with -532C, -793G, and -1074G. Since allele -6A is the predominant allele in African-Americans, the AGT gene can be subdivided into two main haplotypes, -6A:-217A (AA) and -6A:-217G (AG). To understand the role of these haplotypes on hAGT gene expression and on blood pressure regulation in an in vivo situation, we have generated double transgenic mice containing human renin gene and either AA or AG haplotype of the hAGT gene using knock-in strategy at the hypoxanthine phosphoribosyltransferase locus. We show here that 1) hAGT mRNA level is increased in the liver by 60% and in the kidney by 40%; and 2) plasma AGT level is increased by approximately 40%, and plasma angiotensin II level is increased by approximately 50% in male double transgenic mice containing AA haplotype of the hAGT gene compared with the AG haplotype. In addition, systolic blood pressure is increased by 8 mmHg in transgenic mice containing the AA haplotype compared with the AG haplotype. This is the first report to show the effect of polymorphisms in the promoter of a human gene on its transcription in an in vivo situation that ultimately leads to an increase in blood pressure.

  11. Different patterns of evolution in the centromeric and telomeric regions of group A and B haplotypes of the human killer cell Ig-like receptor locus.

    Directory of Open Access Journals (Sweden)

    Chul-Woo Pyo

    Full Text Available The fast evolving human KIR gene family encodes variable lymphocyte receptors specific for polymorphic HLA class I determinants. Nucleotide sequences for 24 representative human KIR haplotypes were determined. With three previously defined haplotypes, this gave a set of 12 group A and 15 group B haplotypes for assessment of KIR variation. The seven gene-content haplotypes are all combinations of four centromeric and two telomeric motifs. 2DL5, 2DS5 and 2DS3 can be present in centromeric and telomeric locations. With one exception, haplotypes having identical gene content differed in their combinations of KIR alleles. Sequence diversity varied between haplotype groups and between centromeric and telomeric halves of the KIR locus. The most variable A haplotype genes are in the telomeric half, whereas the most variable genes characterizing B haplotypes are in the centromeric half. Of the highly polymorphic genes, only the 3DL3 framework gene exhibits a similar diversity when carried by A and B haplotypes. Phylogenetic analysis and divergence time estimates, point to the centromeric gene-content motifs that distinguish A and B haplotypes having emerged ~6 million years ago, contemporaneously with the separation of human and chimpanzee ancestors. In contrast, the telomeric motifs that distinguish A and B haplotypes emerged more recently, ~1.7 million years ago, before the emergence of Homo sapiens. Thus the centromeric and telomeric motifs that typify A and B haplotypes have likely been present throughout human evolution. The results suggest the common ancestor of A and B haplotypes combined a B-like centromeric region with an A-like telomeric region.

  12. Chloride and other anions inhibit dichloroacetate-induced inactivation of human liver GSTZ1 in a haplotype-dependent manner.

    Science.gov (United States)

    Zhong, Guo; Li, Wenjun; Gu, Yuan; Langaee, Taimour; Stacpoole, Peter W; James, Margaret O

    2014-05-25

    The in vivo elimination rate of dichloroacetate (DCA), an investigational drug; is determined by the rate of its biotransformation to glyoxylate, catalyzed by glutathione transferase ζ1 (GSTZ1). DCA is a mechanism-based inactivator of GSTZ1, thus elimination of DCA is slowed with repeated dosing. We observed that chloride, a physiologically important anion, attenuated DCA-induced GSTZ1 inactivation in human liver cytosol in a concentration and GSTZ1 haplotype-dependent way. In the absence of chloride, incubation with 0.5mM DCA resulted in inactivation of GSTZ1 with a half-life of 0.4h (samples with the KRT haplotype) to 0.5h (EGT haplotype). At the hepatic physiological chloride concentration, 38mM, samples with the EGT haplotype retained more activity (80%) following a 2-h incubation with 0.5mM DCA than those possessing the KRT haplotype (55%). The chloride concentration that protected 50% of the GSTZ1 activity following 2-h incubation with 0.5mM DCA (EC50) was 15.0±3.1mM (mean±S.D., n=3) for EGT samples and 36.2±2.2mM for KRT samples. Bromide, iodide and sulfite also protected GSTZ1 from inactivation by DCA, however fluoride, sulfate, carbonate, acetate, cyanide did not. Protection by bromide varied by GSTZ1 haplotype: EC50 was 1.3±0.3mM for the EGT haplotype and 5.0±0.60mM for the KRT haplotype. The EC50 values for iodide and sulfite in liver cytosol samples with EGT haplotype were respectively 0.14±0.06mM and 9.6±1.1mM (mean±S.D., n=3). Because the in vivo half-life of DCA is determined by the fraction of active GSTZ1 in the liver, identifying factors that regulate GSTZ1 activity is important in determining appropriate DCA dosing in humans.

  13. Mapping quantitative trait loci in plant breeding populations : Use of parental haplotype sharing

    NARCIS (Netherlands)

    Jansen, Ritsert C.; Jannink, Jean-Luc; Beavis, William D.

    2003-01-01

    Applied breeding programs evaluate large numbers of progeny derived from multiple related crosses for a wide range of agronomic traits and for tens to hundreds of molecular markers. This study was conducted to determine how these phenotypic and genetic data could be used for routinely mapping quanti

  14. A Revised Map of the Human Chromosomes.

    Science.gov (United States)

    Offner, Susan

    1993-01-01

    Presents an updated map of the human chromosomes, building on a "plain English map" that was previously published. A brief summary of genes research is included in the gene explanations accompanying the map. (PR)

  15. Neanderthal origin of the haplotypes carrying the functional variant Val92Met in the MC1R in modern humans.

    Science.gov (United States)

    Ding, Qiliang; Hu, Ya; Xu, Shuhua; Wang, Chuan-Chao; Li, Hui; Zhang, Ruyue; Yan, Shi; Wang, Jiucun; Jin, Li

    2014-08-01

    Skin color is one of the most visible and important phenotypes of modern humans. Melanocyte-stimulating hormone and its receptor played an important role in regulating skin color. In this article, we present evidence of Neanderthal introgression encompassing the melanocyte-stimulating hormone receptor gene MC1R. The haplotypes from Neanderthal introgression diverged with the Altai Neanderthal 103.3 ka, which postdates the anatomically modern human-Neanderthal divergence. We further discovered that all of the putative Neanderthal introgressive haplotypes carry the Val92Met variant, a loss-of-function variant in MC1R that is associated with multiple dermatological traits including skin color and photoaging. Frequency of this Neanderthal introgression is low in Europeans (∼5%), moderate in continental East Asians (∼30%), and high in Taiwanese aborigines (60-70%). As the putative Neanderthal introgressive haplotypes carry a loss-of-function variant that could alter the function of MC1R and is associated with multiple traits related to skin color, we speculate that the Neanderthal introgression may have played an important role in the local adaptation of Eurasians to sunlight intensity.

  16. The Effect of Haplotype-Block Definitions on Inference of Haplotype-Block Structure and htSNPs Selection

    Institute of Scientific and Technical Information of China (English)

    KeyueDing; KaixinZhou; JingZhang; JoanneKnight; XuegongZhang; YanShen

    2005-01-01

    It has been recently suggested that the human genome is organized as a series of haplotype blocks, and efforts to create a genome-wide haplotype map are already underway. Several computational algorithms have been proposed to partition the genome. However, little is known about their behaviors in relation to the haplotype-block partitioning and haplotypetagging SNPs selection. Here, we present a systematic comparison of three classes of haplotype-block partition definitions, a diversity-based method, a linkage-disequilibrium (LD)-based method, and a recombination-based method.The data used were derived from a coalescent simulation under both a uniform recombination model and one that assumes recombination hotspots. There were considerable differences in haplotype information loss in the measure of entropy when the partition methods were compared under different population-genetics scenarios. Under both recombination models, the results from the LD-based definition and the recombination-based definition were more similar to each other than were the results from the diversity-based definition. This work demonstrates that when undertaking haplotype-based association mapping, the choice of haplotype-block definition and SNP selection requires careful consideration.

  17. Haplotype identity between individuals who share a CFTR mutation allele ''identical by descent'' : Demonstration of the usefulness of the haplotype-sharing concept for gene mapping in real populations

    NARCIS (Netherlands)

    deVries, HG; vanderMeulen, MA; Rozen, R; Halley, DJJ; Scheffer, H; tenKate, LP; Buys, CHCM; teMeerman, GJ

    1996-01-01

    Cystic fibrosis (CF) patients with the A455E mutation, in both the French Canadian and the Dutch population, share a common haplotype over distances of up to 25 cM. French Canadian patients with the 621+1G-->T mutation share a common haplotype of more than 14 cM. In contrast, haplotypes containing t

  18. Analysis of polymorphisms and haplotype structure of the human thymidylate synthase genetic region: a tool for pharmacogenetic studies.

    Directory of Open Access Journals (Sweden)

    Soma Ghosh

    Full Text Available 5-Fluorouracil (5FU, a widely used chemotherapeutic drug, inhibits the DNA replicative enzyme, thymidylate synthase (Tyms. Prior studies implicated a VNTR (variable numbers of tandem repeats polymorphism in the 5'-untranslated region (5'-UTR of the TYMS gene as a determinant of Tyms expression in tumors and normal tissues and proposed that these VNTR genotypes could help decide fluoropyrimidine dosing. Clinical associations between 5FU-related toxicity and the TYMS VNTR were reported, however, results were inconsistent, suggesting that additional genetic variation in the TYMS gene might influence Tyms expression. We thus conducted a detailed genetic analysis of this region, defining new polymorphisms in this gene including mononucleotide (poly A:T repeats and novel single nucleotide polymorphisms (SNPs flanking the VNTR in the TYMS genetic region. Our haplotype analysis of this region used data from both established and novel genetic variants and found nine SNP haplotypes accounting for more than 90% of the studied population. We observed non-exclusive relationships between the VNTR and adjacent SNP haplotypes, such that each type of VNTR commonly occurred on several haplotype backgrounds. Our results confirmed the expectation that the VNTR alleles exhibit homoplasy and lack the common ancestry required for a reliable marker of a linked adjacent locus that might govern toxicity. We propose that it may be necessary in a clinical trial to assay multiple types of genetic polymorphisms in the TYMS region to meaningfully model linkage of genetic markers to 5FU-related toxicity. The presence of multiple long (up to 26 nt, polymorphic monothymidine repeats in the promoter region of the sole human thymidylate synthetic enzyme is intriguing.

  19. Complex high-resolution linkage disequilibrium and haplotype patterns of single-nucleotide polymorphisms in 2.5 Mb of sequence on human chromosome 21.

    Science.gov (United States)

    Olivier, M; Bustos, V I; Levy, M R; Smick, G A; Moreno, I; Bushard, J M; Almendras, A A; Sheppard, K; Zierten, D L; Aggarwal, A; Carlson, C S; Foster, B D; Vo, N; Kelly, L; Liu, X; Cox, D R

    2001-11-01

    One approach to identify potentially important segments of the human genome is to search for DNA regions with nonrandom patterns of human sequence variation. Previous studies have investigated these patterns primarily in and around candidate gene regions. Here, we determined patterns of DNA sequence variation in 2.5 Mb of finished sequence from five regions on human chromosome 21. By sequencing 13 individual chromosomes, we identified 1460 single-nucleotide polymorphisms (SNPs) and obtained unambiguous haplotypes for all chromosomes. For all five chromosomal regions, we observed segments with high linkage disequilibrium (LD), extending from 1.7 to>81 kb (average 21.7 kb), disrupted by segments of similar or larger size with no significant LD between SNPs. At least 25% of the contig sequences consisted of segments with high LD between SNPs. Each of these segments was characterized by a restricted number of observed haplotypes,with the major haplotype found in over 60% of all chromosomes. In contrast, the interspersed segments with low LD showed significantly more haplotype patterns. The position and extent of the segments of high LD with restricted haplotype variability did not coincide with the location of coding sequences. Our results indicate that LD and haplotype patterns need to be investigated with closely spaced SNPs throughout the human genome, independent of the location of coding sequences, to reliably identify regions with significant LD useful for disease association studies.

  20. Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qian-fei; Liu, Xin; O' Connell, Jeff; Peng, Ze; Krauss, Ronald M.; Rainwater, David L.; VandeBerg, John L.; Rubin, Edward M.; Cheng, Jan-Fang; Pennacchio, Len A.

    2003-09-15

    Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however, whether independently arising polymorphisms in orthologous regions of non-human primates leads to similar variation in a quantitative trait found in both species. To explore this paradigm, we studied a baboon apolipoprotein gene cluster (APOA1/C3/A4/A5) for which the human gene orthologs have well established roles in influencing plasma HDL-cholesterol and triglyceride concentrations. Our extensive polymorphism analysis of this 68 kb gene cluster in 96 pedigreed baboons identified several haplotype blocks each with limited diversity, consistent with haplotype findings in humans. To determine whether baboons, like humans, also have particular haplotypes associated with lipid phenotypes, we genotyped 634 well characterized baboons using 16 haplotype tagging SNPs. Genetic analysis of single SNPs, as well as haplotypes, revealed an association of APOA5 and APOC3 variants with HDL cholesterol and triglyceride concentrations, respectively. Thus, independent variation in orthologous genomic intervals does associate with similar quantitative lipid traits in both species, supporting the possibility of uncovering human QTL genes in a highly controlled non-human primate model.

  1. The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol.

    Science.gov (United States)

    Leduc, Magalie S; Lyons, Malcolm; Darvishi, Katayoon; Walsh, Kenneth; Sheehan, Susan; Amend, Sarah; Cox, Allison; Orho-Melander, Marju; Kathiresan, Sekar; Paigen, Beverly; Korstanje, Ron

    2011-06-01

    Genome-wide association (GWA) studies represent a powerful strategy for identifying susceptibility genes for complex diseases in human populations but results must be confirmed and replicated. Because of the close homology between mouse and human genomes, the mouse can be used to add evidence to genes suggested by human studies. We used the mouse quantitative trait loci (QTL) map to interpret results from a GWA study for genes associated with plasma HDL cholesterol levels. We first positioned single nucleotide polymorphisms (SNPs) from a human GWA study on the genomic map for mouse HDL QTL. We then used mouse bioinformatics, sequencing, and expression studies to add evidence for one well-known HDL gene (Abca1) and three newly identified genes (Galnt2, Wwox, and Cdh13), thus supporting the results of the human study. For GWA peaks that occur in human haplotype blocks with multiple genes, we examined the homologous regions in the mouse to prioritize the genes using expression, sequencing, and bioinformatics from the mouse model, showing that some genes were unlikely candidates and adding evidence for candidate genes Mvk and Mmab in one haplotype block and Fads1 and Fads2 in the second haplotype block. Our study highlights the value of mouse genetics for evaluating genes found in human GWA studies.

  2. [Genetic ecological monitoring in human populations: heterozygosity, mtDNA haplotype variation, and genetic load].

    Science.gov (United States)

    Balanovskiĭ, O P; Koshel', S M; Zaporozhchenko, V V; Pshenichnov, A S; Frolova, S A; Kuznetsova, M A; Baranova, E E; Teuchezh, I E; Kuznetsova, A A; Romashkina, M V; Utevskaia, O M; Churnosov, M I; Villems, R; Balanovskaia, E V

    2011-11-01

    Yu. P. Altukhov suggested that heterozygosity is an indicator of the state of the gene pool. The idea and a linked concept of genetic ecological monitoring were applied to a new dataset on mtDNA variation in East European ethnic groups. Haplotype diversity (an analog of the average heterozygosity) was shown to gradually decrease northwards. Since a similar trend is known for population density, interlinked changes were assumed for a set of parameters, which were ordered to form a causative chain: latitude increases, land productivity decreases, population density decreases, effective population size decreases, isolation of subpopulations increases, genetic drift increases, and mtDNA haplotype diversity decreases. An increase in genetic drift increases the random inbreeding rate and, consequently, the genetic load. This was confirmed by a significant correlation observed between the incidence of autosomal recessive hereditary diseases and mtDNA haplotype diversity. Based on the findings, mtDNA was assumed to provide an informative genetic system for genetic ecological monitoring; e.g., analyzing the ecology-driven changes in the gene pool.

  3. Maori origins, Y-chromosome haplotypes and implications for human history in the Pacific.

    Science.gov (United States)

    Underhill, P A; Passarino, G; Lin, A A; Marzuki, S; Oefner, P J; Cavalli-Sforza, L L; Chambers, G K

    2001-04-01

    An assessment of 28 pertinent binary genetic markers on the non-recombining portion of the Y chromosome (NRY) in New Zealand Maori and other relevant populations has revealed a diverse genetic paternal heritage of extant Maori. A maximum parsimony phylogeny was constructed in which nine of the 25 possible binary haplotypes were observed. Although approximately 40% of the samples have haplotypes of unequivocal European origin, an equivalent number of samples have a single binary haplotype that is also observed in Indonesia and New Guinea, indicative of common indigenous Melanesian ancestry. The balance of the lineages has either typical East Asian signatures or alternative compositions consistent with their affinity to Melanesia or New Guinea. Molecular analysis of mtDNA variation confirms the presence of a single predominant characteristic Southeast Asian (9-bp deletion in the Region V) lineage. The Y-chromosome results support a pattern of complex interrelationships between Southeast Asia, Melanesia, and Polynesia, in contrast to mtDNA and linguistic data, which uphold a rapid and homogeneous Austronesian expansion. The Y-chromosome data highlight a distinctive gender-modulated pattern of differential gene flow in the history of Polynesia. Copyright 2001 Wiley-Liss, Inc.

  4. Human genetic affinities for Y-chromosome P49a,f/TaqI haplotypes show strong correspondence with linguistics

    OpenAIRE

    Poloni, Estella S; Semino, O.; Passarino, G.; Santachiara-Benerecetti, A S; Dupanloup, I.; Langaney, André; Excoffier, Laurent Georges Louis

    1997-01-01

    Numerous population samples from around the world have been tested for Y chromosome-specific p49a,f/TaqI restriction polymorphisms. Here we review the literature as well as unpublished data on Y-chromosome p49a,f/TaqI haplotypes and provide a new nomenclature unifying the notations used by different laboratories. We use this large data set to study worldwide genetic variability of human populations for this paternally transmitted chromosome segment. We observe, for the Y chromosome, an import...

  5. Haplotyping as perfect phylogeny: a direct approach.

    Science.gov (United States)

    Bafna, Vineet; Gusfield, Dan; Lancia, Giuseppe; Yooseph, Shibu

    2003-01-01

    A full haplotype map of the human genome will prove extremely valuable as it will be used in large-scale screens of populations to associate specific haplotypes with specific complex genetic-influenced diseases. A haplotype map project has been announced by NIH. The biological key to that project is the surprising fact that some human genomic DNA can be partitioned into long blocks where genetic recombination has been rare, leading to strikingly fewer distinct haplotypes in the population than previously expected (Helmuth, 2001; Daly et al., 2001; Stephens et al., 2001; Friss et al., 2001). In this paper we explore the algorithmic implications of the no-recombination in long blocks observation, for the problem of inferring haplotypes in populations. This assumption, together with the standard population-genetic assumption of infinite sites, motivates a model of haplotype evolution where the haplotypes in a population are assumed to evolve along a coalescent, which as a rooted tree is a perfect phylogeny. We consider the following algorithmic problem, called the perfect phylogeny haplotyping problem (PPH), which was introduced by Gusfield (2002) - given n genotypes of length m each, does there exist a set of at most 2n haplotypes such that each genotype is generated by a pair of haplotypes from this set, and such that this set can be derived on a perfect phylogeny? The approach taken by Gusfield (2002) to solve this problem reduces it to established, deep results and algorithms from matroid and graph theory. Although that reduction is quite simple and the resulting algorithm nearly optimal in speed, taken as a whole that approach is quite involved, and in particular, challenging to program. Moreover, anyone wishing to fully establish, by reading existing literature, the correctness of the entire algorithm would need to read several deep and difficult papers in graph and matroid theory. However, as stated by Gusfield (2002), many simplifications are possible and the

  6. Haplotype identity between individuals who share a CFTR mutation allele 'identical by descent': Demonstration of the usefulness of the haplotype-sharing concept for gene mapping in real populations

    NARCIS (Netherlands)

    H.G. de Vries (Hendrik); M.A. van der Meulen (Martin); R. Rozen (Rima); D.J.J. Halley (Dicky); H. Scheffer (Hans); L.P. ten Kate; C.H.C.M. Buys; G.J. Te Meerman (Gerard)

    1996-01-01

    markdownabstractAbstract Cystic fibrosis (CF) patients with the A455E mutation, in both the French Canadian and the Dutch population, share a common haplotype over distances of up to 25 cM. French Canadian patients with the 621+1G→T mutation share a common haplotype of more than 14 cM. In contras

  7. A haplotype of human angiotensinogen gene containing −217A increases blood pressure in transgenic mice compared with −217G

    Science.gov (United States)

    Jain, Sudhir; Vinukonda, Govindaiah; Fiering, Steven N.; Kumar, Ashok

    2008-01-01

    The human angiotensinogen (hAGT) gene contains an A/G polymorphism at −217, and frequency of −217A allele is increased in African-American hypertensive patients. The hAGT gene has seven polymorphic sites in the 1.2-kb region of its promoter, and variant −217A almost always occurs with −532T, −793A, and −1074T, whereas variant −217G almost always occurs with −532C, −793G, and −1074G. Since allele −6A is the predominant allele in African-Americans, the AGT gene can be subdivided into two main haplotypes, −6A:−217A (AA) and −6A:−217G (AG). To understand the role of these haplotypes on hAGT gene expression and on blood pressure regulation in an in vivo situation, we have generated double transgenic mice containing human renin gene and either AA or AG haplotype of the hAGT gene using knock-in strategy at the hypoxanthine phosphoribosyltransferase locus. We show here that 1) hAGT mRNA level is increased in the liver by 60% and in the kidney by 40%; and 2) plasma AGT level is increased by ∼40%, and plasma angiotensin II level is increased by ∼50% in male double transgenic mice containing AA haplotype of the hAGT gene compared with the AG haplotype. In addition, systolic blood pressure is increased by 8 mmHg in transgenic mice containing the AA haplotype compared with the AG haplotype. This is the first report to show the effect of polymorphisms in the promoter of a human gene on its transcription in an in vivo situation that ultimately leads to an increase in blood pressure. PMID:18945948

  8. Haplotype-based case-control study of the human AGTR1 gene and essential hypertension in Han Chinese subjects.

    Science.gov (United States)

    Nie, Sheng-jie; Wen-ru, Tang; Bi-feng, Chen; Jin, Li; Wen, Zhang; Sheng-jun, Luo; Wei-wei, Li; Hai-jing, Yu; Chun-jie, Xiao

    2010-02-01

    Essential hypertension is considered to be a multifactorial trait resulting from the combined influence of environmental and genetic determinants. The aim of the study is to assess the association between the human AGTR1 gene and essential hypertension (EH) using a haplotype-based case-control study in Han Chinese subjects. Seven tag SNPs and the A1166C polymorphism of the AGTR1 gene were genotyped in 510 hypertension subjects and 510 normotensive subjects using PCR-RFLP method. Single SNP analyses indicated that the rs12695895 was significantly associated with hypertension, adjusted for covariates. Compared with the other haplotypes, Hap4 (AGGACTT) which carry the susceptible rs12695895 A allele was found to significantly increase the risk of EH with odds ratios equal to 1.84 (p=0.0002). The present results indicate that rs12695895 might be a genetic marker for EH and Hap4 (AGGACTT) was associated with hypertension in Han Chinese population. (c) 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  9. Human C4 haplotypes with duplicated C4A or C4B.

    OpenAIRE

    Raum, D; Awdeh, Z; Anderson, J.; Strong, L; Granados, J.; Teran, L; Giblett, E; Yunis, E J; Alper, C A

    1984-01-01

    In the course of study of families for the sixth chromosome markers HLA-A, C, B, D/DR, BF, and C2, the two loci for C4, C4A, and C4B, and glyoxalase I, we encountered five examples of probable duplication of one or the other of the two loci for C4. In one of these, both parents and one sib expressed two different structural genes for C4B, one sib expressed one, and one sib expressed none, suggesting that two C4B alleles were carried on a single haplotype: HLA-A2, B7, DR3, BFS1, C2C, C4A2, C4B...

  10. Mapping of the Pim-1 oncogene in mouse t-haplotypes and its use to define the relative map positions of the tcl loci t0(t6) and tw12 and the marker tf (tufted).

    Science.gov (United States)

    Ark, B; Gummere, G; Bennett, D; Artzt, K

    1991-06-01

    Pim-1 is an oncogene activated in mouse T-cell lymphomas induced by Moloney and AKR mink cell focus (MCF) viruses. Pim-1 was previously mapped to chromosome 17 by somatic cell hybrids, and subsequently to the region between the hemoglobin alpha-chain pseudogene 4 (Hba-4ps) and the alpha-crystalline gene (Crya-1) by Southern blot analysis of DNA obtained from panels of recombinant inbred strains. We have now mapped Pim-1 more accurately in t-haplotypes by analysis of recombinant t-chromosomes. The recombinants were derived from Tts6tf/t12 parents backcrossed to + tf/ + tf, and scored for recombination between the loci of T and tf. For simplicity all t-complex lethal genes properly named tcl-tx are shortened to tx. The Pim-1 gene was localized 0.6 cM proximal to the tw12 lethal gene, thus placing the Pim-1 gene 5.2 cM distal to the H-2 region in t-haplotypes. Once mapped, the Pim-1 gene was used as a marker for further genetic analysis of t-haplotypes. tw12 is so close to tf that even with a large number of recombinants it was not possible to determine whether it is proximal or distal to tf. Southern blot analysis of DNA from T-tf recombinants with a separation of tw12 and tf indicated that tw12 is proximal to tf. The mapping of two allelic t-lethals, t0 and t6 with respect to tw12 and tf has also been a problem.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. The susceptibility gene for familial nasopharyngeal carcinoma is mapped on chromosome 4p11-p14 by haplotype analyses

    Institute of Scientific and Technical Information of China (English)

    CHEN Hankui; FENG Bingjian; LIANG Hui; ZHANG Ruhua; ZENG Yixin

    2003-01-01

    In our previous study, one candidate susceptibility locus for familialnasopharyngeal carcinoma (NPC) has been defined to a 14.21-cM region on 4p15.1-q12, whereas the distal minimum boundary of this region remained to be further determined in respect that the two markers D4S2996 and D4S428 were uninformative.In the present study, we carried out a haplotype analysis to identify the exactboundary by using the combination of a set of microsatellite markers and singlenucleotide polymorphism (SNP) markers in two major NPC families. We defined theexact distal boundary between D4S1577 and D4S3347, and consequently shortened the susceptibility locus to an 8.29-cM segment on 4p11-p14.

  12. Fine genetic mapping of the Batten disease locus (CLN3) by haplotype analysis and demonstration of allelic association with chromosome 16p microsatellite loci

    Energy Technology Data Exchange (ETDEWEB)

    Mitchison, H.M.; McKay, T.R. [Univ. College London Medical School (United Kingdom); Thompson, A.D.; Mulley, J.C.; Kozman, H.M.; Richards, R.I.; Callen, D.F. [Women and Children`s Hospital, Adelaide (Australia); Stallings, R.L.; Doggett, N.A. [Los Alamos National Lab., NM (United States); Attwood, J. [Galton Lab., London (United Kingdom)] [and others

    1993-05-01

    Batten disease, juvenile onset neuronal ceroid lipofuscinosis, is an autosomal recessive neurodegenerative disorder characterized by accumulation of autofluorescent lipopigment in neurons and other cell types. The disease locus (CLN3) has previously been assigned to chromosome 16p. The genetic localization of CLN3 has been refined by analyzing 70 families using a high-resolution map of 15 marker loci encompassing the CLN3 region on 16p. Crossovers in three maternal meioses allowed localization of CLN3 to the interval between D16S297 and D16S57. Within that interval alleles at three highly polymorphic dinucleotide repeat loci (D16S288, D16S298, D16S299) were found to be in strong linkage disequilibrium with CLN3. Analysis of haplotypes suggests that a majority of CLN3 chromosomes have arisen from a single founder mutation. 15 refs., 2 figs., 5 tabs.

  13. Pure Parsimony Xor Haplotyping

    CERN Document Server

    Bonizzoni, Paola; Dondi, Riccardo; Pirola, Yuri; Rizzi, Romeo

    2010-01-01

    The haplotype resolution from xor-genotype data has been recently formulated as a new model for genetic studies. The xor-genotype data is a cheaply obtainable type of data distinguishing heterozygous from homozygous sites without identifying the homozygous alleles. In this paper we propose a formulation based on a well-known model used in haplotype inference: pure parsimony. We exhibit exact solutions of the problem by providing polynomial time algorithms for some restricted cases and a fixed-parameter algorithm for the general case. These results are based on some interesting combinatorial properties of a graph representation of the solutions. Furthermore, we show that the problem has a polynomial time k-approximation, where k is the maximum number of xor-genotypes containing a given SNP. Finally, we propose a heuristic and produce an experimental analysis showing that it scales to real-world large instances taken from the HapMap project.

  14. Pure parsimony xor haplotyping.

    Science.gov (United States)

    Bonizzoni, Paola; Della Vedova, Gianluca; Dondi, Riccardo; Pirola, Yuri; Rizzi, Romeo

    2010-01-01

    The haplotype resolution from xor-genotype data has been recently formulated as a new model for genetic studies. The xor-genotype data is a cheaply obtainable type of data distinguishing heterozygous from homozygous sites without identifying the homozygous alleles. In this paper, we propose a formulation based on a well-known model used in haplotype inference: pure parsimony. We exhibit exact solutions of the problem by providing polynomial time algorithms for some restricted cases and a fixed-parameter algorithm for the general case. These results are based on some interesting combinatorial properties of a graph representation of the solutions. Furthermore, we show that the problem has a polynomial time k-approximation, where k is the maximum number of xor-genotypes containing a given single nucleotide polymorphisms (SNP). Finally, we propose a heuristic and produce an experimental analysis showing that it scales to real-world large instances taken from the HapMap project.

  15. High resolution linkage disequilibrium and haplotype maps for the genes in the centromeric region of chromo- some 15 in Tibetans and comparisons with Han population

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Genetic variations and their functional implications have been one of the focuses in recent genome research. With the release of the HapMap by the International Consortium, and the availability of the ultra-high-volume genotyping platform, it will soon be possible to use genome-wide association approach to identify genetic variations responsible for complex traits/diseases. While the power of this approach is generally agreed, it is a debated issue as to how much population difference should be exploited, and how best it should be applied. To address this issue we have sequenced 7 genes in the centromeric region of chromosome 15, investigated their SNPs, SNP frequencies, tagSNPs, LD structures, and haplotypes in 50 Tibetan subjects, and compared them with those from the Han population. Genetic diversities between the two populations were also quantified. Our results show that the overall genetic variation between the two populations is very little, but there are differences, primarily in allele frequencies, which is a dominating factor for haplotypes and tagSNPs. In general Tibetans have longer LD and less diversity in the region studied. These data provide genetic evidence for the close relationship between the two populations, and support the idea that all populations are fundamentally the same, but also indicate population variations, particularly in allele frequency, should be taken into account in complex traits/ diseases analysis. Data obtained in this investigation not only help us understand the genome region, but also provide road maps for variation study in the genes/ region in Tibetan population.

  16. Human leucocyte antigens class II allele and haplotype association with Type 1 Diabetes in Madeira Island (Portugal).

    Science.gov (United States)

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

    2017-08-20

    This study confirms for Madeira Island (Portugal) population the Type 1 Diabetes (T1D) susceptible and protective Human leucocyte antigens (HLA) markers previously reported in other populations and adds some local specificities. Among the strongest T1D HLA associations, stands out, as susceptible, the alleles DRB1*04:05 (OR = 7.3), DQB1*03:02 (OR = 6.1) and DQA1*03:03 (OR = 4.5), as well as the haplotypes DRB1*04:05-DQA1*03:03-DQB1*03:02 (OR = 100.9) and DRB1*04:04-DQA1*03:01-DQB1*03:02 (OR = 22.1), and DQB1*06:02 (OR = 0.07) and DRB1*15:01-DQA1*01:02-DQB1*06:02 (OR = 0.04) as protective. HLA-DQA1 positive for Arginine at position 52 (Arg52) (OR = 15.2) and HLA-DQB1 negative for Aspartic acid at the position 57 (Asp57) (OR = 9.0) alleles appear to be important genetic markers for T1D susceptibility, with higher odds ratio values than any single allele and than most of the haplotypes. Genotypes generated by the association of markers Arg52 DQA1 positive and Asp57 DQB1 negative increase T1D susceptibility much more than one would expected by a simple additive effect of those markers separately (OR = 26.9). This study also confirms an increased risk for DRB1*04/DRB1*03 heterozygote genotypes (OR = 16.8) and also a DRB1*04-DQA1*03:01-DQB1*03:02 haplotype susceptibility dependent on the DRB1*04 allele (DRB1*04:01, OR = 7.9; DRB1*04:02, OR = 3.2; DRB1*04:04, OR = 22.1). © 2017 John Wiley & Sons Ltd.

  17. Protective human leucocyte antigen haplotype, HLA-DRB1*01-B*14, against chronic Chagas disease in Bolivia.

    Directory of Open Access Journals (Sweden)

    Florencia del Puerto

    Full Text Available BACKGROUND: Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8-10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. METHODOLOGY: Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG, and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% megacolon and 58.1% showed neither of them. A further 62 seropositive megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. PRINCIPAL FINDINGS: The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from megacolon as well as in those with ECG alteration and/or megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD, and the HLA-DRB1*01-B*14-MICA*011 haplotype was associated with resistance against chronic Chagas disease. CONCLUSIONS: This is the first report of HLA haplotype association with resistance to chronic Chagas disease.

  18. Protective human leucocyte antigen haplotype, HLA-DRB1*01-B*14, against chronic Chagas disease in Bolivia.

    Directory of Open Access Journals (Sweden)

    Florencia del Puerto

    Full Text Available BACKGROUND: Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8-10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. METHODOLOGY: Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG, and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% megacolon and 58.1% showed neither of them. A further 62 seropositive megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. PRINCIPAL FINDINGS: The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from megacolon as well as in those with ECG alteration and/or megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD, and the HLA-DRB1*01-B*14-MICA*011 haplotype was associated with resistance against chronic Chagas disease. CONCLUSIONS: This is the first report of HLA haplotype association with resistance to chronic Chagas disease.

  19. Mapping tonotopy in human auditory cortex

    NARCIS (Netherlands)

    van Dijk, Pim; Langers, Dave R M; Moore, BCJ; Patterson, RD; Winter, IM; Carlyon, RP; Gockel, HE

    2013-01-01

    Tonotopy is arguably the most prominent organizational principle in the auditory pathway. Nevertheless, the layout of tonotopic maps in humans is still debated. We present neuroimaging data that robustly identify multiple tonotopic maps in the bilateral auditory cortex. In contrast with some earlier

  20. Haplotype block structure is conserved across mammals

    NARCIS (Netherlands)

    Guryev, Victor; Smits, Bart M G; van de Belt, Jose; Verheul, Mark; Hubner, Norbert; Cuppen, Edwin

    2006-01-01

    Genetic variation in genomes is organized in haplotype blocks, and species-specific block structure is defined by differential contribution of population history effects in combination with mutation and recombination events. Haplotype maps characterize the common patterns of linkage disequilibrium i

  1. BATTEN-DISEASE GENE, CLN3 - LINKAGE DISEQUILIBRIUM MAPPING IN THE FINNISH POPULATION, AND ANALYSIS OF EUROPEAN HAPLOTYPES

    NARCIS (Netherlands)

    MITCHISON, HM; ORAWE, AM; TASCHNER, PEM; SANDKUIJL, LA; SANTAVUORI, P; DEVOS, N; BREUNING, MH; MOLE, SE; GARDINER, RM; JARVELA, IE

    The gene for Batten disease (juvenile-onset neuronal ceroid lipofuscinosis, or Spielmeyer-Sjogren disease), CLN3, maps to 16p11.2-12.1. Four microsatellite markers-D16S288, D16S299, D16S298, and SPN-are in strong linkage disequilibrium with CLN3 in 142 families from 16 different countries. These

  2. Physical mapping of human chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, G.R.

    1992-01-01

    Project aims for the past year have been to refine the cytogenetic based physical map of human chromosome 16. This has been achieved by extending the panel of mouse/human hybrids of chromosome 16 to over sixty hybrids and mapping approximately 250 DNA makers. The high resolution of this physical map, with an average distance between breakpoints of less than 1.6 Mb, and the availability of at least one STS in the majority of these intervals, will be the basis for constructing extensive contigs of cloned DNA.

  3. High-resolution haplotype block structure in the cattle genome

    Directory of Open Access Journals (Sweden)

    Choi Jungwoo

    2009-04-01

    Full Text Available Abstract Background The Bovine HapMap Consortium has generated assay panels to genotype ~30,000 single nucleotide polymorphisms (SNPs from 501 animals sampled from 19 worldwide taurine and indicine breeds, plus two outgroup species (Anoa and Water Buffalo. Within the larger set of SNPs we targeted 101 high density regions spanning up to 7.6 Mb with an average density of approximately one SNP per 4 kb, and characterized the linkage disequilibrium (LD and haplotype block structure within individual breeds and groups of breeds in relation to their geographic origin and use. Results From the 101 targeted high-density regions on bovine chromosomes 6, 14, and 25, between 57 and 95% of the SNPs were informative in the individual breeds. The regions of high LD extend up to ~100 kb and the size of haplotype blocks ranges between 30 bases and 75 kb (10.3 kb average. On the scale from 1–100 kb the extent of LD and haplotype block structure in cattle has high similarity to humans. The estimation of effective population sizes over the previous 10,000 generations conforms to two main events in cattle history: the initiation of cattle domestication (~12,000 years ago, and the intensification of population isolation and current population bottleneck that breeds have experienced worldwide within the last ~700 years. Haplotype block density correlation, block boundary discordances, and haplotype sharing analyses were consistent in revealing unexpected similarities between some beef and dairy breeds, making them non-differentiable. Clustering techniques permitted grouping of breeds into different clades given their similarities and dissimilarities in genetic structure. Conclusion This work presents the first high-resolution analysis of haplotype block structure in worldwide cattle samples. Several novel results were obtained. First, cattle and human share a high similarity in LD and haplotype block structure on the scale of 1–100 kb. Second, unexpected

  4. Functional promoter haplotypes of the human FAS gene are associated with the phenotype of SLE characterized by thrombocytopenia

    DEFF Research Database (Denmark)

    Nolsøe, R L; Kelly, J A; Pociot, F;

    2005-01-01

    to SLE or subphenotypes in 126 multiplex American SLE pedigrees and found association of the FAS codon214 AC(C/T) as well as the FAS-670G>A'-codon214 AC(C/T)' haplotype to thrombocytopenia in SLE. Furthermore we have functionally characterized the FAS/FASL promoter polymorphisms associated with SLE...... variant, determines the promoter activity. We conclude that the FAS/FASL promoter haplotypes are functional and that polymorphisms in FAS may contribute to thrombocytopenia in SLE....

  5. [Mapping and human genome sequence program].

    Science.gov (United States)

    Weissenbach, J

    1997-03-01

    Until recently, human genome programs focused primarily on establishing maps that would provide signposts to researchers seeking to identify genes responsible for inherited diseases, as well as a basis for genome sequencing studies. Preestablished gene mapping goals have been reached. The over 7,000 microsatellite markers identified to date provide a map of sufficient density to allow localization of the gene of a monogenic disease with a precision of 1 to 2 million base pairs. The physical map, based on systematically arranged overlapping sets of artificial yeast chromosomes (YACs), has also made considerable headway during the last few years. The most recently published map covers more than 90% of the genome. However, currently available physical maps cannot be used for sequencing studies because multiple rearrangements occur in YACs. The recently developed sets of radioinduced hybrids are extremely useful for incorporating genes into existing maps. A network of American and European laboratories has successfully used these radioinduced hybrids to map 15,000 gene tags from large-scale cDNA library sequencing programs. There are increasingly pressing reasons for initiating large scale human genome sequencing studies.

  6. Malaria haplotype frequency estimation.

    Science.gov (United States)

    Wigger, Leonore; Vogt, Julia E; Roth, Volker

    2013-09-20

    We present a Bayesian approach for estimating the relative frequencies of multi-single nucleotide polymorphism (SNP) haplotypes in populations of the malaria parasite Plasmodium falciparum by using microarray SNP data from human blood samples. Each sample comes from a malaria patient and contains one or several parasite clones that may genetically differ. Samples containing multiple parasite clones with different genetic markers pose a special challenge. The situation is comparable with a polyploid organism. The data from each blood sample indicates whether the parasites in the blood carry a mutant or a wildtype allele at various selected genomic positions. If both mutant and wildtype alleles are detected at a given position in a multiply infected sample, the data indicates the presence of both alleles, but the ratio is unknown. Thus, the data only partially reveals which specific combinations of genetic markers (i.e. haplotypes across the examined SNPs) occur in distinct parasite clones. In addition, SNP data may contain errors at non-negligible rates. We use a multinomial mixture model with partially missing observations to represent this data and a Markov chain Monte Carlo method to estimate the haplotype frequencies in a population. Our approach addresses both challenges, multiple infections and data errors.

  7. Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations.

    Science.gov (United States)

    Fernandez Vina, Marcelo A; Hollenbach, Jill A; Lyke, Kirsten E; Sztein, Marcelo B; Maiers, Martin; Klitz, William; Cano, Pedro; Mack, Steven; Single, Richard; Brautbar, Chaim; Israel, Shosahna; Raimondi, Eduardo; Khoriaty, Evelyne; Inati, Adlette; Andreani, Marco; Testi, Manuela; Moraes, Maria Elisa; Thomson, Glenys; Stastny, Peter; Cao, Kai

    2012-03-19

    The human leucocyte antigen (HLA) system shows extensive variation in the number and function of loci and the number of alleles present at any one locus. Allele distribution has been analysed in many populations through the course of several decades, and the implementation of molecular typing has significantly increased the level of diversity revealing that many serotypes have multiple functional variants. While the degree of diversity in many populations is equivalent and may result from functional polymorphism(s) in peptide presentation, homogeneous and heterogeneous populations present contrasting numbers of alleles and lineages at the loci with high-density expression products. In spite of these differences, the homozygosity levels are comparable in almost all of them. The balanced distribution of HLA alleles is consistent with overdominant selection. The genetic distances between outbred populations correlate with their geographical locations; the formal genetic distance measurements are larger than expected between inbred populations in the same region. The latter present many unique alleles grouped in a few lineages consistent with limited founder polymorphism in which any novel allele may have been positively selected to enlarge the communal peptide-binding repertoire of a given population. On the other hand, it has been observed that some alleles are found in multiple populations with distinctive haplotypic associations suggesting that convergent evolution events may have taken place as well. It appears that the HLA system has been under strong selection, probably owing to its fundamental role in varying immune responses. Therefore, allelic diversity in HLA should be analysed in conjunction with other genetic markers to accurately track the migrations of modern humans.

  8. Haplotyping and copy number estimation of the highly polymorphic human beta-defensin locus on 8p23 by 454 amplicon sequencing

    Directory of Open Access Journals (Sweden)

    Rosenstiel Philip

    2010-04-01

    Full Text Available Abstract Background The beta-defensin gene cluster (DEFB at chromosome 8p23.1 is one of the most copy number (CN variable regions of the human genome. Whereas individual DEFB CNs have been suggested as independent genetic risk factors for several diseases (e.g. psoriasis and Crohn's disease, the role of multisite sequence variations (MSV is less well understood and to date has only been reported for prostate cancer. Simultaneous assessment of MSVs and CNs can be achieved by PCR, cloning and Sanger sequencing, however, these methods are labour and cost intensive as well as prone to methodological bias introduced by bacterial cloning. Here, we demonstrate that amplicon sequencing of pooled individual PCR products by the 454 technology allows in-depth determination of MSV haplotypes and estimation of DEFB CNs in parallel. Results Six PCR products spread over ~87 kb of DEFB and harbouring 24 known MSVs were amplified from 11 DNA samples, pooled and sequenced on a Roche 454 GS FLX sequencer. From ~142,000 reads, ~120,000 haplotype calls (HC were inferred that identified 22 haplotypes ranging from 2 to 7 per amplicon. In addition to the 24 known MSVs, two additional sequence variations were detected. Minimal CNs were estimated from the ratio of HCs and compared to absolute CNs determined by alternative methods. Concordance in CNs was found for 7 samples, the CNs differed by one in 2 samples and the estimated minimal CN was half of the absolute in one sample. For 7 samples and 2 amplicons, the 454 haplotyping results were compared to those by cloning/Sanger sequencing. Intrinsic problems related to chimera formation during PCR and differences between haplotyping by 454 and cloning/Sanger sequencing are discussed. Conclusion Deep amplicon sequencing using the 454 technology yield thousands of HCs per amplicon for an affordable price and may represent an effective method for parallel haplotyping and CN estimation in small to medium-sized cohorts. The

  9. Haplotype-based banking of human pluripotent stem cells for transplantation: potential and limitations.

    Science.gov (United States)

    Zimmermann, Anna; Preynat-Seauve, Olivier; Tiercy, Jean-Marie; Krause, Karl-Heinz; Villard, Jean

    2012-09-01

    High expectations surround the area of stem cells therapeutics. However, the cells' source-adult or embryonic-and the cells' origin-patient-derived autologous or healthy donor genetically unrelated-remain subjects of debate. Autologous origins have the advantage of a theoretical absence of immune rejection by the recipient. However, this approach has several limitations with regard to the disease of the recipient and to potential problems with the generation, expansion, and manipulation of autologous induced pluripotent stem cells (iPS cells) preparation. An alternative to using autologous cells is the establishment of a bank of well-characterized adult cells that would be used to generate iPS cells and their derivatives. In the context of transplantation, such cells would come from genetically unrelated donors and the immune system of the recipient would reject the graft without immunosuppressive therapy. To minimize the risk of rejection, human leukocyte antigen (HLA) compatibility is certainly the best option, and the establishment of an HLA-organized bank would mean having a limited number of stem cells that would be sufficient for a large number of recipients. The concept of haplobanking with HLA homozygous cell lines would also limit the number of HLA mismatches, but such an approach will not necessarily be less immunogenic in terms of selection criteria, because of the limited number of HLA-compatible loci and the level of HLA typing resolution.

  10. Coverage and characteristics of the Affymetrix GeneChip Human Mapping 100K SNP set.

    Directory of Open Access Journals (Sweden)

    2006-05-01

    Full Text Available Improvements in technology have made it possible to conduct genome-wide association mapping at costs within reach of academic investigators, and experiments are currently being conducted with a variety of high-throughput platforms. To provide an appropriate context for interpreting results of such studies, we summarize here results of an investigation of one of the first of these technologies to be publicly available, the Affymetrix GeneChip Human Mapping 100K set of single nucleotide polymorphisms (SNPs. In a systematic analysis of the pattern and distribution of SNPs in the Mapping 100K set, we find that SNPs in this set are undersampled from coding regions (both nonsynonymous and synonymous and oversampled from regions outside genes, relative to SNPs in the overall HapMap database. In addition, we utilize a novel multilocus linkage disequilibrium (LD coefficient based on information content (analogous to the information content scores commonly used for linkage mapping that is equivalent to the familiar measure r2 in the special case of two loci. Using this approach, we are able to summarize for any subset of markers, such as the Affymetrix Mapping 100K set, the information available for association mapping in that subset, relative to the information available in the full set of markers included in the HapMap, and highlight circumstances in which this multilocus measure of LD provides substantial additional insight about the haplotype structure in a region over pairwise measures of LD.

  11. The Haplotyping Problem: An Overview of Computational Models and Solutions

    Institute of Scientific and Technical Information of China (English)

    Paola Bonizzoni; Gianluca Della Vedova; Riccardo Dondi; Jing Li

    2003-01-01

    The investigation of genetic differences among humans has given evidence that mutations in DNA sequences are responsible for some genetic diseases. The most common mutation is the one that involves only a single nucleotide of the DNA sequence, which is called a single nucleotide polymorphism (SNP). As a consequence, computing a complete map of all SNPs occurring in the human populations is one of the primary goals of recent studies in human genomics. The construction of such a map requires to determine the DNA sequences that from all chromosomes. In diploid organisms like humans, each chromosome consists of two sequences called haplotypes. Distinguishing the information contained in both haplotypes when analyzing chromosome sequences poses several new computational issues which collectively form a new emerging topic of Computational Biology known as Haplotyping.This paper is a comprehensive study of some new combinatorial approaches proposed in this research area and it mainly focuses on the formulations and algorithmic solutions of some basic biological problems. Three statistical approaches are briefly discussed at the end of the paper.

  12. Mapping Prefrontal Cortex Functions in Human Infancy

    Science.gov (United States)

    Grossmann, Tobias

    2013-01-01

    It has long been thought that the prefrontal cortex, as the seat of most higher brain functions, is functionally silent during most of infancy. This review highlights recent work concerned with the precise mapping (localization) of brain activation in human infants, providing evidence that prefrontal cortex exhibits functional activation much…

  13. Frequency of alleles and haplotypes of the human leukocyte antigen system in Bauru, São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Luana de Cassia Salvadori

    2014-04-01

    Full Text Available Background: HLA allele identification is used in bone marrow transplant programs as HLA compatibility between the donor and recipient may prevent graft rejection. Objective: This study aimed to estimate the frequency of alleles and haplotypes of the HLA system in the region of Bauru and compare these with the frequencies found in other regions of the country. Methods: HLA-A*, HLA-B*, and HLA-DRB1* allele frequencies and haplotypes were analyzed in a sample of 3542 volunteer donors at the National Registry of Voluntary Bone Marrow Donors (REDOME in Bauru. HLA low resolution typing was performed using reverse line blot with the Dynal Reli(tm SSO-HLA Typing Kit and automated Dynal AutoReli(tm48 device (Invitrogen, USA. Results: Twenty, 36, and 13 HLA-A*, HLA-B*, and HLA-DRB1* allele groups, respectively, were identified. The most common alleles for each locus were HLA-A*02, HLA-B*35, and HLA-DRB1*07. The most frequent haplotype was A*01-B*08-DRB1*03. Allele and haplotype frequencies were compared to other regions in Brazil and the similarities and differences among populations are shown. Conclusion: The knowledge of the immunogenic profile of a population contributes to the comprehension of the historical and anthropological aspects of different regions. Moreover, this helps to find suitable donors quickly, thereby shortening waiting lists for transplants and thus increasing survival rates among recipients.

  14. Constructing an initial map of transmission distortion based on high density HapMap SNPs across the human autosomes.

    Science.gov (United States)

    Deng, Libin; Zhang, Dake; Richards, Elliott; Tang, Xiaoli; Fang, Jin; Long, Fei; Wang, Yan

    2009-12-01

    Transmission distortion (TD) is a significant departure from Mendelian predictions of genes or chromosomes to offspring. While many biological processes have been implicated, there is still much to be understood about TD in humans. Here we present our findings from a genome-wide scan for evidence of TD using haplotype data of 60 trio families from the International HapMap Project. Fisher's exact test was applied to assess the extent of TD in 629,958 SNPs across the autosomes. Based on the empirical distribution of P(Fisher) and further permutation tests, we identified 1,205 outlier loci and 224 candidate genes with TD. Using the PANTHER gene ontology database, we found 19 categories of biological processes with an enrichment of candidate genes. In particular, the "protein phosphorylation" category contained the largest number of candidates in both HapMap samples. Further analysis uncovered an intriguing non-synonymous change in PPP1R12B, a gene related to protein phosphorylation, which appears to influence the allele transmission from male parents in the YRI (Yoruba from Ibadan, Nigeria) population. Our findings also indicate an ethnicity-related property of TD signatures in HapMap samples and provide new clues for our understanding of TD in humans.

  15. Mapping and Sequencing the Human Genome

    Science.gov (United States)

    1988-01-01

    Numerous meetings have been held and a debate has developed in the biological community over the merits of mapping and sequencing the human genome. In response a committee to examine the desirability and feasibility of mapping and sequencing the human genome was formed to suggest options for implementing the project. The committee asked many questions. Should the analysis of the human genome be left entirely to the traditionally uncoordinated, but highly successful, support systems that fund the vast majority of biomedical research. Or should a more focused and coordinated additional support system be developed that is limited to encouraging and facilitating the mapping and eventual sequencing of the human genome. If so, how can this be done without distorting the broader goals of biological research that are crucial for any understanding of the data generated in such a human genome project. As the committee became better informed on the many relevant issues, the opinions of its members coalesced, producing a shared consensus of what should be done. This report reflects that consensus.

  16. Human neuronal acetylcholine receptor A5-A3-B4 haplotypes are associated with multiple nicotine dependence phenotypes

    Science.gov (United States)

    Weiss, Robert B.; Bolt, Daniel; von Niederhausern, Andrew; Fiore, Michael C.; Dunn, Diane M.; Piper, Megan E.; Matsunami, Nori; Smith, Stevens S.; Coon, Hilary; McMahon, William M.; Scholand, Mary B.; Singh, Nanda; Hoidal, John R.; Kim, Su-Young; Leppert, Mark F.; Cannon, Dale S.

    2009-01-01

    Introduction: Previous research revealed significant associations between haplotypes in the CHRNA5-A3-B4 subunit cluster and scores on the Fagerström Test for Nicotine Dependence among individuals reporting daily smoking by age 17. The present study used subsamples of participants from that study to investigate associations between the CHRNA5-A3-B4 haplotypes and an array of phenotypes not analyzed previously (i.e., withdrawal severity, ability to stop smoking, and specific scales on the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) that reflect loss of control, strong craving, and heavy smoking. Methods: Two cohorts of current or former smokers (N = 886) provided both self-report data and DNA samples. One sample (Wisconsin) comprised smokers making a quit smoking attempt, which permitted the assessment of withdrawal and relapse during the attempt. The other sample (Utah) comprised participants studied for risk factors for nicotine dependence and chronic obstructive pulmonary disease and included individuals originally recruited in the Lung Health Study. Results: The CHRNA5-A3-B4 haplotypes were significantly associated with the targeted WISDM-68 scales (Tolerance, Craving, Loss of Control) in both samples of participants but only among individuals who began smoking early in life. The haplotypes were significantly associated with relapse likelihood and withdrawal severity, but these associations showed no evidence of an interaction with age at daily smoking. Discussion: The CHRNA5-A3-B4 haplotypes are associated with a broad range of nicotine dependence phenotypes, but these associations are not consistently moderated by age at initial smoking. PMID:19436041

  17. Identification of HAVCR1 gene haplotypes associated with mRNA expression levels and susceptibility to autoimmune diseases.

    Science.gov (United States)

    García-Lozano, José Raúl; Abad, Cristina; Escalera, Ana; Torres, Belén; Fernández, Olga; García, Alicia; Sánchez-Román, Julio; Sabio, José-Mario; Ortego-Centeno, Norberto; Raya-Alvarez, Enrique; Núñez-Roldán, Antonio; Martín, Javier; González-Escribano, María Francisca

    2010-08-01

    Human HAVCR1 gene maps on 5q33.2, a region linked with susceptibility to allergic and autoimmune diseases. The aims of the present study were to define the haplotypes of HAVCR1 gene taking into account both HapMap Project SNP haplotypes and exon 4 variants, to investigate a possible relationship between these haplotypes and mRNA expression levels, and to assess whether HAVCR1 gene is involved in susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Genotyping of three ins/del variants in the exon 4 was performed by fragment length analysis. Five tag SNPs genotypes and mRNA levels were determined using TaqMan assays. We defined four major haplotypes in our population: the two major haplotypes (named haplotypes A and B) bear both the 5383_5397del variant and the two most common SNP sets found in the CEU population. Quantification analysis revealed that genotype B/B had the highest median of mRNA expression levels (vs. BX + XX, p < 0.0001). Additionally, frequency of the genotype BB was significantly higher in RA patients than in controls (12.3 vs. 5.9% in controls, p = 0.0046, p (c) = 0.014, OR = 2.23, 95% CI 1.23-4.10). Our results support a relationship between HAVCR1 haplotypes and mRNA expression levels, and suggest an association of this gene with autoimmune diseases.

  18. Analysis of a human brain transcriptome map

    Directory of Open Access Journals (Sweden)

    Greene Jonathan R

    2002-04-01

    Full Text Available Abstract Background Genome wide transcriptome maps can provide tools to identify candidate genes that are over-expressed or silenced in certain disease tissue and increase our understanding of the structure and organization of the genome. Expressed Sequence Tags (ESTs from the public dbEST and proprietary Incyte LifeSeq databases were used to derive a transcript map in conjunction with the working draft assembly of the human genome sequence. Results Examination of ESTs derived from brain tissues (excluding brain tumor tissues suggests that these genes are distributed on chromosomes in a non-random fashion. Some regions on the genome are dense with brain-enriched genes while some regions lack brain-enriched genes, suggesting a significant correlation between distribution of genes along the chromosome and tissue type. ESTs from brain tumor tissues have also been mapped to the human genome working draft. We reveal that some regions enriched in brain genes show a significant decrease in gene expression in brain tumors, and, conversely that some regions lacking in brain genes show an increased level of gene expression in brain tumors. Conclusions This report demonstrates a novel approach for tissue specific transcriptome mapping using EST-based quantitative assessment.

  19. Mapping genes on human chromosome 20

    Energy Technology Data Exchange (ETDEWEB)

    Keith, T.; Phipps, P.; Serino, K. [Collaborative Research, Inc., Waltham, MA (United States)] [and others

    1994-09-01

    While a substantial number of genes have been physically localized to human chromosome 20, few have been genetically mapped. In the process of developing a genetic linkage map of chromosome 20, we have mapped microsatellite polymorphisms associated with six genes. Three of these had highly informative polymorphisms (greater than 0.70) that were originally identified by other investigators. These include avian sarcoma oncogene homolog (SRC), ribophorin II (RPN2), and phosphoenolpyruvate carboxykinase (PCK1). Polymorphisms associated with two genes were determined following a screen of their DNA sequences in GenBank. These include dinucleotide polymorphisms in introl II of cystatin c (CST3) and in the promoter region of neuroendocrine convertase 2 (NEC2) with heterozygosities of 0.52 and 0.54, respectively. A sixth gene, prodynorphin (PDYN) was mapped following the identification of a dinucleotide repeat polymorphism (heterozygosity of 0.35) in a cosmid subclone from a YAC homologous to the original phage clone. CA-positive cosmid subclones from a YAC for an additional gene, guanine nucleotide binding protein, alpha (GNAS10), have been identified and sequencing is in progress. Similar efforts were utilized to identify a microsatellite polymorphism from a half-YAC cloned by W. Brown and localized by FISH to 20pter. This polymorphism is highly informative, with a heterozygosity of 0.83, and serves to delimit the genetic map of the short arm of this chromosome.

  20. Comparison of linear mixed model analysis and genealogy-based haplotype clustering with a Bayesian approach for association mapping in a pedigreed population

    DEFF Research Database (Denmark)

    Dashab, Golam Reza; Kadri, Naveen Kumar; Mahdi Shariati, Mohammad;

    2012-01-01

    ) Mixed model analysis (MMA), 2) Random haplotype model (RHM), 3) Genealogy-based mixed model (GENMIX), and 4) Bayesian variable selection (BVS). The data consisted of phenotypes of 2000 animals from 20 sire families and were genotyped with 9990 SNPs on five chromosomes. Results: Out of the eight...

  1. Efficiency of haplotype-based methods to fine-map QTLs and embryonic lethals variants affecting fertility: illustration with a deletion segregating in Nordic Red cattle Corresponding

    DEFF Research Database (Denmark)

    Kadri, Naveen Kumar; Sahana, Goutam; Guldbrandtsen, Bernt;

    2014-01-01

    -negligible fraction of the fertility decline. Therefore identification of such embryonic lethal variants is essential to improve fertility. We herein illustrate, with an example of a large recessive lethal deletion recently identified in Nordic Red cattle, that haplotype-based method are particularly efficient...

  2. HaplotypeCN: copy number haplotype inference with Hidden Markov Model and localized haplotype clustering.

    Directory of Open Access Journals (Sweden)

    Yen-Jen Lin

    Full Text Available Copy number variation (CNV has been reported to be associated with disease and various cancers. Hence, identifying the accurate position and the type of CNV is currently a critical issue. There are many tools targeting on detecting CNV regions, constructing haplotype phases on CNV regions, or estimating the numerical copy numbers. However, none of them can do all of the three tasks at the same time. This paper presents a method based on Hidden Markov Model to detect parent specific copy number change on both chromosomes with signals from SNP arrays. A haplotype tree is constructed with dynamic branch merging to model the transition of the copy number status of the two alleles assessed at each SNP locus. The emission models are constructed for the genotypes formed with the two haplotypes. The proposed method can provide the segmentation points of the CNV regions as well as the haplotype phasing for the allelic status on each chromosome. The estimated copy numbers are provided as fractional numbers, which can accommodate the somatic mutation in cancer specimens that usually consist of heterogeneous cell populations. The algorithm is evaluated on simulated data and the previously published regions of CNV of the 270 HapMap individuals. The results were compared with five popular methods: PennCNV, genoCN, COKGEN, QuantiSNP and cnvHap. The application on oral cancer samples demonstrates how the proposed method can facilitate clinical association studies. The proposed algorithm exhibits comparable sensitivity of the CNV regions to the best algorithm in our genome-wide study and demonstrates the highest detection rate in SNP dense regions. In addition, we provide better haplotype phasing accuracy than similar approaches. The clinical association carried out with our fractional estimate of copy numbers in the cancer samples provides better detection power than that with integer copy number states.

  3. HaplotypeCN: Copy Number Haplotype Inference with Hidden Markov Model and Localized Haplotype Clustering

    Science.gov (United States)

    Lin, Yen-Jen; Chen, Yu-Tin; Hsu, Shu-Ni; Peng, Chien-Hua; Tang, Chuan-Yi; Yen, Tzu-Chen; Hsieh, Wen-Ping

    2014-01-01

    Copy number variation (CNV) has been reported to be associated with disease and various cancers. Hence, identifying the accurate position and the type of CNV is currently a critical issue. There are many tools targeting on detecting CNV regions, constructing haplotype phases on CNV regions, or estimating the numerical copy numbers. However, none of them can do all of the three tasks at the same time. This paper presents a method based on Hidden Markov Model to detect parent specific copy number change on both chromosomes with signals from SNP arrays. A haplotype tree is constructed with dynamic branch merging to model the transition of the copy number status of the two alleles assessed at each SNP locus. The emission models are constructed for the genotypes formed with the two haplotypes. The proposed method can provide the segmentation points of the CNV regions as well as the haplotype phasing for the allelic status on each chromosome. The estimated copy numbers are provided as fractional numbers, which can accommodate the somatic mutation in cancer specimens that usually consist of heterogeneous cell populations. The algorithm is evaluated on simulated data and the previously published regions of CNV of the 270 HapMap individuals. The results were compared with five popular methods: PennCNV, genoCN, COKGEN, QuantiSNP and cnvHap. The application on oral cancer samples demonstrates how the proposed method can facilitate clinical association studies. The proposed algorithm exhibits comparable sensitivity of the CNV regions to the best algorithm in our genome-wide study and demonstrates the highest detection rate in SNP dense regions. In addition, we provide better haplotype phasing accuracy than similar approaches. The clinical association carried out with our fractional estimate of copy numbers in the cancer samples provides better detection power than that with integer copy number states. PMID:24849202

  4. A Plain English Map of the Human Chromosomes.

    Science.gov (United States)

    Offner, Susan

    1992-01-01

    Presents a chromosome map for 19 known chromosomes in human genetics. Describes the characteristics attributed to the genetic codes for each of the chromosomes and discusses the teaching applications of the chromosome map. (MDH)

  5. Comparison of linear mixed model analysis and genealogy-based haplotype clustering with a Bayesian approach for association mapping in a pedigreed population

    DEFF Research Database (Denmark)

    Dashab, Golam Reza; Kadri, Naveen Kumar; Mahdi Shariati, Mohammad

    2012-01-01

    Background: Despite many success stories of genome wide association studies (GWAS), challenges exist in QTL detection especially in datasets with many levels of relatedness. In this study we compared four methods of GWA on a dataset simulated for the 15th QTL-MAS workshop. The four methods were 1......) Mixed model analysis (MMA), 2) Random haplotype model (RHM), 3) Genealogy-based mixed model (GENMIX), and 4) Bayesian variable selection (BVS). The data consisted of phenotypes of 2000 animals from 20 sire families and were genotyped with 9990 SNPs on five chromosomes. Results: Out of the eight...

  6. Human leukocyte antigen class II (DRB1 and DQB1) alleles and haplotypes frequencies in patients with pemphigus vulgaris among the Serbian population.

    Science.gov (United States)

    Zivanovic, D; Bojic, S; Medenica, L; Andric, Z; Popadic, D

    2016-05-01

    The etiology of pemphigus vulgaris (PV) is multifactorial and includes genetic, environmental, hormonal, and immunological factors. Inheritance of certain Human class II leukocyte antigen (HLA) alleles is by far the best-established predisposing factor for the development of PV. Class II HLA alleles vary among racial/ethnic backgrounds. We have determined an association between HLA class II alleles and PV among the Serbian population. A total of 72 patients with confirmed diagnosis of PV were genotyped for HLA class II alleles. HLA frequencies were compared with unrelated healthy bone marrow donors. The statistical significance of differences between patients and controls was evaluated using Fisher's exact test. The DRB1*04 and DRB1*14 allelic groups were associated with PV (P adj = 4.45 × 10(-13) and 4.06 × 10(-19) respectively), while HLA-DRB1*11 was negatively associated with PV (P adj = 0.0067) suggesting a protective role. DRB1*04:02, DRB1*14:04, DQB1*03:02 and DQB1*05:03 alleles were shown to be strongly associated with PV (P adj = 1.63 × 10(-12), 5.20 × 10(-7), 1.28 × 10(-6), and 4.44 × 10(-5), respectively). The frequency of HLA DRB1*04-DQB1*03 and HLA DRB1*14-DQB1*05 haplotypes in PV patients was significantly higher than in controls (31.3% vs 8.8%, P adj =7.66 × 10(-8) and 30.6% vs 6.3%, P adj = 3.22 × 10(-10), respectively). At high-resolution level, statistical significance was observed in HLA-DRB1*04:02-DQB1*03:02 and HLA-DRB1*14:04-DQB1*05:03 haplotypes (P adj = 5.55 × 10(-12), and P adj = 3.91 × 10(-6), respectively). Our findings suggest that HLA-DRB1*04:02, DRB1*14:04, HLA-DQB1* 03:02 and DQB1*05:03 alleles and HLA-DRB1*04:02-DQB1*03:02 and HLA-DRB1*14:04-DQB1*05:03 haplotypes are genetic markers for susceptibility for PV, while DRB1*11 allelic group appears protective in Serbian population.

  7. Extended HLA-D region haplotype associated with celiac disease

    Energy Technology Data Exchange (ETDEWEB)

    Howell, M.D.; Smith, J.R.; Austin, R.K.; Kelleher, D.; Nepom, G.T.; Volk, B.; Kagnoff, M.F.

    1988-01-01

    Celiac disease has one of the strongest associations with HLA (human leukocyte antigen) class II markers of the known HLA-linked diseases. This association is primarily with the class II serologic specificities HLA-DR3 and -DQw2. The authors previously described a restriction fragment length polymorphism (RFLP) characterized by the presence of a 4.0-kilobase Rsa I fragment derived from an HLA class II ..beta..-chain gene, which distinguishes the class II HLA haplotype of celiac disease patients from those of many serologically matched controls. They now report the isolation of this ..beta..-chain gene from a bacteriophage genomic library constructed from the DNA of a celiac disease patient. Based on restriction mapping and differential hybridization with class II cDNA and oligonucleotide probes, this gene was identified as one encoding an HLA-DP ..beta..-chain. This celiac disease-associated HLA-DP ..beta..-chain gene was flanked by HLA-DP ..cap alpha..-chain genes and, therefore, was probably in its normal chromosomal location. The HLA-DP..cap alpha..-chain genes of celiac disease patients also were studied by RFLP analysis. Celiac disease is associated with a subset of HLA-DR3, -DQw2 haplotypes characterized by HLA-DP ..cap alpha..- and ..beta..-chain gene RFLPs. Within the celiac-disease patient population, the joint segregation of these HLA-DP genes with those encoding the serologic specificities HLA-DR3 and -DQw2 indicates: (i) that the class II HLA haplotype associated with celiac disease is extended throughout the entire HLA-D region, and (ii) that celiac-disease susceptibility genes may reside as far centromeric on this haplotype as the HLA-DP subregion.

  8. Consideration of the haplotype diversity at nonallelic homologous recombination hotspots improves the precision of rearrangement breakpoint identification.

    Science.gov (United States)

    Hillmer, Morten; Summerer, Anna; Mautner, Victor-Felix; Högel, Josef; Cooper, David N; Kehrer-Sawatzki, Hildegard

    2017-09-01

    Precise characterization of nonallelic homologous recombination (NAHR) breakpoints is key to identifying those features that influence NAHR frequency. Until now, analysis of NAHR-mediated rearrangements has generally been performed by comparison of the breakpoint-spanning sequences with the human genome reference sequence. We show here that the haplotype diversity of NAHR hotspots may interfere with breakpoint-mapping. We studied the transmitting parents of individuals with germline type-1 NF1 deletions mediated by NAHR within the paralogous recombination site 1 (PRS1) or paralogous recombination site 2 (PRS2) hotspots. Several parental wild-type PRS1 and PRS2 haplotypes were identified that exhibited considerable sequence differences with respect to the reference sequence, which also affected the number of predicted PRDM9-binding sites. Sequence comparisons between the parental wild-type PRS1 or PRS2 haplotypes and the deletion breakpoint-spanning sequences from the patients (method #2) turned out to be an accurate means to assign NF1 deletion breakpoints and proved superior to crude reference sequence comparisons that neglect to consider haplotype diversity (method #1). The mean length of the deletion breakpoint regions assigned by method #2 was 269-bp in contrast to 502-bp by method #1. Our findings imply that paralog-specific haplotype diversity of NAHR hotspots (such as PRS2) and population-specific haplotype diversity must be taken into account in order to accurately ascertain NAHR-mediated rearrangement breakpoints. © 2017 Wiley Periodicals, Inc.

  9. Molecular definition of red cell Rh haplotypes by tightly linked SphI RFLPs.

    Science.gov (United States)

    Huang, C H; Reid, M E; Chen, Y; Coghlan, G; Okubo, Y

    1996-01-01

    The Rh blood group system of human red cells contains five major antigens D, C/c, and E/e (the latter four designated "non-D") that are specified by eight gene complexes known as Rh haplotypes. In this paper, we report on the mapping of RH locus and identification of a set of SphI RFLPs that are tightly linked with the Rh structural genes. Using exon-specific probes, we have localized the SphI cleavage sites resulting in these DNA markers and derived a comprehensive map for the RH locus. It was found that the SphI fragments encompassing exons 4-7 of the Rh genes occur in four banding patterns or frameworks that correspond to the distribution and segregation of the common Rh haplotypes. This linkage disequilibrium allowed a genotype-phenotype correlation and direct determination of Rh zygosity related to the Rh-positive or Rh-negative status (D/D, D/d, and d/d). Studies on the occurrence of SphI RFLPs in a number of rare Rh variants indicated that Rh phenotypic diversity has taken place on different haplotype backgrounds and has arisen by diverse genetic mechanisms. The molecular definition of Rh haplotypes by SphI RFLP frameworks should provide a useful procedure for genetic counseling and prenatal assessment of Rh alloimmunization.

  10. iHAP – integrated haplotype analysis pipeline for characterizing the haplotype structure of genes

    Directory of Open Access Journals (Sweden)

    Lim Yun Ping

    2006-12-01

    Full Text Available Abstract Background The advent of genotype data from large-scale efforts that catalog the genetic variants of different populations have given rise to new avenues for multifactorial disease association studies. Recent work shows that genotype data from the International HapMap Project have a high degree of transferability to the wider population. This implies that the design of genotyping studies on local populations may be facilitated through inferences drawn from information contained in HapMap populations. Results To facilitate analysis of HapMap data for characterizing the haplotype structure of genes or any chromosomal regions, we have developed an integrated web-based resource, iHAP. In addition to incorporating genotype and haplotype data from the International HapMap Project and gene information from the UCSC Genome Browser Database, iHAP also provides capabilities for inferring haplotype blocks and selecting tag SNPs that are representative of haplotype patterns. These include block partitioning algorithms, block definitions, tag SNP definitions, as well as SNPs to be "force included" as tags. Based on the parameters defined at the input stage, iHAP performs on-the-fly analysis and displays the result graphically as a webpage. To facilitate analysis, intermediate and final result files can be downloaded. Conclusion The iHAP resource, available at http://ihap.bii.a-star.edu.sg, provides a convenient yet flexible approach for the user community to analyze HapMap data and identify candidate targets for genotyping studies.

  11. A proteome-scale map of the human interactome network

    Science.gov (United States)

    Rolland, Thomas; Taşan, Murat; Charloteaux, Benoit; Pevzner, Samuel J.; Zhong, Quan; Sahni, Nidhi; Yi, Song; Lemmens, Irma; Fontanillo, Celia; Mosca, Roberto; Kamburov, Atanas; Ghiassian, Susan D.; Yang, Xinping; Ghamsari, Lila; Balcha, Dawit; Begg, Bridget E.; Braun, Pascal; Brehme, Marc; Broly, Martin P.; Carvunis, Anne-Ruxandra; Convery-Zupan, Dan; Corominas, Roser; Coulombe-Huntington, Jasmin; Dann, Elizabeth; Dreze, Matija; Dricot, Amélie; Fan, Changyu; Franzosa, Eric; Gebreab, Fana; Gutierrez, Bryan J.; Hardy, Madeleine F.; Jin, Mike; Kang, Shuli; Kiros, Ruth; Lin, Guan Ning; Luck, Katja; MacWilliams, Andrew; Menche, Jörg; Murray, Ryan R.; Palagi, Alexandre; Poulin, Matthew M.; Rambout, Xavier; Rasla, John; Reichert, Patrick; Romero, Viviana; Ruyssinck, Elien; Sahalie, Julie M.; Scholz, Annemarie; Shah, Akash A.; Sharma, Amitabh; Shen, Yun; Spirohn, Kerstin; Tam, Stanley; Tejeda, Alexander O.; Trigg, Shelly A.; Twizere, Jean-Claude; Vega, Kerwin; Walsh, Jennifer; Cusick, Michael E.; Xia, Yu; Barabási, Albert-László; Iakoucheva, Lilia M.; Aloy, Patrick; De Las Rivas, Javier; Tavernier, Jan; Calderwood, Michael A.; Hill, David E.; Hao, Tong; Roth, Frederick P.; Vidal, Marc

    2014-01-01

    SUMMARY Just as reference genome sequences revolutionized human genetics, reference maps of interactome networks will be critical to fully understand genotype-phenotype relationships. Here, we describe a systematic map of ~14,000 high-quality human binary protein-protein interactions. At equal quality, this map is ~30% larger than what is available from small-scale studies published in the literature in the last few decades. While currently available information is highly biased and only covers a relatively small portion of the proteome, our systematic map appears strikingly more homogeneous, revealing a “broader” human interactome network than currently appreciated. The map also uncovers significant inter-connectivity between known and candidate cancer gene products, providing unbiased evidence for an expanded functional cancer landscape, while demonstrating how high quality interactome models will help “connect the dots” of the genomic revolution. PMID:25416956

  12. A proteome-scale map of the human interactome network.

    Science.gov (United States)

    Rolland, Thomas; Taşan, Murat; Charloteaux, Benoit; Pevzner, Samuel J; Zhong, Quan; Sahni, Nidhi; Yi, Song; Lemmens, Irma; Fontanillo, Celia; Mosca, Roberto; Kamburov, Atanas; Ghiassian, Susan D; Yang, Xinping; Ghamsari, Lila; Balcha, Dawit; Begg, Bridget E; Braun, Pascal; Brehme, Marc; Broly, Martin P; Carvunis, Anne-Ruxandra; Convery-Zupan, Dan; Corominas, Roser; Coulombe-Huntington, Jasmin; Dann, Elizabeth; Dreze, Matija; Dricot, Amélie; Fan, Changyu; Franzosa, Eric; Gebreab, Fana; Gutierrez, Bryan J; Hardy, Madeleine F; Jin, Mike; Kang, Shuli; Kiros, Ruth; Lin, Guan Ning; Luck, Katja; MacWilliams, Andrew; Menche, Jörg; Murray, Ryan R; Palagi, Alexandre; Poulin, Matthew M; Rambout, Xavier; Rasla, John; Reichert, Patrick; Romero, Viviana; Ruyssinck, Elien; Sahalie, Julie M; Scholz, Annemarie; Shah, Akash A; Sharma, Amitabh; Shen, Yun; Spirohn, Kerstin; Tam, Stanley; Tejeda, Alexander O; Trigg, Shelly A; Twizere, Jean-Claude; Vega, Kerwin; Walsh, Jennifer; Cusick, Michael E; Xia, Yu; Barabási, Albert-László; Iakoucheva, Lilia M; Aloy, Patrick; De Las Rivas, Javier; Tavernier, Jan; Calderwood, Michael A; Hill, David E; Hao, Tong; Roth, Frederick P; Vidal, Marc

    2014-11-20

    Just as reference genome sequences revolutionized human genetics, reference maps of interactome networks will be critical to fully understand genotype-phenotype relationships. Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions. At equal quality, this map is ?30% larger than what is available from small-scale studies published in the literature in the last few decades. While currently available information is highly biased and only covers a relatively small portion of the proteome, our systematic map appears strikingly more homogeneous, revealing a "broader" human interactome network than currently appreciated. The map also uncovers significant interconnectivity between known and candidate cancer gene products, providing unbiased evidence for an expanded functional cancer landscape, while demonstrating how high-quality interactome models will help "connect the dots" of the genomic revolution.

  13. Determination of haplotypes at structurally complex regions using emulsion haplotype fusion PCR

    Directory of Open Access Journals (Sweden)

    Tyson Jess

    2012-12-01

    Full Text Available Abstract Background Genotyping and massively-parallel sequencing projects result in a vast amount of diploid data that is only rarely resolved into its constituent haplotypes. It is nevertheless this phased information that is transmitted from one generation to the next and is most directly associated with biological function and the genetic causes of biological effects. Despite progress made in genome-wide sequencing and phasing algorithms and methods, problems assembling (and reconstructing linear haplotypes in regions of repetitive DNA and structural variation remain. These dynamic and structurally complex regions are often poorly understood from a sequence point of view. Regions such as these that are highly similar in their sequence tend to be collapsed onto the genome assembly. This is turn means downstream determination of the true sequence haplotype in these regions poses a particular challenge. For structurally complex regions, a more focussed approach to assembling haplotypes may be required. Results In order to investigate reconstruction of spatial information at structurally complex regions, we have used an emulsion haplotype fusion PCR approach to reproducibly link sequences of up to 1kb in length to allow phasing of multiple variants from neighbouring loci, using allele-specific PCR and sequencing to detect the phase. By using emulsion systems linking flanking regions to amplicons within the CNV, this led to the reconstruction of a 59kb haplotype across the DEFA1A3 CNV in HapMap individuals. Conclusion This study has demonstrated a novel use for emulsion haplotype fusion PCR in addressing the issue of reconstructing structural haplotypes at multiallelic copy variable regions, using the DEFA1A3 locus as an example.

  14. Mapping Human Brain Function with MRI at 7 Tesla

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ In the past decade, the most significant development in MRI is the introduction of fMRI, which permits the mapping of human brain function with exquisite details noninvasively. Functional mapping can be achieved by measuring changes in the blood oxygenation level (I.e. The BOLD contrast) or cerebral blood flow.

  15. Haplotypes versus genotypes on pedigrees

    Directory of Open Access Journals (Sweden)

    Kirkpatrick Bonnie B

    2011-04-01

    Full Text Available Abstract Background Genome sequencing will soon produce haplotype data for individuals. For pedigrees of related individuals, sequencing appears to be an attractive alternative to genotyping. However, methods for pedigree analysis with haplotype data have not yet been developed, and the computational complexity of such problems has been an open question. Furthermore, it is not clear in which scenarios haplotype data would provide better estimates than genotype data for quantities such as recombination rates. Results To answer these questions, a reduction is given from genotype problem instances to haplotype problem instances, and it is shown that solving the haplotype problem yields the solution to the genotype problem, up to constant factors or coefficients. The pedigree analysis problems we will consider are the likelihood, maximum probability haplotype, and minimum recombination haplotype problems. Conclusions Two algorithms are introduced: an exponential-time hidden Markov model (HMM for haplotype data where some individuals are untyped, and a linear-time algorithm for pedigrees having haplotype data for all individuals. Recombination estimates from the general haplotype HMM algorithm are compared to recombination estimates produced by a genotype HMM. Having haplotype data on all individuals produces better estimates. However, having several untyped individuals can drastically reduce the utility of haplotype data.

  16. Mapping Frontier Research in the Humanities

    DEFF Research Database (Denmark)

    Whereas the classical sciences were organized around academic disciplines, knowledge production today is increasingly interdisciplinary and distributed across a variety of societal sectors. Classical disciplines have not only specialized and multiplied; they are increasingly interacting with extra...... of impact and styles of reasoning, both in classical and interdisciplinary fields of the humanities. From this perspective, a more composite picture of human culture, language and history can emerge from humanities research. It goes beyond the picture of rational agents, and situates human interaction...

  17. Casein haplotypes and their association with milk production traits in Norwegian Red cattle.

    Science.gov (United States)

    Nilsen, Heidi; Olsen, Hanne Gro; Hayes, Ben; Sehested, Erling; Svendsen, Morten; Nome, Torfinn; Meuwissen, Theo; Lien, Sigbjørn

    2009-02-20

    A high resolution SNP map was constructed for the bovine casein region to identify haplotype structures and study associations with milk traits in Norwegian Red cattle. Our analyses suggest separation of the casein cluster into two haplotype blocks, one consisting of the CSN1S1, CSN2 and CSN1S2 genes and another one consisting of the CSN3 gene. Highly significant associations with both protein and milk yield were found for both single SNPs and haplotypes within the CSN1S1-CSN2-CSN1S2 haplotype block. In contrast, no significant association was found for single SNPs or haplotypes within the CSN3 block. Our results point towards CSN2 and CSN1S2 as the most likely loci harbouring the underlying causative DNA variation. In our study, the most significant results were found for the SNP CSN2_67 with the C allele consistently associated with both higher protein and milk yields. CSN2_67 calls a C to an A substitution at codon 67 in beta-casein gene resulting in histidine replacing proline in the amino acid sequence. This polymorphism determines the protein variants A1/B (CSN2_67 A allele) versus A2/A3 (CSN2_67 C allele). Other studies have suggested that a high consumption of A1/B milk may affect human health by increasing the risk of diabetes and heart diseases. Altogether these results argue for an increase in the frequency of the CSN2_67 C allele or haplotypes containing this allele in the Norwegian Red cattle population by selective breeding.

  18. Physical mapping of human chromosome 16. Annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, G.R.

    1992-08-01

    Project aims for the past year have been to refine the cytogenetic based physical map of human chromosome 16. This has been achieved by extending the panel of mouse/human hybrids of chromosome 16 to over sixty hybrids and mapping approximately 250 DNA makers. The high resolution of this physical map, with an average distance between breakpoints of less than 1.6 Mb, and the availability of at least one STS in the majority of these intervals, will be the basis for constructing extensive contigs of cloned DNA.

  19. Molecular definition of red cell Rh haplotypes by tightly linked SphI RFLPs.

    OpenAIRE

    Huang, C. H.; Reid, M.E.; Chen, Y.; Coghlan, G.; Okubo, Y

    1996-01-01

    The Rh blood group system of human red cells contains five major antigens D, C/c, and E/e (the latter four designated "non-D") that are specified by eight gene complexes known as Rh haplotypes. In this paper, we report on the mapping of RH locus and identification of a set of SphI RFLPs that are tightly linked with the Rh structural genes. Using exon-specific probes, we have localized the SphI cleavage sites resulting in these DNA markers and derived a comprehensive map for the RH locus. It w...

  20. A physical map of 30,000 human genes.

    Science.gov (United States)

    Deloukas, P; Schuler, G D; Gyapay, G; Beasley, E M; Soderlund, C; Rodriguez-Tomé, P; Hui, L; Matise, T C; McKusick, K B; Beckmann, J S; Bentolila, S; Bihoreau, M; Birren, B B; Browne, J; Butler, A; Castle, A B; Chiannilkulchai, N; Clee, C; Day, P J; Dehejia, A; Dibling, T; Drouot, N; Duprat, S; Fizames, C; Fox, S; Gelling, S; Green, L; Harrison, P; Hocking, R; Holloway, E; Hunt, S; Keil, S; Lijnzaad, P; Louis-Dit-Sully, C; Ma, J; Mendis, A; Miller, J; Morissette, J; Muselet, D; Nusbaum, H C; Peck, A; Rozen, S; Simon, D; Slonim, D K; Staples, R; Stein, L D; Stewart, E A; Suchard, M A; Thangarajah, T; Vega-Czarny, N; Webber, C; Wu, X; Hudson, J; Auffray, C; Nomura, N; Sikela, J M; Polymeropoulos, M H; James, M R; Lander, E S; Hudson, T J; Myers, R M; Cox, D R; Weissenbach, J; Boguski, M S; Bentley, D R

    1998-10-23

    A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.

  1. A fast and accurate algorithm for diploid individual haplotype reconstruction.

    Science.gov (United States)

    Wu, Jingli; Liang, Binbin

    2013-08-01

    Haplotypes can provide significant information in many research fields, including molecular biology and medical therapy. However, haplotyping is much more difficult than genotyping by using only biological techniques. With the development of sequencing technologies, it becomes possible to obtain haplotypes by combining sequence fragments. The haplotype reconstruction problem of diploid individual has received considerable attention in recent years. It assembles the two haplotypes for a chromosome given the collection of fragments coming from the two haplotypes. Fragment errors significantly increase the difficulty of the problem, and which has been shown to be NP-hard. In this paper, a fast and accurate algorithm, named FAHR, is proposed for haplotyping a single diploid individual. Algorithm FAHR reconstructs the SNP sites of a pair of haplotypes one after another. The SNP fragments that cover some SNP site are partitioned into two groups according to the alleles of the corresponding SNP site, and the SNP values of the pair of haplotypes are ascertained by using the fragments in the group that contains more SNP fragments. The experimental comparisons were conducted among the FAHR, the Fast Hare and the DGS algorithms by using the haplotypes on chromosome 1 of 60 individuals in CEPH samples, which were released by the International HapMap Project. Experimental results under different parameter settings indicate that the reconstruction rate of the FAHR algorithm is higher than those of the Fast Hare and the DGS algorithms, and the running time of the FAHR algorithm is shorter than those of the Fast Hare and the DGS algorithms. Moreover, the FAHR algorithm has high efficiency even for the reconstruction of long haplotypes and is very practical for realistic applications.

  2. Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups

    Directory of Open Access Journals (Sweden)

    Wang Jun

    2009-03-01

    Full Text Available Abstract Background A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, ERCC1, ERCC2, and PPP1R13L (aka RAI are related to DNA repair and cell survival, and one, CD3EAP, aka ASE1, may be related to cell proliferation. The whole region seems related to the cellular response to external damaging agents and markers in it are associated with risk of several cancers. Methods We downloaded the genotypes of all markers typed in the 19q13.3 region in the HapMap populations of European, Asian and African descent and inferred haplotypes. We combined the European HapMap individuals with a Danish breast cancer case-control data set and inferred the association between HapMap haplotypes and disease risk. Results We found that the susceptibility haplotype in our European sample had increased from 2 to 50 percent very recently in the European population, and to almost the same extent in the Asian population. The cause of this increase is unknown. The maximal proportion of overall genetic variation due to differences between groups for Europeans versus Africans and Europeans versus Asians (the Fst value closely matched the putative location of the susceptibility variant as judged from haplotype-based association mapping. Conclusion The combined observation that a common haplotype causing an increased risk of cancer in Europeans and a high differentiation between human populations is highly unusual and suggests a causal relationship with a recent increase in Europeans caused either by genetic drift overruling selection against the susceptibility variant or a positive selection for the same haplotype. The data does not allow us to distinguish between these two scenarios. The analysis suggests that the region is not involved in cancer risk in Africans and that the susceptibility variants may be more finely mapped in Asian populations.

  3. Mapping cumulative human impacts in the eastern North Sea

    DEFF Research Database (Denmark)

    Stock, A.; Andersen, Jesper; Heinänen, S.

    of the MSFD; and 3) to deepen the understanding of how errors in expert judgment affect the resulting cumulative human impact maps by means of Monte Carlo simulations. We combined existing data sets on the spatial distribution of 33 anthropogenic stressors (linked to the MSFD pressures) and 28 key habitats....... In contrast, the predicted impacts for much of the Norwegian EEZ and areas far offshore were lower. The Monte Carlo simulations confirmed earlier findings that mapping cumulative impacts is generally "robust", but also showed that specific combinations of errors can seriously change local and regional...... on marine ecosystems have only recently been developed. The aims of our study were: 1) to develop a map of cumulative human impacts for the Danish, Swedish, Norwegian and German parts of the Greater North Sea; 2) to adjust the existing methods for mapping cumulative human impacts to fit the requirements...

  4. A method for haplotype inference in general pedigrees without recombination

    Institute of Scientific and Technical Information of China (English)

    WANG ChunKao; WANG ZhiPeng; QIU XiaoTian; ZHANG Qin

    2007-01-01

    The abundance of single nucleotide polymorphisms (SNPs) makes the haplotype-based method instead of single-maker-oriented method the main approach to association studies on QTL mapping. The key problem in haploptype-based method is how to reconstruct haplotypes from genotype data. Directly assaying haplotypes in diploid individuals by experimental methods is too expensive, therefore the in silico haplotyping-determination methods are the major choice at the present. This paper presents a rapid and reliable algorithm for haplotype reconstruction for tightly linked SNPs in general pedigrees. It is based on six rules and consists of three steps. First, the parental origins of alleles in offspring are assigned conditional on genotypes in parent-offspring trios; second, the redundant haplotypes are eliminated based on the six rules; and finally, the most likely haplotype combinations are chosen via maximum likelihood method. Our method was verified and compared with PEDPHASE by simulated data with different pedigree sizes, numbers of loci, and proportions of missing genotypes. The result shows that our algorithm was superior to PEDPHASE in terms of computing time and accuracy of haplotype estimation. The computing time for 100 runs was 10-15 times less and the accuracy was 4%-10% higher than PEDPHASE. The result also indicates that our method was very robust and was hardly affected by pedigree size, number of loci, and proportion of missing genotypes.

  5. CRESST Human Performance Knowledge Mapping System

    Science.gov (United States)

    2002-12-01

    team processes and team outcomes. Computers in Human Behavior , 15, 463-494. 0 Herl, H. E. (1995). Construct validation of an approach to modeling...system to measure content understanding. Computers in Human Behavior , 15, 315-334. Johnson, R.F. (2001). Statistical measures of marksmanship (ARI...problem-solving. Computers in Human Behavior , 15, 403-418. West, C. D., Pomeroy, J. R., Park, J. K., Gerstenberger, E. A., & Sandoval, J. (2000

  6. Nonlinear functional mapping of the human brain

    OpenAIRE

    Allgaier, Nicholas; Banaschewski, Tobias; Barker, Gareth; Arun L W Bokde; Bongard, Josh C.; Bromberg, Uli; Büchel, Christian; Cattrell, Anna; Conrod, Patricia J.; Danforth, Christopher M.; Desrivières, Sylvane; Peter S. Dodds; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen

    2015-01-01

    The field of neuroimaging has truly become data rich, and novel analytical methods capable of gleaning meaningful information from large stores of imaging data are in high demand. Those methods that might also be applicable on the level of individual subjects, and thus potentially useful clinically, are of special interest. In the present study, we introduce just such a method, called nonlinear functional mapping (NFM), and demonstrate its application in the analysis of resting state fMRI fro...

  7. Does the pain-protective GTP cyclohydrolase haplotype significantly alter the pattern or severity of pain in humans with chronic pancreatitis?

    Directory of Open Access Journals (Sweden)

    Anderson Michelle A

    2008-11-01

    Full Text Available Abstract Background Pain is often a dominant clinical feature of chronic pancreatitis but the frequency and severity is highly variable between subjects. We hypothesized that genetic polymorphisms contribute to variations in clinical pain patterns. Since genetic variations in the GTP cyclohydrolase (GCH1 gene have been reported to protect some patients from pain, we investigated the effect of the "pain protective haplotype" in well characterized patients with chronic pancreatitis (CP or recurrent acute pancreatitis (RAP from the North American Pancreatitis Study 2 (NAPS2. Results Subjects in the NAPS2 study were asked to rank their pain in one of 5 categories reflecting different levels of pain frequency and severity. All subjects were genotyped at rs8007267 and rs3783641 to determine the frequency of the GCH1 pain-protective haplotype. In Caucasian subjects the frequency of the pain-protective GCH1 haplotype was no different in the control group (n = 236, CP patients (n = 265, RAP patients (N = 131, or in CP patients subclassified by pain category compared to previously reported haplotype frequencies in the general Caucasian population. Conclusion The GCH1 pain-protective haplotype does not have a significant effect on pain patterns or severity in RAP or CP. These results are important for helping to define the regulators of visceral pain, and to distinguish different mechanisms of pain.

  8. Correlation of physical and genetic maps of human chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, G.R.

    1991-01-01

    This project aimed to divide chromosome 16 into approximately 50 intervals of {approximately}2Mb in size by constructing a series of mouse/human somatic cell hybrids each containing a rearranged chromosome 16. Using these hybrids, DNA probes would be regionally mapped by Southern blot or PCR analysis. Preference would be given to mapping probes which demonstrated polymorphisms for which the CEPH panel of families had been typed. This would allow a correlation of the physical and linkage maps of this chromosome. The aims have been substantially achieved. 49 somatic cell hybrids have been constructed which have allowed definition of 46, and potentially 57, different physical intervals on the chromosome. 164 loci have been fully mapped into these intervals. A correlation of the physical and genetic maps of the chromosome is in an advanced stage of preparation. The somatic cell hybrids constructed have been widely distributed to groups working on chromosome 16 and other genome projects.

  9. Human cDNA mapping using fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Korenberg, J.R.

    1993-03-04

    Genetic mapping is approached using the techniques of high resolution fluorescence in situ hybridization (FISH). This technology and the results of its application are designed to rapidly generate whole genome as tool box of expressed sequence to speed the identification of human disease genes. The results of this study are intended to dovetail with and to link the results of existing technologies for creating backbone YAC and genetic maps. In the first eight months, this approach generated 60--80% of the expressed sequence map, the remainder expected to be derived through more long-term, labor-intensive, regional chromosomal gene searches or sequencing. The laboratory has made significant progress in the set-up phase, in mapping fetal and adult brain and other cDNAs, in testing a model system for directly linking genetic and physical maps using FISH with small fragments, in setting up a database, and in establishing the validity and throughput of the system.

  10. Haplotype-resolved genome sequencing of a Gujarati Indian individual.

    Science.gov (United States)

    Kitzman, Jacob O; Mackenzie, Alexandra P; Adey, Andrew; Hiatt, Joseph B; Patwardhan, Rupali P; Sudmant, Peter H; Ng, Sarah B; Alkan, Can; Qiu, Ruolan; Eichler, Evan E; Shendure, Jay

    2011-01-01

    Haplotype information is essential to the complete description and interpretation of genomes, genetic diversity and genetic ancestry. Although individual human genome sequencing is increasingly routine, nearly all such genomes are unresolved with respect to haplotype. Here we combine the throughput of massively parallel sequencing with the contiguity information provided by large-insert cloning to experimentally determine the haplotype-resolved genome of a South Asian individual. A single fosmid library was split into a modest number of pools, each providing ∼3% physical coverage of the diploid genome. Sequencing of each pool yielded reads overwhelmingly derived from only one homologous chromosome at any given location. These data were combined with whole-genome shotgun sequence to directly phase 94% of ascertained heterozygous single nucleotide polymorphisms (SNPs) into long haplotype blocks (N50 of 386 kilobases (kbp)). This method also facilitates the analysis of structural variation, for example, to anchor novel insertions to specific locations and haplotypes.

  11. Integration of the cytogenetic, genetic, and physical maps of the human genome by FISH mapping of CEPH YAC clones

    Energy Technology Data Exchange (ETDEWEB)

    Bray-Ward, P.; Menninger, J.; Lieman, J. [Yale Univ. School of Medicine, New Haven, CT (United States)] [and others

    1996-02-15

    This article discusses the genetic mapping of over 950 yeast artificial chromosome (YAC) clones on human chromosomes. This integration of the cytogenetic, genetic and physical maps of the human genome was accomplished using fluorescence in situ hybridization (FISH) mapping and the CEPH library of YAC clones. 27 refs., 2 figs., 1 tab.

  12. A Method for Calling Copy Number Polymorphism Using Haplotypes

    Directory of Open Access Journals (Sweden)

    Gun Ho eJang

    2013-09-01

    Full Text Available Single nucleotide polymorphism (SNP and copy number variation (CNV are both widespread characteristic of the human genome, but are often called separately on common genotyping platforms. To capture integrated SNP and CNV information, methods have been developed for calling allelic specific copy numbers or so called copy number polymorphism (CNP, using limited inter-marker correlation. In this paper, we proposed a haplotype-based maximum likelihood method to call CNP, which takes advantage of the valuable multi-locus linkage disequilibrium (LD information in the population. We also developed a computationally efficient EM algorithm to estimate haplotype frequencies and optimize individual CNP calls simultaneously, even at presence of missing data. Through simulations, we demonstrated our model is more sensitive and accurate in detecting various CNV regions, compared with commonly-used CNV calling methods including PennCNV, another hidden Markov model using CNP, a scan statistic, segCNV, and cnvHap. Our method often performs better in the regions with higher LD, in longer CNV regions, and in common CNV than the opposite. We implemented our method on the genotypes of 90 HapMap CEU samples and 23 patients with acute lung injury (ALI. For each ALI patient the genotyping was performed twice. The CNPs from our method show good consistency and accuracy comparable to others.

  13. Reconstruction of N-acetyltransferase 2 haplotypes using PHASE.

    Science.gov (United States)

    Golka, Klaus; Blaszkewicz, Meinolf; Samimi, Mirabutaleb; Bolt, Hermann M; Selinski, Silvia

    2008-04-01

    The genotyping of N-acetyltransferase 2 (NAT2) by PCR/RFLP methods yields in a considerable percentage ambiguous results. To resolve this methodical problem a statistical approach was applied. PHASE v2.1.1, a statistical program for haplotype reconstruction was used to estimate haplotype pairs from NAT2 genotyping data, obtained by the analysis of seven single nucleotide polymorphisms relevant for Caucasians. In 1,011 out of 2,921 (35%) subjects the haplotype pairs were clearcut by the PCR/RFLP data only. For the majority of the data the applied method resulted in a multiplicity (2-4) of possible haplotype pairs. Haplotype reconstruction using PHASE v2.1.1 cleared this ambiguity in all cases but one, where an alternative haplotype pair was considered with a probability of 0.029. The estimation of the NAT2 haplotype is important because the assignment of the NAT2 alleles *12A, *12B, *12C or *13 to the rapid or slow NAT2 genotype has been discussed controversially. A clear assignment is indispensable in surveys of human bladder cancer caused by aromatic amine exposures. In conclusion, PHASE v2.1.1 software allowed an unambiguous haplotype reconstruction in 2,920 of 2,921 cases (>99.9%).

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

    Directory of Open Access Journals (Sweden)

    Sophia S Wang

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

  15. HapMap scanning of novel human minor histocompatibility antigens.

    Science.gov (United States)

    Kamei, Michi; Nannya, Yasuhito; Torikai, Hiroki; Kawase, Takakazu; Taura, Kenjiro; Inamoto, Yoshihiro; Takahashi, Taro; Yazaki, Makoto; Morishima, Satoko; Tsujimura, Kunio; Miyamura, Koichi; Ito, Tetsuya; Togari, Hajime; Riddell, Stanley R; Kodera, Yoshihisa; Morishima, Yasuo; Takahashi, Toshitada; Kuzushima, Kiyotaka; Ogawa, Seishi; Akatsuka, Yoshiki

    2009-05-21

    Minor histocompatibility antigens (mHags) are molecular targets of allo-immunity associated with hematopoietic stem cell transplantation (HSCT) and involved in graft-versus-host disease, but they also have beneficial antitumor activity. mHags are typically defined by host SNPs that are not shared by the donor and are immunologically recognized by cytotoxic T cells isolated from post-HSCT patients. However, the number of molecularly identified mHags is still too small to allow prospective studies of their clinical importance in transplantation medicine, mostly due to the lack of an efficient method for isolation. Here we show that when combined with conventional immunologic assays, the large data set from the International HapMap Project can be directly used for genetic mapping of novel mHags. Based on the immunologically determined mHag status in HapMap panels, a target mHag locus can be uniquely mapped through whole genome association scanning taking advantage of the unprecedented resolution and power obtained with more than 3 000 000 markers. The feasibility of our approach could be supported by extensive simulations and further confirmed by actually isolating 2 novel mHags as well as 1 previously identified example. The HapMap data set represents an invaluable resource for investigating human variation, with obvious applications in genetic mapping of clinically relevant human traits.

  16. Physical mapping of human chromosome 16. Annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, G.R.

    1993-08-01

    We aim to isolate cDNAs mapping to human chromosome 16 and localise such cDNAs on the high resolution physical map. In collaboration with LANL, PCR primers will be synthesised from cDNA sequences mapped to chromosome 16 and used as ESTs in the generation of mega-YAC contigs for this chromosome. Probing of high density cosmid grids will enable integration of the ESTs into cosmid contigs and location of the cosmid contigs on the YAC contig. A hn-cDNA library has been constructed from the hybrid CY18 which contains chromosome 16 as the only human chromosome. A modified screening protocol has been successfully developed and 15 hn-cDNA clones have been sequenced and localised on the hybrid map. Sequence analysis of four of these revealed that they were known cDNAs, which are now mapped to chromosome 16. Development of techniques to allow the isolation of longer cDNAs from the identified exons is in progress. This will depend on PCR amplification of cDNAs from a total human CDNA library.

  17. Human brain mapping: Experimental and computational approaches

    Energy Technology Data Exchange (ETDEWEB)

    Wood, C.C.; George, J.S.; Schmidt, D.M.; Aine, C.J. [Los Alamos National Lab., NM (US); Sanders, J. [Albuquerque VA Medical Center, NM (US); Belliveau, J. [Massachusetts General Hospital, Boston, MA (US)

    1998-11-01

    This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). This program developed project combined Los Alamos' and collaborators' strengths in noninvasive brain imaging and high performance computing to develop potential contributions to the multi-agency Human Brain Project led by the National Institute of Mental Health. The experimental component of the project emphasized the optimization of spatial and temporal resolution of functional brain imaging by combining: (a) structural MRI measurements of brain anatomy; (b) functional MRI measurements of blood flow and oxygenation; and (c) MEG measurements of time-resolved neuronal population currents. The computational component of the project emphasized development of a high-resolution 3-D volumetric model of the brain based on anatomical MRI, in which structural and functional information from multiple imaging modalities can be integrated into a single computational framework for modeling, visualization, and database representation.

  18. Human brain mapping: Experimental and computational approaches

    Energy Technology Data Exchange (ETDEWEB)

    Wood, C.C.; George, J.S.; Schmidt, D.M.; Aine, C.J. [Los Alamos National Lab., NM (US); Sanders, J. [Albuquerque VA Medical Center, NM (US); Belliveau, J. [Massachusetts General Hospital, Boston, MA (US)

    1998-11-01

    This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). This program developed project combined Los Alamos' and collaborators' strengths in noninvasive brain imaging and high performance computing to develop potential contributions to the multi-agency Human Brain Project led by the National Institute of Mental Health. The experimental component of the project emphasized the optimization of spatial and temporal resolution of functional brain imaging by combining: (a) structural MRI measurements of brain anatomy; (b) functional MRI measurements of blood flow and oxygenation; and (c) MEG measurements of time-resolved neuronal population currents. The computational component of the project emphasized development of a high-resolution 3-D volumetric model of the brain based on anatomical MRI, in which structural and functional information from multiple imaging modalities can be integrated into a single computational framework for modeling, visualization, and database representation.

  19. Linking human factors to corporate strategy with cognitive mapping techniques.

    Science.gov (United States)

    Village, Judy; Greig, Michael; Salustri, Filippo A; Neumann, W Patrick

    2012-01-01

    For human factors (HF) to avoid being considered of "side-car" status, it needs to be positioned within the organization in such a way that it affects business strategies and their implementation. Tools are needed to support this effort. This paper explores the feasibility of applying a technique from operational research called cognitive mapping to link HF to corporate strategy. Using a single case study, a cognitive map is drawn to reveal the complex relationships between human factors and achieving an organization's strategic goals. Analysis of the map for central concepts and reinforcing loops enhances understanding that can lead to discrete initiatives to facilitate integration of HF. It is recommended that this technique be used with senior managers to understand the organizations` strategic goals and enhance understanding of the potential for HF to contribute to the strategic goals.

  20. Maslow Revisited: Constructing a Road Map of Human Nature

    Science.gov (United States)

    O'Connor, Dennis; Yballe, Leodones

    2007-01-01

    Given the scope and intent of Maslow's work, the current textbook treatment is wanting. Therefore, an inductive exercise has been created and is offered here to build "the road map of human nature." This age-old, philosophic focus on our true nature has been a way to successfully engage and inspire both our students and our pedagogy. In the spirit…

  1. Maslow Revisited: Constructing a Road Map of Human Nature

    Science.gov (United States)

    O'Connor, Dennis; Yballe, Leodones

    2007-01-01

    Given the scope and intent of Maslow's work, the current textbook treatment is wanting. Therefore, an inductive exercise has been created and is offered here to build "the road map of human nature." This age-old, philosophic focus on our true nature has been a way to successfully engage and inspire both our students and our pedagogy. In the spirit…

  2. Mapping the calcitonin receptor in human brain stem

    DEFF Research Database (Denmark)

    Bower, Rebekah L; Eftekhari, Sajedeh; Waldvogel, Henry J

    2016-01-01

    understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract...

  3. Maximum-likelihood estimation of haplotype frequencies in nuclear families.

    Science.gov (United States)

    Becker, Tim; Knapp, Michael

    2004-07-01

    The importance of haplotype analysis in the context of association fine mapping of disease genes has grown steadily over the last years. Since experimental methods to determine haplotypes on a large scale are not available, phase has to be inferred statistically. For individual genotype data, several reconstruction techniques and many implementations of the expectation-maximization (EM) algorithm for haplotype frequency estimation exist. Recent research work has shown that incorporating available genotype information of related individuals largely increases the precision of haplotype frequency estimates. We, therefore, implemented a highly flexible program written in C, called FAMHAP, which calculates maximum likelihood estimates (MLEs) of haplotype frequencies from general nuclear families with an arbitrary number of children via the EM-algorithm for up to 20 SNPs. For more loci, we have implemented a locus-iterative mode of the EM-algorithm, which gives reliable approximations of the MLEs for up to 63 SNP loci, or less when multi-allelic markers are incorporated into the analysis. Missing genotypes can be handled as well. The program is able to distinguish cases (haplotypes transmitted to the first affected child of a family) from pseudo-controls (non-transmitted haplotypes with respect to the child). We tested the performance of FAMHAP and the accuracy of the obtained haplotype frequencies on a variety of simulated data sets. The implementation proved to work well when many markers were considered and no significant differences between the estimates obtained with the usual EM-algorithm and those obtained in its locus-iterative mode were observed. We conclude from the simulations that the accuracy of haplotype frequency estimation and reconstruction in nuclear families is very reliable in general and robust against missing genotypes.

  4. The human tyrosine aminotransferase gene: characterization of restriction fragment length polymorphisms and haplotype analysis in a family with tyrosinemia type II.

    Science.gov (United States)

    Westphal, E M; Natt, E; Grimm, T; Odievre, M; Scherer, G

    1988-07-01

    Deficiency in hepatic tyrosine aminotransferase (TAT) causes tyrosinemia type II, an autosomal recessively inherited disorder. Using a TAT cosmid clone, we have identified an MspI restriction fragment length polymorphism (RFLP) 5' to the TAT gene, with allele frequencies of 0.63 and 0.37. Analysis of the cloned maternal and paternal TAT alleles from a patient with tyrosinemia type II led to the identification of a HaeIII RFLP at the 3' end of the TAT gene, with allele frequencies of 0.94 and 0.06. The two RFLPs are 27 kb apart and in no allelic association. From haplotype frequencies, a polymorphism information content (PIC) value of 0.44 was obtained. The two RFLPs have allowed the unambiguous identification of the mutant TAT alleles in the patient's pedigree by haplotype analysis.

  5. Optoacoustic mapping of cerebral blood oxygenation in humans

    Science.gov (United States)

    Petrov, Yuriy; Prough, Donald S.; Petrov, Irene Y.; Richardson, C. Joan; Fonseca, Rafael A.; Robertson, Claudia S.; Esenaliev, Rinat O.

    2017-03-01

    Noninvasive, transcranial mapping, monitoring, and imaging are highly important for detection and management of cerebral abnormalities and neuroscience research. Mapping, imaging, and monitoring of cerebral blood oxygenation are necessary for diagnostics and management of patients with traumatic brain injury, stroke, and other neurological conditions. We proposed to use optoacoustic technology for noninvasive, transcranial monitoring and imaging. In this work, we developed optoacoustic systems for mapping of cerebral blood oxygenation in humans and tested them in adults and neonates. The systems provide noninvasive, transcranial optoacoustic measurements in the transmission (forward) and reflection (backward) modes in the near infrared spectral range. Novel, ultra-sensitive probes were built for detection of optoacoustic signals and measurement of blood oxygenation in neonates and adults. Cerebral oxygenation was measured at different lateral sites from the superior sagittal sinus (SSS), a large central cerebral vein, located immediately beneath the midline of the human skull. In neonates, cerebral oxygenation was measured through open anterior and posterior fontanelles. Optoacoustic signal detection at different locations allowed for mapping of cerebral blood oxygenation. Our future studies will be focused on 3D mapping of cerebral blood oxygenation.

  6. Genetic mapping of high caries experience on human chromosome 13.

    Science.gov (United States)

    Küchler, Erika C; Deeley, Kathleen; Ho, Bao; Linkowski, Samantha; Meyer, Chelsea; Noel, Jacqueline; Kouzbari, M Zahir; Bezamat, Mariana; Granjeiro, José M; Antunes, Leonardo S; Antunes, Livia Azeredo; de Abreu, Fernanda Volpe; Costa, Marcelo C; Tannure, Patricia N; Seymen, Figen; Koruyucu, Mine; Patir, Asli; Mereb, Juan C; Poletta, Fernando A; Castilla, Eduardo E; Orioli, Ieda M; Marazita, Mary L; Vieira, Alexandre R

    2013-11-05

    Our previous genome-wide linkage scan mapped five loci for caries experience. The purpose of this study was to fine map one of these loci, the locus 13q31.1, in order to identify genetic contributors to caries. Seventy-two pedigrees from the Philippines were studied. Caries experience was recorded and DNA was extracted from blood samples obtained from all subjects. Sixty-one single nucleotide polymorphisms (SNPs) in 13q31.1 were genotyped. Association between caries experience and alleles was tested. We also studied 1,481 DNA samples obtained from saliva of subjects from the USA, 918 children from Brazil, and 275 children from Turkey, in order to follow up the results found in the Filipino families. We used the AliBaba2.1 software to determine if the nucleotide changes of the associated SNPs changed the prediction of the presence of transcription-binding site sequences and we also analyzed the gene expression of the genes selected based on binding predictions. Mutation analysis was also performed in 33 Filipino individuals of a segment of 13q31.1 that is highly conserved in mammals. Statistically significant association with high caries experience was found for 11 markers in 13q31.1 in the Filipino families. Haplotype analysis also confirmed these results. In the populations used for follow-up purposes, associations were found between high caries experience and a subset of these markers. Regarding the prediction of the transcription-binding site, the base change of the SNP rs17074565 was found to change the predicted-binding of genes that could be involved in the pathogenesis of caries. When the sequence has the allele C of rs17074565, the potential transcription factors binding the sequence are GR and GATA1. When the subject carries the G allele of rs17074565, the potential transcription factor predicted to bind to the sequence is GATA3. The expression of GR in whole saliva was higher in individuals with low caries experience when compared to individuals with high

  7. [Developing a physical map of human chromosome 22]. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Simon, M.I.

    1991-12-31

    We have developed bacterial F-factor based systems for cloning large fragments of human DNA in E. coli. In addition to large size, these systems are capable of maintaining human DNA with a high degree of stability. The cosmid size clones are called Fosmids and the clones containing larger inserts (100--200 kb) are called bacterial artificial chromosomes (BACs). The ultimate test of the effectiveness of cloning and mapping technology is the degree to which it can be efficiently applied to solve complex mapping problems. We, therefore, plan to use the large fragment cloning procedure as well as a variety of other approaches to generate a complete map of overlapping clones corresponding to human chromosome 22. We have thus far prepared two human chromosome 22 specific Fosmid libraries and we are in the process of constructing a chromosome 22 specific BAC library composed of fragments larger than 100 kb. We will further optimize the technology so that libraries of fragments larger than 200 kb can be readily prepared.

  8. (Developing a physical map of human chromosome 22)

    Energy Technology Data Exchange (ETDEWEB)

    Simon, M.I.

    1991-01-01

    We have developed bacterial F-factor based systems for cloning large fragments of human DNA in E. coli. In addition to large size, these systems are capable of maintaining human DNA with a high degree of stability. The cosmid size clones are called Fosmids and the clones containing larger inserts (100--200 kb) are called bacterial artificial chromosomes (BACs). The ultimate test of the effectiveness of cloning and mapping technology is the degree to which it can be efficiently applied to solve complex mapping problems. We, therefore, plan to use the large fragment cloning procedure as well as a variety of other approaches to generate a complete map of overlapping clones corresponding to human chromosome 22. We have thus far prepared two human chromosome 22 specific Fosmid libraries and we are in the process of constructing a chromosome 22 specific BAC library composed of fragments larger than 100 kb. We will further optimize the technology so that libraries of fragments larger than 200 kb can be readily prepared.

  9. A quantitative transcriptome reference map of the normal human brain.

    Science.gov (United States)

    Caracausi, Maria; Vitale, Lorenza; Pelleri, Maria Chiara; Piovesan, Allison; Bruno, Samantha; Strippoli, Pierluigi

    2014-10-01

    We performed an innovative systematic meta-analysis of 60 gene expression profiles of whole normal human brain, to provide a quantitative transcriptome reference map of it, i.e. a reference typical value of expression for each of the 39,250 known, mapped and 26,026 uncharacterized (unmapped) transcripts. To this aim, we used the software named Transcriptome Mapper (TRAM), which is able to generate transcriptome maps based on gene expression data from multiple sources. We also analyzed differential expression by comparing the brain transcriptome with those derived from human foetal brain gene expression, from a pool of human tissues (except the brain) and from the two normal human brain regions cerebellum and cerebral cortex, which are two of the main regions severely affected when cognitive impairment occurs, as happens in the case of trisomy 21. Data were downloaded from microarray databases, processed and analyzed using TRAM software and validated in vitro by assaying gene expression through several magnitude orders by 'real-time' reverse transcription polymerase chain reaction (RT-PCR). The excellent agreement between in silico and experimental data suggested that our transcriptome maps may be a useful quantitative reference benchmark for gene expression studies related to the human brain. Furthermore, our analysis yielded biological insights about those genes which have an intrinsic over-/under-expression in the brain, in addition offering a basis for the regional analysis of gene expression. This could be useful for the study of chromosomal alterations associated to cognitive impairment, such as trisomy 21, the most common genetic cause of intellectual disability.

  10. Integrating population dynamics into mapping human exposure to seismic hazard

    Directory of Open Access Journals (Sweden)

    S. Freire

    2012-11-01

    Full Text Available Disaster risk is not fully characterized without taking into account vulnerability and population exposure. Assessment of earthquake risk in urban areas would benefit from considering the variation of population distribution at more detailed spatial and temporal scales, and from a more explicit integration of this improved demographic data with existing seismic hazard maps. In the present work, "intelligent" dasymetric mapping is used to model population dynamics at high spatial resolution in order to benefit the analysis of spatio-temporal exposure to earthquake hazard in a metropolitan area. These night- and daytime-specific population densities are then classified and combined with seismic intensity levels to derive new spatially-explicit four-class-composite maps of human exposure. The presented approach enables a more thorough assessment of population exposure to earthquake hazard. Results show that there are significantly more people potentially at risk in the daytime period, demonstrating the shifting nature of population exposure in the daily cycle and the need to move beyond conventional residence-based demographic data sources to improve risk analyses. The proposed fine-scale maps of human exposure to seismic intensity are mainly aimed at benefiting visualization and communication of earthquake risk, but can be valuable in all phases of the disaster management process where knowledge of population densities is relevant for decision-making.

  11. Haplotype allelic classes for detecting ongoing positive selection.

    Science.gov (United States)

    Hussin, Julie; Nadeau, Philippe; Lefebvre, Jean-François; Labuda, Damian

    2010-01-28

    Natural selection eliminates detrimental and favors advantageous phenotypes. This process leaves characteristic signatures in underlying genomic segments that can be recognized through deviations in allelic or haplotypic frequency spectra. To provide an identifiable signature of recent positive selection that can be detected by comparison with the background distribution, we introduced a new way of looking at genomic polymorphisms: haplotype allelic classes. The model combines segregating sites and haplotypic information in order to reveal useful data characteristics. We developed a summary statistic, Svd, to compare the distribution of the haplotypes carrying the selected allele with the distribution of the remaining ones. Coalescence simulations are used to study the distributions under standard population models assuming neutrality, demographic scenarios and selection models. To test, in practice, haplotype allelic class performance and the derived statistic in capturing deviation from neutrality due to positive selection, we analyzed haplotypic variation in detail in the locus of lactase persistence in the three HapMap Phase II populations. We showed that the Svd statistic is less sensitive than other tests to confounding factors such as demography or recombination. Our approach succeeds in identifying candidate loci, such as the lactase-persistence locus, as targets of strong positive selection and provides a new tool complementary to other tests to study natural selection in genomic data.

  12. Haplotype allelic classes for detecting ongoing positive selection

    Directory of Open Access Journals (Sweden)

    Lefebvre Jean-François

    2010-01-01

    Full Text Available Abstract Background Natural selection eliminates detrimental and favors advantageous phenotypes. This process leaves characteristic signatures in underlying genomic segments that can be recognized through deviations in allelic or haplotypic frequency spectra. To provide an identifiable signature of recent positive selection that can be detected by comparison with the background distribution, we introduced a new way of looking at genomic polymorphisms: haplotype allelic classes. Results The model combines segregating sites and haplotypic information in order to reveal useful data characteristics. We developed a summary statistic, Svd, to compare the distribution of the haplotypes carrying the selected allele with the distribution of the remaining ones. Coalescence simulations are used to study the distributions under standard population models assuming neutrality, demographic scenarios and selection models. To test, in practice, haplotype allelic class performance and the derived statistic in capturing deviation from neutrality due to positive selection, we analyzed haplotypic variation in detail in the locus of lactase persistence in the three HapMap Phase II populations. Conclusions We showed that the Svd statistic is less sensitive than other tests to confounding factors such as demography or recombination. Our approach succeeds in identifying candidate loci, such as the lactase-persistence locus, as targets of strong positive selection and provides a new tool complementary to other tests to study natural selection in genomic data.

  13. An extended anchored linkage map and virtual mapping for the american mink genome based on homology to human and dog

    DEFF Research Database (Denmark)

    Anistoroaei, Razvan Marian; Ansari, S.; Farid, A.;

    2009-01-01

    In this report we present an extended linkage map of the American mink (Neovison vison) consisting of 157 microsatellite markers and comprising at least one linkage group for each of the autosomes. Each linkage group has been assigned to a chromosome and oriented by fluorescence in situ hybridiza......In this report we present an extended linkage map of the American mink (Neovison vison) consisting of 157 microsatellite markers and comprising at least one linkage group for each of the autosomes. Each linkage group has been assigned to a chromosome and oriented by fluorescence in situ...... comparative human/dog/mink data, these assignments represent useful virtual maps for the American mink genome. Comparison of the current human/dog assembled sequential map with the existing Zoo-FISH-based human/dog/mink maps helped to refine the human/dog/mink comparative map. Furthermore, comparison...

  14. Mapping human whole-brain structural networks with diffusion MRI.

    Directory of Open Access Journals (Sweden)

    Patric Hagmann

    Full Text Available Understanding the large-scale structural network formed by neurons is a major challenge in system neuroscience. A detailed connectivity map covering the entire brain would therefore be of great value. Based on diffusion MRI, we propose an efficient methodology to generate large, comprehensive and individual white matter connectional datasets of the living or dead, human or animal brain. This non-invasive tool enables us to study the basic and potentially complex network properties of the entire brain. For two human subjects we find that their individual brain networks have an exponential node degree distribution and that their global organization is in the form of a small world.

  15. Tissue-based map of the human proteome

    DEFF Research Database (Denmark)

    Uhlén, Mathias; Fagerberg, Linn; Hallström, Björn M.

    2015-01-01

    transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human......Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative...... secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns...

  16. Quantitative trait loci and the relevance of phased haplotypes

    DEFF Research Database (Denmark)

    Gregersen, Vivi Raundahl

    underlying gentic control both as traditional linkage studies relying on genetic maps and as GWAS where an approach of phasing haplotypes within the QTL have been conducted to validate the regions. Overall, regions of interest have been identified for chronic pleuritis and osteochondrosis in addition to meat...

  17. G16R single nucleotide polymorphism but not haplotypes of the ß2-adrenergic receptor gene alters cardiac output in humans

    DEFF Research Database (Denmark)

    Rokamp, Kim Z; Staalsø, Jonatan M; Gartmann, Martin

    2013-01-01

    studied. Five SNPs within ADRB2 (46G>A, 79C>G, 491C>T, 523C>A and 1053G>C by a pairwise tagging principle) and the I/D (insertion/deletion) polymorphism in ACE were genotyped in 143 subjects. Cardiovascular variables were evaluated by the Model flow method at rest and during incremental cycling exercise......Variation in genes encoding the ß2-adrenergic receptor (ADRB2) and angiotensin-converting enzyme (ACE) may influence Q¿ (cardiac output). The 46G>A (G16R) SNP (single nucleotide polymorphism) has been associated with ß2-mediated vasodilation, but the effect of ADRB2 haplotypes on Q¿ has not been...... V¿O2 (oxygen uptake) in G16G subjects, but the increase was 0.5 (0.0-0.9) l/min lower in Arg16 carriers (P=0.035). A similar effect size was observed for the Arg16 haplotypes ACCCG and ACCCC. No interaction was found between ADRB2 and ACE polymorphisms. During exercise, the increase in Q¿ was 0...

  18. Combining an Evolution-guided Clustering Algorithm and Haplotype-based LRT in Family Association Studies

    Directory of Open Access Journals (Sweden)

    Huang Su-Yun

    2011-05-01

    Full Text Available Abstract Background With the completion of the international HapMap project, many studies have been conducted to investigate the association between complex diseases and haplotype variants. Such haplotype-based association studies, however, often face two difficulties; one is the large number of haplotype configurations in the chromosome region under study, and the other is the ambiguity in haplotype phase when only genotype data are observed. The latter complexity may be handled based on an EM algorithm with family data incorporated, whereas the former can be more problematic, especially when haplotypes of rare frequencies are involved. Here based on family data we propose to cluster long haplotypes of linked SNPs in a biological sense, so that the number of haplotypes can be reduced and the power of statistical tests of association can be increased. Results In this paper we employ family genotype data and combine a clustering scheme with a likelihood ratio statistic to test the association between quantitative phenotypes and haplotype variants. Haplotypes are first grouped based on their evolutionary closeness to establish a set containing core haplotypes. Then, we construct for each family the transmission and non-transmission phase in terms of these core haplotypes, taking into account simultaneously the phase ambiguity as weights. The likelihood ratio test (LRT is next conducted with these weighted and clustered haplotypes to test for association with disease. This combination of evolution-guided haplotype clustering and weighted assignment in LRT is able, via its core-coding system, to incorporate into analysis both haplotype phase ambiguity and transmission uncertainty. Simulation studies show that this proposed procedure is more informative and powerful than three family-based association tests, FAMHAP, FBAT, and an LRT with a group consisting exclusively of rare haplotypes. Conclusions The proposed procedure takes into account the

  19. HaploForge: A Comprehensive Pedigree Drawing and Haplotype Visualisation Web Application.

    Science.gov (United States)

    Tekman, Mehmet; Medlar, Alan; Mozere, Monika; Kleta, Robert; Stanescu, Horia

    2017-08-14

    Haplotype reconstruction is an important tool for understanding the aetiology of human disease. Haplotyping infers the most likely phase of observed genotypes conditional on constraints imposed by the genotypes of other pedigree members. The results of haplotype reconstruction, when visualised appropriately, show which alleles are identical by descent despite the presence of untyped individuals. When used in concert with linkage analysis, haplotyping can help delineate a locus of interest and provide a succinct explanation for the transmission of the trait locus. Unfortunately, the design choices made by existing haplotype visualisation programs do not scale to large numbers of markers. Indeed, following haplotypes from generation to generation requires excessive scrolling back and forth. In addition, the most widely-used program for haplotype visualisation produces inconsistent recombination artefacts for the X chromosome. To resolve these issues, we developed HaploForge, a novel web application for haplotype visualisation and pedigree drawing. HaploForge takes advantage of HTML5 to be fast, portable and avoid the need for local installation. It can accurately visualise autosomal and X-linked haplotypes from both outbred and consanguineous pedigrees. Haplotypes are coloured based on identity by descent using a novel A* search algorithm and we provide a flexible viewing mode to aid visual inspection. HaploForge can currently process haplotype reconstruction output from Allegro, GeneHunter, Merlin and Simwalk. HaploForge is licensed under GPLv3 and is hosted and maintained via GitHub. Supplementary data is available from Bioinformatics online.

  20. Retrieving HapMap Data via Bulk Download.

    Science.gov (United States)

    Smith, Albert Vernon

    2008-07-01

    INTRODUCTIONThe primary goal of the International Haplotype Map Project has been to develop a haplotype map of the human genome that describes the common patterns of genetic variation, in order to accelerate the search for the genetic causes of human disease. Within the project, ~3.9 million distinct single-nucleotide polymorphisms (SNPs) have been genotyped in 270 individuals from four worldwide populations. The project data are available for unrestricted public use at the HapMap Web site. This site, which is the primary portal to genotype data produced by the project, offers bulk downloads of the data set, as well as interactive data browsing and analysis tools that are not available elsewhere. Bulk downloads of chromosome- or genome-wide data provide text dumps of the entire HapMap data set. Although complete, such downloads do not provide any filtering or selection services. This protocol describes the retrieval of HapMap data via bulk download.

  1. Chromosomal mapping of the human M6 genes

    Energy Technology Data Exchange (ETDEWEB)

    Olinsky, S.; Loop, B.T.; DeKosky, A. [Univ. of Pittsburgh, PA (United States)] [and others

    1996-05-01

    M6 is a neuronal membrane glycoprotein that may have an important role in neural development. This molecule was initially defined by a monoclonal antibody that affected the survival of cultured cerebellar neurons and the outgrowth of neurites. The nature of the antigen was discovered by expression cDNA cloning using this monoclonal antibody. Two distinct murine M6 cDNAs (designated M6a and M6b) whose deduced amino acid sequences were remarkably similar to that of the myelin proteolipid protein human cDNA and genomic clones encoding M6a and M6b and have characterized them by restriction mapping, Southern hybridization with cDNA probes, and sequence analysis. We have localized these genes within the human genome by FISH (fluorescence in situ hybridization). The human M6a gene is located at 4q34, and the M6b gene is located at Xp22.2 A number of human neurological disorders have been mapped to the Xp22 region, including Aicardi syndrome (MIM 304050), Rett syndrome (MIM 312750), X-linked Charcot-Marie-Tooth neuropathy (MIM 302801), and X-linked mental retardation syndromes (MRX1, MIM 309530). This raises the possibility that a defect in the M6b gene is responsible for one of these neurological disorders. 8 refs., 3 figs.

  2. Cloud computing-based TagSNP selection algorithm for human genome data.

    Science.gov (United States)

    Hung, Che-Lun; Chen, Wen-Pei; Hua, Guan-Jie; Zheng, Huiru; Tsai, Suh-Jen Jane; Lin, Yaw-Ling

    2015-01-05

    Single nucleotide polymorphisms (SNPs) play a fundamental role in human genetic variation and are used in medical diagnostics, phylogeny construction, and drug design. They provide the highest-resolution genetic fingerprint for identifying disease associations and human features. Haplotypes are regions of linked genetic variants that are closely spaced on the genome and tend to be inherited together. Genetics research has revealed SNPs within certain haplotype blocks that introduce few distinct common haplotypes into most of the population. Haplotype block structures are used in association-based methods to map disease genes. In this paper, we propose an efficient algorithm for identifying haplotype blocks in the genome. In chromosomal haplotype data retrieved from the HapMap project website, the proposed algorithm identified longer haplotype blocks than an existing algorithm. To enhance its performance, we extended the proposed algorithm into a parallel algorithm that copies data in parallel via the Hadoop MapReduce framework. The proposed MapReduce-paralleled combinatorial algorithm performed well on real-world data obtained from the HapMap dataset; the improvement in computational efficiency was proportional to the number of processors used.

  3. Cloud Computing-Based TagSNP Selection Algorithm for Human Genome Data

    Science.gov (United States)

    Hung, Che-Lun; Chen, Wen-Pei; Hua, Guan-Jie; Zheng, Huiru; Tsai, Suh-Jen Jane; Lin, Yaw-Ling

    2015-01-01

    Single nucleotide polymorphisms (SNPs) play a fundamental role in human genetic variation and are used in medical diagnostics, phylogeny construction, and drug design. They provide the highest-resolution genetic fingerprint for identifying disease associations and human features. Haplotypes are regions of linked genetic variants that are closely spaced on the genome and tend to be inherited together. Genetics research has revealed SNPs within certain haplotype blocks that introduce few distinct common haplotypes into most of the population. Haplotype block structures are used in association-based methods to map disease genes. In this paper, we propose an efficient algorithm for identifying haplotype blocks in the genome. In chromosomal haplotype data retrieved from the HapMap project website, the proposed algorithm identified longer haplotype blocks than an existing algorithm. To enhance its performance, we extended the proposed algorithm into a parallel algorithm that copies data in parallel via the Hadoop MapReduce framework. The proposed MapReduce-paralleled combinatorial algorithm performed well on real-world data obtained from the HapMap dataset; the improvement in computational efficiency was proportional to the number of processors used. PMID:25569088

  4. Understanding Y haplotype matching probability.

    Science.gov (United States)

    Brenner, Charles H

    2014-01-01

    The Y haplotype population-genetic terrain is better explored from a fresh perspective rather than by analogy with the more familiar autosomal ideas. For haplotype matching probabilities, versus for autosomal matching probabilities, explicit attention to modelling - such as how evolution got us where we are - is much more important while consideration of population frequency is much less so. This paper explores, extends, and explains some of the concepts of "Fundamental problem of forensic mathematics - the evidential strength of a rare haplotype match". That earlier paper presented and validated a "kappa method" formula for the evidential strength when a suspect matches a previously unseen haplotype (such as a Y-haplotype) at the crime scene. Mathematical implications of the kappa method are intuitive and reasonable. Suspicions to the contrary raised in rest on elementary errors. Critical to deriving the kappa method or any sensible evidential calculation is understanding that thinking about haplotype population frequency is a red herring; the pivotal question is one of matching probability. But confusion between the two is unfortunately institutionalized in much of the forensic world. Examples make clear why (matching) probability is not (population) frequency and why uncertainty intervals on matching probabilities are merely confused thinking. Forensic matching calculations should be based on a model, on stipulated premises. The model inevitably only approximates reality, and any error in the results comes only from error in the model, the inexactness of the approximation. Sampling variation does not measure that inexactness and hence is not helpful in explaining evidence and is in fact an impediment. Alternative haplotype matching probability approaches that various authors have considered are reviewed. Some are based on no model and cannot be taken seriously. For the others, some evaluation of the models is discussed. Recent evidence supports the adequacy of

  5. Cytoarchitecture and probability maps of the human medial orbitofrontal cortex.

    Science.gov (United States)

    Henssen, Anton; Zilles, Karl; Palomero-Gallagher, Nicola; Schleicher, Axel; Mohlberg, Hartmut; Gerboga, Fatma; Eickhoff, Simon B; Bludau, Sebastian; Amunts, Katrin

    2016-02-01

    Previous architectonical studies of human orbitofrontal cortex (OFC) provided divergent maps regarding number, location, and extent of areas. To solve this controversy, an observer-independent cytoarchitectonical mapping of medial OFC (mOFC) was performed. Borders of cortical areas were detected in histological sections of ten human post-mortem brains using a quantitative, statistically testable method, and their stereotaxic localization and intersubject variability were determined. Three areas were identified: granular Fo1 mainly on the rostral Gyrus rectus and medial of the olfactory sulcus; granular to dysgranular Fo2, mainly on the posterior part of the ventromedial Gyrus rectus and the medial and lateral banks of the olfactory sulcus; granular Fo3 between the olfactory and medial or intermediate orbital sulci. Fo3 was bordered medially by Fo1 and Fo2 and laterally by the lateral OFC (lOFC). A cluster analysis of the cytoarchitectonical features of Fo1-Fo3, subgenual cingulate areas, BA12, lateral and medial areas of the frontopolar cortex, lOFC and areas of Broca's region demonstrated the cytoarchitectonical similarity between the mOFC areas in contrast to all other frontal areas. Probabilistic maps of mOFC areas show a considerable intersubject variability in extent and position in stereotaxic space, and provide spatial templates for anatomical localization of in vivo neuroimaging data via the JuBrain atlas and the Anatomy Toolbox.

  6. A three dimensional nerve map of human bladder trigone.

    Science.gov (United States)

    Purves, J Todd; Spruill, Laura; Rovner, Eric; Borisko, Elyse; McCants, Alden; Mugo, Elizabeth; Wingard, Ainsley; Trusk, Thomas C; Bacro, Thierry; Hughes, Francis M

    2017-04-01

    Central efferent and afferent neural pathways to and from the human urinary bladder are well-characterized, but the location and arborization of these nerves as they traverse the serosa, muscularis, and urothelial layers are not clearly defined. The purpose of this study was to create a three dimensional map of the innervation of the human bladder trigone from the extrinsic perivesical adventitial nerve trunks to the urothelium. A male and a female human bladder were harvested from fresh frozen cadavers and fixed in formalin. The bladder neck and trigone region were serially sectioned (5 μm) and every 20th slide was stained (S100), scanned and aligned to create 3D maps. Nerve penetration into the detrusor muscle occurs with the highest frequency at the bladder neck and interureteric ridge. Nerves traveling parallel to the bladder lumen do so in the adventitia, beyond the outer border of detrusor. In females, the depth of these nerve bands is uniform at 0.7-1.7 cm below the luminal surface, the outer limits of which include the anterior vaginal wall. In the male, depth is more variable owing to detrusor hypertrophy with the minimum depth of nerves approximately 0.5 cm near the interureteric ridge and over 1 cm near the bladder neck. Myelinated neural pathways traversing in the human bladder in the region of the trigone have a discreet regional density. This 3D map of trigonal innervation may provide guidance to more precisely direct therapies for urinary incontinence or pelvic pain. Neurourol. Urodynam. 36:1015-1019, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Acute chest syndrome is associated with single nucleotide polymorphism-defined beta globin cluster haplotype in children with sickle cell anaemia.

    Science.gov (United States)

    Bean, Christopher J; Boulet, Sheree L; Yang, Genyan; Payne, Amanda B; Ghaji, Nafisa; Pyle, Meredith E; Hooper, W Craig; Bhatnagar, Pallav; Keefer, Jeffrey; Barron-Casella, Emily A; Casella, James F; Debaun, Michael R

    2013-10-01

    Genetic diversity at the human β-globin locus has been implicated as a modifier of sickle cell anaemia (SCA) severity. However, haplotypes defined by restriction fragment length polymorphism sites across the β-globin locus have not been consistently associated with clinical phenotypes. To define the genetic structure at the β-globin locus more thoroughly, we performed high-density single nucleotide polymorphism (SNP) mapping in 820 children who were homozygous for the sickle cell mutation (HbSS). Genotyping results revealed very high linkage disequilibrium across a large region spanning the locus control region and the HBB (β-globin gene) cluster. We identified three predominant haplotypes accounting for 96% of the β(S) -carrying chromosomes in this population that could be distinguished using a minimal set of common SNPs. Consistent with previous studies, fetal haemoglobin level was significantly associated with β(S) -haplotypes. After controlling for covariates, an association was detected between haplotype and rate of hospitalization for acute chest syndrome (ACS) (incidence rate ratio 0·51, 95% confidence interval 0·29-0·89) but not incidence rate of vaso-occlusive pain or presence of silent cerebral infarct (SCI). Our results suggest that these SNP-defined β(S) -haplotypes may be associated with ACS, but not pain or SCI in a study population of children with SCA.

  8. High resolution regional elasticity mapping of the human prostate.

    Science.gov (United States)

    Murayama, Yoshinobu; Omata, Sadao; Yajima, Toshikuni; Peng, Qiyu; Shishido, Keiichi; Peehl, Donna M; Constantinou, Christos E

    2007-01-01

    What is it that the clinician "feels" during a digital rectal examination? To answer this question, it is necessary to measure the elastic properties of the prostate and verify the stiffness values with histological examination. Therefore, we devised an Elasticity Mapping System to evaluate the elastic properties of various histopathological grades of prostate cancer in relation to benign prostatic hyperplasia (BPH) and normal tissue. The system consists of a micro tactile sensor, a three-axis (XYZ) with one (fine Z) micromanipulation stage, a stereoscope camera and a measurement chamber. Using this methodology we mapped the elasticity of human prostate cancer (CaP) and it was obviously observed that the node was significantly harder than surrounding normal tissues and had some textures.

  9. Ex vivo quantitative multiparametric MRI mapping of human meniscus degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Nebelung, Sven; Kuhl, Christiane; Truhn, Daniel [Aachen University Hospital, Department of Diagnostic and Interventional Radiology, Aachen (Germany); Tingart, Markus; Jahr, Holger [Aachen University Hospital, Department of Orthopaedics, Aachen (Germany); Pufe, Thomas [RWTH Aachen University, Institute of Anatomy and Cell Biology, Aachen (Germany)

    2016-12-15

    To evaluate the diagnostic performance of T1, T1ρ, T2, T2*, and UTE-T2* (ultrashort-echo time-enhanced T2*) mapping in the refined graduation of human meniscus degeneration with histology serving as standard-of-reference. This IRB-approved intra-individual comparative ex vivo study was performed on 24 lateral meniscus body samples obtained from 24 patients undergoing total knee replacement. Samples were assessed on a 3.0-T MRI scanner using inversion-recovery (T1), spin-lock multi-gradient-echo (T1ρ), multi-spin-echo (T2) and multi-gradient-echo (T2* and UTE-T2*) sequences to determine relaxation times of quantitative MRI (qMRI) parameters. Relaxation times were calculated on the respective maps, averaged to the entire meniscus and to its zones. Histologically, samples were analyzed on a four-point score according to Williams (0-III). QMRI results and Williams (sub)scores were correlated using Spearman's ρ, while Williams grade-dependent differences were assessed using Kruskal-Wallis and Dunn's tests. Sensitivities and specificities in the detection of intact (Williams grade [WG]-0) and severely degenerate meniscus (WG-II-III) were calculated. Except for T2*, significant increases in qMRI parameters with increasing Williams grades were observed. T1, T1ρ, T2, and UTE-T2* exhibited high sensitivity and variable specificity rates. Significant marked-to-strong correlations were observed for these parameters with each other, with histological WGs and the subscores tissue integrity and cellularity. QMRI mapping holds promise in the objective evaluation of human meniscus. Although sufficient discriminatory power of T1, T1ρ, T2, and UTE-T2* was only demonstrated for the histological extremes, these data may aid in the future MRI-based parameterization and quantification of human meniscus degeneration. (orig.)

  10. Mapping genetic influences on the corticospinal motor system in humans

    DEFF Research Database (Denmark)

    Cheeran, B J; Ritter, C; Rothwell, J C

    2009-01-01

    It is becoming increasingly clear that genetic variations account for a certain amount of variance in the acquisition and maintenance of different skills. Until now, several levels of genetic influences were examined, ranging from global heritability estimates down to the analysis...... of the contribution of single nucleotide polymorphisms (SNP) and variable number tandem repeats. In humans, the corticospinal motor system is essential to the acquisition of fine manual motor skills which require a finely tuned coordination of activity in distal forelimb muscles. Here we review recent brain mapping...

  11. A general approach for haplotype phasing across the full spectrum of relatedness.

    Directory of Open Access Journals (Sweden)

    Jared O'Connell

    2014-04-01

    Full Text Available Many existing cohorts contain a range of relatedness between genotyped individuals, either by design or by chance. Haplotype estimation in such cohorts is a central step in many downstream analyses. Using genotypes from six cohorts from isolated populations and two cohorts from non-isolated populations, we have investigated the performance of different phasing methods designed for nominally 'unrelated' individuals. We find that SHAPEIT2 produces much lower switch error rates in all cohorts compared to other methods, including those designed specifically for isolated populations. In particular, when large amounts of IBD sharing is present, SHAPEIT2 infers close to perfect haplotypes. Based on these results we have developed a general strategy for phasing cohorts with any level of implicit or explicit relatedness between individuals. First SHAPEIT2 is run ignoring all explicit family information. We then apply a novel HMM method (duoHMM to combine the SHAPEIT2 haplotypes with any family information to infer the inheritance pattern of each meiosis at all sites across each chromosome. This allows the correction of switch errors, detection of recombination events and genotyping errors. We show that the method detects numbers of recombination events that align very well with expectations based on genetic maps, and that it infers far fewer spurious recombination events than Merlin. The method can also detect genotyping errors and infer recombination events in otherwise uninformative families, such as trios and duos. The detected recombination events can be used in association scans for recombination phenotypes. The method provides a simple and unified approach to haplotype estimation, that will be of interest to researchers in the fields of human, animal and plant genetics.

  12. The UK Human Genome Mapping Project online computing service.

    Science.gov (United States)

    Rysavy, F R; Bishop, M J; Gibbs, G P; Williams, G W

    1992-04-01

    This paper presents an overview of computing and networking facilities developed by the Medical Research Council to provide online computing support to the Human Genome Mapping Project (HGMP) in the UK. The facility is connected to a number of other computing facilities in various centres of genetics and molecular biology research excellence, either directly via high-speed links or through national and international wide-area networks. The paper describes the design and implementation of the current system, a 'client/server' network of Sun, IBM, DEC and Apple servers, gateways and workstations. A short outline of online computing services currently delivered by this system to the UK human genetics research community is also provided. More information about the services and their availability could be obtained by a direct approach to the UK HGMP-RC.

  13. ParaHaplo 2.0: a program package for haplotype-estimation and haplotype-based whole-genome association study using parallel computing

    Directory of Open Access Journals (Sweden)

    Kamatani Naoyuki

    2010-06-01

    Full Text Available Abstract Background The use of haplotype-based association tests can improve the power of genome-wide association studies. Since the observed genotypes are unordered pairs of alleles, haplotype phase must be inferred. However, estimating haplotype phase is time consuming. When millions of single-nucleotide polymorphisms (SNPs are analyzed in genome-wide association study, faster methods for haplotype estimation are required. Methods We developed a program package for parallel computation of haplotype estimation. Our program package, ParaHaplo 2.0, is intended for use in workstation clusters using the Intel Message Passing Interface (MPI. We compared the performance of our algorithm to that of the regular permutation test on both Japanese in Tokyo, Japan and Han Chinese in Beijing, China of the HapMap dataset. Results Parallel version of ParaHaplo 2.0 can estimate haplotypes 100 times faster than a non-parallel version of the ParaHaplo. Conclusion ParaHaplo 2.0 is an invaluable tool for conducting haplotype-based genome-wide association studies (GWAS. The need for fast haplotype estimation using parallel computing will become increasingly important as the data sizes of such projects continue to increase. The executable binaries and program sources of ParaHaplo are available at the following address: http://en.sourceforge.jp/projects/parallelgwas/releases/

  14. Novel strategies to mine alcoholism-related haplotypes and genes by combining existing knowledge framework.

    Science.gov (United States)

    Zhang, RuiJie; Li, Xia; Jiang, YongShuai; Liu, GuiYou; Li, ChuanXing; Zhang, Fan; Xiao, Yun; Gong, BinSheng

    2009-02-01

    High-throughout single nucleotide polymorphism detection technology and the existing knowledge provide strong support for mining the disease-related haplotypes and genes. In this study, first, we apply four kinds of haplotype identification methods (Confidence Intervals, Four Gamete Tests, Solid Spine of LD and fusing method of haplotype block) into high-throughout SNP genotype data to identify blocks, then use cluster analysis to verify the effectiveness of the four methods, and select the alcoholism-related SNP haplotypes through risk analysis. Second, we establish a mapping from haplotypes to alcoholism-related genes. Third, we inquire NCBI SNP and gene databases to locate the blocks and identify the candidate genes. In the end, we make gene function annotation by KEGG, Biocarta, and GO database. We find 159 haplotype blocks, which relate to the alcoholism most possibly on chromosome 1 approximately 22, including 227 haplotypes, of which 102 SNP haplotypes may increase the risk of alcoholism. We get 121 alcoholism-related genes and verify their reliability by the functional annotation of biology. In a word, we not only can handle the SNP data easily, but also can locate the disease-related genes precisely by combining our novel strategies of mining alcoholism-related haplotypes and genes with existing knowledge framework.

  15. Novel strategies to mine alcoholism-related haplotypes and genes by combining existing knowledge framework

    Institute of Scientific and Technical Information of China (English)

    ZHANG RuiJie; LI Xia; JIANG YongShuai; LIU GuiYou; LI ChuanXing; ZHANG Fan; XIAO Yun; GONG BinSheng

    2009-01-01

    High-throughout single nucleotide polymorphism detection technology and the existing knowledge provide strong support for mining the disease-related haplotypes and genes. In this study, first, we apply four kinds of haplotype identification methods (Confidence Intervals, Four Gamete Testa, Solid Spine of LD and fusing method of haplotype block) into high-throughout SNP genotype data to identify blocks, then use cluster analysis to verify the effectiveness of the four methods, and select the alcoholism-related SNP haplotypes through risk analysis. Second, we establish a mapping from haplotypes to alcoholism-related genes. Third, we inquire NCBI SNP and gene databases to locate the blocks and identify the candidate genes. In the end, we make gene function annotation by KEGG, Biocarta, and GO database. We find 159 haplotype blocks, which relate to the alcoholism most possibly on chromosome 1-22, including 227 haplotypes, of which 102 SNP haplotypes may increase the risk of alcoholism. We get 121 alcoholism-related genes and verify their reliability by the functional annotation of biology. In a word, we not only can handle the SNP data easily, but also can locate the disease-related genes precisely by combining our novel strategies of mining alcoholism-related haplotypes and genes with existing knowledge framework.

  16. Novel strategies to mine alcoholism-related haplotypes and genes by combining existing knowledge framework

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    High-throughout single nucleotide polymorphism detection technology and the existing knowledge provide strong support for mining the disease-related haplotypes and genes. In this study, first, we apply four kinds of haplotype identification methods (Confidence Intervals, Four Gamete Tests, Solid Spine of LD and fusing method of haplotype block) into high-throughout SNP genotype data to identify blocks, then use cluster analysis to verify the effectiveness of the four methods, and select the alco- holism-related SNP haplotypes through risk analysis. Second, we establish a mapping from haplotypes to alcoholism-related genes. Third, we inquire NCBI SNP and gene databases to locate the blocks and identify the candidate genes. In the end, we make gene function annotation by KEGG, Biocarta, and GO database. We find 159 haplotype blocks, which relate to the alcoholism most possibly on chromosome 1~22, including 227 haplotypes, of which 102 SNP haplotypes may increase the risk of alcoholism. We get 121 alcoholism-related genes and verify their reliability by the functional annotation of biology. In a word, we not only can handle the SNP data easily, but also can locate the disease-related genes pre- cisely by combining our novel strategies of mining alcoholism-related haplotypes and genes with ex- isting knowledge framework.

  17. Functionality and opposite roles of two interleukin 4 haplotypes in immune cells

    Science.gov (United States)

    Anovazzi, G; Medeiros, M C; Pigossi, S C; Finoti, L S; Souza Moreira, T M; Mayer, M P A; Zanelli, C F; Valentini, S R; Rossa-Junior, C; Scarel-Caminaga, R M

    2017-01-01

    Cytokines expression can be influenced by polymorphisms in their respective coding genes. We associated the CTI/TTD haplotype (Hap-1) and TCI/CCI haplotype (Hap-2) in the IL4 gene formed by the −590, +33 and variable number of tandem repeat polymorphisms with the severity of chronic periodontitis in humans. The functionality of these IL4 haplotypes in the response of immune cells to phorbol 12-myristate 13-acetate (PMA) with Ionomycin and IL-1β (as inflammatory stimuli) was evaluated. Gene expression (quantitative real-time PCR), profile of secreted cytokines (multiplex) and phenotypic polarization of T cells (flow cytometry) were the outcomes assessed. Green fluorescent protein reporter plasmid constructs containing specific IL4 haplotype were transiently transfected into JM cells to assess the influence of the individual haplotypes on promoter activity. In response to inflammatory stimuli the immune cells from Hap-1 haplotype had increased expression of anti-inflammatory IL4; conversely, the Hap-2 haplotype showed higher levels of pro-inflammatory cytokines. The haplotype CTI proved to be the most important for the regulation of IL4 promoter, regardless of the nature of the inflammatory stimulation; whereas the polymorphism in the promoter region had the least functional effect. In conclusion, IL4 haplotypes studied are functional and trigger opposite immune responses: anti-inflammatory (Hap-1) and pro-inflammatory (Hap-2). In addition, we identified the CTI haplotype as the main responsible for the regulation of IL4 transcriptional activity. PMID:28053321

  18. Mapping of potential neurogenic niche in the human temporal lobe

    Directory of Open Access Journals (Sweden)

    Adriano Barreto Nogueira

    2014-10-01

    Full Text Available The subgranular zone (SGZ of the dentate gyrus and the subventricular zone (SVZ are known neurogenic niches in adult mammals. Nonetheless, the existence of neurogenic niches in adult humans is controversial. We hypothesized that mapping neurogenic niches in the human temporal lobe could clarify this issue. Neurogenic niches and neurogenesis were investigated in 28 temporal lobes via immunostaining for nestin and doublecortin (DCX, respectively. Nestin was observed in a continuous layer formed by the SVZ, the subpial zone of the medial temporal lobe and the SGZ, terminating in the subiculum. In the subiculum, remarkable DCX expression was observed through the principal efferent pathway of the hippocampus to the fimbria. A possible explanation for the results is that the SVZ, the subpial zone of the medial temporal lobe and the SGZ form a unit containing neural stem cells that differentiate into neurons in the subiculum. Curiously, the area previously identified as the human rostral migratory stream may in truth be the fornix, which contains axons that originate in the subiculum. This study suggests that neurogenesis may occur in an orchestrated manner in a broad area of the human temporal lobe.

  19. Genome sequence, comparative analysis and haplotype structure of the domestic dog.

    Science.gov (United States)

    Lindblad-Toh, Kerstin; Wade, Claire M; Mikkelsen, Tarjei S; Karlsson, Elinor K; Jaffe, David B; Kamal, Michael; Clamp, Michele; Chang, Jean L; Kulbokas, Edward J; Zody, Michael C; Mauceli, Evan; Xie, Xiaohui; Breen, Matthew; Wayne, Robert K; Ostrander, Elaine A; Ponting, Chris P; Galibert, Francis; Smith, Douglas R; DeJong, Pieter J; Kirkness, Ewen; Alvarez, Pablo; Biagi, Tara; Brockman, William; Butler, Jonathan; Chin, Chee-Wye; Cook, April; Cuff, James; Daly, Mark J; DeCaprio, David; Gnerre, Sante; Grabherr, Manfred; Kellis, Manolis; Kleber, Michael; Bardeleben, Carolyne; Goodstadt, Leo; Heger, Andreas; Hitte, Christophe; Kim, Lisa; Koepfli, Klaus-Peter; Parker, Heidi G; Pollinger, John P; Searle, Stephen M J; Sutter, Nathan B; Thomas, Rachael; Webber, Caleb; Baldwin, Jennifer; Abebe, Adal; Abouelleil, Amr; Aftuck, Lynne; Ait-Zahra, Mostafa; Aldredge, Tyler; Allen, Nicole; An, Peter; Anderson, Scott; Antoine, Claudel; Arachchi, Harindra; Aslam, Ali; Ayotte, Laura; Bachantsang, Pasang; Barry, Andrew; Bayul, Tashi; Benamara, Mostafa; Berlin, Aaron; Bessette, Daniel; Blitshteyn, Berta; Bloom, Toby; Blye, Jason; Boguslavskiy, Leonid; Bonnet, Claude; Boukhgalter, Boris; Brown, Adam; Cahill, Patrick; Calixte, Nadia; Camarata, Jody; Cheshatsang, Yama; Chu, Jeffrey; Citroen, Mieke; Collymore, Alville; Cooke, Patrick; Dawoe, Tenzin; Daza, Riza; Decktor, Karin; DeGray, Stuart; Dhargay, Norbu; Dooley, Kimberly; Dooley, Kathleen; Dorje, Passang; Dorjee, Kunsang; Dorris, Lester; Duffey, Noah; Dupes, Alan; Egbiremolen, Osebhajajeme; Elong, Richard; Falk, Jill; Farina, Abderrahim; Faro, Susan; Ferguson, Diallo; Ferreira, Patricia; Fisher, Sheila; FitzGerald, Mike; Foley, Karen; Foley, Chelsea; Franke, Alicia; Friedrich, Dennis; Gage, Diane; Garber, Manuel; Gearin, Gary; Giannoukos, Georgia; Goode, Tina; Goyette, Audra; Graham, Joseph; Grandbois, Edward; Gyaltsen, Kunsang; Hafez, Nabil; Hagopian, Daniel; Hagos, Birhane; Hall, Jennifer; Healy, Claire; Hegarty, Ryan; Honan, Tracey; Horn, Andrea; Houde, Nathan; Hughes, Leanne; Hunnicutt, Leigh; Husby, M; Jester, Benjamin; Jones, Charlien; Kamat, Asha; Kanga, Ben; Kells, Cristyn; Khazanovich, Dmitry; Kieu, Alix Chinh; Kisner, Peter; Kumar, Mayank; Lance, Krista; Landers, Thomas; Lara, Marcia; Lee, William; Leger, Jean-Pierre; Lennon, Niall; Leuper, Lisa; LeVine, Sarah; Liu, Jinlei; Liu, Xiaohong; Lokyitsang, Yeshi; Lokyitsang, Tashi; Lui, Annie; Macdonald, Jan; Major, John; Marabella, Richard; Maru, Kebede; Matthews, Charles; McDonough, Susan; Mehta, Teena; Meldrim, James; Melnikov, Alexandre; Meneus, Louis; Mihalev, Atanas; Mihova, Tanya; Miller, Karen; Mittelman, Rachel; Mlenga, Valentine; Mulrain, Leonidas; Munson, Glen; Navidi, Adam; Naylor, Jerome; Nguyen, Tuyen; Nguyen, Nga; Nguyen, Cindy; Nguyen, Thu; Nicol, Robert; Norbu, Nyima; Norbu, Choe; Novod, Nathaniel; Nyima, Tenchoe; Olandt, Peter; O'Neill, Barry; O'Neill, Keith; Osman, Sahal; Oyono, Lucien; Patti, Christopher; Perrin, Danielle; Phunkhang, Pema; Pierre, Fritz; Priest, Margaret; Rachupka, Anthony; Raghuraman, Sujaa; Rameau, Rayale; Ray, Verneda; Raymond, Christina; Rege, Filip; Rise, Cecil; Rogers, Julie; Rogov, Peter; Sahalie, Julie; Settipalli, Sampath; Sharpe, Theodore; Shea, Terrance; Sheehan, Mechele; Sherpa, Ngawang; Shi, Jianying; Shih, Diana; Sloan, Jessie; Smith, Cherylyn; Sparrow, Todd; Stalker, John; Stange-Thomann, Nicole; Stavropoulos, Sharon; Stone, Catherine; Stone, Sabrina; Sykes, Sean; Tchuinga, Pierre; Tenzing, Pema; Tesfaye, Senait; Thoulutsang, Dawa; Thoulutsang, Yama; Topham, Kerri; Topping, Ira; Tsamla, Tsamla; Vassiliev, Helen; Venkataraman, Vijay; Vo, Andy; Wangchuk, Tsering; Wangdi, Tsering; Weiand, Michael; Wilkinson, Jane; Wilson, Adam; Yadav, Shailendra; Yang, Shuli; Yang, Xiaoping; Young, Geneva; Yu, Qing; Zainoun, Joanne; Zembek, Lisa; Zimmer, Andrew; Lander, Eric S

    2005-12-08

    Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.

  20. Bringing transcranial mapping into shape: Sulcus-aligned mapping captures motor somatotopy in human primary motor hand area

    DEFF Research Database (Denmark)

    Raffin, Estelle; Pellegrino, Giovanni; Di Lazzaro, Vincenzo;

    2015-01-01

    of the central sulcus following the bending of the central sulcus (CURVED). CURVED mapping employed a fixed (CURVED-450 FIX) or flexible coil orientation producing always a current perpendicular to the sulcal wall (CURVED-900 FLEX). During relaxation, CURVED but not STRAIGHT mapping revealed distinct......Motor representations express some degree of somatotopy in human primary motor hand area (M1HAND), but within-M1HAND corticomotor somatotopy has been difficult to study with transcranial magnetic stimulation (TMS). Here we introduce a “linear” TMS mapping approach based on the individual shape...... was lowest for CURVED-900 FLEX. Together, the results show that within-M1HAND somatotopy can be readily probed with linear TMS mapping aligned to the sulcal shape. Sulcus-aligned linear mapping will benefit non-invasive studies of representational plasticity in human M1HAND....

  1. Approximation properties of haplotype tagging

    Directory of Open Access Journals (Sweden)

    Dreiseitl Stephan

    2006-01-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are locations at which the genomic sequences of population members differ. Since these differences are known to follow patterns, disease association studies are facilitated by identifying SNPs that allow the unique identification of such patterns. This process, known as haplotype tagging, is formulated as a combinatorial optimization problem and analyzed in terms of complexity and approximation properties. Results It is shown that the tagging problem is NP-hard but approximable within 1 + ln((n2 - n/2 for n haplotypes but not approximable within (1 - ε ln(n/2 for any ε > 0 unless NP ⊂ DTIME(nlog log n. A simple, very easily implementable algorithm that exhibits the above upper bound on solution quality is presented. This algorithm has running time O((2m - p + 1 ≤ O(m(n2 - n/2 where p ≤ min(n, m for n haplotypes of size m. As we show that the approximation bound is asymptotically tight, the algorithm presented is optimal with respect to this asymptotic bound. Conclusion The haplotype tagging problem is hard, but approachable with a fast, practical, and surprisingly simple algorithm that cannot be significantly improved upon on a single processor machine. Hence, significant improvement in computatational efforts expended can only be expected if the computational effort is distributed and done in parallel.

  2. A network of topographic numerosity maps in human association cortex.

    NARCIS (Netherlands)

    Harvey, Ben M.; Dumoulin, Serge O.

    2017-01-01

    Sensory and motor cortices each contain multiple topographic maps with the structure of sensory organs (such as the retina or cochlea) mapped onto the cortical surface. These sensory maps are hierarchically organized. For example, visual field maps contain neurons that represent increasingly large

  3. A network of topographic numerosity maps in human association cortex.

    NARCIS (Netherlands)

    Harvey, Ben M.; Dumoulin, Serge O.

    2017-01-01

    Sensory and motor cortices each contain multiple topographic maps with the structure of sensory organs (such as the retina or cochlea) mapped onto the cortical surface. These sensory maps are hierarchically organized. For example, visual field maps contain neurons that represent increasingly large p

  4. Visual field map clusters in human frontoparietal cortex.

    Science.gov (United States)

    Mackey, Wayne E; Winawer, Jonathan; Curtis, Clayton E

    2017-06-19

    The visual neurosciences have made enormous progress in recent decades, in part because of the ability to drive visual areas by their sensory inputs, allowing researchers to define visual areas reliably across individuals and across species. Similar strategies for parcellating higher-order cortex have proven elusive. Here, using a novel experimental task and nonlinear population receptive field modeling, we map and characterize the topographic organization of several regions in human frontoparietal cortex. We discover representations of both polar angle and eccentricity that are organized into clusters, similar to visual cortex, where multiple gradients of polar angle of the contralateral visual field share a confluent fovea. This is striking because neural activity in frontoparietal cortex is believed to reflect higher-order cognitive functions rather than external sensory processing. Perhaps the spatial topography in frontoparietal cortex parallels the retinotopic organization of sensory cortex to enable an efficient interface between perception and higher-order cognitive processes. Critically, these visual maps constitute well-defined anatomical units that future studies of frontoparietal cortex can reliably target.

  5. A map of recent positive selection in the human genome.

    Directory of Open Access Journals (Sweden)

    Benjamin F Voight

    2006-03-01

    Full Text Available The identification of signals of very recent positive selection provides information about the adaptation of modern humans to local conditions. We report here on a genome-wide scan for signals of very recent positive selection in favor of variants that have not yet reached fixation. We describe a new analytical method for scanning single nucleotide polymorphism (SNP data for signals of recent selection, and apply this to data from the International HapMap Project. In all three continental groups we find widespread signals of recent positive selection. Most signals are region-specific, though a significant excess are shared across groups. Contrary to some earlier low resolution studies that suggested a paucity of recent selection in sub-Saharan Africans, we find that by some measures our strongest signals of selection are from the Yoruba population. Finally, since these signals indicate the existence of genetic variants that have substantially different fitnesses, they must indicate loci that are the source of significant phenotypic variation. Though the relevant phenotypes are generally not known, such loci should be of particular interest in mapping studies of complex traits. For this purpose we have developed a set of SNPs that can be used to tag the strongest approximately 250 signals of recent selection in each population.

  6. Definition of gene content for nine common group B haplotypes of the Caucasoid population: KIR haplotypes contain between seven and eleven KIR genes.

    Science.gov (United States)

    Uhrberg, Markus; Parham, Peter; Wernet, Peter

    2002-07-01

    The segregation of killer cell immunoglobulin-like receptor ( KIR) genes was determined for a panel of 21 Caucasoid families: 23 different KIR gene patterns were found and could be assigned to combinations of 16 different haplotypes. Four loci were held in common by all haplotypes: KIR2DL4, KIR3DL2, the putative pseudogene KIR3DL3 and KIR2DL2/KIR2DL3, the latter likely being alleles of one gene. Group A haplotypes, which have a unique combination of seven KIR genes, were found at 80% frequency in the family panel, the polygenic group B haplotypes at 65% frequency. KIR gene segregation was fully determined for the nine group B haplotypes, which occurred at highest frequencies in both the family panel and a panel of unrelated individuals. The group B haplotypes carried between seven and 11 KIR genes and encoded inhibitory KIR for one, two, or all three major HLA class I epitopes. Analysis of human leucocyte antigen (HLA) class I genotypes revealed that most, but not all, individuals possess an inhibitory KIR for a self HLA class I epitope. The number of stimulatory KIR genes in group B haplotypes varied considerably between one and five. The data show that group B haplotypes possess a broad spectrum of KIR gene patterns, which is largely complementary to the KIR gene set of group A haplotypes. The results suggest that rapid diversification of group B haplotypes is the result of pathogen-mediated selection for KIR genotypes that have more than the set of KIR genes provided by the group A haplotype.

  7. The mapping of novel genes to human chromosome 19

    Energy Technology Data Exchange (ETDEWEB)

    Buenaventura, J.M. [Sarah Lawrence College, Bronxville, NY (United States)

    1994-12-01

    The principle goal of our laboratory is the discovery of new genes on human chromosome 19. One of the strategies to achieve this goal is through the use of cDNA clones known as {open_quotes}expressed sequence tags{close_quotes} (ESTs). ESTs, short segments of sequence from a cDNA clone that correspond to the mRNA, occur as unique regions in the genome and, therefore, can be used as markers for specific positions. In collaboration with researchers from Genethon in France, fifteen cDNA clones from a normalized human infant brain cDNA library were tested and determined to map to chromosome 19. A verification procedure is then followed to confirm assignment to chromosome 19. First, primers for each cDNA clone are developed and then amplified by polymerase chain reaction from genomic DNA. Next, a {sup 32}P-radiolabeled probe is made by polymerase chain reaction for each clone and then hybridized against filters containing an LLNL chromosome 19-specific cosmid library to find putative locations on the chromosome. The location is then verified by running a polymerase chain reactions from the positive cosmids. With the Browser database at LLNL, additional information about the positive cosmids can be found. Through use of the BLAST database at the National Library of Medicine, homologous sequences to the clones can be found. Among the fifteen cDNA clones received from Genethon, all have been amplified by polymerase chain reaction. Three have turned out as repetitive elements in the genome. Ten have been mapped to specific locations on chromosome 19. Putative locations have been found for the remaining two clones and thus verification testing will proceed.

  8. Inheritance of the 8.1 ancestral haplotype in recurrent pregnancy loss

    DEFF Research Database (Denmark)

    Kolte, Astrid M; Nielsen, Henriette S; Steffensen, Rudi;

    2015-01-01

    BACKGROUND AND OBJECTIVES: The 8.1 ancestral haplotype (AH) (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2) is a remarkably long and conserved haplotype in the human major histocompatibility complex. It has been associated with both beneficial and detrimental effects, consistent with antagonistic pleiotr...

  9. Complementarity of Binding Motifs is a General Property of HLA-A and HLA-B Molecules and Does Not Seem to Effect HLA Haplotype Composition

    OpenAIRE

    2013-01-01

    Different human leukocyte antigen (HLA) haplotypes (i.e., the specific combinations of HLA-A, -B, -DR alleles inherited together from one parent) are observed in different frequencies in human populations. Some haplotypes, like HLA-A1-B8, are very frequent, reaching up to 10% in the Caucasian population, while others are very rare. Numerous studies have identified associations between HLA haplotypes and diseases, and differences in haplotype frequencies can in part be explained by these assoc...

  10. Fine localization of the Nijmegen breakage syndrome gene to 8q21: Evidence for a common founder haplotype

    Energy Technology Data Exchange (ETDEWEB)

    Cerosaletti, K.M. [Univ. of Washington School of Medicine, Seattle, WA (United States); Lange, E.; Stringham, H.M. [Univ. of Michigan School of Public Health, Ann Arbor, MI (United States). Dept. of Biostatistics] [and others

    1998-07-01

    Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by microcephaly, a birdlike face, growth retardation, immunodeficiency, lack of secondary sex characteristics in females, and increased incidence of lymphoid cancers. NBS cells display a phenotype similar to that of cells from ataxia-telangiectasia patients, including chromosomal instability, radiation sensitivity, and aberrant cell-cycle-checkpoint control following exposure to ionizing radiation. A recent study reported genetic linkage of NBs to human chromosome 8q21, with strong linkage disequilibrium detected at marker D8S1811 in eastern European NBS families. The authors collected a geographically diverse group of NBS families and tested them for linkage, using an expanded panel of markers at 8q21. In this article, the authors report linkage of NBS to 8q21 in 6/7 of these families, with a maximum LOD score of 3.58. Significant linkage disequilibrium was detected for 8/13 markers tested in the 8q21 region, including D8S1811. In order to further localize the gene for NBS, the authors generated a radiation-hybrid map of markers at 8q21 and constructed haplotypes based on this map. Examination of disease haplotypes segregating in 11 NBS pedigrees revealed recombination events that place the NBS gene between D8S1757 and D8S270. A common founder haplotype was present on 15/18 disease chromosomes from 9/11 NBS families. Inferred (ancestral) recombination events involving this common haplotype suggest that NBS can be localized further, to an interval flanked by markers D8S273 and D8S88.

  11. The application of next-generation sequencing in the autozygosity mapping of human recessive diseases.

    Science.gov (United States)

    Alkuraya, Fowzan S

    2013-11-01

    Autozygosity, or the inheritance of two copies of an ancestral allele, has the potential to not only reveal phenotypes caused by biallelic mutations in autosomal recessive genes, but to also facilitate the mapping of such mutations by flagging the surrounding haplotypes as tractable runs of homozygosity (ROH), a process known as autozygosity mapping. Since SNPs replaced microsatellites as markers for the purpose of genomewide identification of ROH, autozygosity mapping of Mendelian genes has witnessed a significant acceleration. Historically, successful mapping traditionally required favorable family structure that permits the identification of an autozygous interval that is amenable to candidate gene selection and confirmation by Sanger sequencing. This requirement presented a major bottleneck that hindered the utilization of simplex cases and many multiplex families with autosomal recessive phenotypes. However, the advent of next-generation sequencing that enables massively parallel sequencing of DNA has largely bypassed this bottleneck and thus ushered in an era of unprecedented pace of Mendelian disease gene discovery. The ability to identify a single causal mutation among a massive number of variants that are uncovered by next-generation sequencing can be challenging, but applying autozygosity as a filter can greatly enhance the enrichment process and its throughput. This review will discuss the power of combining the best of both techniques in the mapping of recessive disease genes and offer some tips to troubleshoot potential limitations.

  12. Rivers in the Anthropocene: Mapping Human Water Security

    Science.gov (United States)

    Vorosmarty, C. J.; Green, P.

    2014-12-01

    Fresh water underpins countless benefits to society and is pivotal to the success of the food and energy sectors, industry and commerce, and the expanding urban domain. It provides essential cultural, recreational, and aesthetic values and also plays a critical role in the maintenance of ecosystem services and biodiversity. Recent analyses of water systems across the planet, summarized using high resolution, geospatial indicator maps of rivers, demonstrate that a wide array of stressors combine to produce a pattern of worldwide threat to much of the freshwater resource base that sustains human water supply and aquatic biodiversity. A pervasive, globally-significant pattern of management is evident in the contemporary setting, through which impairment accumulates as a function of wealth, but is then remedied by costly, after-the-fact technological investments. This strategy of treating symptoms while leaving unabated the underlying causes is practiced widely across rich countries, but it strands poor nations and much of the world's aquatic lifeforms at high levels of vulnerability. The seeds of such an approach to water management are hardly new and are evident throughout human history. This talk will explore the implications of these global realities and will focus on the role of 21st century engineering as in both contributing to the growing water crisis and stimulating innovation for more effective stewardship of our water resource systems. It will also present a first global synthesis of the geography of freshwater provisioning source areas, evaluating jointly the quantity and condition of freshwater produced from these areas, and the downstream populations served by these resources. A geospatial indicator is derived, the freshwater provisioning index for humans (FPIh), which constitutes an objective measure of the state of the resource base and its role in supporting human water security.

  13. Transcriptional defect of an inherited NKX2-5 haplotype comprising a SNP, a nonsynonymous and a synonymous mutation, associated with human congenital heart disease.

    Directory of Open Access Journals (Sweden)

    Stella Marie Reamon-Buettner

    Full Text Available Germline mutations in cardiac-specific transcription factor genes have been associated with congenital heart disease (CHD and the homeodomain transcription factor NKX2-5 is an important member of this group. Indeed, more than 40 heterozygous NKX2-5 germline mutations have been observed in individuals with CHD, and these are spread along the coding region, with many shown to impact protein function. In pursuit of understanding causes of CHD, we analyzed n = 49 cardiac biopsies from 28 patients and identified by direct sequencing two nonsynonymous NKX2-5 alterations affecting alanine 119, namely c.356C>A (p.A119E and c.355G>T, (p.A119S, in patients with AVSD and HLHS, respectively. In functional assays, a significant reduction in transcriptional activities could be determined for the NKX2-5 variants. Importantly, in one family the mother, besides p.A119E, carried a synonymous mutant allele in the homeodomain (c.543G>A, p.Q181, and a synonymous dbSNP (c.63A>G, p.E21 in the transactivation domain of the protein, that were transmitted to the CHD daughter. The presence of these variants in-cis with the p.A119E mutation led to a further reduction in transcriptional activities. Such difference in activity may be in part related to reduced protein expression for the double variant c.356C>A and c.543G>A. We propose changes in mRNA stability and folding, due to a silent mutation and a dbSNP in the NKX2-5 coding region to contribute to the functional defect. Although the clinical significance of the NKX2-5 haplotype identified in the CHD patients remains to be ascertained, we provide evidence of an interaction of a dbSNP, with synonymous and nonsynonymous mutations to negatively impact NKX2-5 transcriptional activity.

  14. Optimal Mapping of Torus Self-Organizing Map for Human Forearm Motions Discrimination on the Basis of Myoelectric Signals

    Science.gov (United States)

    Kiso, Atsushi; Seki, Hirokazu

    This paper describes an optimal mapping of the torus self-organizing map for a human forearm motion discrimination on the basis of the myoelectric signals. This study uses the torus self-organizing map (Torus-SOM) for the motion discrimination. The normal SOM identify input data into the same feature group by using the all units of map. Then there is a possibility of the misrecognition motion around the boundary lines of the motion groups. Therefore, this study proposes the mapping method of SOM that the learning units of the same motion concentrate on one local range and the learning unit groups of each motion separates enough. As a result, the variance in the same motion group becomes small and the variance between each motion groups becomes big. Some experiments on the myoelectric hand simulator show the effectiveness of the proposed motion discrimination method.

  15. Concept Maps: Practice Applications in Adult Education and Human Resource Development

    Science.gov (United States)

    Daley, Barbara J.

    2010-01-01

    Concept maps can be used as both a cognitive and constructivist learning strategy in teaching and learning in adult education and human resource development. The maps can be used to understand course readings, analyze case studies, develop reflective thinking and enhance research skills. The creation of concept maps can also be supported by the…

  16. The putative oncogene Pim-1 in the mouse: its linkage and variation among t haplotypes.

    Science.gov (United States)

    Nadeau, J H; Phillips, S J

    1987-11-01

    Pim-1, a putative oncogene involved in T-cell lymphomagenesis, was mapped between the pseudo-alpha globin gene Hba-4ps and the alpha-crystallin gene Crya-1 on mouse chromosome 17 and therefore within the t complex. Pim-1 restriction fragment variants were identified among t haplotypes. Analysis of restriction fragment sizes obtained with 12 endonucleases demonstrated that the Pim-1 genes in some t haplotypes were indistinguishable from the sizes for the Pim-1b allele in BALB/c inbred mice. There are now three genes, Pim-1, Crya-1 and H-2 I-E, that vary among independently derived t haplotypes and that have indistinguishable alleles in t haplotypes and inbred strains. These genes are closely linked within the distal inversion of the t complex. Because it is unlikely that these variants arose independently in t haplotypes and their wild-type homologues, we propose that an exchange of chromosomal segments, probably through double crossingover, was responsible for indistinguishable Pim-1 genes shared by certain t haplotypes and their wild-type homologues. There was, however, no apparent association between variant alleles of these three genes among t haplotypes as would be expected if a single exchange introduced these alleles into t haplotypes. If these variant alleles can be shown to be identical to the wild-type allele, then lack of association suggests that multiple exchanges have occurred during the evolution of the t complex.

  17. Haplotype and missing data inference in nuclear families.

    Science.gov (United States)

    Lin, Shin; Chakravarti, Aravinda; Cutler, David J

    2004-08-01

    Determining linkage phase from population samples with statistical methods is accurate only within regions of high linkage disequilibrium (LD). Yet, affected individuals in a genetic mapping study, including those involving cases and controls, may share sequences identical-by-descent stretching on the order of 10s to 100s of kilobases, quite possibly over regions of low LD in the population. At the same time, inferring phase from nuclear families may be hampered by missing family members, missing genotypes, and the noninformativity of certain genotype patterns. In this study, we reformulate our previous haplotype reconstruction algorithm, and its associated computer program, to phase parents with information derived from population samples as well as from their offspring. In applications of our algorithm to 100-kb stretches, simulated in accordance to a Wright-Fisher model with typical levels of LD in humans, we find that phase reconstruction for 160 trios with 10% missing data is highly accurate (>90%) over the entire length. Furthermore, our algorithm can estimate allelic status for missing data at high accuracy (>95%). Finally, the input capacity of the program is vast, easily handling thousands of segregating sites in > or = 1000 chromosomes.

  18. Single-molecule optical genome mapping of a human HapMap and a colorectal cancer cell line.

    Science.gov (United States)

    Teo, Audrey S M; Verzotto, Davide; Yao, Fei; Nagarajan, Niranjan; Hillmer, Axel M

    2015-01-01

    Next-generation sequencing (NGS) technologies have changed our understanding of the variability of the human genome. However, the identification of genome structural variations based on NGS approaches with read lengths of 35-300 bases remains a challenge. Single-molecule optical mapping technologies allow the analysis of DNA molecules of up to 2 Mb and as such are suitable for the identification of large-scale genome structural variations, and for de novo genome assemblies when combined with short-read NGS data. Here we present optical mapping data for two human genomes: the HapMap cell line GM12878 and the colorectal cancer cell line HCT116. High molecular weight DNA was obtained by embedding GM12878 and HCT116 cells, respectively, in agarose plugs, followed by DNA extraction under mild conditions. Genomic DNA was digested with KpnI and 310,000 and 296,000 DNA molecules (≥ 150 kb and 10 restriction fragments), respectively, were analyzed per cell line using the Argus optical mapping system. Maps were aligned to the human reference by OPTIMA, a new glocal alignment method. Genome coverage of 6.8× and 5.7× was obtained, respectively; 2.9× and 1.7× more than the coverage obtained with previously available software. Optical mapping allows the resolution of large-scale structural variations of the genome, and the scaffold extension of NGS-based de novo assemblies. OPTIMA is an efficient new alignment method; our optical mapping data provide a resource for genome structure analyses of the human HapMap reference cell line GM12878, and the colorectal cancer cell line HCT116.

  19. Haplotype studies in Wilson disease

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, G.R.; Bull, P.C.; Roberts, E.A.; Cox, D.W.; Walshe, J.M. (Univ. of Toronto (Canada))

    1994-01-01

    In 51 families with Wilson disease, the authors have studied DNA haplotypes of dinucleotide repeat polymorphisms (CA repeats) in the 13q14.3 region, to examine these markers for association with the Wilson disease gene (WND). In addition to a marker (D13S133) described elsewhere, the authors have developed three new highly polymorphic markers (D13S314, D13S315, and D13S316) close to the WND locus. The authors have examined the distribution of marker alleles at the loci studied and have found that D13S314, D13S133, and D13S316 each show nonrandom distribution on chromosomes carrying the WND mutation. The authors have studied haplotypes of these three markers and have found that there are highly significant differences between WND and normal haplotypes in northern European families. These findings have important implications for mutation detection and molecular diagnosis in families with Wilson disease. 25 refs., 2 figs., 5 tabs.

  20. 北京汉族和约鲁巴人群ROR2基因单核苷酸多态性的比较研究%Comparison of minor allele frequencies and haplotype frequencies for single nucleotide polymorphisms in ROR2 gene using HapMap data for Chinese Hans in Beijing and Yoruban in Ibadan in Nigeria

    Institute of Scientific and Technical Information of China (English)

    王红; 赵凯平

    2011-01-01

    Objective:To provide basis for single nucleotide polymorphisms (SNPs) determination and analysis for R0R2 genes related etiologic studies in Chinese Hans in Beijing (CHB) and Yoruban in Iba-dan in Nigeria ( YRI) populations. Methods: SNPs in R0R2 gene were analyzed and compared for minor allele frequencies (MAFs) , haplotype frequencies, linkage disequilibrium patterns, and tag SNPs using CHB and YRI data from HapMap by Haploview 4. 2 program. SNPs were screened for eligibility using quality control criteria of genotyping call rate >80% , Hardy-Weinberg equilibrium test P >0.01, gender difference P>0. 05 and MAF >0. 01. Tag SNPs were determined under the criteria for r2≥0. 8 and logarithm of the odds radio ≥3 in pairwise eligible SNPs and compared between the CHB and YRI samples. Common Tag SNPs for CHB and YRI were reported by Haploview program directly or identified a-mong SNPs which were higly related to Haploview program directly reported tag SNPs by SPSS 13. 0. Results: Among the 404 and 403 SNPs genotyped in ROR2 genes in the CHB and YRI samples released by HapMap project, there were five SNPs located at exon 6 or 9 where changes of alleles for rs 1076112 and rs 10820900 caused missense mutation. Among the 394 SNPs genotyped in both the populations, a total number of 101 (25. 6% ) SNPs were monotonic among which 66 (65. 3% ) SNPs were common in both CHB and YRI. The rs 1135150 and rs2230577 which were monotonic in YRI and eligible in CHB located at exon 9. Nine ungenotyped SNPs in CHB were all eligible in YRI, and 6 out of 10 ungenotyped SNPs in YRI were eligible in CHB. The proportion of common SNPs (214) were 81.4% and 73. 3% in eligible CHB (263) and YRI (292) SNPs where 177 (82. 7% ) had the same minor alleles and 30 SNPs also had MAF difference ratios<20% that represented 11.4% and 10.3% of the total number of eligible SNPs in CHB and YRI respectively. Among the 18 and 26 haplotype blocks formed in 214 common eligible SNPs, two independent

  1. Expression cartography of human tissues using self organizing maps

    Science.gov (United States)

    2011-01-01

    Background Parallel high-throughput microarray and sequencing experiments produce vast quantities of multidimensional data which must be arranged and analyzed in a concerted way. One approach to addressing this challenge is the machine learning technique known as self organizing maps (SOMs). SOMs enable a parallel sample- and gene-centered view of genomic data combined with strong visualization and second-level analysis capabilities. The paper aims at bridging the gap between the potency of SOM-machine learning to reduce dimension of high-dimensional data on one hand and practical applications with special emphasis on gene expression analysis on the other hand. Results The method was applied to generate a SOM characterizing the whole genome expression profiles of 67 healthy human tissues selected from ten tissue categories (adipose, endocrine, homeostasis, digestion, exocrine, epithelium, sexual reproduction, muscle, immune system and nervous tissues). SOM mapping reduces the dimension of expression data from ten of thousands of genes to a few thousand metagenes, each representing a minicluster of co-regulated single genes. Tissue-specific and common properties shared between groups of tissues emerge as a handful of localized spots in the tissue maps collecting groups of co-regulated and co-expressed metagenes. The functional context of the spots was discovered using overrepresentation analysis with respect to pre-defined gene sets of known functional impact. We found that tissue related spots typically contain enriched populations of genes related to specific molecular processes in the respective tissue. Analysis techniques normally used at the gene-level such as two-way hierarchical clustering are better represented and provide better signal-to-noise ratios if applied to the metagenes. Metagene-based clustering analyses aggregate the tissues broadly into three clusters containing nervous, immune system and the remaining tissues. Conclusions The SOM technique

  2. Expression cartography of human tissues using self organizing maps

    Directory of Open Access Journals (Sweden)

    Löffler Markus

    2011-07-01

    Full Text Available Abstract Background Parallel high-throughput microarray and sequencing experiments produce vast quantities of multidimensional data which must be arranged and analyzed in a concerted way. One approach to addressing this challenge is the machine learning technique known as self organizing maps (SOMs. SOMs enable a parallel sample- and gene-centered view of genomic data combined with strong visualization and second-level analysis capabilities. The paper aims at bridging the gap between the potency of SOM-machine learning to reduce dimension of high-dimensional data on one hand and practical applications with special emphasis on gene expression analysis on the other hand. Results The method was applied to generate a SOM characterizing the whole genome expression profiles of 67 healthy human tissues selected from ten tissue categories (adipose, endocrine, homeostasis, digestion, exocrine, epithelium, sexual reproduction, muscle, immune system and nervous tissues. SOM mapping reduces the dimension of expression data from ten of thousands of genes to a few thousand metagenes, each representing a minicluster of co-regulated single genes. Tissue-specific and common properties shared between groups of tissues emerge as a handful of localized spots in the tissue maps collecting groups of co-regulated and co-expressed metagenes. The functional context of the spots was discovered using overrepresentation analysis with respect to pre-defined gene sets of known functional impact. We found that tissue related spots typically contain enriched populations of genes related to specific molecular processes in the respective tissue. Analysis techniques normally used at the gene-level such as two-way hierarchical clustering are better represented and provide better signal-to-noise ratios if applied to the metagenes. Metagene-based clustering analyses aggregate the tissues broadly into three clusters containing nervous, immune system and the remaining tissues

  3. Expression cartography of human tissues using self organizing maps.

    Science.gov (United States)

    Wirth, Henry; Löffler, Markus; von Bergen, Martin; Binder, Hans

    2011-07-27

    Parallel high-throughput microarray and sequencing experiments produce vast quantities of multidimensional data which must be arranged and analyzed in a concerted way. One approach to addressing this challenge is the machine learning technique known as self organizing maps (SOMs). SOMs enable a parallel sample- and gene-centered view of genomic data combined with strong visualization and second-level analysis capabilities. The paper aims at bridging the gap between the potency of SOM-machine learning to reduce dimension of high-dimensional data on one hand and practical applications with special emphasis on gene expression analysis on the other hand. The method was applied to generate a SOM characterizing the whole genome expression profiles of 67 healthy human tissues selected from ten tissue categories (adipose, endocrine, homeostasis, digestion, exocrine, epithelium, sexual reproduction, muscle, immune system and nervous tissues). SOM mapping reduces the dimension of expression data from ten of thousands of genes to a few thousand metagenes, each representing a minicluster of co-regulated single genes. Tissue-specific and common properties shared between groups of tissues emerge as a handful of localized spots in the tissue maps collecting groups of co-regulated and co-expressed metagenes. The functional context of the spots was discovered using overrepresentation analysis with respect to pre-defined gene sets of known functional impact. We found that tissue related spots typically contain enriched populations of genes related to specific molecular processes in the respective tissue. Analysis techniques normally used at the gene-level such as two-way hierarchical clustering are better represented and provide better signal-to-noise ratios if applied to the metagenes. Metagene-based clustering analyses aggregate the tissues broadly into three clusters containing nervous, immune system and the remaining tissues. The SOM technique provides a more intuitive and

  4. Comparative mapping of the actin-binding protein 280 genes in human and mouse

    Energy Technology Data Exchange (ETDEWEB)

    Gariboldi, M.; Canzian, F.; Manenti, G.; De Gregorio, L. (Istituto Nazionale Tumori, Milan (Italy)); Maestrini, E.; Rivella, S. (Istituto di Genetica Biochimica ed Evoluzionistica, Pavia (Italy)); Chatterjee, A.; Herman, G.E. (Universita di Bari (Italy)); Archidiacono, N.; Antonacci, R. (Institute for Molecular Genetics, Houston, TX (United States)) (and others)

    1994-05-15

    Two genes encode actin-binding protein 280 isoforms. ABP-280 or filamin (FLN1) is present in the cytoskeleton of many cell types, whereas expression of FLN2 is limited to skeletal muscle and heart. FLN1 maps to human chromosome Xq28, and, by physical mapping in YAC clones, the authors have mapped the homologous murine locus (Fln1) to mouse chromosome X, in a region of syntenic homology with human chromosome X. They mapped FLN2 to human chromosome 7q32-q35 by analysis of somatic cell hybrids containing portions of chromosome 7, and, by using a mapping panel from an interspecific murine cross, they mapped the corresponding murine locus (Fln2) to murine chromosome 6 in a region homologous to human chromosome 7. 21 refs., 1 fig., 1 tab.

  5. Comparative mapping of the actin-binding protein 280 genes in human and mouse.

    Science.gov (United States)

    Gariboldi, M; Maestrini, E; Canzian, F; Manenti, G; De Gregorio, L; Rivella, S; Chatterjee, A; Herman, G E; Archidiacono, N; Antonacci, R

    1994-05-15

    Two genes encode actin-binding protein 280 isoforms. ABP-280 or filamin (FLN1) is present in the cytoskeleton of many cell types, whereas expression of FLN2 is limited to skeletal muscle and heart. FLN1 maps to human chromosome Xq28, and, by physical mapping in YAC clones, we have mapped the homologous murine locus (Fln1) to mouse chromosome X, in a region of syntenic homology with human chromosome X. We mapped FLN2 to human chromosome 7q32-q35 by analysis of somatic cell hybrids containing portions of chromosome 7, and, by using a mapping panel from an interspecific murine cross, we mapped the corresponding murine locus (Fln2) to murine chromosome 6 in a region homologous to human chromosome 7.

  6. cDNA/STS map of human genome. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-11-01

    The human gene identification and transcript mapping project has generated over 3,000 3`ESTs derived from human brain cDNA libraries and mapped over 300 of these. The data have been submitted to the appropriate gene sequence and mapping databases. Clones are either available from Greg Lennon at Lawrence Livermore or from ATCC. A summary of this work is provided and a News and Views article from the same issue is included which highlights this paper. The strategy developed by this laboratory is now being used by an international consortium to generate the first comprehensive human gene (transcript) map over the next year or two.

  7. A novel approach to rapid determination of betaS-globin haplotypes: sequencing of the Agamma-IVS-II region.

    Science.gov (United States)

    Vinson, Amy E; Walker, Aisha; Elam, Dedrey; Glendenning, Michele; Kutlar, Ferdane; Clair, Betsy; Harbin, Jeanette; Kutlar, Abdullah

    2004-01-01

    beta-Globin gene cluster haplotypes were originally determined by restriction endonuclease mapping with Southern blots of polymorphic sites around the gene cluster. Over the years, haplotyping has been found to be useful, not only in population genetics but also in predicting the severity of hemoglobinopathies such as sickle cell disease. The sickle mutation occurs on five distinct haplotypes. The hitherto used methods are cumbersome and time-consuming, making haplotype determination a tedious procedure. We report our experience with a novel, rapid approach to haplotyping based on sequence polymorphisms in the Agamma-IVS-II region. We provide an algorithm that allows rapid assignment of the four African haplotypes carrying the sickle mutation.

  8. Mapping the governance of human resources for health in Serbia.

    Science.gov (United States)

    Santric Milicevic, Milena; Vasic, Milena; Edwards, Matt

    2015-12-01

    This article maps the current governance of human resources for health (HRH) in relation to universal health coverage in Serbia since the health sector reforms in 2003. The study adapts the Global Health Workforce Alliance/World Health Organization four-dimensional framework of HRH in the context of governance for universal health coverage. A set of proxies was established for the availability, accessibility, acceptability and quality of HRH. Analysis of official HRH documentation from relevant institutions and reports were used to construct a governance profile of HRH for Serbia from the introduction of the reform in 2003 up to 2013. The results show that all Serbian districts (except Sremski) surpass the availability threshold of 59.4 skilled midwives, nurses and physicians per 10,000 inhabitants. District accessibility of health workforce greatly differed from the national average with variances from +26% to -34%. Analysis of national averages and patient load of general practitioners showed variances among districts by ± 21%, whilst hospital discharges per 100 inhabitants deviated between +52% and -45%. Pre-service and in-service education of health workforce is regulated and accredited. However, through its efforts to respond to population health needs Serbia lacks a single coordinating entity to take overall responsibility for effective and coordinated HRH planning, management and development within the broader landscape of health strategy development. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. HapMap and mapping genes for cardiovascular disease.

    Science.gov (United States)

    Musunuru, Kiran; Kathiresan, Sekar

    2008-10-01

    A key goal of biomedical science is to understand why individuals differ in their susceptibility to disease. Family history is among the established risk factors for most forms of cardiovascular disease, in part because inherited DNA sequence variants play a causal role in disease susceptibility. Consequently, the search for these variants has intensified over the past decade. One class of DNA sequence variants takes the form of single nucleotide changes(single nucleotide polymorphisms, or SNPs), usually with two variants or alleles for each SNP. SNPs are scattered throughout the 23 pairs of chromosomes of the human genome, and roughly 11 million common polymorphisms (ie,those > 1% frequency) are estimated to exist. A combination of SNP alleles along a chromosome is termed a haplotype. The International Haplotype Map Project was designed to create a public genome-wide database of common SNPs and, consequently, enable systematic studies of most common SNPs for their potential role in human disease. We review the following: (1) the concept of linkage disequilibrium orallelic association, (2) the HapMap project, and (3) several examples of the utility of HapMap data in genetic mapping for cardiovascular disease phenotypes.

  10. DNA sequence and haplotype variation in two candidate genes for dilated cardiomyopathy in the turkey Meleagris gallopavo.

    Science.gov (United States)

    Lin, Kuan-chin; Xu, Jun; Kamara, Davida; Geng, Tuoyu; Gyenai, Kwaku; Reed, Kent M; Smith, Edward J

    2007-05-01

    Determining variation in genes is fundamental to understanding their function in the disease state. Cardiac troponin T (cTnT) and phospholamban (PLN) genes have been implicated in dilated cardiomyopathy (DCM) in human and model species. To investigate the role of these 2 candidate genes in DCM in the turkey Meleagris gallopavo, understanding sequence variants and map position distribution is necessary. To this end, a total of 1854 and 1771 bp of cTnT and PLN gene sequences, respectively, were scanned for single nucleotide polymorphisms (SNPs) in a randomly bred population. A total of 15 SNPs was identified in the cTnT and PLN genomic sequences. Nine haplotypes, 5 in cTnT and 4 in PLN, were identified. Observed heterozygosities (0.02-0.39) in the turkey population were low for both genes. Within each gene, 1 SNP corresponding to a restriction enzyme site was identified and used to develop a PCR-restriction fragment length polymorphism (RFLP) genotyping assay. The PLN gene was genetically mapped to turkey chromosome 2, equivalent to Gallus gallus chromosome 3, and cTnT mapped to a turkey microchromosome. Although limited because of the relatively small sample size of 55 birds, the data from this SNP analysis of PLN and cTnT provide a foundation from which to evaluate the function of cTnT and PLN in the turkey. Information about the distribution of the SNPs and haplotypes will facilitate future association and linkage studies.

  11. A 1463 gene cattle-human comparative map with anchor points defined by human genome sequence coordinates.

    Science.gov (United States)

    Everts-van der Wind, Annelie; Kata, Srinivas R; Band, Mark R; Rebeiz, Mark; Larkin, Denis M; Everts, Robin E; Green, Cheryl A; Liu, Lei; Natarajan, Shreedhar; Goldammer, Tom; Lee, Jun Heon; McKay, Stephanie; Womack, James E; Lewin, Harris A

    2004-07-01

    A second-generation 5000 rad radiation hybrid (RH) map of the cattle genome was constructed primarily using cattle ESTs that were targeted to gaps in the existing cattle-human comparative map, as well as to sparsely populated map intervals. A total of 870 targeted markers were added, bringing the number of markers mapped on the RH(5000) panel to 1913. Of these, 1463 have significant BLASTN hits (E genes) were identified between the cattle and human genomes, of which 31 are newly discovered and 34 were extended singletons on the first-generation map. The new map represents an improvement of 20% genome-wide comparative coverage compared with the first-generation map. Analysis of gene content within human genome regions where there are gaps in the comparative map revealed gaps with both significantly greater and significantly lower gene content. The new, more detailed cattle-human comparative map provides an improved resource for the analysis of mammalian chromosome evolution, the identification of candidate genes for economically important traits, and for proper alignment of sequence contigs on cattle chromosomes. Copyright 2004 Cold Spring Harbor Laboratory Press ISSN

  12. Progress towards construction of a total restriction fragment map of a human chromosome.

    NARCIS (Netherlands)

    H. Vissing; F.G. Grosveld (Frank); E. Solomon; G. Moore; N. Lench; N. Shennan; R. Williamson

    1987-01-01

    textabstractWe present an approach to the construction of an overlapping restriction fragment map of a single human chromosome. A genomic cosmid library genome was constructed from a mouse-human hybrid cell line containing chromosome 17 as its only human genetic component. Cosmids containing human i

  13. Whole-genome molecular haplotyping of single cells

    OpenAIRE

    Fan, H. Christina; Wang, Jianbin; Potanina, Anastasia; Quake, Stephen R

    2010-01-01

    Conventional experimental methods of studying the human genome are limited by the inability to independently study the combination of alleles, or haplotype, on each of the homologous copies of the chromosomes. We developed a microfluidic device capable of separating and amplifying homologous copies of each chromosome from a single human metaphase cell. Single-nucleotide polymorphism (SNP) array analysis of amplified DNA enabled us to achieve completely deterministic, whole-genome, personal ha...

  14. Haplotypes in the lipoprotein lipase gene influence fasting insulin and discovery of a new risk haplotype.

    Science.gov (United States)

    Goodarzi, Mark O; Taylor, Kent D; Guo, Xiuqing; Hokanson, John E; Haffner, Steven M; Cui, Jinrui; Chen, Yii-Der I; Wagenknecht, Lynne E; Bergman, Richard N; Rotter, Jerome I

    2007-01-01

    Prior studies of Mexican Americans described association of lipoprotein lipase (LPL) gene haplotypes with insulin sensitivity/resistance and atherosclerosis. The most common haplotype (haplotype 1) was protective, whereas the fourth most common haplotype (haplotype 4) conferred risk for insulin resistance and atherosclerosis. In this study of Hispanics in the Insulin Resistance Atherosclerosis Study Family Study, we sought to replicate LPL haplotype association with insulin sensitivity/resistance. LPL haplotypes based on 12 single nucleotide polymorphisms were analyzed for association with indexes of insulin sensitivity and other metabolic and adiposity measures. This study was conducted in the general community of San Antonio, Texas, and San Luis Valley, Colorado. Participants in this study were 978 members of 86 Hispanic families. LPL haplogenotype, metabolic phenotypes, and adiposity were measured in this study. The haplotype structure was identical with that observed in prior studies. Among 978 phenotyped subjects, haplotype 1 was associated with decreased fasting insulin (P = 0.01), and haplotype 4 was associated with increased fasting insulin (P = 0.02) and increased visceral fat mass (P = 0.002). Insulin sensitivity, derived from iv glucose tolerance testing, tended (P > 0.1) to be higher with haplotype 1 (S(I) = 1.72) and lower with haplotype 4 (S(I)=1.38). Haplotype 2 was associated with increases in fasting insulin, triglycerides (TGs), TG to high-density lipoprotein-cholesterol ratio, and apolipoprotein B (P = 0.01-0.04). This study independently replicates our prior results of LPL haplotypes 1 and 4 as associated with measures of insulin sensitivity and resistance, respectively. Haplotype 4 may confer insulin resistance by increasing visceral fat. Haplotype 2 was identified as a new risk haplotype, suggesting the complex nature of LPL's effect on features of the insulin resistance syndrome.

  15. Dengue fever virus and Japanese encephalitis virus synthetic peptides, with motifs to fit HLA class I haplotypes prevalent in human populations in endemic regions, can be used for application to skin Langerhans cells to prime antiviral CD8+ cytotoxic T cells (CTLs)--a novel approach to the protection of humans.

    Science.gov (United States)

    Becker, Y

    1994-09-01

    Flaviviruses were reported to induce CD8+ cytotoxic T cells in infected individuals, indicating that nonapeptides, proteolytic cleavage products of the viral precursor protein, enter the endoplasmic reticulum in infected cells and interact with HLA class I molecules. The assembled HLA class I molecules are transported to the plasma membrane and prime CD8+ T cells. Current knowledge of the interaction of viral peptides with HLA molecules is reviewed. Based on this review, an idea is presented to use synthetic flavivirus peptides with an amino acid motif to fit with the HLA class I peptide binding group of HLA haplotypes prevalent in a given population in an endemic area. These synthetic viral peptides may be introduced into the human skin using a lotion containing the peptides ("Peplotion") together with substances capable of enhancing the penetration of these peptides into the skin to reach Langerhans cells. The peptide-treated Langerhans cells, professional antigen-presenting cells, may bind the synthetic viral peptides by their HLA class I peptide-binding grooves. Antigens carrying Langerhans cells are able to migrate and induce the cellular immune response in the lymph nodes. This approach to the priming of antiviral CD8+ cytotoxic T cells may provide cellular immune protection from flavivirus infection without inducing the humoral immune response, which can lead to the shock syndrome in Dengue fever patients. To be able to develop anti-Dengue virus synthetic peptides for populations with different HLA class I haplotypes, it is necessary to develop computational studies to design HLA class I Dengue virus synthetic peptides with motifs to fit the HLA haplotypes of the population living in an endemic region for Dengue fever. Experiments to study Dengue virus and Japanese encephalitis peptides vaccines and their effectiveness in protection against Dengue fever and Japanese encephalitis are needed. The development of human antiviral vaccines for application of viral

  16. The CEPH consortium linkage map of human chromosome 13

    Energy Technology Data Exchange (ETDEWEB)

    Bowcock, A.M.; Barnes, R.I. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States); Gerken, S.C.; Leppert, M. [Univ. of Utah School of Medicine, Salt Lake City, UT (United States); Shiang, R. [Univ. of Iowa, Iowa City, IA (United States); Jabs, E.W.; Warren, A.C.; Antonarakis, S. [Johns Hopkins School of Medicine, Baltimore, MD (United States); Retief, A.E. [Univ. of Stellenbosch, Tygerberg (South Africa); Vergnaud, G. [Centre d`Etudes du Bouchet, Vert le Petit (France)] [and others

    1993-05-01

    The CEPH consortium map of chromosome 13 is presented. This map contains 59 loci defined by genotypes generated from CEPH family DNAs with 94 different probe and restriction enzyme combinations contributed by 9 laboratories. A total of 25 loci have been placed on the map with likelihood support of at least 1000:1. The map extends from loci in the centromeric region of chromosome 13 to the terminal band of the long arm. Multipoint linkage analyses provided estimates that the male, female, and sex-averaged maps extend for 158, 203, and 178cM respectively. The largest interval is 24 cM and is between D13Z1 (alphaRI) and ATP1AL1. The mean genetic distance between the 25 uniquely placed loci is 7 cM. 76 refs., 3 figs., 5 tabs.

  17. Practical interpretation of CYP2D6 haplotypes: Comparison and integration of automated and expert calling.

    Science.gov (United States)

    Ruaño, Gualberto; Kocherla, Mohan; Graydon, James S; Holford, Theodore R; Makowski, Gregory S; Goethe, John W

    2016-05-01

    We describe a population genetic approach to compare samples interpreted with expert calling (EC) versus automated calling (AC) for CYP2D6 haplotyping. The analysis represents 4812 haplotype calls based on signal data generated by the Luminex xMap analyzers from 2406 patients referred to a high-complexity molecular diagnostics laboratory for CYP450 testing. DNA was extracted from buccal swabs. We compared the results of expert calls (EC) and automated calls (AC) with regard to haplotype number and frequency. The ratio of EC to AC was 1:3. Haplotype frequencies from EC and AC samples were convergent across haplotypes, and their distribution was not statistically different between the groups. Most duplications required EC, as only expansions with homozygous or hemizygous haplotypes could be automatedly called. High-complexity laboratories can offer equivalent interpretation to automated calling for non-expanded CYP2D6 loci, and superior interpretation for duplications. We have validated scientific expert calling specified by scoring rules as standard operating procedure integrated with an automated calling algorithm. The integration of EC with AC is a practical strategy for CYP2D6 clinical haplotyping.

  18. Analysis of Swine Leukocyte Antigen Haplotypes in Yucatan Miniature Pigs Used as Biomedical Model Animal.

    Science.gov (United States)

    Choi, Nu-Ri; Seo, Dong-Won; Choi, Ki-Myung; Ko, Na-Young; Kim, Ji-Ho; Kim, Hyun-Il; Jung, Woo-Young; Lee, Jun-Heon

    2016-03-01

    The porcine major histocompatibility complex (MHC) is called swine leukocyte antigen (SLA), which controls immune responses and transplantation reactions. The SLA is mapped on pig chromosome 7 (SSC7) near the centromere. In this study, 3 class I (SLA-1, SLA-3, and SLA-2) and 3 class II (DRB1, DQB1, and DQA) genes were used for investigation of SLA haplotypes in Yucatan miniature pigs in Korea. This pig breed is a well-known model organism for biomedical research worldwide. The current study indicated that Korean Yucatan pig population had 3 Class I haplotypes (Lr-4.0, Lr-6.0, and Lr-25.0) and 3 class II haplotypes (Lr-0.5, Lr-0.7, and Lr-0.25). The combinations of SLA class I and II haplotype together, 2 homozygous (Lr-4.5/4.5 and Lr-6.7/6.7) and 3 heterozygous (Lr-4.5/6.7, Lr-4.5/25.25, and Lr-6.7/25.25) haplotypes were identified, including previously unidentified new heterozygous haplotypes (Lr-4.5/4.7). In addition, a new SLA allele typing method using Agilent 2100 bioanalyzer was developed that permitted more rapid identification of SLA haplotypes. These results will facilitate the breeding of SLA homozygous Yucatan pigs and will expedite the possible use of these pigs for the biomedical research, especially xenotransplantation research.

  19. Evaluation of logistic Bayesian LASSO for identifying association with rare haplotypes.

    Science.gov (United States)

    Biswas, Swati; Papachristou, Charalampos

    2014-01-01

    It has been hypothesized that rare variants may hold the key to unraveling the genetic transmission mechanism of many common complex traits. Currently, there is a dearth of statistical methods that are powerful enough to detect association with rare haplotypes. One of the recently proposed methods is logistic Bayesian LASSO for case-control data. By penalizing the regression coefficients through appropriate priors, logistic Bayesian LASSO weeds out the unassociated haplotypes, making it possible for the associated rare haplotypes to be detected with higher powers. We used the Genetic Analysis Workshop 18 simulated data to evaluate the behavior of logistic Bayesian LASSO in terms of its power and type I error under a complex disease model. We obtained knowledge of the simulation model, including the locations of the functional variants, and we chose to focus on two genomic regions in the MAP4 gene on chromosome 3. The sample size was 142 individuals and there were 200 replicates. Despite the small sample size, logistic Bayesian LASSO showed high power to detect two haplotypes containing functional variants in these regions while maintaining low type I errors. At the same time, a commonly used approach for haplotype association implemented in the software hapassoc failed to converge because of the presence of rare haplotypes. Thus, we conclude that logistic Bayesian LASSO can play an important role in the search for rare haplotypes.

  20. A haplotype of human angiotensinogen gene containing −217A increases blood pressure in transgenic mice compared with −217G

    OpenAIRE

    Jain, Sudhir; Vinukonda, Govindaiah; Fiering, Steven N; Kumar, Ashok

    2008-01-01

    The human angiotensinogen (hAGT) gene contains an A/G polymorphism at −217, and frequency of −217A allele is increased in African-American hypertensive patients. The hAGT gene has seven polymorphic sites in the 1.2-kb region of its promoter, and variant −217A almost always occurs with −532T, −793A, and −1074T, whereas variant −217G almost always occurs with −532C, −793G, and −1074G. Since allele −6A is the predominant allele in African-Americans, the AGT gene can be subdivided into two main h...

  1. Global haplotype partitioning for maximal associated SNP pairs

    Directory of Open Access Journals (Sweden)

    Pezeshk Hamid

    2009-08-01

    Full Text Available Abstract Background Global partitioning based on pairwise associations of SNPs has not previously been used to define haplotype blocks within genomes. Here, we define an association index based on LD between SNP pairs. We use the Fisher's exact test to assess the statistical significance of the LD estimator. By this test, each SNP pair is characterized as associated, independent, or not-statistically-significant. We set limits on the maximum acceptable proportion of independent pairs within all blocks and search for the partitioning with maximal proportion of associated SNP pairs. Essentially, this model is reduced to a constrained optimization problem, the solution of which is obtained by iterating a dynamic programming algorithm. Results In comparison with other methods, our algorithm reports blocks of larger average size. Nevertheless, the haplotype diversity within the blocks is captured by a small number of tagSNPs. Resampling HapMap haplotypes under a block-based model of recombination showed that our algorithm is robust in reproducing the same partitioning for recombinant samples. Our algorithm performed better than previously reported models in a case-control association study aimed at mapping a single locus trait, based on simulation results that were evaluated by a block-based statistical test. Compared to methods of haplotype block partitioning, we performed best on detection of recombination hotspots. Conclusion Our proposed method divides chromosomes into the regions within which allelic associations of SNP pairs are maximized. This approach presents a native design for dimension reduction in genome-wide association studies. Our results show that the pairwise allelic association of SNPs can describe various features of genomic variation, in particular recombination hotspots.

  2. Comparing human and automatic thesaurus mapping approaches in the agricultural domain

    CERN Document Server

    Lauser, Boris; Caracciolo, Caterina; Keizer, Johannes; van Hage, Willem Robert; Mayr, Philipp

    2008-01-01

    Knowledge organization systems (KOS), like thesauri and other controlled vocabularies, are used to provide subject access to information systems across the web. Due to the heterogeneity of these systems, mapping between vocabularies becomes crucial for retrieving relevant information. However, mapping thesauri is a laborious task, and thus big efforts are being made to automate the mapping process. This paper examines two mapping approaches involving the agricultural thesaurus AGROVOC, one machine-created and one human created. We are addressing the basic question "What are the pros and cons of human and automatic mapping and how can they complement each other?" By pointing out the difficulties in specific cases or groups of cases and grouping the sample into simple and difficult types of mappings, we show the limitations of current automatic methods and come up with some basic recommendations on what approach to use when.

  3. Spatial humanities: mapping Edinburgh in the first age of Enlightenment

    OpenAIRE

    Pittock, Murray; Lamont, Craig Ronald

    2016-01-01

    Describes the first phase of a digital project mapping social and cultural relationships in early 18th century Edinburgh, Scotland, part of a larger AHRC grant-funded study Allan Ramsay and Edinburgh in the First Age of the Enlightenment; explores interrelations between urban history, digital mapping, and emerging interest in the field of memory studies; and suggests links between the heterogeneous and cosmopolitan nature of housing in early 18th century Edinburgh and the Scottish Enlightenme...

  4. Mitogen-activated protein kinase kinase 4 (MAP2K4 promotes human prostate cancer metastasis.

    Directory of Open Access Journals (Sweden)

    Janet M Pavese

    Full Text Available Prostate cancer (PCa is the second leading cause of cancer death in the US. Death from PCa primarily results from metastasis. Mitogen-activated protein kinase kinase 4 (MAP2K4 is overexpressed in invasive PCa lesions in humans, and can be inhibited by small molecule therapeutics that demonstrate favorable activity in phase II studies. However, MAP2K4's role in regulating metastatic behavior is controversial and unknown. To investigate, we engineered human PCa cell lines which overexpress either wild type or constitutive active MAP2K4. Orthotopic implantation into mice demonstrated MAP2K4 increases formation of distant metastasis. Constitutive active MAP2K4, though not wild type, increases tumor size and circulating tumor cells in the blood and bone marrow. Complementary in vitro studies establish stable MAP2K4 overexpression promotes cell invasion, but does not affect cell growth or migration. MAP2K4 overexpression increases the expression of heat shock protein 27 (HSP27 protein and protease production, with the largest effect upon matrix metalloproteinase 2 (MMP-2, both in vitro and in mouse tumor samples. Further, MAP2K4-mediated increases in cell invasion are dependent upon heat shock protein 27 (HSP27 and MMP-2, but not upon MAP2K4's immediate downstream targets, p38 MAPK or JNK. We demonstrate that MAP2K4 increases human PCa metastasis, and prolonged over expression induces long term changes in cell signaling pathways leading to independence from p38 MAPK and JNK. These findings provide a mechanistic explanation for human studies linking increases in HSP27 and MMP-2 to progression to metastatic disease. MAP2K4 is validated as an important therapeutic target for inhibiting human PCa metastasis.

  5. Effect of donor CTLA-4 alleles and haplotypes on graft-versus-host disease occurrence in Tunisian patients receiving a human leukocyte antigen-identical sibling hematopoietic stem cell transplant.

    Science.gov (United States)

    Sellami, Mohamed Hichem; Bani, Meriem; Torjemane, Lamia; Kaabi, Houda; Ladeb, Saloua; Ben Othmane, Tarek; Hmida, Slama

    2011-02-01

    The CTLA-4 genetic variation, such as single nucleotide polymorphisms (SNPs) may be critical and can affect the functional activity of cells that initiate the graft-versus-host disease (GVHD) effects. The aim of this study is to examine the effect of donor CTLA-4 alleles and haplotypes for the -318C>T and the 49A>G polymorphisms on the occurrence of GVHD in Tunisians recipients of HSCs. A total of 112 patients and their 112 respective sibling donors of HSCs were enrolled in this study. All patients had either grades 0-I or grades II-IV acute GVHD, or chronic GVHD. The SNPs genotyping assay was performed using sets of sequence specific primers (SSP-PCR). The single marker association analysis showed that the 49G allele, in a genetic recessive model, may be a potential risk factor only for the chronic GVHD (p = 0.032, odds ratio [OR] = 2.58, 95% confidence interval = 1.05-6.32). The haplotypes analyses showed that the CTLA-4 -318C49G nucleotide combination is significantly associated with the incidence of chronic GVHD (p = 0.043, χ² = 3.27). Donor CTLA-4 -318C49G haplotype may be a significant risk factor for developing chronic GVHD after allo-stem cell transplantation. We suppose that donor T cells expressing this haplotype in a homozygous state have higher proliferation than those expressing other haplotypes, especially after recognition of the recipient's minor histocompatibility antigens.

  6. Estimating haplotype effects for survival data

    DEFF Research Database (Denmark)

    Scheike, Thomas; Martinussen, Torben; Silver, J

    2010-01-01

    Genetic association studies often investigate the effect of haplotypes on an outcome of interest. Haplotypes are not observed directly, and this complicates the inclusion of such effects in survival models. We describe a new estimating equations approach for Cox's regression model to assess haplo...

  7. Abnormal visual field maps in human cortex : A mini-review and a case report

    NARCIS (Netherlands)

    Haak, Koen V.; Langers, Dave R. M.; Renken, Remco; van Dijk, Pim; Borgstein, Johannes; Cornelissen, Frans W.

    2014-01-01

    Human visual cortex contains maps of the visual field. Much research has been dedicated to answering whether and when these visual field maps change if critical components of the visual circuitry are damaged. Here, we first provide a focused mini-review of the functional magnetic resonance imaging (

  8. An integrated physical map covering 25 cM of human chromosome 8

    Energy Technology Data Exchange (ETDEWEB)

    Chen, W.; Hou, J.; Wagner, M.J.; Wells, D.E. [Univ. of Houston, TX (United States)

    1996-02-15

    This article reports on an integrated physical map of human chromosome 8 using STS content analysis of somatic cell hybrids and YAC contigs. Such mapping efforts will help to localize genes linked to hereditary diseases. 17 refs., 1 fig., 1 tab.

  9. Mapping visual cortex in monkeys and humans using surface-based atlases

    Science.gov (United States)

    Van Essen, D. C.; Lewis, J. W.; Drury, H. A.; Hadjikhani, N.; Tootell, R. B.; Bakircioglu, M.; Miller, M. I.

    2001-01-01

    We have used surface-based atlases of the cerebral cortex to analyze the functional organization of visual cortex in humans and macaque monkeys. The macaque atlas contains multiple partitioning schemes for visual cortex, including a probabilistic atlas of visual areas derived from a recent architectonic study, plus summary schemes that reflect a combination of physiological and anatomical evidence. The human atlas includes a probabilistic map of eight topographically organized visual areas recently mapped using functional MRI. To facilitate comparisons between species, we used surface-based warping to bring functional and geographic landmarks on the macaque map into register with corresponding landmarks on the human map. The results suggest that extrastriate visual cortex outside the known topographically organized areas is dramatically expanded in human compared to macaque cortex, particularly in the parietal lobe.

  10. A high-resolution radiation hybrid map of the human genome draft sequence.

    Science.gov (United States)

    Olivier, M; Aggarwal, A; Allen, J; Almendras, A A; Bajorek, E S; Beasley, E M; Brady, S D; Bushard, J M; Bustos, V I; Chu, A; Chung, T R; De Witte, A; Denys, M E; Dominguez, R; Fang, N Y; Foster, B D; Freudenberg, R W; Hadley, D; Hamilton, L R; Jeffrey, T J; Kelly, L; Lazzeroni, L; Levy, M R; Lewis, S C; Liu, X; Lopez, F J; Louie, B; Marquis, J P; Martinez, R A; Matsuura, M K; Misherghi, N S; Norton, J A; Olshen, A; Perkins, S M; Perou, A J; Piercy, C; Piercy, M; Qin, F; Reif, T; Sheppard, K; Shokoohi, V; Smick, G A; Sun, W L; Stewart, E A; Fernando, J; Tejeda; Tran, N M; Trejo, T; Vo, N T; Yan, S C; Zierten, D L; Zhao, S; Sachidanandam, R; Trask, B J; Myers, R M; Cox, D R

    2001-02-16

    We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.

  11. Architectonic Mapping of the Human Brain beyond Brodmann.

    Science.gov (United States)

    Amunts, Katrin; Zilles, Karl

    2015-12-16

    Brodmann has pioneered structural brain mapping. He considered functional and pathological criteria for defining cortical areas in addition to cytoarchitecture. Starting from this idea of structural-functional relationships at the level of cortical areas, we will argue that the cortical architecture is more heterogeneous than Brodmann's map suggests. A triple-scale concept is proposed that includes repetitive modular-like structures and micro- and meso-maps. Criteria for defining a cortical area will be discussed, considering novel preparations, imaging and optical methods, 2D and 3D quantitative architectonics, as well as high-performance computing including analyses of big data. These new approaches contribute to an understanding of the brain on multiple levels and challenge the traditional, mosaic-like segregation of the cerebral cortex. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. MAGELLAN: a cognitive map-based model of human wayfinding.

    Science.gov (United States)

    Manning, Jeremy R; Lew, Timothy F; Li, Ningcheng; Sekuler, Robert; Kahana, Michael J

    2014-06-01

    In an unfamiliar environment, searching for and navigating to a target requires that spatial information be acquired, stored, processed, and retrieved. In a study encompassing all of these processes, participants acted as taxicab drivers who learned to pick up and deliver passengers in a series of small virtual towns. We used data from these experiments to refine and validate MAGELLAN, a cognitive map-based model of spatial learning and wayfinding. MAGELLAN accounts for the shapes of participants' spatial learning curves, which measure their experience-based improvement in navigational efficiency in unfamiliar environments. The model also predicts the ease (or difficulty) with which different environments are learned and, within a given environment, which landmarks will be easy (or difficult) to localize from memory. Using just 2 free parameters, MAGELLAN provides a useful account of how participants' cognitive maps evolve over time with experience, and how participants use the information stored in their cognitive maps to navigate and explore efficiently.

  13. Optimal design method to minimize users' thinking mapping load in human-machine interactions.

    Science.gov (United States)

    Huang, Yanqun; Li, Xu; Zhang, Jie

    2015-01-01

    The discrepancy between human cognition and machine requirements/behaviors usually results in serious mental thinking mapping loads or even disasters in product operating. It is important to help people avoid human-machine interaction confusions and difficulties in today's mental work mastered society. Improving the usability of a product and minimizing user's thinking mapping and interpreting load in human-machine interactions. An optimal human-machine interface design method is introduced, which is based on the purpose of minimizing the mental load in thinking mapping process between users' intentions and affordance of product interface states. By analyzing the users' thinking mapping problem, an operating action model is constructed. According to human natural instincts and acquired knowledge, an expected ideal design with minimized thinking loads is uniquely determined at first. Then, creative alternatives, in terms of the way human obtains operational information, are provided as digital interface states datasets. In the last, using the cluster analysis method, an optimum solution is picked out from alternatives, by calculating the distances between two datasets. Considering multiple factors to minimize users' thinking mapping loads, a solution nearest to the ideal value is found in the human-car interaction design case. The clustering results show its effectiveness in finding an optimum solution to the mental load minimizing problems in human-machine interaction design.

  14. Direct determination of MUC5B promoter haplotypes based on the method of single-strand conformation polymorphism and their statistical estimation.

    Science.gov (United States)

    Kamio, Koichiro; Matsushita, Ikumi; Tanaka, Goh; Ohashi, Jun; Hijikata, Minako; Nakata, Koh; Tokunaga, Katsushi; Azuma, Arata; Kudoh, Shoji; Keicho, Naoto

    2004-09-01

    Haplotype-based human genome research is important in identifying disease susceptibility genes efficiently. Although haplotype reconstruction by statistical methods is widely used, direct haplotype determination by molecular techniques has also been developed as a complementary method for statistical estimation. In this study, we demonstrate a molecular haplotyping method making use of single-strand conformation polymorphism (SSCP) gels. We identified 10 common SNPs and a dinucleotide insertion/deletion polymorphism within 2-kb region upstream of the transcription initiation site of MUC5B and determined haplotype structure, dividing the region into two DNA fragments. Real haplotypes were determined unambiguously by our SSCP-based analysis with fragments longer than 1 kb. Haplotypes reconstructed from diploid genotypes in the same region by the statistical methods including EM algorithm were also evaluated. Direct comparison between statistical estimation and direct determination of haplotypes revealed that major haplotypes containing multiple marker sites showing strong LD are estimated in great accuracy but that a variety of haplotypes reflecting weak LD are not reconstructed precisely enough. Our data can be helpful in implementing molecular haplotyping or statistical estimation, since usage of these methods may be determined depending on the haplotype structures.

  15. FISH-mapped CEPH YACs spanning 0 to 46 cM on human chromosome 6

    Energy Technology Data Exchange (ETDEWEB)

    Bray-Ward, P.; Bowlus, C.; Choi, J. [Yale Univ. School of Medicine, New Haven, CT (United States)] [and others

    1996-08-15

    Seventy-six CEPH YACs were mapped by fluorescence in situ hybridization (FISH) to human metaphase chromosomes. These clones have been ordered from pter to 46 cM by combining the results of FISH with sequence-tagged site content mapping using data from the public databases. This created a minimal tiling path containing at least 37 Mb of human genomic DNA from 0 to 46 cM on chromosome 6 that contains up to four gaps not greater than 200 kb. These data provide an integration of the FLpter physical map values with cytogenetic band localization and markers on the genetic and radiation hybrid maps. We also assessed YAC chimerism and placed three additional Whitehead contigs within the integrated map. 27 refs., 1 fig., 1 tab.

  16. Multisite haplotype on cattle chromosome 3 is associated with quantitative trait locus effects on lactation traits.

    Science.gov (United States)

    Cohen-Zinder, Miri; Donthu, Ravikiran; Larkin, Denis M; Kumar, Charu Gupta; Rodriguez-Zas, Sandra L; Andropolis, Kalista E; Oliveira, Rosane; Lewin, Harris A

    2011-11-07

    The goal of this study was to identify candidate genes and DNA polymorphisms for quantitative trait loci (QTL) affecting milk yield (MY), fat yield (FY), and protein yield (PY) previously mapped to bovine chromosome 3 (BTA3). To accomplish this, 373 half-siblings sired by three bulls previously shown to be segregating for lactation trait QTL, and 263 additional sires in the U.S. Dairy Bull DNA Repository (DBDR) were genotyped for 2,500 SNPs within a 16.3 Mbp QTL critical region on BTA3. Targeted resequencing of ∼1.8 Mbp within the QTL critical region of one of the QTL heterozygous sires identified additional polymorphisms useful for association studies. Twenty-three single nucleotide polymorphisms (SNPs) within a fine-mapped region were associated with effects on breeding values for MY, FY, or PY in DBDR sires, of which five SNPs were in strong linkage disequilibrium in the population. This multisite haplotype included SNPs located within exons or promoters of four tightly linked genes: RAP1A, ADORA3, OVGP1, and C3H1orf88. An SNP within RAP1A showed strong evidence of a recent selective sweep based on integrated haplotype score and was also associated with breeding value for PY. Because of its known function in alveolar lumen formation in the mammary gland, RAP1A is thus a strong candidate gene for QTL effects on lactation traits. Our results provide a detailed assessment of a QTL region that will be a useful guide for complex traits analysis in humans and other noninbred species.

  17. Bringing transcranial mapping into shape: Sulcus-aligned mapping captures motor somatotopy in human primary motor hand area.

    Science.gov (United States)

    Raffin, Estelle; Pellegrino, Giovanni; Di Lazzaro, Vincenzo; Thielscher, Axel; Siebner, Hartwig Roman

    2015-10-15

    Motor representations express some degree of somatotopy in human primary motor hand area (M1HAND), but within-M1HAND corticomotor somatotopy has been difficult to study with transcranial magnetic stimulation (TMS). Here we introduce a "linear" TMS mapping approach based on the individual shape of the central sulcus to obtain mediolateral corticomotor excitability profiles of the abductor digiti minimi (ADM) and first dorsal interosseus (FDI) muscles. In thirteen young volunteers, we used stereotactic neuronavigation to stimulate the right M1HAND with a small eight-shaped coil at 120% of FDI resting motor threshold. We pseudorandomly stimulated six targets located on a straight mediolateral line corresponding to the overall orientation of the central sulcus with a fixed coil orientation of 45° to the mid-sagittal line (STRAIGHT-450FIX) or seven targets in the posterior part of the crown of the central sulcus following the bending of the central sulcus (CURVED). CURVED mapping employed a fixed (CURVED-450FIX) or flexible coil orientation producing always a current perpendicular to the sulcal wall (CURVED-900FLEX). During relaxation, CURVED but not STRAIGHT mapping revealed distinct corticomotor excitability peaks in M1HAND with the excitability maximum of ADM located medially to the FDI maximum. This mediolateral somatotopy was still present during tonic contraction of the ADM or FDI. During ADM contraction, cross-correlation between the spatial excitability profiles of ADM and FDI was lowest for CURVED-900FLEX. Together, the results show that within-M1HAND somatotopy can be readily probed with linear TMS mapping aligned to the sulcal shape. Sulcus-aligned linear mapping will benefit non-invasive studies of representational plasticity in human M1HAND.

  18. Complementarity of Binding Motifs is a General Property of HLA-A and HLA-B Molecules and Does Not Seem to Effect HLA Haplotype Composition.

    Science.gov (United States)

    Rao, Xiangyu; De Boer, Rob J; van Baarle, Debbie; Maiers, Martin; Kesmir, Can

    2013-01-01

    Different human leukocyte antigen (HLA) haplotypes (i.e., the specific combinations of HLA-A, -B, -DR alleles inherited together from one parent) are observed in different frequencies in human populations. Some haplotypes, like HLA-A1-B8, are very frequent, reaching up to 10% in the Caucasian population, while others are very rare. Numerous studies have identified associations between HLA haplotypes and diseases, and differences in haplotype frequencies can in part be explained by these associations: the stronger the association with a severe (autoimmune) disease, the lower the expected HLA haplotype frequency. The peptide repertoires of the HLA molecules composing a haplotype can also influence the frequency of a haplotype. For example, it would seem advantageous to have HLA molecules with non-overlapping binding specificities within a haplotype, as individuals expressing such an haplotype would present a diverse set of peptides from viruses and pathogenic bacteria on the cell surface. To test this hypothesis, we collect the proteome data from a set of common viruses, and estimate the total ligand repertoire of HLA class I haplotypes (HLA-A-B) using in silico predictions. We compare the size of these repertoires to the HLA haplotype frequencies reported in the National Marrow Donor Program (NMDP). We find that in most HLA-A and HLA-B pairs have fairly distinct binding motifs, and that the observed haplotypes do not contain HLA-A and -B molecules with more distinct binding motifs than random HLA-A and HLA-B pairs. In addition, the population frequency of a haplotype is not correlated to the distinctness of its HLA-A and HLA-B peptide binding motifs. These results suggest that there is a not a strong selection pressure on the haplotype level favoring haplotypes having HLA molecules with distinct binding motifs, which would result the largest possible presented peptide repertoires in the context of infectious diseases.

  19. Correlation of physical and genetic maps of human chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, G.R.

    1990-01-01

    This project is now progressing strongly. Thirteen somatic cell hybrids containing rearranged {number sign}16 chromosomes have been constructed, bringing the total number of hybrids constructed by the group to 27 which divides chromosome 16 into 29 regions. 170 probes have been mapped into these regions. Although this is the second progress report for this contract it essentially contains all the work carried out since the first progress report covered a period of less than three months during which little had been done other than setting up. The project has been progressing very well and has led to numerous collaborations with other groups involved in mapping this chromosome or studying genes on it. 7 refs., 1 fig., 2 tabs.

  20. Topographic hub maps of the human structural neocortical network.

    Directory of Open Access Journals (Sweden)

    Emil H J Nijhuis

    Full Text Available Hubs within the neocortical structural network determined by graph theoretical analysis play a crucial role in brain function. We mapped neocortical hubs topographically, using a sample population of 63 young adults. Subjects were imaged with high resolution structural and diffusion weighted magnetic resonance imaging techniques. Multiple network configurations were then constructed per subject, using random parcellations to define the nodes and using fibre tractography to determine the connectivity between the nodes. The networks were analysed with graph theoretical measures. Our results give reference maps of hub distribution measured with betweenness centrality and node degree. The loci of the hubs correspond with key areas from known overlapping cognitive networks. Several hubs were asymmetrically organized across hemispheres. Furthermore, females have hubs with higher betweenness centrality and males have hubs with higher node degree. Female networks have higher small-world indices.

  1. Putting the Human Hair Follicle Cycle on the Map.

    Science.gov (United States)

    Panteleyev, Andrey A

    2016-01-01

    A detailed characterization of the normal (in situ) human hair follicle cycle, supplemented with expressional data on specific hair follicle markers, has been awaited by basic hair researchers and dermatologists. Combining this hair cycle guide, together with a thorough analysis of the human-on-mouse hair xenograft model, provides solid ground for examining human hair cycle biology and pathology and for hair cycle-related pharmacological testing.

  2. A human motion model based on maps for navigation systems

    Directory of Open Access Journals (Sweden)

    Kaiser Susanna

    2011-01-01

    Full Text Available Abstract Foot-mounted indoor positioning systems work remarkably well when using additionally the knowledge of floor-plans in the localization algorithm. Walls and other structures naturally restrict the motion of pedestrians. No pedestrian can walk through walls or jump from one floor to another when considering a building with different floor-levels. By incorporating known floor-plans in sequential Bayesian estimation processes such as particle filters (PFs, long-term error stability can be achieved as long as the map is sufficiently accurate and the environment sufficiently constraints pedestrians' motion. In this article, a new motion model based on maps and floor-plans is introduced that is capable of weighting the possible headings of the pedestrian as a function of the local environment. The motion model is derived from a diffusion algorithm that makes use of the principle of a source effusing gas and is used in the weighting step of a PF implementation. The diffusion algorithm is capable of including floor-plans as well as maps with areas of different degrees of accessibility. The motion model more effectively represents the probability density function of possible headings that are restricted by maps and floor-plans than a simple binary weighting of particles (i.e., eliminating those that crossed walls and keeping the rest. We will show that the motion model will help for obtaining better performance in critical navigation scenarios where two or more modes may be competing for some of the time (multi-modal scenarios.

  3. Mapping blood flow directionality in the human brain.

    Science.gov (United States)

    Park, Sung-Hong; Do, Won-Joon; Choi, Seung Hong; Zhao, Tiejun; Bae, Kyongtae Ty

    2016-07-01

    Diffusion properties of tissue are often expressed on the basis of directional variance, i.e., diffusion tensor imaging. In comparison, common perfusion-weighted imaging such as arterial spin labeling yields perfusion in a scalar quantity. The purpose of this study was to test the feasibility of mapping cerebral blood flow directionality using alternate ascending/descending directional navigation (ALADDIN), a recently-developed arterial spin labeling technique with sensitivity to blood flow directions. ALADDIN was applied along 3 orthogonal directions to assess directional blood flow in a vector form and also along 6 equally-spaced directions to extract blood flow tensor matrix (P) based on a blood flow ellipsoid model. Tensor elements (eigenvalues, eigenvectors, etc) were calculated to investigate characteristics of the blood flow tensor, in comparison with time-of-flight MR angiogram. While the directions of the main eigenvectors were heterogeneous throughout the brain, regional clusters of blood flow directionality were reproducible across subjects. The technique could show heterogeneous blood flow directionality within and around brain tumor, which was different from that of the contralateral normal side. The proposed method is deemed to provide information of blood flow directionality, which has not been demonstrated before. The results warrant further studies to assess changes in the directionality map as a function of scan parameters, to understand the signal sources, to investigate the possibility of mapping local blood perfusion directionality, and to evaluate its usefulness for clinical diagnosis.

  4. Genetic mapping of complex discrete human diseases by discriminant analysis

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The objective of the present study is to propose and evaluate a novel multivariate approach for genetic mapping of complex categorical diseases. This approach results from an application of standard stepwise discriminant analysis to detect linkage based on the differential marker identity-by-descent (IBD) distributions among the different groups of sib pairs. Two major advantages of this method are that it allows for simultaneously testing all markers, together with other genetic and environmental factors in a single multivariate setting and it avoids explicitly modeling the complex relationship between the affection status of sib pairs and the underlying genetic determinants. The efficiency and properties of the method are demonstrated via simulations. The proposed multivariate approach has successfully located the true position(s) under various genetic scenarios. The more important finding is that using highly densely spaced markers (1~2 cM) leads to only a marginal loss of statistical efficiency of the proposed methods in terms of gene localization and statistical power. These results have well established its utility and advantages as a fine-mapping tool. A unique property of the proposed method is the ability to map multiple linked trait loci to their precise positions due to its sequential nature, as demonstrated via simulations.

  5. Mind Mapping on Development of Human Resource of Education

    Science.gov (United States)

    Fauzi, Anis

    2016-01-01

    Human resources in the field of education consists of students, teachers, administrative staff, university students, lecturers, structural employees, educational bureaucrats, stakeholders, parents, the society around the school, and the society around the campus. The existence of human resources need to be cultivated and developed towards the…

  6. Origin of celiac disease: How old are predisposing haplotypes?

    Institute of Scientific and Technical Information of China (English)

    Giovanni Gasbarrini; Olga Rickards; Cristina Martínez-Labarga; Elsa Pacciani; Filiberto Chilleri; Lucrezia Laterza; Giuseppe Marangi; Franco Scaldaferri; Antonio Gasbarrini

    2012-01-01

    We recently presented the case of a first century AD young woman,found in the archaeological site of Cosa,showing clinical signs of malnutrition,such as short height,osteoporosis,dental enamel hypoplasia and cribra orbitalia,indirect sign of anemia,all strongly suggestive for celiac disease (CD).However,whether these findings were actually associated to CD was not shown based on genetic parameters.To investigate her human leukocyte antigen (HLA) class Ⅱ polymorphism,we extracted DNA from a bone sample and a tooth and genotyped HLA using three HLA-tagging single nucleotide polymorphisms for DQ8,DQ2.2 and DQ2.5,specifically associated to CD.She displayed HLA DQ 2.5,the haplotype associated to the highest risk of CD.This is the first report showing the presence of a HLA haplotype compatible for CD in archaeological specimens.

  7. Mapping the differential distribution of glycosaminoglycans in the adult human retina, choroid, and sclera

    NARCIS (Netherlands)

    Clark, S. J.; Keenan, T.D.; Fielder, H.L.; Collinson, L.J.; Holley, R.J.; Merry, C.L.; Kuppevelt, A.H.M.S.M. van; Day, A.J.; Bishop, P.N.

    2011-01-01

    PURPOSE. To map the distribution of different classes of glycosaminoglycans (GAGs) in the healthy human retina, choroid, and sclera. METHODS. Frozen tissue sections were made from adult human donor eyes. The GAG chains of proteoglycans (PGs) were detected with antibodies directed against various GAG

  8. Perspectives on human genetic variation from the HapMap Project.

    Science.gov (United States)

    McVean, Gil; Spencer, Chris C A; Chaix, Raphaelle

    2005-10-01

    The completion of the International HapMap Project marks the start of a new phase in human genetics. The aim of the project was to provide a resource that facilitates the design of efficient genome-wide association studies, through characterising patterns of genetic variation and linkage disequilibrium in a sample of 270 individuals across four geographical populations. In total, over one million SNPs have been typed across these genomes, providing an unprecedented view of human genetic diversity. In this review we focus on what the HapMap Project has taught us about the structure of human genetic variation and the fundamental molecular and evolutionary processes that shape it.

  9. Hydrochromic conjugated polymers for human sweat pore mapping.

    Science.gov (United States)

    Lee, Joosub; Pyo, Minkyeong; Lee, Sang-hwa; Kim, Jaeyong; Ra, Moonsoo; Kim, Whoi-Yul; Park, Bum Jun; Lee, Chan Woo; Kim, Jong-Man

    2014-04-29

    Hydrochromic materials have been actively investigated in the context of humidity sensing and measuring water contents in organic solvents. Here we report a sensor system that undergoes a brilliant blue-to-red colour transition as well as 'Turn-On' fluorescence upon exposure to water. Introduction of a hygroscopic element into a supramolecularly assembled polydiacetylene results in a hydrochromic conjugated polymer that is rapidly responsive (polymer. As a result, the sensor can be used to construct a precise map of active sweat pores on fingertips. The sensor technology, developed in this study, has the potential of serving as new method for fingerprint analysis and for the clinical diagnosis of malfunctioning sweat pores.

  10. Complementarity of binding motifs is a general property of HLA-A and HLA-B molecules and does not seem to effect HLA haplotype composition

    Directory of Open Access Journals (Sweden)

    Xiangyu eRao

    2013-11-01

    Full Text Available Different HLA haplotypes (i.e., the specific combinations of HLA-A, -B, -DR alleles inherited together from one parent are observed in different frequencies in human populations. Some haplotypes, like HLA-A1-B8, are very frequent, reaching up to 10% in the Caucasian population, while others are very rare. Numerous studies have identified associations between HLA haplotypes and diseases, and differences in haplotype frequencies can in part be explained by these associations: the stronger the association with a severe (autoimmune disease, the lower the expected HLA haplotype frequency. The peptide repertoires of the HLA molecules composing a haplotype can also influence the frequency of a haplotype. For example, it would seem advantageous to have HLA molecules with non-overlapping binding specificities within a haplotype, as individuals expressing such an haplotype would present a diverse set of peptides from viruses and pathogenic bacteria on the cell surface. To test this hypothesis, we collect the proteome data from a set of common viruses, and estimate the total ligand repertoire of HLA class I haplotypes (HLA-A-B using in silico predictions. We compare the size of these repertoires to the HLA haplotype frequencies reported in the National Marrow Donor Program (NMDP. We find that in most HLA-A and HLA-B pairs have fairly distinct binding motifs, and that the observed haplotypes do not contain HLA-A and –B molecules with more distinct binding motifs than random HLA-A and HLA-B pairs. In addition, the population frequency of a haplotype is not correlated to the distinctness of its HLA-A and HLA-B peptide binding motifs. These results suggest that there is a not a strong selection pressure on the haplotype level favouring haplotypes having HLA molecules with distinct binding motifs, which would result the largest possible presented peptide repertoires in the context of infectious diseases.

  11. Empirical vs Bayesian approach for estimating haplotypes from genotypes of unrelated individuals

    Directory of Open Access Journals (Sweden)

    Cheng Jacob

    2007-01-01

    Full Text Available Abstract Background The completion of the HapMap project has stimulated further development of haplotype-based methodologies for disease associations. A key aspect of such development is the statistical inference of individual diplotypes from unphased genotypes. Several methodologies for inferring haplotypes have been developed, but they have not been evaluated extensively to determine which method not only performs well, but also can be easily incorporated in downstream haplotype-based association analyses. In this paper, we attempt to do so. Our evaluation was carried out by comparing the two leading Bayesian methods, implemented in PHASE and HAPLOTYPER, and the two leading empirical methods, implemented in PL-EM and HPlus. We used these methods to analyze real data, namely the dense genotypes on X-chromosome of 30 European and 30 African trios provided by the International HapMap Project, and simulated genotype data. Our conclusions are based on these analyses. Results All programs performed very well on X-chromosome data, with an average similarity index of 0.99 and an average prediction rate of 0.99 for both European and African trios. On simulated data with approximation of coalescence, PHASE implementing the Bayesian method based on the coalescence approximation outperformed other programs on small sample sizes. When the sample size increased, other programs performed as well as PHASE. PL-EM and HPlus implementing empirical methods required much less running time than the programs implementing the Bayesian methods. They required only one hundredth or thousandth of the running time required by PHASE, particularly when analyzing large sample sizes and large umber of SNPs. Conclusion For large sample sizes (hundreds or more, which most association studies require, the two empirical methods might be used since they infer the haplotypes as accurately as any Bayesian methods and can be incorporated easily into downstream haplotype

  12. Training Methods to Build Human Terrain Mapping Skills

    Science.gov (United States)

    2010-10-01

    the Behavioral and Social Sciences 121 Morande Street ATTN: DAPE-ARI-IK Fort Knox, KY 40121-4141 8. PERFORMING ORGANIZATION REPORT NUMBER 9...windows, graffiti , roadwork, and unpaved roads, they focused more on cues stemming from humans. Several human cues that may provide valuable HTM...harmonizing sections and providing content cohesion. 5. Patterns. Art elements that use planned or random repetition to enhance composition and increase

  13. A haplotype based study of lithium responding patients with bipolar affective disorder on the Faroe Islands

    DEFF Research Database (Denmark)

    Ewald. H.; Wang, M.; Vang, A.G.

    1999-01-01

    , the Faroese population is perhaps the most valuable European population for genetic mapping of complex disease genes. The present study searched for haplotype sharing on chromosome 18 among eight lithium responding patients with bipolar affective disorder related, on average, 6.2 generations ago, using 30 DNA...

  14. AFM friction and adhesion mapping of the substructures of human hair cuticles

    Energy Technology Data Exchange (ETDEWEB)

    Smith, James R., E-mail: james.smith@port.ac.uk [School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael' s Building, White Swan Road, Portsmouth, PO1 2DT (United Kingdom); Tsibouklis, John; Nevell, Thomas G. [School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael' s Building, White Swan Road, Portsmouth, PO1 2DT (United Kingdom); Breakspear, Steven [School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael' s Building, White Swan Road, Portsmouth, PO1 2DT (United Kingdom); Global R and D–Hair Beauty Laboratory, Kao Corporation, 2-1-3, Bunka Sumida-ku, Tokyo, 131-8501 (Japan)

    2013-11-15

    Using atomic force microscopy, values of the microscale friction coefficient, the tip (silicon nitride) - surface adhesion force and the corresponding adhesion energy, for the substructures that constitute the surface of human hair (European brown hair) have been determined from Amonton plots. The values, mapped for comparison with surface topography, corresponded qualitatively with the substructures’ plane surface characteristics. Localised maps and values of the frictional coefficient, extracted avoiding scale edge effects, are likely to inform the formulation of hair-care products and treatments.

  15. In-vitro Thermal Maps to Characterize Human Dental Enamel and Dentin.

    Science.gov (United States)

    Lancaster, Paula; Brettle, David; Carmichael, Fiona; Clerehugh, Val

    2017-01-01

    The crown of a human tooth has an outer layer of highly-mineralized tissue called enamel, beneath which is dentin, a less-mineralized tissue which forms the bulk of the tooth-crown and root. The composition and structure of enamel and dentin are different, resulting in different thermal properties. This gives an opportunity to characterize enamel and dentin from their thermal properties and to visually present the findings as a thermal map. The thermal properties of demineralized enamel and dentin may also be sufficiently different from sound tissue to be seen on a thermal map, underpinning future thermal assessment of caries. The primary aim of this novel study was to produce a thermal map of a sound, human tooth-slice to visually characterize enamel and dentin. The secondary aim was to map a human tooth-slice with demineralized enamel and dentin to consider future diagnostic potential of thermal maps for caries-detection. Two human slices of teeth, one sound and one demineralized from a natural carious lesion, were cooled on ice, then transferred to a hotplate at 30°C where the rewarming-sequence was captured by an infra-red thermal camera. Calculation of thermal diffusivity and thermal conductivity was undertaken, and two methods of data-processing used customized software to produce thermal maps from the thermal characteristic-time-to-relaxation and heat-exchange. The two types of thermal maps characterized enamel and dentin. In addition, sound and demineralized enamel and dentin were distinguishable within both maps. This supports thermal assessment of caries and requires further investigation on a whole tooth.

  16. [Multiplexing mapping of human cDNAs]. Final report, September 1, 1991--February 28, 1994

    Energy Technology Data Exchange (ETDEWEB)

    1994-04-01

    Using PCR with automated product analysis, 329 human brain cDNA sequences have been assigned to individual human chromosomes. Primers were designed from single-pass cDNA sequences expressed sequence tags (ESTs). Primers were used in PCR reactions with DNA from somatic cell hybrid mapping panels as templates, often with multiplexing. Many ESTs mapped match sequence database records. To evaluate of these matches, the position of the primers relative to the matching region (In), the BLAST scores and the Poisson probability values of the EST/sequence record match were determined. In cases where the gene product was stringently identified by the sequence match had already been mapped, the gene locus determined by EST was consistent with the previous position which strongly supports the validity of assigning unknown genes to human chromosomes based on the EST sequence matches. In the present cases mapping the ESTs to a chromosome can also be considered to have mapped the known gene product: rolipram-sensitive cAMP phosphodiesterase, chromosome 1; protein phosphatase 2A{beta}, chromosome 4; alpha-catenin, chromosome 5; the ELE1 oncogene, chromosome 10q11.2 or q2.1-q23; MXII protein, chromosome l0q24-qter; ribosomal protein L18a homologue, chromosome 14; ribosomal protein L3, chromosome 17; and moesin, Xp11-cen. There were also ESTs mapped that were closely related to non-human sequence records. These matches therefore can be considered to identify human counterparts of known gene products, or members of known gene families. Examples of these include membrane proteins, translation-associated proteins, structural proteins, and enzymes. These data then demonstrate that single pass sequence information is sufficient to design PCR primers useful for assigning cDNA sequences to human chromosomes. When the EST sequence matches previous sequence database records, the chromosome assignments of the EST can be used to make preliminary assignments of the human gene to a chromosome.

  17. Mapping and annotating obesity-related genes in pig and human genomes.

    Science.gov (United States)

    Martelli, Pier Luigi; Fontanesi, Luca; Piovesan, Damiano; Fariselli, Piero; Casadio, Rita

    2014-01-01

    Background. Obesity is a major health problem in both developed and emerging countries. Obesity is a complex disease whose etiology involves genetic factors in strong interplay with environmental determinants and lifestyle. The discovery of genetic factors and biological pathways underlying human obesity is hampered by the difficulty in controlling the genetic background of human cohorts. Animal models are then necessary to further dissect the genetics of obesity. Pig has emerged as one of the most attractive models, because of the similarity with humans in the mechanisms regulating the fat deposition. Results. We collected the genes related to obesity in humans and to fat deposition traits in pig. We localized them on both human and pig genomes, building a map useful to interpret comparative studies on obesity. We characterized the collected genes structurally and functionally with BAR+ and mapped them on KEGG pathways and on STRING protein interaction network. Conclusions. The collected set consists of 361 obesity related genes in human and pig genomes. All genes were mapped on the human genome, and 54 could not be localized on the pig genome (release 2012). Only for 3 human genes there is no counterpart in pig, confirming that this animal is a good model for human obesity studies. Obesity related genes are mostly involved in regulation and signaling processes/pathways and relevant connection emerges between obesity-related genes and diseases such as cancer and infectious diseases.

  18. Building the sequence map of the human pan-genome

    DEFF Research Database (Denmark)

    Li, Ruiqiang; Li, Yingrui; Zheng, Hancheng

    2010-01-01

    Here we integrate the de novo assembly of an Asian and an African genome with the NCBI reference human genome, as a step toward constructing the human pan-genome. We identified approximately 5 Mb of novel sequences not present in the reference genome in each of these assemblies. Most novel...... analysis of predicted genes indicated that the novel sequences contain potentially functional coding regions. We estimate that a complete human pan-genome would contain approximately 19-40 Mb of novel sequence not present in the extant reference genome. The extensive amount of novel sequence contributing...... to the genetic variation of the pan-genome indicates the importance of using complete genome sequencing and de novo assembly....

  19. Mapping multiplex hubs in human functional brain networks

    Directory of Open Access Journals (Sweden)

    Alex Arenas

    2016-07-01

    Full Text Available Typical brain networks consist of many peripheral regions and a few highly centralones, i.e. hubs, playing key functional roles in cerebral inter-regional interactions. Studieshave shown that networks, obtained from the analysis of specific frequency components ofbrain activity, present peculiar architectures with unique profiles of region centrality. However,the identification of hubs in networks built from different frequency bands simultaneouslyis still a challenging problem, remaining largely unexplored. Here we identify eachfrequency component with one layer of a multiplex network and face this challenge by exploitingthe recent advances in the analysis of multiplex topologies. First, we show that eachfrequency band carries unique topological information, fundamental to accurately modelbrain functional networks. We then demonstrate that hubs in the multiplex network, in generaldifferent from those ones obtained after discarding or aggregating the measured signalsas usual, provide a more accurate map of brain’s most important functional regions, allowingto distinguish between healthy and schizophrenic populations better than conventionalnetwork approaches.

  20. Open Source Software for Mapping Human Impacts on Marine Ecosystems with an Additive Model

    Directory of Open Access Journals (Sweden)

    Andy Stock

    2016-06-01

    Full Text Available This paper describes an easy-to-use open source software tool implementing a commonly used additive model (Halpern et al., 'Science', 2008 for mapping human impacts on marine ecosystems. The tool has been used to map the potential for cumulative human impacts in Arctic marine waters and can support future human impact mapping projects by 1 making the model easier to use; 2 making updates of model results straightforward when better input data become available; 3 storing input data and information about processing steps in a defined format and thus facilitating data sharing and reproduction of modeling results; 4 supporting basic visualization of model inputs and outputs without the need for advanced technical skills. The tool, called EcoImpactMapper, was implemented in Java and is thus platform-independent. A tutorial, example data, the tool and the source code are available online.

  1. Virtual Character Animations from Human Body Motion by Automatic Direct and Inverse Kinematics-based Mapping

    Directory of Open Access Journals (Sweden)

    Andrea Sanna

    2015-02-01

    Full Text Available Motion capture systems provide an efficient and interactive solution for extracting information related to a human skeleton, which is often exploited to animate virtual characters. When the character cannot be assimilated to an anthropometric shape, the task to map motion capture data onto the armature to be animated could be extremely challenging. This paper presents two methodologies for the automatic mapping of a human skeleton onto virtual character armatures. Kinematics chains of the human skeleton are analyzed in order to map joints, bones and end-effectors onto an arbitrary shaped armatures. Both forward and inverse kinematics are considered. A prototype implementation has been developed by using the Microsoft Kinect as body tracking device. Results show that the proposed solution can already be used to animate truly different characters ranging from a Pixar-like lamp to different kinds of animals.

  2. Trajectory learning from human demonstrations via manifold mapping

    CSIR Research Space (South Africa)

    Hiratsuka, M

    2016-10-01

    Full Text Available This work proposes a framework that enables arbitrary robots with unknown kinematics models to imitate human demonstrations to acquire a skill, and reproduce it in real-time. The diversity of robots active in non-laboratory environments is growing...

  3. Mapping the genetic architecture of gene expression in human liver.

    Directory of Open Access Journals (Sweden)

    Eric E Schadt

    2008-05-01

    Full Text Available Genetic variants that are associated with common human diseases do not lead directly to disease, but instead act on intermediate, molecular phenotypes that in turn induce changes in higher-order disease traits. Therefore, identifying the molecular phenotypes that vary in response to changes in DNA and that also associate with changes in disease traits has the potential to provide the functional information required to not only identify and validate the susceptibility genes that are directly affected by changes in DNA, but also to understand the molecular networks in which such genes operate and how changes in these networks lead to changes in disease traits. Toward that end, we profiled more than 39,000 transcripts and we genotyped 782,476 unique single nucleotide polymorphisms (SNPs in more than 400 human liver samples to characterize the genetic architecture of gene expression in the human liver, a metabolically active tissue that is important in a number of common human diseases, including obesity, diabetes, and atherosclerosis. This genome-wide association study of gene expression resulted in the detection of more than 6,000 associations between SNP genotypes and liver gene expression traits, where many of the corresponding genes identified have already been implicated in a number of human diseases. The utility of these data for elucidating the causes of common human diseases is demonstrated by integrating them with genotypic and expression data from other human and mouse populations. This provides much-needed functional support for the candidate susceptibility genes being identified at a growing number of genetic loci that have been identified as key drivers of disease from genome-wide association studies of disease. By using an integrative genomics approach, we highlight how the gene RPS26 and not ERBB3 is supported by our data as the most likely susceptibility gene for a novel type 1 diabetes locus recently identified in a large

  4. Haplotype-phenotype relationships of paraoxonase-1.

    Science.gov (United States)

    Chen, Jia; Chan, Wendy; Wallenstein, Sylvan; Berkowitz, Gertrud; Wetmur, James G

    2005-03-01

    Paraoxonase 1 (PON1) is an enzyme with multiple activities, including detoxification of organophosphates. It is believed to be important in preventing neurotoxic damage and has also been implicated in atherosclerosis. The PON1 gene contains five common polymorphisms, three in the promoter (-909G > C, -162A > G, -108C > T) and two in the coding region (M55L, Q192R) with varying but incomplete linkage disequilibrium. Our previous study showed that functional polymorphisms in PON1 were strongly associated with enzymatic activity in both pregnant women [26-30 weeks of gestation] and neonates. However, there was substantial overlapping of enzyme activities between genotypes. In this study, we investigated whether haplotype (genotype + phase) information would strengthen the genotype-phenotype relationship for PON1. The study consisted of a multiethnic population of 402 mothers and 229 neonates. Haplotypes were imputed by two widely used programs, PHASE and tagSNPs, which yielded very similar results. There were seven haplotypes with a frequency of 5% or higher in at least one ethnic group of the study population. Haplotype composition varied substantially with respect to ethnicity. Haplotypes in Caucasians and African-Americans showed the largest difference, and Caribbean Hispanics seemed to be a mixture of Caucasian and African ancestry. Collectively, the genetic (genotype or haplotype) contribution to PON1 enzymatic activity (measured as phenylacetate hydrolysis) was greater in neonates compared with mothers. Specifically, 16.6% of PON1 variability was explained by genotypes in mothers compared with 30.9% in neonates. Haplotype information offered a slightly increased power in predicting PON1 activity; they explained 35.5% and 19.3% of PON1 variability in neonates and mothers, respectively.

  5. Mapping Multiplex Hubs in Human Functional Brain Networks

    Science.gov (United States)

    De Domenico, Manlio; Sasai, Shuntaro; Arenas, Alex

    2016-01-01

    Typical brain networks consist of many peripheral regions and a few highly central ones, i.e., hubs, playing key functional roles in cerebral inter-regional interactions. Studies have shown that networks, obtained from the analysis of specific frequency components of brain activity, present peculiar architectures with unique profiles of region centrality. However, the identification of hubs in networks built from different frequency bands simultaneously is still a challenging problem, remaining largely unexplored. Here we identify each frequency component with one layer of a multiplex network and face this challenge by exploiting the recent advances in the analysis of multiplex topologies. First, we show that each frequency band carries unique topological information, fundamental to accurately model brain functional networks. We then demonstrate that hubs in the multiplex network, in general different from those ones obtained after discarding or aggregating the measured signals as usual, provide a more accurate map of brain's most important functional regions, allowing to distinguish between healthy and schizophrenic populations better than conventional network approaches. PMID:27471443

  6. Manipulating HapMap Data Using HaploView.

    Science.gov (United States)

    Smith, Albert Vernon

    2008-07-01

    INTRODUCTIONThe primary goal of the International Haplotype Map Project has been to develop a haplotype map of the human genome that describes the common patterns of genetic variation, in order to accelerate the search for the genetic causes of human disease. Within the project, ~3.9 million distinct single-nucleotide polymorphisms (SNPs) have been genotyped in 270 individuals from four worldwide populations. The project data are available for unrestricted public use at the HapMap website. This site, which is the primary portal to genotype data produced by the project, offers bulk downloads of the data set, as well as interactive data browsing and analysis tools that are not available elsewhere. Advanced users who wish to exercise fine control over the display of regions of high linkage disequilibrium (LD) or who wish to experiment with new algorithms for tag-SNP picking may wish to analyze HapMap data using the HaploView program. This program works well in combination with the HapMap website genome browser. A big advantage of HaploView over the genome browser is that it displays simultaneous high- and low-power views of regions of LD, and gives immediate feedback during scrolling and zooming operations. This protocol describes the use of HaploView to manipulate HapMap data.

  7. Founder mitochondrial haplotypes in Amerindian populations.

    Science.gov (United States)

    Bailliet, G; Rothhammer, F; Carnese, F R; Bravi, C M; Bianchi, N O

    1994-07-01

    It had been proposed that the colonization of the New World took place by three successive migrations from northeastern Asia. The first one gave rise to Amerindians (Paleo-Indians), the second and third ones to Nadene and Aleut-Eskimo, respectively. Variation in mtDNA has been used to infer the demographic structure of the Amerindian ancestors. The study of RFLP all along the mtDNA and the analysis of nucleotide substitutions in the D-loop region of the mitochondrial genome apparently indicate that most or all full-blooded Amerindians cluster in one of four different mitochondrial haplotypes that are considered to represent the founder maternal lineages of Paleo-Indians. We have studied the mtDNA diversity in 109 Amerindians belonging to 3 different tribes, and we have reanalyzed the published data on 482 individuals from 18 other tribes. Our study confirms the existence of four major Amerindian haplotypes. However, we also found evidence supporting the existence of several other potential founder haplotypes or haplotype subsets in addition to the four ancestral lineages reported. Confirmation of a relatively high number of founder haplotypes would indicate that early migration into America was not accompanied by a severe genetic bottleneck.

  8. Association of ORAI1 haplotypes with the risk of HLA-B27 positive ankylosing spondylitis.

    Directory of Open Access Journals (Sweden)

    James Cheng-Chung Wei

    Full Text Available Ankylosing spondylitis (AS is a chronic inflammation of the sacroiliac joints, spine and peripheral joints. The aetiology of ankylosing spondylitis is still unclear. Previous studies have indicated that genetics factors such as human leukocyte antigen HLA-B27 associates to AS susceptibility. We carried out a case-control study to determine whether the genetic polymorphisms of ORAI1 gene, a major component of store-operated calcium channels that involved the regulation of immune system, is a susceptibility factor to AS in a Taiwanese population. We enrolled 361 AS patients fulfilled the modified New York criteria and 379 controls from community. Five tagging single nucleotides polymorphisms (tSNPs at ORAI1 were selected from the data of Han Chinese population in HapMap project. Clinical statuses of AS were assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI, and Bath Ankylosing Spondylitis Global Index (BAS-G. Our results indicated that subjects carrying the minor allele homozygote (CC of the promoter SNP rs12313273 or TT homozygote of the SNP rs7135617 had an increased risk of HLA-B27 positive AS. The minor allele C of 3'UTR SNP rs712853 exerted a protective effect to HLA-B27 positive AS. Furthermore, the rs12313273/rs7135617 pairwise allele analysis found that C-G (OR 1.69, 95% CI 1.27, 2.25; p = 0.0003 and T-T (OR 1.75, 95% CI 1.36, 2.27; p<0.0001 haplotypes had a significantly association with the risk of HLA-B27-positive AS in comparison with the T-G carriers. This is the first study that indicate haplotypes of ORAI1 (rs12313273 and rs7135617 are associated with the risk of HLA-B27 positive AS.

  9. Rare missense variants within a single gene form yin yang haplotypes.

    Science.gov (United States)

    Curtis, David

    2016-01-01

    Yin yang haplotype pairs differ at every SNP. They would not be accounted for by population models that incorporate sequential mutation, with or without recombination. Previous reports have claimed that there is a tendency for common SNPs to form yin yang haplotypes more often than would be expected by sequential mutation or by a random sample of all possible haplotypic arrangements of alleles. In the course of analysing next-generation sequencing data, instances of yin yang haplotypes being formed by very rare variants within a single gene were observed. As an example, this report describes a completely yin yang haplotype formed by eight rare missense variants in the ABCA13 gene. Of 1000 genome subjects, 21 have a copy of the alternate allele at all eight of these positions and a single subject is homozygous for all of them. None of the other 1070 subjects possesses any of the altetrnates. Thus, the eight alternate alleles are always found together and never occur separately. The existence of such yin yang haplotypes has important implications for statistical methods for analysing rare variants. Also, they may be of use for gaining a better understanding of the history of human populations.

  10. A Spatiotemporal Database to Track Human Scrub Typhus Using the VectorMap Application

    Science.gov (United States)

    Kelly, Daryl J.; Foley, Desmond H.; Richards, Allen L.

    2015-01-01

    Scrub typhus is a potentially fatal mite-borne febrile illness, primarily of the Asia-Pacific Rim. With an endemic area greater than 13 million km2 and millions of people at risk, scrub typhus remains an underreported, often misdiagnosed febrile illness. A comprehensive, updatable map of the true distribution of cases has been lacking, and therefore the true risk of disease within the very large endemic area remains unknown. The purpose of this study was to establish a database and map to track human scrub typhus. An online search using PubMed and the United States Armed Forces Pest Management Board Literature Retrieval System was performed to identify articles describing human scrub typhus cases both within and outside the traditionally accepted endemic regions. Using World Health Organization guidelines, stringent criteria were used to establish diagnoses for inclusion in the database. The preliminary screening of 181 scrub typhus publications yielded 145 publications that met the case criterion, 267 case records, and 13 serosurvey records that could be georeferenced, describing 13,739 probable or confirmed human cases in 28 countries. A map service has been established within VectorMap (www.vectormap.org) to explore the role that relative location of vectors, hosts, and the pathogen play in the transmission of mite-borne scrub typhus. The online display of scrub typhus cases in VectorMap illustrates their presence and provides an up-to-date geographic distribution of proven scrub typhus cases. PMID:26678263

  11. A Spatiotemporal Database to Track Human Scrub Typhus Using the VectorMap Application.

    Directory of Open Access Journals (Sweden)

    Daryl J Kelly

    2015-12-01

    Full Text Available Scrub typhus is a potentially fatal mite-borne febrile illness, primarily of the Asia-Pacific Rim. With an endemic area greater than 13 million km2 and millions of people at risk, scrub typhus remains an underreported, often misdiagnosed febrile illness. A comprehensive, updatable map of the true distribution of cases has been lacking, and therefore the true risk of disease within the very large endemic area remains unknown. The purpose of this study was to establish a database and map to track human scrub typhus. An online search using PubMed and the United States Armed Forces Pest Management Board Literature Retrieval System was performed to identify articles describing human scrub typhus cases both within and outside the traditionally accepted endemic regions. Using World Health Organization guidelines, stringent criteria were used to establish diagnoses for inclusion in the database. The preliminary screening of 181 scrub typhus publications yielded 145 publications that met the case criterion, 267 case records, and 13 serosurvey records that could be georeferenced, describing 13,739 probable or confirmed human cases in 28 countries. A map service has been established within VectorMap (www.vectormap.org to explore the role that relative location of vectors, hosts, and the pathogen play in the transmission of mite-borne scrub typhus. The online display of scrub typhus cases in VectorMap illustrates their presence and provides an up-to-date geographic distribution of proven scrub typhus cases.

  12. Powerful haplotype-based Hardy-Weinberg equilibrium tests for tightly linked loci.

    Directory of Open Access Journals (Sweden)

    Wei-Gao Mao

    Full Text Available Recently, there have been many case-control studies proposed to test for association between haplotypes and disease, which require the Hardy-Weinberg equilibrium (HWE assumption of haplotype frequencies. As such, haplotype inference of unphased genotypes and development of haplotype-based HWE tests are crucial prior to fine mapping. The goodness-of-fit test is a frequently-used method to test for HWE for multiple tightly-linked loci. However, its degrees of freedom dramatically increase with the increase of the number of loci, which may lack the test power. Therefore, in this paper, to improve the test power for haplotype-based HWE, we first write out two likelihood functions of the observed data based on the Niu's model (NM and inbreeding model (IM, respectively, which can cause the departure from HWE. Then, we use two expectation-maximization algorithms and one expectation-conditional-maximization algorithm to estimate the model parameters under the HWE, IM and NM models, respectively. Finally, we propose the likelihood ratio tests LRT[Formula: see text] and LRT[Formula: see text] for haplotype-based HWE under the NM and IM models, respectively. We simulate the HWE, Niu's, inbreeding and population stratification models to assess the validity and compare the performance of these two LRT tests. The simulation results show that both of the tests control the type I error rates well in testing for haplotype-based HWE. If the NM model is true, then LRT[Formula: see text] is more powerful. While, if the true model is the IM model, then LRT[Formula: see text] has better performance in power. Under the population stratification model, LRT[Formula: see text] is still more powerful. To this end, LRT[Formula: see text] is generally recommended. Application of the proposed methods to a rheumatoid arthritis data set further illustrates their utility for real data analysis.

  13. Mapping internal connectivity through human migration in malaria endemic countries.

    Science.gov (United States)

    Sorichetta, Alessandro; Bird, Tom J; Ruktanonchai, Nick W; Zu Erbach-Schoenberg, Elisabeth; Pezzulo, Carla; Tejedor, Natalia; Waldock, Ian C; Sadler, Jason D; Garcia, Andres J; Sedda, Luigi; Tatem, Andrew J

    2016-08-16

    Human mobility continues to increase in terms of volumes and reach, producing growing global connectivity. This connectivity hampers efforts to eliminate infectious diseases such as malaria through reintroductions of pathogens, and thus accounting for it becomes important in designing global, continental, regional, and national strategies. Recent works have shown that census-derived migration data provides a good proxy for internal connectivity, in terms of relative strengths of movement between administrative units, across temporal scales. To support global malaria eradication strategy efforts, here we describe the construction of an open access archive of estimated internal migration flows in endemic countries built through pooling of census microdata. These connectivity datasets, described here along with the approaches and methods used to create and validate them, are available both through the WorldPop website and the WorldPop Dataverse Repository.

  14. Selection and fine mapping of chromosome-specific cDNAs: application to human chromosome 1.

    Science.gov (United States)

    Mancini, M; Sala, C; Rivella, S; Toniolo, D

    1996-12-01

    We have developed a methodology for identification and fine mapping of chromosome-specific transcripts. Combining digestion of DNA with different restriction enzymes, ligation to "bubble" linkers, and PCR amplification from Alu and "bubble" primers, we have synthesized human chromosome 1-specific sequences from DNA of a somatic cell hybrid, A9Neol. After hybridization to human fetal brain cDNA, we could efficiently capture chromosome 1-specific cDNAs. The cDNAs were sequenced and used as probes in hybridizations to high-density filters containing the arrayed CEPH Mega-YAC library and to the arrayed cDNA library from infant brain made by B. Soares, which has been extensively sequenced. By this approach we have been able to select chromosome 1-specific cDNAs, to map them to chromosome 1 YAC contigs, and to identify and map corresponding longer cDNAs and ESTs.

  15. Spatial and temporal distribution of the neutral polymorphisms in the last ZFX intron: analysis of the haplotype structure and genealogy.

    Science.gov (United States)

    Jaruzelska, J; Zietkiewicz, E; Batzer, M; Cole, D E; Moisan, J P; Scozzari, R; Tavaré, S; Labuda, D

    1999-07-01

    With 10 segregating sites (simple nucleotide polymorphisms) in the last intron (1089 bp) of the ZFX gene we have observed 11 haplotypes in 336 chromosomes representing a worldwide array of 15 human populations. Two haplotypes representing 77% of all chromosomes were distributed almost evenly among four continents. Five of the remaining haplotypes were detected in Africa and 4 others were restricted to Eurasia and the Americas. Using the information about the ancestral state of the segregating positions (inferred from human-great ape comparisons), we applied coalescent analysis to estimate the age of the polymorphisms and the resulting haplotypes. The oldest haplotype, with the ancestral alleles at all the sites, was observed at low frequency only in two groups of African origin. Its estimated age of 740 to 1100 kyr corresponded to the time to the most recent common ancestor. The two most frequent worldwide distributed haplotypes were estimated at 550 to 840 and 260 to 400 kyr, respectively, while the age of the continentally restricted polymorphisms was 120 to 180 kyr and smaller. Comparison of spatial and temporal distribution of the ZFX haplotypes suggests that modern humans diverged from the common ancestral stock in the Middle Paleolithic era. Subsequent range expansion prevented substantial gene flow among continents, separating African groups from populations that colonized Eurasia and the New World.

  16. Perspectives on human genetic variation from the HapMap Project.

    OpenAIRE

    2005-01-01

    ABSTRACT The completion of the International HapMap Project marks the start of a new phase in human genetics. The aim of the project was to provide a resource that facilitates the design of efficient genome-wide association studies, through characterising patterns of genetic variation and linkage disequilibrium in a sample of 270 individuals across four geographical populations. In total, over one million SNPs have been typed across these genomes, providing an unprecedented view of human gene...

  17. Neighborhoods in Development: Human Development Index and Self-Organizing Maps

    Science.gov (United States)

    Rende, Sevinc; Donduran, Murat

    2013-01-01

    The Human Development Index (HDI) has been instrumental in broadening the discussion of economic development beyond money-metric progress, in particular, by ranking a country against other countries in terms of the well being of their citizens. We propose self-organizing maps to explore similarities among countries using the components of the HDI…

  18. Neighborhoods in Development: Human Development Index and Self-Organizing Maps

    Science.gov (United States)

    Rende, Sevinc; Donduran, Murat

    2013-01-01

    The Human Development Index (HDI) has been instrumental in broadening the discussion of economic development beyond money-metric progress, in particular, by ranking a country against other countries in terms of the well being of their citizens. We propose self-organizing maps to explore similarities among countries using the components of the HDI…

  19. Report of the Second International Workshop on Human Chromosome 5 Mapping

    Energy Technology Data Exchange (ETDEWEB)

    Westbrook, C.A.; Neuman, W.L. [Chicago Univ., IL (United States); McPherson, J.; Wasmuth, J. [California Univ., Irvine, CA (United States). Dept. of Biological Chemistry; Camper, S. [Michigan Univ., Ann Arbor, MI (United States). Medical School; Plaetke, R. [Eceles Inst. of Human Genetics, Salt Lake City, UT (United States). Dept. of Human Genetics; Williamson, R. [St. Mary`s Hospital Medical School, London (United Kingdom). Dept. of Biochemistry and Molecular Genetics

    1993-12-31

    This report describes the accomplishments of the Second International Workshop on Human Chromosome 5 as was held May 11--13,1992 at the University of Chicago. Included in the report are abstract of individual presentations and a consensus map of the chromosome.

  20. Mapping gene associations in human mitochondria using clinical disease phenotypes.

    Directory of Open Access Journals (Sweden)

    Curt Scharfe

    2009-04-01

    Full Text Available Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects

  1. Separation of Y-chromosomal haplotypes from male DNA mixtures via multiplex haplotype-specific extraction.

    Science.gov (United States)

    Rothe, Jessica; Nagy, Marion

    2015-11-01

    In forensic analysis, the interpretation of DNA mixtures is the subject of ongoing debate and requires expertise knowledge. Haplotype-specific extraction (HSE) is an alternative method that enables the separation of large chromosome fragments or haplotypes by using magnetic beads in conjunction with allele-specific probes. HSE thus allows physical separation of the components of a DNA mixture. Here, we present the first multiplex HSE separation of a Y-chromosomal haplotype consisting of six Yfiler short tandem repeat markers from a mixture of male DNA.

  2. Mental and Physical (MAP) Training: a neurogenesis-inspired intervention that enhances health in humans.

    Science.gov (United States)

    Shors, Tracey J; Olson, Ryan L; Bates, Marsha E; Selby, Edward A; Alderman, Brandon L

    2014-11-01

    New neurons are generated in the hippocampus each day and their survival is greatly enhanced through effortful learning (Shors, 2014). The numbers of cells produced can be increased by physical exercise (van Praag, Kempermann, & Gage, 1999). These findings inspired us to develop a clinical intervention for humans known as Mental and Physical Training, or MAP Training. Each session consists of 30min of mental training with focused attention meditation (20min sitting and 10min walking). Meditation is an effortful training practice that involves learning about the transient nature of thoughts and thought patterns, and acquiring skills to recognize them without necessarily attaching meaning and/or emotions to them. The mental training component is followed by physical training with 30min of aerobic exercise performed at moderate intensity. During this component, participants learn choreographed dance routines while engaging in aerobic exercise. In a pilot "proof-of-concept" study, we provided supervised MAP Training (2 sessions per week for 8weeks) to a group of young mothers in the local community who were recently homeless, most of them having previously suffered from physical and sexual abuse, addiction, and depression. Preliminary data suggest that MAP Training improves dependent measures of aerobic fitness (as assessed by maximal rate of oxygen consumed) while decreasing symptoms of depression and anxiety. Similar changes were not observed in a group of recently homeless women who did not participate in MAP Training. It is not currently possible to determine whether new neurons in the human brain increase in number as a result of MAP Training. Rather these preliminary results of MAP Training illustrate how neuroscientific research can be translated into novel clinical interventions that benefit human health and wellness.

  3. Mapping a2 Adrenoceptors of the Human Brain with 11C-Yohimbine

    DEFF Research Database (Denmark)

    Nahimi, Adjmal; Jakobsen, Steen; Munk, Ole

    2015-01-01

    A previous study from this laboratory suggested that 11C-yohimbine, a selective α2-adrenoceptor antagonist, is an appropriate ligand for PET of α2 adrenoceptors that passes readily from blood to brain tissue in pigs but not in rodents. To test usefulness in humans, we determined blood–brain...... adrenoceptors in human brain had the highest values in cortical areas and hippocampus, with moderate values in subcortical structures, as found also in vitro. The results confirm the usefulness of the tracer 11C-yohimbine for mapping α2 adrenoceptors in human brain in vivo....

  4. Human cDNA mapping using fluorescence in situ hybridization. Final progress report, April 1, 1994--July 31, 1997

    Energy Technology Data Exchange (ETDEWEB)

    Korenberg, J.R.

    1997-12-31

    The ultimate goal of this research is to generate and apply novel technologies to speed completion and integration of the human genome map and sequence with biomedical problems. To do this, techniques were developed and genome-wide resources generated. This includes a genome-wide Mapped and Integrated BAC/PAC Resource that has been used for gene finding, map completion and anchoring, breakpoint definition and sequencing. In the last period of the grant, the Human Mapped BAC/PAC Resource was also applied to determine regions of human variation and to develop a novel paradigm of primate evolution through to humans. Further, in order to more rapidly evaluate animal models of human disease, a BAC Map of the mouse was generated in collaboration with the MTI Genome Center, Dr. Bruce Birren.

  5. A high-resolution interval map of the q21 region of the human X chromosome

    Energy Technology Data Exchange (ETDEWEB)

    Philippe, C.; Monaco, A.P. [ICRF Laboratories, Oxford (United Kingdom)] [and others; Arnould, C. [Laboratoire de Genetique Humaine, Vandoeuvre-les-Nancy (France)] [and others

    1995-06-10

    In a previous study, we have developed a panel of chromosomal rearrangements for the physical mapping of the q13-q21 region of the human X chromosome. Here, we report the physical localization of 36 additional polymorphic markers by polymerase chain reaction analysis. The high density of chromosomal breakpoints in Xq21 allows us to map 58 DNA loci in 22 intervals. As a result, this segment of the X chromosome is saturated with approximately three sequence tagged sites per megabase of DNA, which will facilitate the construction of a YAC contig of this region. 26 refs., 1 fig., 1 tab.

  6. New chicken Rfp-Y haplotypes on the basis of MHC class II RFLP and MLC analyses

    DEFF Research Database (Denmark)

    Juul-Madsen, H R; Zoorob, R; Auffray, C;

    1997-01-01

    New chicken Rfp-Y haplotypes were determined by the use of restriction fragment length polymorphism (RFLP) and mixed lymphocyte culture (MLC) in four different chicken haplotypes, B15, B19, B21, B201. The RFLP polymorphism was mapped to the Rfp-Y system by the use of a subclone (18.1) which maps...... near a polymorphic lectin gene located in the Rfp-Y system and DNA from families with known segregation of the implicated RFLP polymorphism. For the first time it is shown that major histocompatibility complex class II genes in the Rfp-Y system have functional implications. Sequence information...

  7. A sequence-ready map for human chromosome 12q15-21.

    Science.gov (United States)

    Lee, S G; Cho, K A; Choi, Y H; Montgomery, K; Lee, E; Miller, A; Kucherlapati, R; Song, K

    2000-01-01

    Construction of sequence-ready clone map is an essential step toward sequencing the human genome. We chose a region that is frequently amplified in liposarcoma between D12S350 and D12S106 in chromosome 12q15-21 to build a PAC/BAC clone contig map. This region was spanned by 4 YACs and contained 30 STS on the YAC and radiation hybrid (RH) framework maps, providing an average STS spacing of 160 kb if each YAC is approximately 1.2 Mb in size. To convert a STS-based YAC map to a STS-based contig map of bacterial clones, 22 non-polymorphic STS markers were used as probes to screen the high density gridded arrays of PAC and BAC clones by filter hybridizations, followed by assembly of clones into contigs by marker content. Contigs have been extended and joined by direct end sequencing of appropriate clones, generating new STSs and rescreening the library as necessary. Using these approaches, we have constructed 5 contigs covering the region with the largest single contig being 1.4 Mb and a final size estimation of 3.6 Mb. The map is comprised of 17 YACs, 187 PACs, 160 BACs, and 17 cosmids; onto this, 6 polymorphic, 97 non-polymorphic, 24 ESTs, and 4 gene-based markers are now placed in a unique order, providing an average resolution of approximately 28 kb. Of a total of 131 markers, 97 were developed in the present study. The sequence-ready map should provide a framework to generate complete DNA sequence and ultimately gene map of this segment of chromosome 12.

  8. Predictive mapping of human risk for West Nile virus (WNV) based on environmental and socioeconomic factors.

    Science.gov (United States)

    Rochlin, Ilia; Turbow, David; Gomez, Frank; Ninivaggi, Dominick V; Campbell, Scott R

    2011-01-01

    A West Nile virus (WNV) human risk map was developed for Suffolk County, New York utilizing a case-control approach to explore the association between the risk of vector-borne WNV and habitat, landscape, virus activity, and socioeconomic variables derived from publically available datasets. Results of logistic regression modeling for the time period between 2000 and 2004 revealed that higher proportion of population with college education, increased habitat fragmentation, and proximity to WNV positive mosquito pools were strongly associated with WNV human risk. Similar to previous investigations from north-central US, this study identified middle class suburban neighborhoods as the areas with the highest WNV human risk. These results contrast with similar studies from the southern and western US, where the highest WNV risk was associated with low income areas. This discrepancy may be due to regional differences in vector ecology, urban environment, or human behavior. Geographic Information Systems (GIS) analytical tools were used to integrate the risk factors in the 2000-2004 logistic regression model generating WNV human risk map. In 2005-2010, 41 out of 46 (89%) of WNV human cases occurred either inside of (30 cases) or in close proximity (11 cases) to the WNV high risk areas predicted by the 2000-2004 model. The novel approach employed by this study may be implemented by other municipal, local, or state public health agencies to improve geographic risk estimates for vector-borne diseases based on a small number of acute human cases.

  9. Retrieving HapMap Data Using HapMart.

    Science.gov (United States)

    Smith, Albert Vernon

    2008-07-01

    INTRODUCTIONThe primary goal of the International Haplotype Map Project has been to develop a haplotype map of the human genome that describes the common patterns of genetic variation, in order to accelerate the search for the genetic causes of human disease. Within the project, ~3.9 million distinct single-nucleotide polymorphisms (SNPs) have been genotyped in 270 individuals from four worldwide populations. The project data are available for unrestricted public use at the HapMap Web site. This site, which is the primary portal to genotype data produced by the project, offers bulk downloads of the data set, as well as interactive data browsing and analysis tools that are not available elsewhere. Because of performance considerations, interactive access to HapMap data via the genome browser on the HapMap Web site is limited to regions no more than 5 Mb wide. Researchers who wish to obtain data for chromosome- or genome-wide data have two choices: Bulk download or HapMart access. HapMart, described in this protocol, allows researchers to select SNPs using diverse criteria and to display just those aspects of the data set that they are interested in.

  10. A comprehensive literature review of haplotyping software and methods for use with unrelated individuals

    Directory of Open Access Journals (Sweden)

    Salem Rany M

    2005-03-01

    Full Text Available Abstract Interest in the assignment and frequency analysis of haplotypes in samples of unrelated individuals has increased immeasurably as a result of the emphasis placed on haplotype analyses by, for example, the International HapMap Project and related initiatives. Although there are many available computer programs for haplotype analysis applicable to samples of unrelated individuals, many of these programs have limitations and/or very specific uses. In this paper, the key features of available haplotype analysis software for use with unrelated individuals, as well as pooled DNA samples from unrelated individuals, are summarised. Programs for haplotype analysis were identified through keyword searches on PUBMED and various internet search engines, a review of citations from retrieved papers and personal communications, up to June 2004. Priority was given to functioning computer programs, rather than theoretical models and methods. The available software was considered in light of a number of factors: the algorithm(s used, algorithm accuracy, assumptions, the accommodation of genotyping error, implementation of hypothesis testing, handling of missing data, software characteristics and web-based implementations. Review papers comparing specific methods and programs are also summarised. Forty-six haplotyping programs were identified and reviewed. The programs were divided into two groups: those designed for individual genotype data (a total of 43 programs and those designed for use with pooled DNA samples (a total of three programs. The accuracy of programs using various criteria are assessed and the programs are categorised and discussed in light of: algorithm and method, accuracy, assumptions, genotyping error, hypothesis testing, missing data, software characteristics and web implementation. Many available programs have limitations (eg some cannot accommodate missing data and/or are designed with specific tasks in mind (eg estimating

  11. Haplotypes, sub-haplotypes and geographical distribution in Omani patients with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Suha Mustafa Hassan

    2015-05-01

    Full Text Available Despite the fact that patients homozygous for the sickle cell disease (SCD mutation have an identical genotype, the severity of the disease can be extremely variable. The hemoglobin (Hb S mutation has been described on five different haplotypes with different clinical expression. Identifying the genotypes, haplotypes and sub-haplotypes of the β gene cluster in Oman needs to be studied in more details to establish a correlation between the genotype/haplotype and phenotype diversity observed in SCD patients for prognostic purposes, accurate diagnosis and thus planning for the best tailored treatment. We have investigated 125 HbS homozygotes from different parts of Oman and determined their haplotypes and sub-haplotypes and correlated this to the hematological and clinical expression. We have found 11 haplotype combinations differently distributed in the country, with the Asian/Asian HbS haplotype being the most predominant. Sub-haplotypes was only found among patients with CAR/OmanI haplotype. As expected, the correlation between haplotypes, sub-haplotypes and disease severity was mainly associated with HbF expression. Our study on haplotype/phenotype correlation has shown which major haplotypes occur in the different regions of Oman. Furthermore, neither the haplotype or sub-haplotype nor the HbF alone appeared to be fully associable with the variable clinical phenotypes. External factors do occur and are associated with the expression of the disease.  尽管镰状细胞突变病(SCD)患者拥有相同的基因类型,但患者的病患程度却大相径庭。血红蛋白(Hb)S突变有五种不同的单体型,各种类型在临床表现上也不相同。为了识别在阿曼地区β基因簇的基因型、单体型,亚单体型,需要研究更多以SCD患者预后为目的,关于其观察到的基因型、单体型,表型多样性之间联系的更多细节,以便作出准确的诊断,为各

  12. Congruence as a measurement of extended haplotype structure across the genome

    Directory of Open Access Journals (Sweden)

    Baschal Erin E

    2012-02-01

    Full Text Available Abstract Background Historically, extended haplotypes have been defined using only a few data points, such as alleles for several HLA genes in the MHC. High-density SNP data, and the increasing affordability of whole genome SNP typing, creates the opportunity to define higher resolution extended haplotypes. This drives the need for new tools that support quantification and visualization of extended haplotypes as defined by as many as 2000 SNPs. Confronted with high-density SNP data across the major histocompatibility complex (MHC for 2,300 complete families, compiled by the Type 1 Diabetes Genetics Consortium (T1DGC, we developed software for studying extended haplotypes. Methods The software, called ExHap (Extended Haplotype, uses a similarity measurement we term congruence to identify and quantify long-range allele identity. Using ExHap, we analyzed congruence in both the T1DGC data and family-phased data from the International HapMap Project. Results Congruent chromosomes from the T1DGC data have between 96.5% and 99.9% allele identity over 1,818 SNPs spanning 2.64 megabases of the MHC (HLA-DRB1 to HLA-A. Thirty-three of 132 DQ-DR-B-A defined haplotype groups have > 50% congruent chromosomes in this region. For example, 92% of chromosomes within the DR3-B8-A1 haplotype are congruent from HLA-DRB1 to HLA-A (99.8% allele identity. We also applied ExHap to all 22 autosomes for both CEU and YRI cohorts from the International HapMap Project, identifying multiple candidate extended haplotypes. Conclusions Long-range congruence is not unique to the MHC region. Patterns of allele identity on phased chromosomes provide a simple, straightforward approach to visually and quantitatively inspect complex long-range structural patterns in the genome. Such patterns aid the biologist in appreciating genetic similarities and differences across cohorts, and can lead to hypothesis generation for subsequent studies.

  13. Synteny mapping of five human chromosome 7 genes on bovine chromosomes 4 and 21.

    Science.gov (United States)

    Antoniou, E; Womack, J E; Grosz, M D

    1999-01-01

    Five genes on human chromosome 7 (HSA 7) were assigned to bovine chromosome 21 (BTA 21) and 4 (BTA 4) using a bovine-rodent somatic hybrid cell panel. These five genes were alpha-I subunit of adenylate cyclase-inhibiting G-protein (GNAI1), alpha/beta preprotachykinin (TAC1), reelin (RELN), c-AMP dependant protein kinase type II beta regulatory chain (PRKAR2B) and apolipoprotein A1 regulatory protein 1 (TFCOUP2). Four genes mapped to BTA 4 (GNAI1, TAC1, RELN, PRKAR2B) while one gene mapped to BTA 21 (TFCOUP2). This study confirms the synteny conservation between HSA 7 and BTA 4, finely maps the breakpoints of conserved synteny on HSA 7 and defines a new synteny conservation between HSA 7 and BTA 21.

  14. Microstructural parcellation of the human cerebral cortex – from Brodmann's post-mortem map to in vivo mapping with high-field magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Stefan Geyer

    2011-02-01

    Full Text Available The year 2009 marked the 100th anniversary of the publication of the famous brain map of Korbinian Brodmann. Although a "classic" guide to microanatomical parcellation of the cerebral cortex, it is – from today's state-of-the-art neuroimaging perspective – problematic to use Brodmann's map as a structural guide to functional units in the cortex. In this article we discuss some of the reasons, especially the problematic compatibility of the "post-mortem world" of microstructural brain maps with the "in vivo world" of neuroimaging. We conclude with some prospects for the future of in vivo structural brain mapping: a new approach which has the enormous potential to make direct correlations between microstructure and function in living human brains: "in vivo Brodmann mapping" with high-field magnetic resonance imaging.

  15. Haplotype reconstruction and estimation of haplotype frequencies from nuclear families with only one parent available.

    Science.gov (United States)

    Ding, Xiangdong; Zhang, Qin; Flury, Christine; Simianer, Henner

    2006-01-01

    Recent literature has suggested that haplotype inference through close relatives, especially from nuclear families can be an alternative strategy in determining the linkage phase. In this paper, haplotype reconstruction and estimation of haplotype frequencies via expectation maximization (EM) algorithm including nuclear families with only one parent available is proposed. Parent and his (her) child are treated as parent-child pair with one shared haplotype. This reduces the number of potential haplotype pairs for both parent and child separately, resulting in a higher accuracy of the estimation. In a series of simulations, the comparisons of PHASE, GENEHUNTER, EM-based approach for complete nuclear families and our approach are carried out. In all situations, EM-based approach for trio data is comparable but slightly worse error rate than PHASE, our approach is slightly better and much faster than PHASE for incomplete trios, the performance of GENEHUNTER is very bad in simple nuclear family settings and dramatically decreased with the number of markers being increased. On the other hand, the comparison result of different sampling designs demonstrates that sampling trios is the most efficient design to estimate haplotype frequencies in populations under same genotyping cost.

  16. Haplotype sharing test maps genes for familial cardiomyopathies

    NARCIS (Netherlands)

    van der Zwaag, P. A.; van Tintelen, J. P.; Gerbens, F.; Jongbloed, J. D. H.; Boven, L. G.; van der Smagt, J. J.; van der Roest, W. P.; van Langen, I. M.; Bikker, H.; Hauer, R. N. W.; van den Berg, M. P.; Hofstra, R. M. W.; te Meerman, Gerhardus

    2011-01-01

    Identifying a mutation in a heterogeneous disease such as inherited cardiomyopathy is a challenge because classical methods, like linkage analysis, can often not be applied as there are too few meioses between affected individuals. However, if affected individuals share the same causal mutation, the

  17. SNP and haplotype mapping for genetic analysis in the rat.

    NARCIS (Netherlands)

    Saar, K.; Beck, A.; Bihoreau, M.; Birney, E.; Brocklebank, D.; Chen, Y.; Cuppen, E.; Demonchy, S.; Dopazo, J.; Flicek, P.; Foglio, M.; Fujiyama, A.; Gut, I.G.; Gauguier, D.; Guigo, R.; Guryev, V.; Heinig, M.; Hummel, O.; Jahn, N.; Klages, S.; Kren, V.; Kube, M.; Kuhl, H.; Kuramoto, T.; Kuroki, Y.; Lechner, D.; Lee, Y.A.; Lopez-Bigas, N.; Lathrop, G.M.; Mashimo, T.; Medina, I.; Mott, R.; Patone, G.; Perrier-Cornet, J.A.; Platzer, M.; Pravenec, M.; Reinhardt, R.; Sakaki, Y.; Schilhabel, M.; Schulz, H.; Serikawa, T.; Shikhagaie, M.; Tatsumoto, S.; Taudien, S.; Toyoda, A.; Voigt, B.; Zelenika, D.; Zimdahl, H.; Hubner, N.

    2008-01-01

    The laboratory rat is one of the most extensively studied model organisms. Inbred laboratory rat strains originated from limited Rattus norvegicus founder populations, and the inherited genetic variation provides an excellent resource for the correlation of genotype to phenotype. Here, we report a s

  18. SNP and haplotype mapping for genetic analysis in the rat

    NARCIS (Netherlands)

    Saar, Kathrin; Beck, Alfred; Bihoreau, Marie-Thérèse; Birney, Ewan; Brocklebank, Denise; Chen, Yuan; Cuppen, Edwin; Demonchy, Stephanie; Dopazo, Joaquin; Flicek, Paul; Foglio, Mario; Fujiyama, Asao; Gut, Ivo G; Gauguier, Dominique; Guigo, Roderic; Guryev, Victor; Heinig, Matthias; Hummel, Oliver; Jahn, Niels; Klages, Sven; Kren, Vladimir; Kube, Michael; Kuhl, Heiner; Kuramoto, Takashi; Kuroki, Yoko; Lechner, Doris; Lee, Young-Ae; Lopez-Bigas, Nuria; Lathrop, G Mark; Mashimo, Tomoji; Medina, Ignacio; Mott, Richard; Patone, Giannino; Perrier-Cornet, Jeanne-Antide; Platzer, Matthias; Pravenec, Michal; Reinhardt, Richard; Sakaki, Yoshiyuki; Schilhabel, Markus; Schulz, Herbert; Serikawa, Tadao; Shikhagaie, Medya; Tatsumoto, Shouji; Taudien, Stefan; Toyoda, Atsushi; Voigt, Birger; Zelenika, Diana; Zimdahl, Heike; Hubner, Norbert

    2008-01-01

    The laboratory rat is one of the most extensively studied model organisms. Inbred laboratory rat strains originated from limited Rattus norvegicus founder populations, and the inherited genetic variation provides an excellent resource for the correlation of genotype to phenotype. Here, we report a s

  19. Three Novel Haplotypes of Theileria bicornis in Black and White Rhinoceros in Kenya.

    Science.gov (United States)

    Otiende, M Y; Kivata, M W; Jowers, M J; Makumi, J N; Runo, S; Obanda, V; Gakuya, F; Mutinda, M; Kariuki, L; Alasaad, S

    2016-02-01

    Piroplasms, especially those in the genera Babesia and Theileria, have been found to naturally infect rhinoceros. Due to natural or human-induced stress factors such as capture and translocations, animals often develop fatal clinical piroplasmosis, which causes death if not treated. This study examines the genetic diversity and occurrence of novel Theileria species infecting both black and white rhinoceros in Kenya. Samples collected opportunistically during routine translocations and clinical interventions from 15 rhinoceros were analysed by polymerase chain reaction (PCR) using a nested amplification of the small subunit ribosomal RNA (18S rRNA) gene fragments of Babesia and Theileria. Our study revealed for the first time in Kenya the presence of Theileria bicornis in white (Ceratotherium simum simum) and black (Diceros bicornis michaeli) rhinoceros and the existence of three new haplotypes: haplotypes H1 and H3 were present in white rhinoceros, while H2 was present in black rhinoceros. No specific haplotype was correlated to any specific geographical location. The Bayesian inference 50% consensus phylogram recovered the three haplotypes monophyleticly, and Theileria bicornis had very high support (BPP: 0.98). Furthermore, the genetic p-uncorrected distances and substitutions between T. bicornis and the three haplotypes were the same in all three haplotypes, indicating a very close genetic affinity. This is the first report of the occurrence of Theileria species in white and black rhinoceros from Kenya. The three new haplotypes reported here for the first time have important ecological and conservational implications, especially for population management and translocation programs and as a means of avoiding the transport of infected animals into non-affected areas.

  20. Identification of a 10/10 matched donor for patients with an uncommon haplotype is unlikely.

    Science.gov (United States)

    Olson, J A; Gibbens, Y; Tram, K; Kempenich, J; Novakovich, J; Buck, K; Dehn, J

    2017-02-01

    Despite over 6 million subjects contributing to the National Marrow Donor Program human leukocyte antigen (HLA) haplotype frequency reference data (HFD), haplotypes cannot be predicted from the HLA assignments of some patients searching for an unrelated donor (URD) in the Be The Match Registry®. We aimed to determine the incidence of these patient searches and whether haplotypes lacking from the HFD can be found among the low-resolution typed URD pool. New NMDP searches with uncommon patient haplotypes (UPH), defined as a lack of haplotype pairs in any single ethnic group in the HFD based upon HLA-A˜C˜B˜DRB1˜DQB1, were identified. Each search had up to 20 potential 10/10 or 8/8 URDs typed to determine the likelihood of an allele match. The incidence of patient searches without haplotype pairs in a single ethnic group in the HFD was 1.2% (N=144 out of 12,172) and a majority of these patients (117; 81%) had one uncommon haplotype previously uncharacterized in the HFD. Non-White patients had the highest incidence of UPH. Importantly, no patients with UPH had a 10/10 URD identified. The transplant rate among UPH patients was 15%, and a majority of these patients utilized cord blood units as their transplant stem cell source. Therefore, the HLA HFD that informs the HapLogic matching algorithm is thorough as UPH patient searches were infrequent. Since such patients are highly unlikely to have a fully 10/10 matched URD identified, this study supports the identification of alternative stem cell sources including cord blood or a mismatched URD early in the search process. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Understanding the contrasting spatial haplotype patterns of malaria-protective β-globin polymorphisms.

    Science.gov (United States)

    Hockham, Carinna; Piel, Frédéric B; Gupta, Sunetra; Penman, Bridget S

    2015-12-01

    The malaria-protective β-globin polymorphisms, sickle-cell (β(S)) and β(0)-thalassaemia, are canonical examples of human adaptation to infectious disease. Occurring on distinct genetic backgrounds, they vary markedly in their patterns of linked genetic variation at the population level, suggesting different evolutionary histories. β(S) is associated with five classical restriction fragment length polymorphism haplotypes that exhibit remarkable specificity in their geographical distributions; by contrast, β(0)-thalassaemia mutations are found on haplotypes whose distributions overlap considerably. Here, we explore why these two polymorphisms display contrasting spatial haplotypic distributions, despite having malaria as a common selective pressure. We present a meta-population genetic model, incorporating individual-based processes, which tracks the evolution of β-globin polymorphisms on different haplotypic backgrounds. Our simulations reveal that, depending on the rate of mutation, a large population size and/or high population growth rate are required for both the β(S)- and the β(0)-thalassaemia-like patterns. However, whilst the β(S)-like pattern is more likely when population subdivision is high, migration low and long-distance migration absent, the opposite is true for β(0)-thalassaemia. Including gene conversion has little effect on the overall probability of each pattern; however, when inter-haplotype fitness variation exists, gene conversion is more likely to have contributed to the diversity of haplotypes actually present in the population. Our findings highlight how the contrasting spatial haplotype patterns exhibited by β(S) and β(0)-thalassaemia may provide important indications as to the evolution of these adaptive alleles and the demographic history of the populations in which they have evolved.

  2. A First Generation Comparative Chromosome Map between Guinea Pig (Cavia porcellus) and Humans.

    Science.gov (United States)

    Romanenko, Svetlana A; Perelman, Polina L; Trifonov, Vladimir A; Serdyukova, Natalia A; Li, Tangliang; Fu, Beiyuan; O'Brien, Patricia C M; Ng, Bee L; Nie, Wenhui; Liehr, Thomas; Stanyon, Roscoe; Graphodatsky, Alexander S; Yang, Fengtang

    2015-01-01

    The domesticated guinea pig, Cavia porcellus (Hystricomorpha, Rodentia), is an important laboratory species and a model for a number of human diseases. Nevertheless, genomic tools for this species are lacking; even its karyotype is poorly characterized. The guinea pig belongs to Hystricomorpha, a widespread and important group of rodents; so far the chromosomes of guinea pigs have not been compared with that of other hystricomorph species or with any other mammals. We generated full sets of chromosome-specific painting probes for the guinea pig by flow sorting and microdissection, and for the first time, mapped the chromosomal homologies between guinea pig and human by reciprocal chromosome painting. Our data demonstrate that the guinea pig karyotype has undergone extensive rearrangements: 78 synteny-conserved human autosomal segments were delimited in the guinea pig genome. The high rate of genome evolution in the guinea pig may explain why the HSA7/16 and HSA16/19 associations presumed ancestral for eutherians and the three syntenic associations (HSA1/10, 3/19, and 9/11) considered ancestral for rodents were not found in C. porcellus. The comparative chromosome map presented here is a starting point for further development of physical and genetic maps of the guinea pig as well as an aid for genome assembly assignment to specific chromosomes. Furthermore, the comparative mapping will allow a transfer of gene map data from other species. The probes developed here provide a genomic toolkit, which will make the guinea pig a key species to unravel the evolutionary biology of the Hystricomorph rodents.

  3. Molecular structure and chromosomal mapping of the human homolog of the agouti gene

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, H.Y.; Woychik, R.P. [Oak Ridge National Lab., TN (United States); Bultman, S.J. [Oak Ridge National Lab., TN (United States)]|[Univ. of Tennessee, Oak Ridge, TN (United States); Loeffler, C.; Hansmann, I. [Universitaet Goettingen (Germany); Chen, W.J.; Furdon, P.J.; Wilkison, W. [Glaxo Research Institute, Research Triangle Park, NC (United States); Powell, J.G.; Usala, A.L. [Eastern Carolina Univ., Greenville, NC (United States)

    1994-10-11

    The agouti (a) locus in mouse chromosome 2 normally regulates coat color pigmentation. The mouse agouti gene was recently cloned and shown to encode a distinctive 131-amino acid protein with a consensus signal peptide. Here the authors describe the cloning of the human homolog of the mouse agouti gene using an interspecies DNA-hybridization approach. Sequence analysis revealed that the coding region of the human agouti gene is 85% identical to the mouse gene and has the potential to encode a protein of 132 amino acids with a consensus signal peptide. Chromosomal assignment using somatic-cell-hybrid mapping panels and fluorescence in situ hybridization demonstrated that the human agouti gene maps to chromosome band 20q11.2. This result revealed that the human agouti gene is closely linked to several traits, including a locus called MODY (for maturity onset diabetes of the young) and another region that is associated with the development of myeloid leukemia. Initial expression studies with RNA from several adult human tissues showed that the human agouti gene is expressed in adipose tissue and testis.

  4. Urea hydrolysis and recovery of nitrogen and phosphorous as MAP from stale human urine

    Institute of Scientific and Technical Information of China (English)

    LIU Zhigang; ZHAO Qingliang; WANG Kun; LEE Duujong; QIU Wei; WANG Jianfang

    2008-01-01

    Laboratory-scale tests for magnesium ammonium phosphate (MAP) precipitation following urea hydrolysis of human urine were conducted using orthogonal experiment design. The effects of initial pH, temperature and the volumetric ratios of stale urine to fresh urine, on urea hydrolysis in urine were studied to determine the final hydrolysis time to recover most nitrogen from separated human urine by MAP. With a volumetric ratio of stale to fresh urine >10% and at temperature of 20℃ and above, urea hydrolysis could be completed in two days. Alkaline pH inhibited urea hydrolysis progress. The final pHs were all around 9.0 following urine hydrolysis, while the suspension pH might act as an indicator to detect the start and extent of urea hydrolysis. Over 95% of ammonium nitrogen and over 85% of phosphorus from hydrolyzed urine as MAP precipitate were obtained using MgCl2·6H2O and Na2HPO4·12H2O as precipitation agents at pH 8.5, molar ratio of Mg2+:NH4+-N:PO43--P at (1.2--1.3):1:1, mixing speed of 120 r/min, and precipitation time and reaction time of 3 h and 15 min, respectively. The precipitate has a structure resembling pure MAP crystal.

  5. Human and Robotic Mission to Small Bodies: Mapping, Planning and Exploration

    Science.gov (United States)

    Neffian, Ara V.; Bellerose, Julie; Beyer, Ross A.; Archinal, Brent; Edwards, Laurence; Lee, Pascal; Colaprete, Anthony; Fong, Terry

    2013-01-01

    This study investigates the requirements, performs a gap analysis and makes a set of recommendations for mapping products and exploration tools required to support operations and scientific discovery for near- term and future NASA missions to small bodies. The mapping products and their requirements are based on the analysis of current mission scenarios (rendezvous, docking, and sample return) and recommendations made by the NEA Users Team (NUT) in the framework of human exploration. The mapping products that sat- isfy operational, scienti c, and public outreach goals include topography, images, albedo, gravity, mass, density, subsurface radar, mineralogical and thermal maps. The gap analysis points to a need for incremental generation of mapping products from low (flyby) to high-resolution data needed for anchoring and docking, real-time spatial data processing for hazard avoidance and astronaut or robot localization in low gravity, high dynamic environments, and motivates a standard for coordinate reference systems capable of describing irregular body shapes. Another aspect investigated in this study is the set of requirements and the gap analysis for exploration tools that support visualization and simulation of operational conditions including soil interactions, environment dynamics, and communications coverage. Building robust, usable data sets and visualisation/simulation tools is the best way for mission designers and simulators to make correct decisions for future missions. In the near term, it is the most useful way to begin building capabilities for small body exploration without needing to commit to specific mission architectures.

  6. The effects of old and recent migration waves in the distribution of HBB*S globin gene haplotypes

    OpenAIRE

    Lindenau, Juliana D.; Sandrine C. Wagner; Simone M. Castro; Mara H. Hutz

    2016-01-01

    Abstract Sickle cell hemoglobin is the result of a mutation at the sixth amino acid position of the beta (β) globin chain. The HBB*S gene is in linkage disequilibrium with five main haplotypes in the β-globin-like gene cluster named according to their ethnic and geographic origins: Bantu (CAR), Benin (BEN), Senegal (SEN), Cameroon (CAM) and Arabian-Indian (ARAB). These haplotypes demonstrated that the sickle cell mutation arose independently at least five times in human history. The...

  7. The origin of human chromosome 2 analyzed by comparative chromosome mapping with a DNA microlibrary

    OpenAIRE

    Wienberg, Johannes; Jauch, Anna; Lüdecke, H J; Senger, G.; Horsthemke, B; Claussen, U.; Cremer, Thomas; Arnold, N; Lengauer, Christoph

    1994-01-01

    Fluorescencein situ hybridization (FISH) of microlibraries established from distinct chromosome subregions can test the evolutionary conservation of chromosome bands as well as chromosomal rearrangements that occurred during primate evolution and will help to clarify phylogenetic relationships. We used a DNA library established by microdissection and microcloning from the entire long arm of human chromosome 2 for fluorescencein situ hybridization and comparative mapping of the chromosomes of ...

  8. In-vitro Thermal Maps to Characterize Human Dental Enamel and Dentin

    OpenAIRE

    Lancaster, Paula; Brettle, David; Carmichael, Fiona; Clerehugh, Val

    2017-01-01

    The crown of a human tooth has an outer layer of highly-mineralized tissue called enamel, beneath which is dentin, a less-mineralized tissue which forms the bulk of the tooth-crown and root. The composition and structure of enamel and dentin are different, resulting in different thermal properties. This gives an opportunity to characterize enamel and dentin from their thermal properties and to visually present the findings as a thermal map. The thermal properties of demineralized enamel and d...

  9. Genetic differences in the two main groups of the Japanese population based on autosomal SNPs and haplotypes.

    Science.gov (United States)

    Yamaguchi-Kabata, Yumi; Tsunoda, Tatsuhiko; Kumasaka, Natsuhiko; Takahashi, Atsushi; Hosono, Naoya; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki

    2012-05-01

    Although the Japanese population has a rather low genetic diversity, we recently confirmed the presence of two main clusters (the Hondo and Ryukyu clusters) through principal component analysis of genome-wide single-nucleotide polymorphism (SNP) genotypes. Understanding the genetic differences between the two main clusters requires further genome-wide analyses based on a dense SNP set and comparison of haplotype frequencies. In the present study, we determined haplotypes for the Hondo cluster of the Japanese population by detecting SNP homozygotes with 388,591 autosomal SNPs from 18,379 individuals and estimated the haplotype frequencies. Haplotypes for the Ryukyu cluster were inferred by a statistical approach using the genotype data from 504 individuals. We then compared the haplotype frequencies between the Hondo and Ryukyu clusters. In most genomic regions, the haplotype frequencies in the Hondo and Ryukyu clusters were very similar. However, in addition to the human leukocyte antigen region on chromosome 6, other genomic regions (chromosomes 3, 4, 5, 7, 10 and 12) showed dissimilarities in haplotype frequency. These regions were enriched for genes involved in the immune system, cell-cell adhesion and the intracellular signaling cascade. These differentiated genomic regions between the Hondo and Ryukyu clusters are of interest because they (1) should be examined carefully in association studies and (2) likely contain genes responsible for morphological or physiological differences between the two groups.

  10. The effects of old and recent migration waves in the distribution of HBB*S globin gene haplotypes

    Directory of Open Access Journals (Sweden)

    Juliana D. Lindenau

    Full Text Available Abstract Sickle cell hemoglobin is the result of a mutation at the sixth amino acid position of the beta (β globin chain. The HBB*S gene is in linkage disequilibrium with five main haplotypes in the β-globin-like gene cluster named according to their ethnic and geographic origins: Bantu (CAR, Benin (BEN, Senegal (SEN, Cameroon (CAM and Arabian-Indian (ARAB. These haplotypes demonstrated that the sickle cell mutation arose independently at least five times in human history. The distribution of βS haplotypes among Brazilian populations showed a predominance of the CAR haplotype. American populations were clustered in two groups defined by CAR or BEN haplotype frequencies. This scenario is compatible with historical records about the slave trade in the Americas. When all world populations where the sickle cell gene occurs were analyzed, three clusters were disclosed based on CAR, BEN or ARAB haplotype predominance. These patterns may change in the next decades due to recent migrations waves. Since these haplotypes show different clinical characteristics, these recent migrations events raise the necessity to develop optimized public health programs for sickle cell disease screening and management.

  11. The effects of old and recent migration waves in the distribution of HBB*S globin gene haplotypes.

    Science.gov (United States)

    Lindenau, Juliana D; Wagner, Sandrine C; Castro, Simone M de; Hutz, Mara H

    2016-01-01

    Sickle cell hemoglobin is the result of a mutation at the sixth amino acid position of the beta (β) globin chain. The HBB*S gene is in linkage disequilibrium with five main haplotypes in the β-globin-like gene cluster named according to their ethnic and geographic origins: Bantu (CAR), Benin (BEN), Senegal (SEN), Cameroon (CAM) and Arabian-Indian (ARAB). These haplotypes demonstrated that the sickle cell mutation arose independently at least five times in human history. The distribution of βS haplotypes among Brazilian populations showed a predominance of the CAR haplotype. American populations were clustered in two groups defined by CAR or BEN haplotype frequencies. This scenario is compatible with historical records about the slave trade in the Americas. When all world populations where the sickle cell gene occurs were analyzed, three clusters were disclosed based on CAR, BEN or ARAB haplotype predominance. These patterns may change in the next decades due to recent migrations waves. Since these haplotypes show different clinical characteristics, these recent migrations events raise the necessity to develop optimized public health programs for sickle cell disease screening and management.

  12. Unexpected observations after mapping LongSAGE tags to the human genome

    Directory of Open Access Journals (Sweden)

    Duret Laurent

    2007-05-01

    Full Text Available Abstract Background SAGE has been used widely to study the expression of known transcripts, but much less to annotate new transcribed regions. LongSAGE produces tags that are sufficiently long to be reliably mapped to a whole-genome sequence. Here we used this property to study the position of human LongSAGE tags obtained from all public libraries. We focused mainly on tags that do not map to known transcripts. Results Using a published error rate in SAGE libraries, we first removed the tags likely to result from sequencing errors. We then observed that an unexpectedly large number of the remaining tags still did not match the genome sequence. Some of these correspond to parts of human mRNAs, such as polyA tails, junctions between two exons and polymorphic regions of transcripts. Another non-negligible proportion can be attributed to contamination by murine transcripts and to residual sequencing errors. After filtering out our data with these screens to ensure that our dataset is highly reliable, we studied the tags that map once to the genome. 31% of these tags correspond to unannotated transcripts. The others map to known transcribed regions, but many of them (nearly half are located either in antisense or in new variants of these known transcripts. Conclusion We performed a comprehensive study of all publicly available human LongSAGE tags, and carefully verified the reliability of these data. We found the potential origin of many tags that did not match the human genome sequence. The properties of the remaining tags imply that the level of sequencing error may have been under-estimated. The frequency of tags matching once the genome sequence but not in an annotated exon suggests that the human transcriptome is much more complex than shown by the current human genome annotations, with many new splicing variants and antisense transcripts. SAGE data is appropriate to map new transcripts to the genome, as demonstrated by the high rate of cross

  13. A comprehensive haplotype analysis of the XPC genomic sequence reveals a cluster of genetic variants associated with sensitivity to tobacco-smoke mutagens.

    Science.gov (United States)

    Rondelli, Catherine M; El-Zein, Randa A; Wickliffe, Jeffrey K; Etzel, Carol J; Abdel-Rahman, Sherif Z

    2010-05-01

    The impact of single-nucleotide polymorphisms (SNPs) of the DNA repair gene XPC on DNA repair capacity (DRC) and genotoxicity has not been comprehensively determined. We constructed a comprehensive haplotype map encompassing all common XPC SNPs and evaluated the effect of Bayesian-inferred haplotypes on DNA damage associated with tobacco smoking, using chromosome aberrations (CA) as a biomarker. We also used the mutagen-sensitivity assay, in which mutagen-induced CA in cultured lymphocytes are determined, to evaluate the haplotype effects on DRC. We hypothesized that if certain XPC haplotypes have functional effects, a correlation between these haplotypes and baseline and/or mutagen-induced CA would exist. Using HapMap and single nucleotide polymorphism (dbSNP) databases, we identified 92 SNPs, of which 35 had minor allele frequencies >or= 0.05. Bayesian inference and subsequent phylogenetic analysis identified 21 unique haplotypes, which segregated into six distinct phylogenetically grouped haplotypes (PGHs A-F). A SNP tagging approach used identified 11 tagSNPs representing these 35 SNPs (r(2) = 0.80). We utilized these tagSNPs to genotype a population of smokers matched to nonsmokers (n = 123). Haplotypes for each individual were reconstituted and PGH designations were assigned. Relationships between XPC haplotypes and baseline and/or mutagen-induced CA were then evaluated. We observed significant interaction among smoking and PGH-C (p = 0.046) for baseline CA where baseline CA was 3.5 times higher in smokers compared to nonsmokers. Significant interactions among smoking and PGH-D (p = 0.023) and PGH-F (p = 0.007) for mutagen-induced CA frequencies were also observed. These data indicate that certain XPC haplotypes significantly alter CA and DRC in smokers and, thus, can contribute to cancer risk.

  14. Polymorphic distribution of Y-chromosome haplotype and mitochondrial DNA in the Bouyei people in China

    Institute of Scientific and Technical Information of China (English)

    李永念; 左丽; 文波; 柯越海; 黄薇; 金力

    2004-01-01

    @@ In the evolution of humans, many kinds of mutations in the human genome have been accumulated, providing credible genetic evidence for the study of human origins and migrations. The "out-of-Africa" hypothesis of modern human evolution and the genetic origin of the Japanese has come about by studying mitochondrial DNA.l,2 Recently, researchers have recognized the power of Y-chromosome markers in resolving migratory patterns of modern humans as more and more Y-chromosome single nucleotide polymorphism markers have been found. The markers on the nonrecombinant part of the Y-chromosome allows for the reconstruction of intact haplotypes which are probably the best genetic tools to study human migrations. We can analyze the paternal history of some people in different areas by Y-chromosome haplotypes.

  15. A High-Density Map for Navigating the Human Polycomb Complexome

    DEFF Research Database (Denmark)

    Hauri, Simon; Comoglio, Federico; Seimiya, Makiko;

    2016-01-01

    Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. Here, we systematically mapped the human PcG complexome using a robust affinity purification mass spectrometry approach. Our high-density protein interaction network uncovered...... complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes...

  16. Cloning and comparative mapping of a human chromosome 4-specific alpha satellite DNA sequence.

    Science.gov (United States)

    D'Aiuto, L; Antonacci, R; Marzella, R; Archidiacono, N; Rocchi, M

    1993-11-01

    We have isolated and characterized two human alphoid DNA clones: p4n1/4 and pZ4.1. Clone p4n1/4 identifies specifically the centromeric region of chromosome 4; pZ4.1 recognizes a subset of alphoid DNA shared by chromosomes 4 and 9. The specificity was determined using fluorescence in situ hybridization experiments on metaphase spreads and Southern blotting analysis of human-hamster somatic cell hybrids. The genomic organization of both subsets was also investigated. Comparative mapping on chimpanzee and gorilla chromosomes was performed. p4n1/4 hybridizes to chimpanzee chromosomes 11 and 13, homologs of human chromosomes 9 and 2q, respectively. On gorilla metaphase spreads, p4n1/4 hybridizes exclusively to the centromeric region of chromosome 19, partially homologous to human chromosome 17. No hybridization signal was detected on chromosome 3 of both chimpanzee and gorilla, in both species homolog of human chromosome 4. Identical comparative mapping results were obtained using pZ4.1 probe, although the latter recognizes an alphoid subset distinct from the one recognized by p4n1/4. The implications of these results in the evolution of centromeric regions of primate chromosomes are discussed.

  17. Cloning and comparative mapping of a human chromosome 4-specific alpha satellite DNA sequence

    Energy Technology Data Exchange (ETDEWEB)

    D' Aiuto, L.; Marzella, R.; Archidiacono, N.; Rocchi, M. (Universita di Bari (Italy)); Antonacci, R. (Instituto Anatomia Umana Normale, Modena (Italy))

    1993-11-01

    The authors have isolated and characterized two human alphoid DNA clones: p4n1/4 and pZ4.1. Clone p4n1/4 identifies specifically the centromeric region of chromosome 4; pZ4.1 recognizes a subset of alphoid DNA shared by chromosomes 4 and 9. The specificity was determined using fluorescence in situ hybridization experiments on metaphase spreads and Southern blotting analysis of human-hamster somatic cell hybrids. The genomic organization of both subsets was also investigated. Comparative mapping on chimpanzee and gorilla chromosomes was performed. p4n1/4 hybridizes to chimpanzee chromosomes 11 and 13, homologs of human chromosomes 9 and 2q, respectively. On gorilla metaphase spreads, p4n1/4 hybridizes exclusively to the centromeric region of chromosome 19, partially homologous to human chromosome 17. No hybridization signal was detected on chromosome 3 of both chimpanzee and gorilla, in both species homolog of human chromosome 4. Identical comparative mapping results were obtained using pZ4.1 probe, although the latter recognizes an alphoid subset distinct from the one recognized by p4n1/4. The implications of these results in the evolution of centromeric regions of primate chromosomes are discussed. 33 refs., 4 figs.

  18. Gene structure of the human DDX3 and chromosome mapping of its related sequences.

    Science.gov (United States)

    Kim, Y S; Lee, S G; Park, S H; Song, K

    2001-10-31

    The human DDX3 gene (GenBank accession No. U50553) is the human homologue of the mouse Ddx3 gene and is a member of the gene family that contains DEAD motifs. Previously, we mapped the gene to the Xp11.3-11.23. In this report, we describe the structural organization of the human DDX3 gene. It consisted of 17 exons that span approximately 16 kb. An Alu element was present in the intron 13. Its organization was the same as that of the human DBY gene, a closely related sequence present on the Y chromosome. We also identified two processed pseudogenes (DDX3) with a sequence that is highly homologous to those of DDX3 cDNAs, but contain a translation termination codon within its open-reading frame. Pseudogenes are mapped on human chromosomes 4 and X, respectively. In this paper, we discuss the relationships between DDX3 and its related sequences that have been isolated.

  19. The human HNRPD locus maps to 4q21 and encodes a highly conserved protein.

    Science.gov (United States)

    Dempsey, L A; Li, M J; DePace, A; Bray-Ward, P; Maizels, N

    1998-05-01

    The hnRNP D protein interacts with nucleic acids both in vivo and in vitro. Like many other proteins that interact with RNA, it contains RBD (or "RRM") domains and arg-gly-gly (RGG) motifs. We have examined the organization and localization of the human and murine genes that encode the hnRNP D protein. Comparison of the predicted sequences of the hnRNP D proteins in human and mouse shows that they are 96.9% identical (98.9% similar). This very high level of conservation suggests a critical function for hnRNP D. Sequence analysis of the human HNRPD gene shows that the protein is encoded by eight exons and that two additional exons specify sequences in the 3' UTR. Use of two of the coding exons is determined by alternative splicing of the HNRPD mRNA. The human HNRPD gene maps to 4q21. The mouse Hnrpd gene maps to the F region of chromosome 3, which is syntenic with the human 4q21 region.

  20. Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy

    DEFF Research Database (Denmark)

    Hor, Hyun; Kutalik, Zoltán; Dauvilliers, Yves;

    2010-01-01

    Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB1*1501-DQB1*0602 haplotype is common in the general population (15-25%), it has been suggested that it is almost necessary but not sufficient for developing ...

  1. The International Human Genome Haplotype Map (HapMap) Project and Its China Chapter%人类基因组单体型图计划及其"中国卷"

    Institute of Scientific and Technical Information of China (English)

    曾长青

    2003-01-01

    国际人类基因组单体型图计划是针对亚、非、欧裔全基因组中的一百万或更多的单核苷酸序列差异位点进行测定和分析,构建出整合了人类遗传多态信息的每条染色体的"单体型图",为疾病相关的基因研究提供全球共享的最基本数据.在这一多国参与的重大国际合作项目中,中国将做出10%的贡献,其具体内容为构建3号、21号染色体和8号染色体短臂的单体型图以及提供一半的亚洲样品.中国团队确定的平台技术有基于引物延伸方法的Sequenom的质谱检测系统和PerkinElmer的荧光偏振检测系统以及基于分子杂交原理的Illumina的光纤磁珠检测系统.

  2. Physical and genetic mapping of the muscle phosphofructokinase gene (PFKM): Reassignment to human chromosome 12q

    Energy Technology Data Exchange (ETDEWEB)

    Howard, T.D.; Akots, G.; Bowden, D.W. [Bowman Gray School of Medicine of Wake Forest Univ., Winston-Salem, NC (United States)

    1996-05-15

    Phosphofructokinase (PFK) is a key rate-limiting enzyme in glycolysis and represents a major control point in the metabolism of glucose. There are at least three known isoforms of PFK in humans, referred to as the muscle, platelet, and liver forms, each of which is differentially expressed in various tissues. The gene for muscle phosphofructokinase, PFKM, is mutated in Tarui disease and conceivably contributes to non-insulin-dependent diabetes mellitus (NIDDM). Based on physical and genetic mapping, we have found that the gene for PFKM does not map to chromosome 1 as previously described, but instead maps to chromosome 12. PCR analysis with a somatic cell hybrid mapping panel using primers derived from intron 6 and exon 18 of the PFKM gene showed consistent amplification of cell lines containing chromosome 12 (concordance, 100%). Fluorescence in situ hybridization analysis with CEPH YAC 762G4, isolated with exon 18 primers, indicated that this clone maps to 12q13, centromeric to the diacylglycerol kinase gene (DAGK) at 12q13.3. A highly informative genetic marker isolated from YAC 762G4 was used to map PFKM genetically between the CHLC framework markers D12S1090 and D12S390. This placement for 762G4 was significantly proximal to the recently reported locus for a third gene for maturity onset diabetes of the young (MODY). The PFKM-associated microsatellite will be a valuable tool in the evaluation of PFKM in diabetic populations as well as in linkage analysis in families with Tarui disease. 23 refs., 3 figs., 2 tabs.

  3. The Wilson disease gene: Haplotypes and mutations

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, G.R.; Roberts, E.A.; Cox, D.W. [Hospital for Sick Children, Toronto (Canada); Walshe, J.M. [Middlesex Hospital, London (United Kingdom)

    1994-09-01

    Wilson disease (WND) is an autosomal recessive defect of copper transport. The gene involved in WND, located on chromosome 13, has recently been shown to be a putative copper transporting P-type ATPase, designated ATP7B. The gene is highly similar to ATP7A, located on the X chromosome, which is defective in Menkes disease, another disorder of copper transport. We have available for study WND families from Canada (34 families), the United Kingdom (32 families), Japan (4 families), Iceland (3 families) and Hong Kong (2 families). We have utilized four highly polymorphic CA repeat markers (D13S296, D13S301, D13S314 and D13S316) surrounding the ATP7B locus to construct haplotypes in these families. Analysis indicates that there are many unique WND haplotypes not present on normal chromosomes and that there may be a large number of different WND mutations. We have screened the WND patients for mutations in the ATP7B gene. Fifty six patients, representing all of the identified haplotypes, have been screened using single strand conformational polymorphism (SSCP), followed by selective sequencing. To date, 19 mutations and 12 polymorphisms have been identified. All of the changes are nucleotide substitutions or small insertions/deletions and there is no evidence for larger deletions as seen in the similar gene on the X chromosome, ATP7A. Haplotypes of close markers and the ability to detect some of the mutations present in the gene allow for more reliable molecular diagnosis of presymptomatic sibs of WND patients. A reassessment of individuals previously diagnosed in the presymptomatic phase is now required, as we have have identified some heterozygotes who are biochemically indistinguishable from affected homozygotes. The identification of specific mutations will soon allow direct diagnosis of WND patients with a high level of certainty.

  4. A linear-time algorithm for reconstructing zero-recombinant haplotype configuration on a pedigree

    Science.gov (United States)

    2012-01-01

    Background When studying genetic diseases in which genetic variations are passed on to offspring, the ability to distinguish between paternal and maternal alleles is essential. Determining haplotypes from genotype data is called haplotype inference. Most existing computational algorithms for haplotype inference have been designed to use genotype data collected from individuals in the form of a pedigree. A haplotype is regarded as a hereditary unit and therefore input pedigrees are preferred that are free of mutational events and have a minimum number of genetic recombinational events. These ideas motivated the zero-recombinant haplotype configuration (ZRHC) problem, which strictly follows the Mendelian law of inheritance, namely that one haplotype of each child is inherited from the father and the other haplotype is inherited from the mother, both without any mutation. So far no linear-time algorithm for ZRHC has been proposed for general pedigrees, even though the number of mating loops in a human pedigree is usually very small and can be regarded as constant. Results Given a pedigree with n individuals, m marker loci, and k mating loops, we proposed an algorithm that can provide a general solution to the zero-recombinant haplotype configuration problem in O(kmn + k2m) time. In addition, this algorithm can be modified to detect inconsistencies within the genotype data without loss of efficiency. The proposed algorithm was subject to 12000 experiments to verify its performance using different (n, m) combinations. The value of k was uniformly distributed between zero and six throughout all experiments. The experimental results show a great linearity in terms of execution time in relation to input size when both n and m are larger than 100. For those experiments where n or m are less than 100, the proposed algorithm runs very fast, in thousandth to hundredth of a second, on a personal desktop computer. Conclusions We have developed the first deterministic linear

  5. Making sense of human ecology mapping: an overview of approaches to integrating socio-spatial data into environmental planning

    Science.gov (United States)

    Rebecca McLain; Melissa R. Poe; Kelly Biedenweg; Lee K. Cerveny; Diane Besser; Dale J. Blahna

    2013-01-01

    Ecosystem-based planning and management have stimulated the need to gather sociocultural values and human uses of land in formats accessible to diverse planners and researchers. Human Ecology Mapping (HEM) approaches offer promising spatial data gathering and analytical tools, while also addressing important questions about human-landscape connections. This article...

  6. Fast and accurate haplotype frequency estimation for large haplotype vectors from pooled DNA data

    Directory of Open Access Journals (Sweden)

    Iliadis Alexandros

    2012-10-01

    Full Text Available Abstract Background Typically, the first phase of a genome wide association study (GWAS includes genotyping across hundreds of individuals and validation of the most significant SNPs. Allelotyping of pooled genomic DNA is a common approach to reduce the overall cost of the study. Knowledge of haplotype structure can provide additional information to single locus analyses. Several methods have been proposed for estimating haplotype frequencies in a population from pooled DNA data. Results We introduce a technique for haplotype frequency estimation in a population from pooled DNA samples focusing on datasets containing a small number of individuals per pool (2 or 3 individuals and a large number of markers. We compare our method with the publicly available state-of-the-art algorithms HIPPO and HAPLOPOOL on datasets of varying number of pools and marker sizes. We demonstrate that our algorithm provides improvements in terms of accuracy and computational time over competing methods for large number of markers while demonstrating comparable performance for smaller marker sizes. Our method is implemented in the "Tree-Based Deterministic Sampling Pool" (TDSPool package which is available for download at http://www.ee.columbia.edu/~anastas/tdspool. Conclusions Using a tree-based determinstic sampling technique we present an algorithm for haplotype frequency estimation from pooled data. Our method demonstrates superior performance in datasets with large number of markers and could be the method of choice for haplotype frequency estimation in such datasets.

  7. Indoor Localization Algorithms for an Ambulatory Human Operated 3D Mobile Mapping System

    Energy Technology Data Exchange (ETDEWEB)

    Corso, N; Zakhor, A

    2013-12-03

    Indoor localization and mapping is an important problem with many applications such as emergency response, architectural modeling, and historical preservation. In this paper, we develop an automatic, off-line pipeline for metrically accurate, GPS-denied, indoor 3D mobile mapping using a human-mounted backpack system consisting of a variety of sensors. There are three novel contributions in our proposed mapping approach. First, we present an algorithm which automatically detects loop closure constraints from an occupancy grid map. In doing so, we ensure that constraints are detected only in locations that are well conditioned for scan matching. Secondly, we address the problem of scan matching with poor initial condition by presenting an outlier-resistant, genetic scan matching algorithm that accurately matches scans despite a poor initial condition. Third, we present two metrics based on the amount and complexity of overlapping geometry in order to vet the estimated loop closure constraints. By doing so, we automatically prevent erroneous loop closures from degrading the accuracy of the reconstructed trajectory. The proposed algorithms are experimentally verified using both controlled and real-world data. The end-to-end system performance is evaluated using 100 surveyed control points in an office environment and obtains a mean accuracy of 10 cm. Experimental results are also shown on three additional datasets from real world environments including a 1500 meter trajectory in a warehouse sized retail shopping center.

  8. Sensorimotor experience and verb-category mapping in human sensory, motor and parietal neurons.

    Science.gov (United States)

    Yang, Ying; Dickey, Michael Walsh; Fiez, Julie; Murphy, Brian; Mitchell, Tom; Collinger, Jennifer; Tyler-Kabara, Elizabeth; Boninger, Michael; Wang, Wei

    2017-07-01

    Semantic grounding is the process of relating meaning to symbols (e.g., words). It is the foundation for creating a representational symbolic system such as language. Semantic grounding for verb meaning is hypothesized to be achieved through two mechanisms: sensorimotor mapping, i.e., directly encoding the sensorimotor experiences the verb describes, and verb-category mapping, i.e., encoding the abstract category a verb belongs to. These two mechanisms were investigated by examining neuronal-level spike (i.e. neuronal action potential) activities from the motor, somatosensory and parietal areas in two human participants. Motor and a portion of somatosensory neurons were found to be involved in primarily sensorimotor mapping, while parietal and some somatosensory neurons were found to be involved in both sensorimotor and verb-category mapping. The time course of the spike activities and the selective tuning pattern of these neurons indicate that they belong to a large neural network used for semantic processing. This study is the first step towards understanding how words are processed by neurons. Published by Elsevier Ltd.

  9. Indoor Localization Algorithms for an Ambulatory Human Operated 3D Mobile Mapping System

    Directory of Open Access Journals (Sweden)

    Nicholas Corso

    2013-12-01

    Full Text Available Indoor localization and mapping is an important problem with many applications such as emergency response, architectural modeling, and historical preservation. In this paper, we develop an automatic, off-line pipeline for metrically accurate, GPS-denied, indoor 3D mobile mapping using a human-mounted backpack system consisting of a variety of sensors. There are three novel contributions in our proposed mapping approach. First, we present an algorithm which automatically detects loop closure constraints from an occupancy grid map. In doing so, we ensure that constraints are detected only in locations that are well conditioned for scan matching. Secondly, we address the problem of scan matching with poor initial condition by presenting an outlier-resistant, genetic scan matching algorithm that accurately matches scans despite a poor initial condition. Third, we present two metrics based on the amount and complexity of overlapping geometry in order to vet the estimated loop closure constraints. By doing so, we automatically prevent erroneous loop closures from degrading the accuracy of the reconstructed trajectory. The proposed algorithms are experimentally verified using both controlled and real-world data. The end-to-end system performance is evaluated using 100 surveyed control points in an office environment and obtains a mean accuracy of 10 cm. Experimental results are also shown on three additional datasets from real world environments including a 1500 meter trajectory in a warehouse sized retail shopping center.

  10. A blueprint for real-time functional mapping via human intracranial recordings.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Lachaux

    Full Text Available BACKGROUND: The surgical treatment of patients with intractable epilepsy is preceded by a pre-surgical evaluation period during which intracranial EEG recordings are performed to identify the epileptogenic network and provide a functional map of eloquent cerebral areas that need to be spared to minimize the risk of post-operative deficits. A growing body of research based on such invasive recordings indicates that cortical oscillations at various frequencies, especially in the gamma range (40 to 150 Hz, can provide efficient markers of task-related neural network activity. PRINCIPAL FINDINGS: Here we introduce a novel real-time investigation framework for mapping human brain functions based on online visualization of the spectral power of the ongoing intracranial activity. The results obtained with the first two implanted epilepsy patients who used the proposed online system illustrate its feasibility and utility both for clinical applications, as a complementary tool to electrical stimulation for presurgical mapping purposes, and for basic research, as an exploratory tool used to detect correlations between behavior and oscillatory power modulations. Furthermore, our findings suggest a putative role for high gamma oscillations in higher-order auditory processing involved in speech and music perception. CONCLUSION/SIGNIFICANCE: The proposed real-time setup is a promising tool for presurgical mapping, the investigation of functional brain dynamics, and possibly for neurofeedback training and brain computer interfaces.

  11. Mapping and Quantification of Vascular Branching in Plants, Animals and Humans by VESGEN Software

    Science.gov (United States)

    Parsons-Wingerter, P. A.; Vickerman, M. B.; Keith, P. A.

    2010-01-01

    Humans face daunting challenges in the successful exploration and colonization of space, including adverse alterations in gravity and radiation. The Earth-determined biology of plants, animals and humans is significantly modified in such extraterrestrial environments. One physiological requirement shared by larger plants and animals with humans is a complex, highly branching vascular system that is dynamically responsive to cellular metabolism, immunological protection and specialized cellular/tissue function. VESsel GENeration (VESGEN) Analysis has been developed as a mature beta version, pre-release research software for mapping and quantification of the fractal-based complexity of vascular branching. Alterations in vascular branching pattern can provide informative read-outs of altered vascular regulation. Originally developed for biomedical applications in angiogenesis, VESGEN 2D has provided novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and other microvascular remodeling phenomena. Vascular trees, networks and tree-network composites are mapped and quantified. Applications include disease progression from clinical ophthalmic images of the human retina; experimental regulation of vascular remodeling in the mouse retina; avian and mouse coronary vasculature, and other experimental models in vivo. We envision that altered branching in the leaves of plants studied on ISS such as Arabidopsis thaliana cans also be analyzed.

  12. A haplotype-based study of lithium responding patients with bipolar affective disorder on the Faroe Islands

    DEFF Research Database (Denmark)

    Ewald, H; Wang, A G; Vang, M

    1999-01-01

    , the Faroese population is perhaps the most valuable European population for genetic mapping of complex disease genes. The present study searched for haplotype sharing on chromosome 18 among eight lithium responding patients with bipolar affective disorder related, on average, 6.2 generations ago, using 30 DNA...

  13. The sensory somatotopic map of the human hand demonstrated at 4 Tesla.

    Science.gov (United States)

    Maldjian, J A; Gottschalk, A; Patel, R S; Detre, J A; Alsop, D C

    1999-07-01

    Recent attempts at high-resolution sensory-stimulated fMRI performed at 1.5 T have had very limited success at demonstrating a somatotopic organization for individual digits. Our purpose was to determine if functional MRI at 4 T can demonstrate the sensory somatotopic map of the human hand. Sensory functional MRI was performed at 4 T in five normal volunteers using a low-frequency vibratory stimulus on the pad of each finger of the left hand. A simple motor control task was also performed. The data were normalized to a standard atlas, and individual and group statistical parametric maps (SPMs) were computed for each task. Volume of activation and distribution of cluster maxima were compared for each task. For three of the subjects, the SPMs demonstrated a somatotopic organization of the sensory cortex. The group SPMs demonstrated a clear somatotopic organization of the sensory cortex. The thumb to fifth finger were organized, in general, with a lateral to medial, inferior to superior, and anterior to posterior relationship. There was overlap in the individual SPMs between fingers. The sensory activation spanned a space of 12-18 mm (thumb to fifth finger) on the primary sensory cortex. The motor activation occurred consistently at the superior-most extent of the sensory activation within and across subjects. The sensory somatotopic map of the human hand can be identified at 4 T. High-resolution imaging at 4 T can be useful for detailed functional imaging studies. Copyright 1999 Academic Press.

  14. Dietary Fiber and the Human Gut Microbiota: Application of Evidence Mapping Methodology

    Directory of Open Access Journals (Sweden)

    Caleigh M. Sawicki

    2017-02-01

    Full Text Available Interest is rapidly growing around the role of the human gut microbiota in facilitating beneficial health effects associated with consumption of dietary fiber. An evidence map of current research activity in this area was created using a newly developed database of dietary fiber intervention studies in humans to identify studies with the following broad outcomes: (1 modulation of colonic microflora; and/or (2 colonic fermentation/short-chain fatty acid concentration. Study design characteristics, fiber exposures, and outcome categories were summarized. A sub-analysis described oligosaccharides and bacterial composition in greater detail. One hundred eighty-eight relevant studies were identified. The fiber categories represented by the most studies were oligosaccharides (20%, resistant starch (16%, and chemically synthesized fibers (15%. Short-chain fatty acid concentration (47% and bacterial composition (88% were the most frequently studied outcomes. Whole-diet interventions, measures of bacterial activity, and studies in metabolically at-risk subjects were identified as potential gaps in the evidence. This evidence map efficiently captured the variability in characteristics of expanding research on dietary fiber, gut microbiota, and physiological health benefits, and identified areas that may benefit from further research. We hope that this evidence map will provide a resource for researchers to direct new intervention studies and meta-analyses.

  15. Two-dimensional liquid separations-mass mapping of proteins from human cancer cell lysates.

    Science.gov (United States)

    Lubman, David M; Kachman, Maureen T; Wang, Haixing; Gong, Siyuan; Yan, Fang; Hamler, Rick L; O'Neil, Kimberly A; Zhu, Kan; Buchanan, Nathan S; Barder, Timothy J

    2002-12-25

    A review of two-dimensional (2D) liquid separation methods used in our laboratory to map the protein content of human cancer cells is presented herein. The methods discussed include various means of fractionating proteins according to isoelectric point (pI) in the first dimension. The proteins in each pI fraction are subsequently separated using nonporous (NPS) reversed-phase high-performance liquid chromatography (RP-HPLC). The liquid eluent of the RP-HPLC separation is directed on-line into an electrospray ionization time-of-flight (ESI-TOF) mass spectrometer where an accurate value of the protein intact M(r) can be obtained. The result is a 2D map of pI versus M(r) analogous to 2D gel electrophoresis; however the highly accurate and reproducible M(r) serves as the basis for interlysate comparisons. In addition, the use of liquid separations allows for the collection of hundreds of purified proteins in the liquid phase for further analysis via peptide mass mapping using matrix assisted laser desorption ionization TOF MS. A description of the methodology used and its applications to analysis of several types of human cancer cell lines is described. The potential of the method for differential proteomic analysis for the identification of biomarkers of disease is discussed.

  16. Cytoarchitectonical analysis and probabilistic mapping of two extrastriate areas of the human posterior fusiform gyrus.

    Science.gov (United States)

    Caspers, Julian; Zilles, Karl; Eickhoff, Simon B; Schleicher, Axel; Mohlberg, Hartmut; Amunts, Katrin

    2013-03-01

    The human extrastriate visual cortex comprises numerous functionally defined areas, which are not identified in the widely used cytoarchitectonical map of Brodmann. The ventral part of the extrastriate cortex is particularly devoted to the identification of visual objects, faces and word forms. We analyzed the region immediately antero-lateral to hOc4v in serially sectioned (20 μm) and cell body-stained human brains using a quantitative observer-independent cytoarchitectonical approach to further identify the anatomical organization of the extrastriate cortex. Two novel cytoarchitectonical areas, FG1 and FG2, were identified on the posterior fusiform gyrus. The results of ten postmortem brains were then registered to their MRI volumes (acquired before histological processing), 3D reconstructed, and spatially normalized to the Montreal Neurological Institute reference brain. Finally, probabilistic maps were generated for each cytoarchitectonical area by superimposing the areas of the individual brains in the reference space. Comparison with recent functional imaging studies yielded that both areas are located within the object-related visual cortex. FG1 fills the gap between the retinotopically mapped area VO-1 and a posterior fusiform face patch. FG2 is probably the correlate of this face patch.

  17. Physical mapping of the retinoid X receptor B gene in mouse and human

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, T.; Kitagawa, K.; Taketo, M. [Banyu Tsukuba Research Institute, Tsukuba (Japan); Weiss, E.H. [Ludwig-Maximilians-Univ., Munich (Germany); Abe, K. [Kumamoto Univ. School of Medicine, Kumamoto (Japan); Ando, A.; Yara-Kikuti, Y.; Inoko, H. [Tokai Univ. School of Medicine, Isehara (Japan); Seldin, M.F. [Duke Univ. Medical Center, Durham, NC (United States); Ozato, K. [National Institutes of Health, Bethesda, MD (United States)

    1995-01-11

    Retinoid X receptors (RXRs) are zinc finger-containing nuclear transcription factors. They belong to the nuclear receptor superfamily that contains retinoid receptors, vitamin D receptors, thyroid hormone receptors, and steroid hormone receptors as well as the so-called orphan receptors. We previously mapped all three RXR genes on mouse chromosomes, using a panel of Mus spretus-Mus musculus interspecific backcross mice: namely, the RXRA-gene (Rxra) on Chr 2 near the centromere, the RXRB gene (Rxrb) on Chr 17 in the H2 region, and the RXRG gene (Rxrg) on distal Chr 1. Using cosmid clones that cover the major histocompatibility complex (MHC) region, we determined the precise physical map positions of the gene encoding mouse and human RXRB, respectively. The mouse gene (Rxrb) maps between H2-Ke4 and H2-Ke5: namely, immediately telomeric to H2-Ke4 which encodes a histidine-rich transmembrane protein, and 12 kilobases centromeric to H2-Ke5 which is expressed in lymphoid tissues, Rxrb and H2-Ke4 are transcribed into opposite directions from a CpG-rich promoter of about 250 base pairs. This gene organization is well conserved also in the human genome at the HLA-DP subregion of Chr 6p, underscoring the strong conservation of the gene organization in the MHC region between the two mammals. 54 refs., 4 figs.

  18. Dietary Fiber and the Human Gut Microbiota: Application of Evidence Mapping Methodology.

    Science.gov (United States)

    Sawicki, Caleigh M; Livingston, Kara A; Obin, Martin; Roberts, Susan B; Chung, Mei; McKeown, Nicola M

    2017-02-10

    Interest is rapidly growing around the role of the human gut microbiota in facilitating beneficial health effects associated with consumption of dietary fiber. An evidence map of current research activity in this area was created using a newly developed database of dietary fiber intervention studies in humans to identify studies with the following broad outcomes: (1) modulation of colonic microflora; and/or (2) colonic fermentation/short-chain fatty acid concentration. Study design characteristics, fiber exposures, and outcome categories were summarized. A sub-analysis described oligosaccharides and bacterial composition in greater detail. One hundred eighty-eight relevant studies were identified. The fiber categories represented by the most studies were oligosaccharides (20%), resistant starch (16%), and chemically synthesized fibers (15%). Short-chain fatty acid concentration (47%) and bacterial composition (88%) were the most frequently studied outcomes. Whole-diet interventions, measures of bacterial activity, and studies in metabolically at-risk subjects were identified as potential gaps in the evidence. This evidence map efficiently captured the variability in characteristics of expanding research on dietary fiber, gut microbiota, and physiological health benefits, and identified areas that may benefit from further research. We hope that this evidence map will provide a resource for researchers to direct new intervention studies and meta-analyses.

  19. Dietary Fiber and the Human Gut Microbiota: Application of Evidence Mapping Methodology

    Science.gov (United States)

    Sawicki, Caleigh M.; Livingston, Kara A.; Obin, Martin; Roberts, Susan B.; Chung, Mei; McKeown, Nicola M.

    2017-01-01

    Interest is rapidly growing around the role of the human gut microbiota in facilitating beneficial health effects associated with consumption of dietary fiber. An evidence map of current research activity in this area was created using a newly developed database of dietary fiber intervention studies in humans to identify studies with the following broad outcomes: (1) modulation of colonic microflora; and/or (2) colonic fermentation/short-chain fatty acid concentration. Study design characteristics, fiber exposures, and outcome categories were summarized. A sub-analysis described oligosaccharides and bacterial composition in greater detail. One hundred eighty-eight relevant studies were identified. The fiber categories represented by the most studies were oligosaccharides (20%), resistant starch (16%), and chemically synthesized fibers (15%). Short-chain fatty acid concentration (47%) and bacterial composition (88%) were the most frequently studied outcomes. Whole-diet interventions, measures of bacterial activity, and studies in metabolically at-risk subjects were identified as potential gaps in the evidence. This evidence map efficiently captured the variability in characteristics of expanding research on dietary fiber, gut microbiota, and physiological health benefits, and identified areas that may benefit from further research. We hope that this evidence map will provide a resource for researchers to direct new intervention studies and meta-analyses. PMID:28208609

  20. Genetic Mapping

    Science.gov (United States)

    ... Fact Sheets Fact Sheets En Español: Mapeo Genético Genetic Mapping What is genetic mapping? How do researchers create ... genetic map? What are genetic markers? What is genetic mapping? Among the main goals of the Human Genome ...

  1. Precision mapping of the human O-GalNAc glycoproteome through SimpleCell technology

    DEFF Research Database (Denmark)

    Steentoft, Catharina; Vakhrushev, Sergey; Joshi, Hiren Jitendra

    2013-01-01

    -glycosylation is highly limited. This type of glycosylation is unique in being regulated by 20 polypeptide GalNAc-transferases attaching the initiating GalNAc monosaccharides to Ser and Thr (and likely some Tyr) residues. We have developed a genetic engineering approach using human cell lines to simplify O......-glycosylation (SimpleCells) that enables proteome-wide discovery of O-glycan sites using 'bottom-up' ETD-based mass spectrometric analysis. We implemented this on 12 human cell lines from different organs, and present a first map of the human O-glycoproteome with almost 3000 glycosites in over 600 O......-glycoproteins as well as an improved NetOGlyc4.0 model for prediction of O-glycosylation. The finding of unique subsets of O-glycoproteins in each cell line provides evidence that the O-glycoproteome is differentially regulated and dynamic. The greatly expanded view of the O-glycoproteome should facilitate...

  2. Comprehensive polyadenylation site maps in yeast and human reveal pervasive alternative polyadenylation.

    Science.gov (United States)

    Ozsolak, Fatih; Kapranov, Philipp; Foissac, Sylvain; Kim, Sang Woo; Fishilevich, Elane; Monaghan, A Paula; John, Bino; Milos, Patrice M

    2010-12-10

    The emerging discoveries on the link between polyadenylation and disease states underline the need to fully characterize genome-wide polyadenylation states. Here, we report comprehensive maps of global polyadenylation events in human and yeast generated using refinements to the Direct RNA Sequencing technology. This direct approach provides a quantitative view of genome-wide polyadenylation states in a strand-specific manner and requires only attomole RNA quantities. The polyadenylation profiles revealed an abundance of unannotated polyadenylation sites, alternative polyadenylation patterns, and regulatory element-associated poly(A)(+) RNAs. We observed differences in sequence composition surrounding canonical and noncanonical human polyadenylation sites, suggesting novel noncoding RNA-specific polyadenylation mechanisms in humans. Furthermore, we observed the correlation level between sense and antisense transcripts to depend on gene expression levels, supporting the view that overlapping transcription from opposite strands may play a regulatory role. Our data provide a comprehensive view of the polyadenylation state and overlapping transcription.

  3. A High-Density Map for Navigating the Human Polycomb Complexome

    Directory of Open Access Journals (Sweden)

    Simon Hauri

    2016-10-01

    Full Text Available Polycomb group (PcG proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. Here, we systematically mapped the human PcG complexome using a robust affinity purification mass spectrometry approach. Our high-density protein interaction network uncovered a diverse range of PcG complexes. Moreover, our analysis identified PcG interactors linking them to the PcG system, thus providing insight into the molecular function of PcG complexes and mechanisms of recruitment to target genes. We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals.

  4. High-throughput mapping of origins of replication in human cells.

    Science.gov (United States)

    Lucas, Isabelle; Palakodeti, Aparna; Jiang, Yanwen; Young, David J; Jiang, Nan; Fernald, Anthony A; Le Beau, Michelle M

    2007-08-01

    Mapping origins of replication has been challenging in higher eukaryotes. We have developed a rapid, genome-wide method to map origins of replication in asynchronous human cells by combining the nascent strand abundance assay with a highly tiled microarray platform, and we validated the technique by two independent assays. We applied this method to analyse the enrichment of nascent DNA in three 50-kb regions containing known origins of replication in the MYC, lamin B2 (LMNB2) and haemoglobin beta (HBB) genes, a 200-kb region containing the rare fragile site, FRAXA, and a 1,075-kb region on chromosome 22; we detected most of the known origins and also 28 new origins. Surprisingly, the 28 new origins were small in size and located predominantly within genes. Our study also showed a strong correlation between origin replication timing and chromatin acetylation.

  5. [HapMap project].

    Science.gov (United States)

    Tanaka, Toshihiro

    2009-06-01

    Haplotype map is the basis of SNP association studies in two aspects. One is to understand how SNPs are organized on chromosomes, thereby helping researchers to select tag SNPs to be examined. The other is to explore the presence of "hidden SNP" by haplotype analyses that is really associated with the disease. Although it is very difficult to forecast the future of SNP studies, the final and ideal methodology should be high--throughput whole genome sequencing with low price. At such stage, data mining technique will be very important since huge amount of genotype data should be handled and analyzed.

  6. Abnormal visual field maps in human cortex: a mini-review and a case report.

    Science.gov (United States)

    Haak, Koen V; Langers, Dave R M; Renken, Remco; van Dijk, Pim; Borgstein, Johannes; Cornelissen, Frans W

    2014-07-01

    Human visual cortex contains maps of the visual field. Much research has been dedicated to answering whether and when these visual field maps change if critical components of the visual circuitry are damaged. Here, we first provide a focused mini-review of the functional magnetic resonance imaging (fMRI) studies that have evaluated the human cortical visual field maps in the face of retinal lesions, brain injury, and atypical retinocortical projections. We find that there is a fair body of research that has found abnormal fMRI activity, but also that this abnormal activity does not necessarily stem from cortical remapping. The abnormal fMRI activity can often be explained in terms of task effects and/or the uncovering of normally hidden system dynamics. We then present the case of a 16-year-old patient who lost the entire left cerebral hemisphere at age three for treatment of chronic focal encephalitis (Rasmussen syndrome) and intractable epilepsy. Using an fMRI retinotopic mapping procedure and population receptive field (pRF) modeling, we found that (1) despite the long period since the hemispherectomy, the retinotopic organization of early visual cortex remained unaffected by the removal of an entire cerebral hemisphere, and (2) the intact lateral occipital cortex contained an exceptionally large representation of the center of the visual field. The same method also indicates that the neuronal receptive fields in these lateral occipital brain regions are extraordinarily small. These features are clearly abnormal, but again they do not necessarily stem from cortical remapping. For example, the abnormal features can also be explained by the notion that the hemispherectomy took place during a critical period in the development of the lateral occipital cortex and therefore arrested its normal development. Thus, caution should be exercised when interpreting abnormal fMRI activity as a marker of cortical remapping; there are often other explanations.

  7. An upgraded camera-based imaging system for mapping venous blood oxygenation in human skin tissue

    Science.gov (United States)

    Li, Jun; Zhang, Xiao; Qiu, Lina; Leotta, Daniel F.

    2016-07-01

    A camera-based imaging system was previously developed for mapping venous blood oxygenation in human skin. However, several limitations were realized in later applications, which could lead to either significant bias in the estimated oxygen saturation value or poor spatial resolution in the map of the oxygen saturation. To overcome these issues, an upgraded system was developed using improved modeling and image processing algorithms. In the modeling, Monte Carlo (MC) simulation was used to verify the effectiveness of the ratio-to-ratio method for semi-infinite and two-layer skin models, and then the relationship between the venous oxygen saturation and the ratio-to-ratio was determined. The improved image processing algorithms included surface curvature correction and motion compensation. The curvature correction is necessary when the imaged skin surface is uneven. The motion compensation is critical for the imaging system because surface motion is inevitable when the venous volume alteration is induced by cuff inflation. In addition to the modeling and image processing algorithms in the upgraded system, a ring light guide was used to achieve perpendicular and uniform incidence of light. Cross-polarization detection was also adopted to suppress surface specular reflection. The upgraded system was applied to mapping of venous oxygen saturation in the palm, opisthenar and forearm of human subjects. The spatial resolution of the oxygenation map achieved is much better than that of the original system. In addition, the mean values of the venous oxygen saturation for the three locations were verified with a commercial near-infrared spectroscopy system and were consistent with previously published data.

  8. Linking retinotopic fMRI mapping and anatomical probability maps of human occipital areas V1 and V2.

    Science.gov (United States)

    Wohlschläger, A M; Specht, K; Lie, C; Mohlberg, H; Wohlschläger, A; Bente, K; Pietrzyk, U; Stöcker, T; Zilles, K; Amunts, K; Fink, G R

    2005-05-15

    Using functional MRI, we characterized field sign maps of the occipital cortex and created three-dimensional maps of these areas. By averaging the individual maps into group maps, probability maps of functionally defined V1 or V2 were determined and compared to anatomical probability maps of Brodmann areas BA17 and BA18 derived from cytoarchitectonic analysis (Amunts, K., Malikovic, A., Mohlberg, H., Schormann, T., Zilles, K., 2000. Brodmann's areas 17 and 18 brought into stereotaxic space-where and how variable? NeuroImage 11, 66-84). Comparison of areas BA17/V1 and BA18/V2 revealed good agreement of the anatomical and functional probability maps. Taking into account that our functional stimulation (due to constraints of the visual angle of stimulation achievable in the MR scanner) only identified parts of V1 and V2, for statistical evaluation of the spatial correlation of V1 and BA17, or V2 and BA18, respectively, the a priori measure kappa was calculated testing the hypothesis that a region can only be part of functionally defined V1 or V2 if it is also in anatomically defined BA17 or BA18, respectively. kappa = 1 means the hypothesis is fully true, kappa = 0 means functionally and anatomically defined visual areas are independent. When applying this measure to the probability maps, kappa was equal to 0.84 for both V1/BA17 and V2/BA18. The data thus show a good correspondence of functionally and anatomically derived segregations of early visual processing areas and serve as a basis for employing anatomical probability maps of V1 and V2 in group analyses to characterize functional activations of early visual processing areas.

  9. Improved IBD detection using incomplete haplotype information

    Directory of Open Access Journals (Sweden)

    Pollak Martin R

    2010-06-01

    Full Text Available Abstract Background The availability of high density genetic maps and genotyping platforms has transformed human genetic studies. The use of these platforms has enabled population-based genome-wide association studies. However, in inheritance-based studies, current methods do not take full advantage of the information present in such genotyping analyses. Results In this paper we describe an improved method for identifying genetic regions shared identical-by-descent (IBD from recent common ancestors. This method improves existing methods by taking advantage of phase information even if it is less than fully accurate or missing. We present an analysis of how using phase information increases the accuracy of IBD detection compared to using only genotype information. Conclusions Our algorithm should have utility in a wide range of genetic studies that rely on identification of shared genetic material in large families or small populations.

  10. Polymorphism and genetic mapping of the human oxytocin receptor gene on chromosome 3

    Energy Technology Data Exchange (ETDEWEB)

    Michelini, S.; Urbanek, M.; Goldman, D. [National Institute of Health-National Institute of Alcohol Abuse and Alcoholism, Rockville, MD (United States)] [and others

    1995-06-19

    Centrally administered oxytocin has been reported to facilitate affiliative and social behaviors, in functional harmony with its well-known peripheral effects on uterine contraction and milk ejection. The biological effects of oxytocin could be perturbed by mutations occurring in the sequence of the oxytocin receptor gene, and it would be of interest to establish the position of this gene on the human linkage map. Therefore we identified a polymorphism at the human oxytocin receptor gene. A portion of the 3{prime} untranslated region containing a 30 bp CA repeat was amplified by polymerase chain reaction (PCR), revealing a polymorphism with two alleles occurring with frequencies of 0.77 and 0.23 in a sample of Caucasian CEPH parents (n = 70). The CA repeat polymorphism we detected was used to map the human oxytocin receptor to chromosome 3p25-3p26, in a region which contains several important genes, including loci for Von Hippel-Lindau disease (VHL) and renal cell carcinoma. 53 refs., 2 figs., 1 tab.

  11. Molecular cloning, chromosomal mapping, and functional expression of human brain glutamate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Sun, W.; Ferrer-Montiel, A.V.; Schinder, A.F.; Montal, M. (Univ. of California, San Diego, La Jolla (United States)); McPherson, J.P. (Univ. of California, Irvine (United States)); Evans, G.A. (Salk Inst. for Biological Studies, La Jolla, CA (United States))

    1992-02-15

    A full-length cDNA clone encoding a glutamate receptor was isolated from a human brain cDNA library, and the gene product was characterized after expression in Xenopus oocytes. Degenerate PCR primers to conserved regions of published rat brain glutamate receptor sequences amplified a 1-kilobase fragment from a human brain cDNA library. This fragment was used as a probe for subsequent hybridization screening. Two clones were isolated that, based on sequence information, code for different receptors: a 3-kilobase clone, HBGR1, contains a full-length glutamate receptor cDNA highly homologous to the rat brain clone GluR1, and a second clone, HBGR2, contains approximately two-thirds of the coding region of a receptor homologous to rat brain clone GluR2. Southern and PCr analysis of a somatic cell-hybrid panel mapped HBGR1 to human chromosome 5q31.3-33.3 and mapped HBGR2 to chromosome 4q25-34.3. Xenopus oocytes injected with in vitro-synthesized HBGR1 cRNA expressed currents activated by glutamate receptor agonists. These results indicate that clone HBGR1 codes for a glutamate receptor of the kainate subtype cognate to members of the glutamate receptor family from rodent brain.

  12. Information on a Major New Initiative: Mapping and Sequencing the Human Genome (1986 DOE Memorandum)

    Science.gov (United States)

    DeLisi, Charles (Associate Director, Health and Environmental Research, DOE Office of Energy Research)

    1986-05-06

    In the history of the Human Genome Program, Dr. Charles DeLisi and Dr. Alvin Trivelpiece of the Department of Energy (DOE) were instrumental in moving the seeds of the program forward. This May 1986 memo from DeLisi to Trivelpiece, Director of DOE's Office of Energy Research, documents this fact. Following the March 1986 Santa Fe workshop on the subject of mapping and sequencing the human genome, DeLisi's memo outlines workshop conclusions, explains the relevance of this project to DOE and the importance of the Department's laboratories and capabilities, notes the critical experience of DOE in managing projects of this scale and potential magnitude, and recognizes the fact that the project will impact biomedical science in ways which could not be fully anticipated at the time. Subsequently, program guidance was further sought from the DOE Health Effects Research Advisory Committee (HERAC) and the April 1987 HERAC report recommended that DOE and the nation commit to a large, multidisciplinary, scientific and technological undertaking to map and sequence the human genome.

  13. Earth Observation Data for Mapping and Evaluation of Ecosystem Services to Improve Human Livelihoods and Conserve Species

    Science.gov (United States)

    Shapiro, Aurelie C.; Bhagabati, Nirmal

    2010-12-01

    Mapping and evaluating ecosystem services is of increasing concern and urgency for conservation organizations such as WWF. Coupling biodiversity assessments with ecosystem services e.g., carbon sequestration, water regulation, sediment reduction, is an effective way to visualize additional financial and human benefits of conservation for decision makers. WWF is eager to apply various Earth Observation data to conservation applications for consistent mapping and monitoring of natural ecosystems and the potential impacts of their loss on humans and wildlife alike. Such examples include forest carbon mapping, integrated evaluation of ecosystem services (via the InVEST tool) and bundling endangered Tiger habitat with various ecosystem services for bundled benefits.

  14. Establishment of a resource population of SLA haplotype-defined Korean native pigs.

    Science.gov (United States)

    Cho, Han-Ok; Ho, Chak-Sum; Lee, Yu-Joo; Cho, In-Cheol; Lee, Sung-Soo; Ko, Moon-Suck; Park, Chankyu; Smith, Douglas M; Jeon, Jin-Tae; Lee, Jun-Heon

    2010-05-01

    The highly polymorphic porcine major histocompatibility complex (MHC), or the swine leukocyte antigens (SLA), has been repeatedly associated with variations in swine immune response to pathogens and vaccines as well as with production traits. The SLA antigens are also important targets for immunological recognition of foreign tissue grafts. We recently established a resource population of Korean native pigs as models for human transplantation and xenotransplantation research. In this study, 115 animals derived from three generations of the Korean native pigs were genotyped for three SLA class I (SLA-2, SLA-3 and SLA-1) and three SLA class II loci (DRB1, DQB1, DQA) using PCR with sequence-specific primers (PCR-SSP) at the allele group resolution. A total of seven SLA haplotypes (Lr-5.34, Lr-7.23, Lr-31.13, Lr-56.23, Lr-56.30, Lr-59.1, Lr-65.34), comprising six unique class I and five unique class II haplotypes, were characterized in the founding animals. Class I haplotype Lr-65.0 and class II haplotype Lr-0.34 were novel; and together with Lr-56.0 these haplotypes appeared to be breed-specific. In the progeny population, Lr-7.23 and Lr-56.30 appeared to be the most prevalent haplotypes with frequencies of 34.7% and 31.6%, respectively; the overall homozygosity was 27.4%. This resource population of SLA-defined Korean native pigs will be useful as large animal models for various transplantation and xenotransplantation experiments, as well as for dissecting the roles of SLA proteins in swine disease resistance and production traits.

  15. Mapping human dimensions of small-scale fisheries in the Northern Gulf of California, Mexico

    Science.gov (United States)

    Moreno-Baez, Marcia

    Recurrent crises due to overexploitation of fishery resources have been among the biggest natural resource management failures of the 20th century. This problem has both biological and socio-political elements and understanding of human dimensions represents a key step toward the formulation of sound management guidelines for natural resources. One of the strategies proposed to understand human dimensions is through the use of local knowledge. Integrating local peoples' knowledge with scientific research and data analysis, could aid in the design of fisheries management strategies in a cost-effective and participatory way. I introduce an approach to incorporating fishers' local knowledge at a large, regional scale. I focused on the spatial and temporal distribution of fishing activities from 17 communities in the Northern Gulf of California, Mexico. Participatory mapping (maps produced by local fishers) through a rapid appraisal (survey methodology) were used to identify the spatial and temporal dimensions of fishing activities. A geographic information system was used to generate 764 map layers used for a preliminary analysis of rapid-appraisal spatial data. Post-survey workshops with fishers were organized to facilitate an internal validation of spatial information using geographic information system software. We characterized the information based on fishing communities, fishing methods, target species and spawning sites. We also applied spatial analysis techniques to understand the relative importance and use of fishing grounds, fishing seasons and the influence that fishing communities have over the region. This dissertation addressed the problem of integrating the human dimensions of small-scale fisheries using geospatial tools and local knowledge (LK) -- data collection, integration, internal validation, analysis and access -- into a multidisciplinary research to support decision making in natural resource planning for small-scale fisheries management and

  16. Cloning, expression and mapping of the full-length cDNA of human CCTβ subunit

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Chaperonins assist the proper folding of target proteins without being a part of the substrates. The eukaryotic cytosolic chaperonin, CCT-Chaperonin Containing TCP-1 (tailless complex polypeptide-1), is mainly involved in the formation of cytoskeletal proteins and is essential for cell viability. Mammalian CCT is commonly a protein complex composed of 7-9 subunit species. We have isolated a novel full-length cDNA from human testis cDNA library. This cDNA of 1935 bp contains a 1605 bp open reading frame (ORF) encoding 535 amino acids (aa). The deduced protein of the cDNA is highly homologous to the CCTβ subunit of saccharomyces cerevisiae, schizosaccharomyces pombe, caenorhabditis elegans and mouse, etc. Especially high homology (97%) is found between the deduced protein and mouse CCTb. On the basis of such high homology, the protein encoded by the new gene was proposed to be a human CCTβ subunit. Northern hybridization showed that human CCTβ gene is expressed as a transcript of about 2.0 kb in various tissues. Overexpression was seen in testis with the expression level 3-24 times of those in other tissues. The CCTβ gene was mapped to human chromosome 12q14 by Radiation Hybrid Mapping. Through homologous search, the 5′-end of the cDNA sequence was found to share intermittent regional homology with the 3′-end of human genomic sequence (U91327). The genomic structure of the 5′-end of CCTβ was also described in detail through comparative analysis.

  17. B- and T-cell epitope mapping of human sapovirus capsid protein: an immunomics approach.

    Science.gov (United States)

    Amin, M Ruhul; Siddiqui, Mohammad S; Ahmed, Dilruba; Ahmed, Firoz; Hossain, Anowar

    2011-01-01

    Human sapovirus is one of the major causes of viral gastroenteritis. Although the capsid protein (VP1) confers antigenic cross-reactivity, immunity against sapovirus is still unclear. Using immunoinformatics approach, we defined putative T- and B-cell epitopes of VP1 and mapped on to its predicted three-dimensional structure. Identified five putative T-cell epitopes also occupied the putative B-cell epitope region. These putative epitopes were conserved in all existing serotypes. Predicted epitopes can be generated through proteasome cleavage and may be useful in designing peptide-based subunit vaccine to confer both humoral and cell-mediated immunity.

  18. Mapping and sequencing the human genome: Science, ethics, and public policy. Final report

    Energy Technology Data Exchange (ETDEWEB)

    McInerney, J.D.

    1993-03-31

    Development of Mapping and Sequencing the Human Genome: Science, Ethics, and Public Policy followed the standard process of curriculum development at the Biological Sciences Curriculum Study (BSCS), the process is described. The production of this module was a collaborative effort between BSCS and the American Medical Association (AMA). Appendix A contains a copy of the module. Copies of reports sent to the Department of Energy (DOE) during the development process are contained in Appendix B; all reports should be on file at DOE. Appendix B also contains copies of status reports submitted to the BSCS Board of Directors.

  19. The active gene that encodes human High Mobility Group 1 protein (HMG1) contains introns and maps to chromosome 13

    Energy Technology Data Exchange (ETDEWEB)

    Ferrari, S. [Dipartimento di Genetica e di Biologia dei Microrganismi, Milan (Italy); Finelli, P.; Rocchi, M. [Istituto di Genetica, Bari (Italy)] [and others

    1996-07-15

    The human genome contains a large number of sequences related to the cDNA for High Mobility Group 1 protein (HMG1), which so far has hampered the cloning and mapping of the active HMG1 gene. We show that the human HMG1 gene contains introns, while the HMG1-related sequences do not and most likely are retrotransposed pseudogenes. We identified eight YACs from the ICI and CEPH libraries that contain the human HMG1 gene. The HMG1 gene is similar in structure to the previously characterized murine homologue and maps to human chromosome 13 and q12, as determined by in situ hybridization. The mouse Hmg1 gene maps to the telomeric region of murine Chromosome 5, which is syntenic to the human 13q12 band. 18 refs., 3 figs.

  20. A high-resolution whole-genome cattle-human comparative map reveals details of mammalian chromosome evolution.

    Science.gov (United States)

    Everts-van der Wind, Annelie; Larkin, Denis M; Green, Cheryl A; Elliott, Janice S; Olmstead, Colleen A; Chiu, Readman; Schein, Jacqueline E; Marra, Marco A; Womack, James E; Lewin, Harris A

    2005-12-20

    Approximately 3,000 cattle bacterial artificial chromosome (BAC)-end sequences were added to the Illinois-Texas 5,000-rad RH (RH, radiation hybrid) map. The BAC-end sequences selected for mapping are approximately 1 Mbp apart on the human chromosomes as determined by blastn analysis. The map has 3,484 ordered markers, of which 3,204 are anchored in the human genome. Two hundred-and-one homologous synteny blocks (HSBs) were identified, of which 27 are previously undiscovered, 79 are extended, 26 were formed by previously unrecognized breakpoints in 18 previously defined HSBs, and 23 are the result of fusions. The comparative coverage relative to the human genome is approximately 91%, or 97% of the theoretical maximum. The positions of 64% of all cattle centromeres and telomeres were reassigned relative to their positions on the previous map, thus facilitating a more detailed comparative analysis of centromere and telomere evolution. As an example of the utility of the high-resolution map, 22 cattle BAC fingerprint contigs were directly anchored to cattle chromosome 19 [Bos taurus, (BTA) 19]. The order of markers on the cattle RH and fingerprint maps of BTA19 and the sequence-based map of human chromosome 17 [Homo sapiens, (HSA) 17] were found to be highly consistent, with only two minor ordering discrepancies between the RH map and fingerprint contigs. The high-resolution Illinois-Texas 5,000-rad RH and comparative maps will facilitate identification of candidate genes for economically important traits, the phylogenomic analysis of mammalian chromosomes, proofing of the BAC fingerprint map and, ultimately, aid the assembly of cattle whole-genome sequence.

  1. Echinococcus equinus and Echinococcus granulosus sensu stricto from the United Kingdom: genetic diversity and haplotypic variation.

    Science.gov (United States)

    Boufana, Belgees; Lett, Wai San; Lahmar, Samia; Buishi, Imad; Bodell, Anthony J; Varcasia, Antonio; Casulli, Adriano; Beeching, Nicholas J; Campbell, Fiona; Terlizzo, Monica; McManus, Donald P; Craig, Philip S

    2015-02-01

    Cystic echinococcosis is endemic in Europe including the United Kingdom. However, information on the molecular epidemiology of Echinococcus spp. from the United Kingdom is limited. Echinococcus isolates from intermediate and definitive animal hosts as well as from human cystic echinococcosis cases were analysed to determine species and genotypes within these hosts. Echinococcus equinus was identified from horse hydatid isolates, cysts retrieved from captive UK mammals and copro-DNA of foxhounds and farm dogs. Echinococcus granulosus sensu stricto (s.s.) was identified from hydatid cysts of sheep and cattle as well as in DNA extracted from farm dog and foxhound faecal samples, and from four human cystic echinococcosis isolates, including the first known molecular confirmation of E. granulosus s.s. infection in a Welsh sheep farmer. Low genetic variability for E. equinus from various hosts and from different geographical locations was detected using the mitochondrial cytochrome c oxidase subunit 1 gene (cox1), indicating the presence of a dominant haplotype (EQUK01). In contrast, greater haplotypic variation was observed for E. granulosus s.s. cox1 sequences. The haplotype network showed a star-shaped network with a centrally placed main haplotype (EgUK01) that had been reported from other world regions.

  2. Musical Aptitude Is Associated with AVPR1A-Haplotypes

    Science.gov (United States)

    Ukkola, Liisa T.; Onkamo, Päivi; Raijas, Pirre; Karma, Kai; Järvelä, Irma

    2009-01-01

    Artistic creativity forms the basis of music culture and music industry. Composing, improvising and arranging music are complex creative functions of the human brain, which biological value remains unknown. We hypothesized that practicing music is social communication that needs musical aptitude and even creativity in music. In order to understand the neurobiological basis of music in human evolution and communication we analyzed polymorphisms of the arginine vasopressin receptor 1A (AVPR1A), serotonin transporter (SLC6A4), catecol-O-methyltranferase (COMT), dopamin receptor D2 (DRD2) and tyrosine hydroxylase 1 (TPH1), genes associated with social bonding and cognitive functions in 19 Finnish families (n = 343 members) with professional musicians and/or active amateurs. All family members were tested for musical aptitude using the auditory structuring ability test (Karma Music test; KMT) and Carl Seashores tests for pitch (SP) and for time (ST). Data on creativity in music (composing, improvising and/or arranging music) was surveyed using a web-based questionnaire. Here we show for the first time that creative functions in music have a strong genetic component (h2 = .84; composing h2 = .40; arranging h2 = .46; improvising h2 = .62) in Finnish multigenerational families. We also show that high music test scores are significantly associated with creative functions in music (p<.0001). We discovered an overall haplotype association with AVPR1A gene (markers RS1 and RS3) and KMT (p = 0.0008; corrected p = 0.00002), SP (p = 0.0261; corrected p = 0.0072) and combined music test scores (COMB) (p = 0.0056; corrected p = 0.0006). AVPR1A haplotype AVR+RS1 further suggested a positive association with ST (p = 0.0038; corrected p = 0.00184) and COMB (p = 0.0083; corrected p = 0.0040) using haplotype-based association test HBAT. The results suggest that the neurobiology of music perception and production is likely to be

  3. Musical aptitude is associated with AVPR1A-haplotypes.

    Directory of Open Access Journals (Sweden)

    Liisa T Ukkola

    Full Text Available Artistic creativity forms the basis of music culture and music industry. Composing, improvising and arranging music are complex creative functions of the human brain, which biological value remains unknown. We hypothesized that practicing music is social communication that needs musical aptitude and even creativity in music. In order to understand the neurobiological basis of music in human evolution and communication we analyzed polymorphisms of the arginine vasopressin receptor 1A (AVPR1A, serotonin transporter (SLC6A4, catecol-O-methyltranferase (COMT, dopamin receptor D2 (DRD2 and tyrosine hydroxylase 1 (TPH1, genes associated with social bonding and cognitive functions in 19 Finnish families (n = 343 members with professional musicians and/or active amateurs. All family members were tested for musical aptitude using the auditory structuring ability test (Karma Music test; KMT and Carl Seashores tests for pitch (SP and for time (ST. Data on creativity in music (composing, improvising and/or arranging music was surveyed using a web-based questionnaire. Here we show for the first time that creative functions in music have a strong genetic component (h(2 = .84; composing h(2 = .40; arranging h(2 = .46; improvising h(2 = .62 in Finnish multigenerational families. We also show that high music test scores are significantly associated with creative functions in music (p<.0001. We discovered an overall haplotype association with AVPR1A gene (markers RS1 and RS3 and KMT (p = 0.0008; corrected p = 0.00002, SP (p = 0.0261; corrected p = 0.0072 and combined music test scores (COMB (p = 0.0056; corrected p = 0.0006. AVPR1A haplotype AVR+RS1 further suggested a positive association with ST (p = 0.0038; corrected p = 0.00184 and COMB (p = 0.0083; corrected p = 0.0040 using haplotype-based association test HBAT. The results suggest that the neurobiology of music perception and production is likely to be related to the pathways affecting intrinsic attachment

  4. Genomic sequence of 'Candidatus Liberibacter solanacearum' haplotype C and its comparison with haplotype A and B genomes

    Science.gov (United States)

    Haapalainen, Minna; Schott, Thomas; Thompson, Sarah M.; Smith, Grant R.; Nissinen, Anne I.; Pirhonen, Minna

    2017-01-01

    Haplotypes A and B of ‘Candidatus Liberibacter solanacearum’ (CLso) are associated with diseases of solanaceous plants, especially Zebra chip disease of potato, and haplotypes C, D and E are associated with symptoms on apiaceous plants. To date, one complete genome of haplotype B and two high quality draft genomes of haplotype A have been obtained for these unculturable bacteria using metagenomics from the psyllid vector Bactericera cockerelli. Here, we present the first genomic sequences obtained for the carrot-associated CLso. These two genomic sequences of haplotype C, FIN114 (1.24 Mbp) and FIN111 (1.20 Mbp), were obtained from carrot psyllids (Trioza apicalis) harboring CLso. Genomic comparisons between the haplotypes A, B and C revealed that the genome organization differs between these haplotypes, due to large inversions and other recombinations. Comparison of protein-coding genes indicated that the core genome of CLso consists of 885 ortholog groups, with the pan-genome consisting of 1327 ortholog groups. Twenty-seven ortholog groups are unique to CLso haplotype C, whilst 11 ortholog groups shared by the haplotypes A and B, are not found in the haplotype C. Some of these ortholog groups that are not part of the core genome may encode functions related to interactions with the different host plant and psyllid species. PMID:28158295

  5. The effect of genealogy-based haplotypes on genomic prediction

    DEFF Research Database (Denmark)

    Edriss, Vahid; Fernando, Rohan L.; Su, Guosheng

    2013-01-01

    Background Genomic prediction uses two sources of information: linkage disequilibrium between markers and quantitative trait loci, and additive genetic relationships between individuals. One way to increase the accuracy of genomic prediction is to capture more linkage disequilibrium by regression...... on haplotypes instead of regression on individual markers. The aim of this study was to investigate the accuracy of genomic prediction using haplotypes based on local genealogy information. Methods A total of 4429 Danish Holstein bulls were genotyped with the 50K SNP chip. Haplotypes were constructed using...... local genealogical trees. Effects of haplotype covariates were estimated with two types of prediction models: (1) assuming that effects had the same distribution for all haplotype covariates, i.e. the GBLUP method and (2) assuming that a large proportion (pi) of the haplotype covariates had zero effect...

  6. HLA-DRB1-DQB1 Haplotypes Confer Susceptibility and Resistance to Multiple Sclerosis in Sardinia

    Science.gov (United States)

    Cocco, Eleonora; Sardu, Claudia; Pieroni, Enrico; Valentini, Maria; Murru, Raffaele; Costa, Gianna; Tranquilli, Stefania; Frau, Jessica; Coghe, Giancarlo; Carboni, Nicola; Floris, Matteo; Contu, Paolo; Marrosu, Maria Giovanna

    2012-01-01

    Introduction Genetic predisposition to multiple sclerosis (MS) in Sardinia (Italy) has been associated with five DRB1*-DQB1* haplotypes of the human leukocyte antigen (HLA). Given the complexity of these associations, an in-depth re-analysis was performed with the specific aims of confirming the haplotype associations; establishing the independence of the associated haplotypes; and assessing patients' genotypic risk of developing MS. Methods and Results A transmission disequilibrium test (TDT) of the DRB1*-DQB1* haplotypes in 943 trio families, confirmed a higher than expected transmission rate (over-transmission) of the *13:03-*03:01 (OR = 2.9, P = 7.6×10−3), *04:05-*03:01 (OR = 2.4, P = 4.4×10−6) and *03:01-*02:01 (OR = 2.1, P = 1.0×10−15) haplotype. In contrast, the *16:01-*05:02 (OR = 0.5, P = 5.4×10−11) and the *15:02-*06:01 (OR = 0.3, P = 1.5×10−3) haplotypes exhibited a lower than expected transmission rate (under-transmission). The independence of the transmission of each positively and negatively associated haplotype was confirmed relative to all positively associated haplotypes, and to the negatively associated *16:01-*05:02 haplotype. In patients, carriage of two predisposing haplotypes, or of protective haplotypes, respectively increased or decreased the patient's risk of developing MS. The risk of MS followed a multiplicative model of genotypes, which was, in order of decreasing ORs: *04:05-*0301/*03:01-*02:01 (OR = 4.5); *03:01-*02:01/*03:01-*02:01 (OR = 4.1); and the *16:01-*05:02/*16:01-*0502 (OR = 0.2) genotypes. Analysis of DRB1 and DQB1 protein chain residues showed that the Val/Gly residue at position 86 of the DRB1 chain was the only difference between the protective *16:01- *15:02 alleles and the predisposing *15:01 one. Similarly, the Ala/Val residue at position 38 of the DQB1 chain differentiated the positively associated *06:02 allele and the negatively associated *05

  7. Human Chromosome 21: Mapping of the chromosomes and cloning of cDNAs

    Energy Technology Data Exchange (ETDEWEB)

    Antonarakis, S.E.

    1991-09-01

    The objective of the research funded by DOE grant DE-FG02-89ER60857 from 6/15/89 to 8/31/91 was to contribute to the physical mapping of human chromosome 21 (HC21) by cloning large fragments of DNA into Yeast Artificial Chromosomes (YACs) and identify YACs that map on HC21. A total of 54 sequence tagged sites (STS) have been developed and mapped in our laboratory to HC21 and can be used as initial reference points for YAC identification and construction of overlapping clones. A small YAC library was constructed which is HC21 specific. DNA from somatic cell hybrid WAV17 or from flow-sorted HC21 was partially digested with EcoRI, ligated into vectors PJS97, PJS98, and YACs have been obtained with average size insert of more than 300 kb. This library has been deposited in D. Patterson's lab for the Joint YAC screening effort. Additional YAC libraries from ICI Pharmaceuticals or from Los Alamos National Laboratories have been screened with several STS and positive YACs have been identified. Work in progress includes screening of YAC libraries in order to construct overlapping clones, characterization of the cloning ends of YACs, characterization of additional STS and cloning of HC21 specific cDNAs. 15 refs., 2 figs., 5 tabs.

  8. Genome-wide maps of nuclear lamina interactions in single human cells

    Science.gov (United States)

    Kind, Jop; Pagie, Ludo; de Vries, Sandra S.; Nahidiazar, Leila; Dey, Siddharth S.; Bienko, Magda; Zhan, Ye; Lajoie, Bryan; de Graaf, Carolyn A.; Amendola, Mario; Fudenberg, Geoffrey; Imakaev, Maxim; Mirny, Leonid A.; Jalink, Kees; Dekker, Job; van Oudenaarden, Alexander; van Steensel, Bas

    2015-01-01

    Summary Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large Lamina Associated Domains (LADs). We report a method to map NL contacts genome-wide in single human cells. Analysis of nearly 400 maps reveals a core architecture of gene-poor LADs that contact the NL with high cell-to-cell consistency, interspersed by LADs with more variable NL interactions. The variable contacts tend to be cell-type specific and are more sensitive to changes in genome ploidy than the consistent contacts. Single-cell maps indicate that NL contacts involve multivalent interactions over hundreds of kilobases. Moreover, we observe extensive intra-chromosomal coordination of NL contacts, even over tens of megabases. Such coordinated loci exhibit preferential interactions as detected by Hi-C. Finally, consistency of NL contacts is inversely linked to gene activity in single cells, and correlates positively with the heterochromatic histone modification H3K9me3. These results highlight fundamental principles of single cell chromatin organization. PMID:26365489

  9. Linkage mapping of the human CSF2 and IL3 genes

    Energy Technology Data Exchange (ETDEWEB)

    Frolova, E.I.; Dolganov, G.M.; Mazo, I.A.; Smirnov, D.V. (M.M. Shemyakin Inst. of Bio-organic Chemistry, Moscow (USSR)); Copeland, P.; Stewart, C.; Dean, M. (Program Resources, Inc./DynCorp., Research Triangle Park, NC (United States)); O' Brien, S.J. (National Cancer Inst., Frederick, MD (United States))

    1991-06-01

    Interleukin 3 (encoded by the IL3 gene) and granulocyte-macrophage colony-stimulating factor (encoded by the CSF2 gene) are small secreted polypeptides that bind to specific cell surface receptors and regulate the growth, gene expression, and differentiation of many of the hematopoietic cell lineages, particularly nonlymphoid cells. The IL3 and CSF2 genes have been cloned and mapped to human chromosome bands 5q23-31. Only 10 kilobases of dna separates the two genes, suggesting that they have a common origin and/or regulation. The authors have cloned 70 kilobases of genomic DNA that includes the IL3 and CSF2 genes, as well as flanking sequences, and report a physical map of this region. Several unique-sequence DNA segments have been identified in this region, and one of these fragments detects two restriction fragment length polymorphisms in DNA from unrelated Caucasians. Segregation of these DNA polymorphisms was followed in the Centre Etude du Polymorphisme Humaine (CEPH) panel of 40 large three-generation pedigrees, and linkage was detected with 17 genetic markers previously typed in these families. Multipoint linkage analysis permits the placement of the region containing the IL3 and CSF2 structural genes on the recombination-genetic linkage map of chromosome 5q and thereby allows the role of these genes in leukemogenesis to be more critically examined.

  10. Musical aptitude is associated with AVPR1A-haplotypes.

    Science.gov (United States)

    Ukkola, Liisa T; Onkamo, Päivi; Raijas, Pirre; Karma, Kai; Järvelä, Irma

    2009-05-20

    Artistic creativity forms the basis of music culture and music industry. Composing, improvising and arranging music are complex creative functions of the human brain, which biological value remains unknown. We hypothesized that practicing music is social communication that needs musical aptitude and even creativity in music. In order to understand the neurobiological basis of music in human evolution and communication we analyzed polymorphisms of the arginine vasopressin receptor 1A (AVPR1A), serotonin transporter (SLC6A4), catecol-O-methyltranferase (COMT), dopamin receptor D2 (DRD2) and tyrosine hydroxylase 1 (TPH1), genes associated with social bonding and cognitive functions in 19 Finnish families (n = 343 members) with professional musicians and/or active amateurs. All family members were tested for musical aptitude using the auditory structuring ability test (Karma Music test; KMT) and Carl Seashores tests for pitch (SP) and for time (ST). Data on creativity in music (composing, improvising and/or arranging music) was surveyed using a web-based questionnaire. Here we show for the first time that creative functions in music have a strong genetic component (h(2) = .84; composing h(2) = .40; arranging h(2) = .46; improvising h(2) = .62) in Finnish multigenerational families. We also show that high music test scores are significantly associated with creative functions in music (pmusic test scores (COMB) (p = 0.0056; corrected p = 0.0006). AVPR1A haplotype AVR+RS1 further suggested a positive association with ST (p = 0.0038; corrected p = 0.00184) and COMB (p = 0.0083; corrected p = 0.0040) using haplotype-based association test HBAT. The results suggest that the neurobiology of music perception and production is likely to be related to the pathways affecting intrinsic attachment behavior.

  11. Inference of population structure using dense haplotype data.

    Directory of Open Access Journals (Sweden)

    Daniel John Lawson

    2012-01-01

    Full Text Available The advent of genome-wide dense variation data provides an opportunity to investigate ancestry in unprecedented detail, but presents new statistical challenges. We propose a novel inference framework that aims to efficiently capture information on population structure provided by patterns of haplotype similarity. Each individual in a sample is considered in turn as a recipient, whose chromosomes are reconstructed using chunks of DNA donated by the other individuals. Results of this "chromosome painting" can be summarized as a "coancestry matrix," which directly reveals key information about ancestral relationships among individuals. If markers are viewed as independent, we show that this matrix almost completely captures the information used by both standard Principal Components Analysis (PCA and model-based approaches such as STRUCTURE in a unified manner. Furthermore, when markers are in linkage disequilibrium, the matrix combines information across successive markers to increase the ability to discern fine-scale population structure using PCA. In parallel, we have developed an efficient model-based approach to identify discrete populations using this matrix, which offers advantages over PCA in terms of interpretability and over existing clustering algorithms in terms of speed, number of separable populations, and sensitivity to subtle population structure. We analyse Human Genome Diversity Panel data for 938 individuals and 641,000 markers, and we identify 226 populations reflecting differences on continental, regional, local, and family scales. We present multiple lines of evidence that, while many methods capture similar information among strongly differentiated groups, more subtle population structure in human populations is consistently present at a much finer level than currently available geographic labels and is only captured by the haplotype-based approach. The software used for this article, ChromoPainter and fineSTRUCTURE, is

  12. High-density SNP genotyping to define beta-globin locus haplotypes.

    Science.gov (United States)

    Liu, Li; Muralidhar, Shalini; Singh, Manisha; Sylvan, Caprice; Kalra, Inderdeep S; Quinn, Charles T; Onyekwere, Onyinye C; Pace, Betty S

    2009-01-01

    Five major beta-globin locus haplotypes have been established in individuals with sickle cell disease (SCD) from the Benin, Bantu, Senegal, Cameroon, and Arab-Indian populations. Historically, beta-haplotypes were established using restriction fragment length polymorphism (RFLP) analysis across the beta-locus, which consists of five functional beta-like globin genes located on chromosome 11. Previous attempts to correlate these haplotypes as robust predictors of clinical phenotypes observed in SCD have not been successful. We speculate that the coverage and distribution of the RFLP sites located proximal to or within the globin genes are not sufficiently dense to accurately reflect the complexity of this region. To test our hypothesis, we performed RFLP analysis and high-density single nucleotide polymorphism (SNP) genotyping across the beta-locus using DNA samples from healthy African Americans with either normal hemoglobin A (HbAA) or individuals with homozygous SS (HbSS) disease. Using the genotyping data from 88 SNPs and Haploview analysis, we generated a greater number of haplotypes than that observed with RFLP analysis alone. Furthermore, a unique pattern of long-range linkage disequilibrium between the locus control region and the beta-like globin genes was observed in the HbSS group. Interestingly, we observed multiple SNPs within the HindIII restriction site located in the Ggamma-globin intervening sequence II which produced the same RFLP pattern. These findings illustrated the inability of RFLP analysis to decipher the complexity of sequence variations that impacts genomic structure in this region. Our data suggest that high-density SNP mapping may be required to accurately define beta-haplotypes that correlate with the different clinical phenotypes observed in SCD.

  13. A high-resolution map of synteny disruptions in gibbon and human genomes.

    Directory of Open Access Journals (Sweden)

    Lucia Carbone

    2006-12-01

    Full Text Available Gibbons are part of the same superfamily (Hominoidea as humans and great apes, but their karyotype has diverged faster from the common hominoid ancestor. At least 24 major chromosome rearrangements are required to convert the presumed ancestral karyotype of gibbons into that of the hominoid ancestor. Up to 28 additional rearrangements distinguish the various living species from the common gibbon ancestor. Using the northern white-cheeked gibbon (2n = 52 (Nomascus leucogenys leucogenys as a model, we created a high-resolution map of the homologous regions between the gibbon and human. The positions of 100 synteny breakpoints relative to the assembled human genome were determined at a resolution of about 200 kb. Interestingly, 46% of the gibbon-human synteny breakpoints occur in regions that correspond to segmental duplications in the human lineage, indicating a common source of plasticity leading to a different outcome in the two species. Additionally, the full sequences of 11 gibbon BACs spanning evolutionary breakpoints reveal either segmental duplications or interspersed repeats at the exact breakpoint locations. No specific sequence element appears to be common among independent rearrangements. We speculate that the extraordinarily high level of rearrangements seen in gibbons may be due to factors that increase the incidence of chromosome breakage or fixation of the derivative chromosomes in a homozygous state.

  14. Rapid gene-based SNP and haplotype marker development in non-model eukaryotes using 3'UTR sequencing

    Directory of Open Access Journals (Sweden)

    Koepke Tyson

    2012-01-01

    Full Text Available Abstract Background Sweet cherry (Prunus avium L., a non-model crop with narrow genetic diversity, is an important member of sub-family Amygdoloideae within Rosaceae. Compared to other important members like peach and apple, sweet cherry lacks in genetic and genomic information, impeding understanding of important biological processes and development of efficient breeding approaches. Availability of single nucleotide polymorphism (SNP-based molecular markers can greatly benefit breeding efforts in such non-model species. RNA-seq approaches employing second generation sequencing platforms offer a unique avenue to rapidly identify gene-based SNPs. Additionally, haplotype markers can be rapidly generated from transcript-based SNPs since they have been found to be extremely utile in identification of genetic variants related to health, disease and response to environment as highlighted by the human HapMap project. Results RNA-seq was performed on two sweet cherry cultivars, Bing and Rainier using a 3' untranslated region (UTR sequencing method yielding 43,396 assembled contigs. In order to test our approach of rapid identification of SNPs without any reference genome information, over 25% (10,100 of the contigs were screened for the SNPs. A total of 207 contigs from this set were identified to contain high quality SNPs. A set of 223 primer pairs were designed to amplify SNP containing regions from these contigs and high resolution melting (HRM analysis was performed with eight important parental sweet cherry cultivars. Six of the parent cultivars were distantly related to Bing and Rainier, the cultivars used for initial SNP discovery. Further, HRM analysis was also performed on 13 seedlings derived from a cross between two of the parents. Our analysis resulted in the identification of 84 (38.7% primer sets that demonstrated variation among the tested germplasm. Reassembly of the raw 3'UTR sequences using upgraded transcriptome assembly software

  15. Rapid detection of structural variation in a human genome using nanochannel-based genome mapping technology

    DEFF Research Database (Denmark)

    Cao, Hongzhi; Hastie, Alex R.; Cao, Dandan

    2014-01-01

    mutations; however, none of the current detection methods are comprehensive, and currently available methodologies are incapable of providing sufficient resolution and unambiguous information across complex regions in the human genome. To address these challenges, we applied a high-throughput, cost......BACKGROUND: Structural variants (SVs) are less common than single nucleotide polymorphisms and indels in the population, but collectively account for a significant fraction of genetic polymorphism and diseases. Base pair differences arising from SVs are on a much higher order (>100 fold) than point...... mapping technology as a comprehensive and cost-effective method for detecting structural variation and studying complex regions in the human genome, as well as deciphering viral integration into the host genome....

  16. Isolation and comparative mapping of a human chromosome 20-specific alpha-satellite DNA clone.

    Science.gov (United States)

    Baldini, A; Archidiacono, N; Carbone, R; Bolino, A; Shridhar, V; Miller, O J; Miller, D A; Ward, D C; Rocchi, M

    1992-01-01

    We have isolated and characterized a human genomic DNA clone (PZ20, locus D20Z2) that identifies, under high-stringency hybridization conditions, an alphoid DNA subset specific for chromosome 20. The specificity was determined using fluorescence in situ hybridization. Sequence analysis confirmed our previously reported data on the great similarity between the chromosome 20 and chromosome 2 alphoid subsets. Comparative mapping of pZ20 on chimpanzee and gorilla chromosomes, also performed under high-stringency conditions, indicates that the alphoid subset has ancestral sequences on chimpanzee chromosome 11 and gorilla chromosome 19. However, no hybridization was observed to chromosomes 21 in the great apes, the homolog of human chromosome 20.

  17. Heritability maps of human face morphology through large-scale automated three-dimensional phenotyping

    Science.gov (United States)

    Tsagkrasoulis, Dimosthenis; Hysi, Pirro; Spector, Tim; Montana, Giovanni

    2017-04-01

    The human face is a complex trait under strong genetic control, as evidenced by the striking visual similarity between twins. Nevertheless, heritability estimates of facial traits have often been surprisingly low or difficult to replicate. Furthermore, the construction of facial phenotypes that correspond to naturally perceived facial features remains largely a mystery. We present here a large-scale heritability study of face geometry that aims to address these issues. High-resolution, three-dimensional facial models have been acquired on a cohort of 952 twins recruited from the TwinsUK registry, and processed through a novel landmarking workflow, GESSA (Geodesic Ensemble Surface Sampling Algorithm). The algorithm places thousands of landmarks throughout the facial surface and automatically establishes point-wise correspondence across faces. These landmarks enabled us to intuitively characterize facial geometry at a fine level of detail through curvature measurements, yielding accurate heritability maps of the human face (www.heritabilitymaps.info).

  18. Maximum likelihood model based on minor allele frequencies and weighted Max-SAT formulation for haplotype assembly.

    Science.gov (United States)

    Mousavi, Sayyed R; Khodadadi, Ilnaz; Falsafain, Hossein; Nadimi, Reza; Ghadiri, Nasser

    2014-06-07

    Human haplotypes include essential information about SNPs, which in turn provide valuable information for such studies as finding relationships between some diseases and their potential genetic causes, e.g., for Genome Wide Association Studies. Due to expensiveness of directly determining haplotypes and recent progress in high throughput sequencing, there has been an increasing motivation for haplotype assembly, which is the problem of finding a pair of haplotypes from a set of aligned fragments. Although the problem has been extensively studied and a number of algorithms have already been proposed for the problem, more accurate methods are still beneficial because of high importance of the haplotypes information. In this paper, first, we develop a probabilistic model, that incorporates the Minor Allele Frequency (MAF) of SNP sites, which is missed in the existing maximum likelihood models. Then, we show that the probabilistic model will reduce to the Minimum Error Correction (MEC) model when the information of MAF is omitted and some approximations are made. This result provides a novel theoretical support for the MEC, despite some criticisms against it in the recent literature. Next, under the same approximations, we simplify the model to an extension of the MEC in which the information of MAF is used. Finally, we extend the haplotype assembly algorithm HapSAT by developing a weighted Max-SAT formulation for the simplified model, which is evaluated empirically with positive results.

  19. Experimental generation of SNP haplotype signatures in patients with sickle cell anaemia.

    Directory of Open Access Journals (Sweden)

    Stephan Menzel

    Full Text Available BACKGROUND: Sickle cell anemia is caused by a single type of mutation, a homozygous A→T substitution in the ß globin gene. Clinical severity is diverse, partially due to additional, disease-modifying genetic factors. We are studying one such modifier locus, HMIP (HBS1L-MYB intergenic polymorphism, chromosome 6q23.3. Working with a genetically admixed patient population, we have encountered the necessity to generate haplotype signatures of genetic markers to label genomic fragments with distinct genealogical origin at this locus. With the goal to generate haplotype signatures from patients experimentally, we have investigated the suitability of an existing nanofluidic assay platform to perform phase alignment with single-nucleotide polymorphism alleles. METHODOLOGY/PRINCIPAL FINDINGS: Patient DNA samples were loaded onto Fluidigm Digital Arrays and individual DNA molecules were assayed with allele-specific probes for SNP markers. Here we present data showing the utility of the nanofluidic approach, yielding haplotype data identical to those obtained with a family-based method. We then determined haplotype composition in a group of patients with sickle cell disease, including in those where a mathematical inference approach gave ambiguous or misleading results. Experimental phasing of genotypes across 3.8 kb for rs9399137, rs9402685, and rs11759553 created unequivocal haplotype signatures for each of the patients. In 68 patients, we found 8 copies of a haplotype signature ('C-C-T', which is known to be prevalent in Europeans but to be absent in West African populations. We have confirmed the identity of our phased allele pairs by single-molecule sequencing and have demonstrated, in principle, that three-allele phasing (using three colors is a potential extension to this method. CONCLUSIONS/SIGNIFICANCE: Phased haplotypes yield more information than the individual marker genotypes. Procedures such as the one described here would therefore

  20. The human renin-binding protein gene (RENBP) maps in Xq28

    Energy Technology Data Exchange (ETDEWEB)

    Ouweland, A.M.W. van der; Verdijk, M.; Oost, B.A. van (Univ. Hospital Nijmegen (Netherlands)); Kiochis, P.; Poustka, A. (Deutsches Krebsforschungszemtrum, Heidelberg (Germany))

    1994-05-01

    The authors report here the successful application of the method by which cDNA libraries are screened with positionally identified genomic clones. Human cosmid clones were selected from a cosmid library derived from the Q1Z cell line. This Q1Z cell line is a hamster-human somatic cell hybrid that contains the Xq28 region as its sole human component. To search for kidney-expressed genes, they screened a kidney cDNA library purchased from Clontech with cosmid-derived probes. Based on the physical mapping of the vasopressin V2 receptor gene close to the L1CAM gene, they analyzed cosmids derived from this region. One of the cosmids was 12B2, located 50 kb from the L1CAM gene. A 20-kb EcoRI subclone from the 12B2 cosmid was used as probe. This fragment did not hybridize to the probe 2-55 in contrast to the whole cosmid 12B2. Screening of 200,000 cDNA clones resulted in the identification of two positive clones. After sequence determination, it appeared that one of the positive cDNA clones contained Escherichia coli DNA as insert (data not shown). The other cDNA (pMV24) contained an open reading frame corresponding to the 243 amino-terminal amino acids of the human renin binding protein. The RENBP gene maps to interval 3 between the loci for DX52 and G-6-PD. This is the same interval as that for the color blindness gene, DXS707, and the AVPR2, L1CAM, and QM genes. This result confirms that the isolated RENBP cDNA originates from the same location as that from which the parental cosmid clone was derived. 28 refs., 1 fig.

  1. Mechanical and biochemical mapping of human auricular cartilage for reliable assessment of tissue-engineered constructs.

    Science.gov (United States)

    Nimeskern, Luc; Pleumeekers, Mieke M; Pawson, Duncan J; Koevoet, Wendy L M; Lehtoviita, Iina; Soyka, Michael B; Röösli, Christof; Holzmann, David; van Osch, Gerjo J V M; Müller, Ralph; Stok, Kathryn S

    2015-07-16

    It is key for successful auricular (AUR) cartilage tissue-engineering (TE) to ensure that the engineered cartilage mimics the mechanics of the native tissue. This study provides a spatial map of the mechanical and biochemical properties of human auricular cartilage, thus establishing a benchmark for the evaluation of functional competency in AUR cartilage TE. Stress-relaxation indentation (instantaneous modulus, Ein; maximum stress, σmax; equilibrium modulus, Eeq; relaxation half-life time, t1/2; thickness, h) and biochemical parameters (content of DNA; sulfated-glycosaminoglycan, sGAG; hydroxyproline, HYP; elastin, ELN) of fresh human AUR cartilage were evaluated. Samples were categorized into age groups and according to their harvesting region in the human auricle (for AUR cartilage only). AUR cartilage displayed significantly lower Ein, σmax, Eeq, sGAG content; and significantly higher t1/2, and DNA content than NAS cartilage. Large amounts of ELN were measured in AUR cartilage (>15% ELN content per sample wet mass). No effect of gender was observed for either auricular or nasoseptal samples. For auricular samples, significant differences between age groups for h, sGAG and HYP, and significant regional variations for Ein, σmax, Eeq, t1/2, h, DNA and sGAG were measured. However, only low correlations between mechanical and biochemical parameters were seen (Rbiochemical map of human auricular cartilage. Regional variations in mechanical and biochemical properties were demonstrated in the auricle. This finding highlights the importance of focusing future research on efforts to produce cartilage grafts with spatially tunable mechanics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Analysis of a Larger SNP Dataset from the HapMap Project Confirmed That the Modern Human A Allele of the ABO Blood Group Genes Is a Descendant of a Recombinant between B and O Alleles.

    Science.gov (United States)

    Itou, Masaya; Sato, Mitsuharu; Kitano, Takashi

    2013-01-01

    The human ABO blood group gene consists of three main alleles (A, B, and O) that encode a glycosyltransferase. The A and B alleles differ by two critical amino acids in exon 7, and the major O allele has a single nucleotide deletion (Δ261) in exon 6. Previous evolutionary studies have revealed that the A allele is the most ancient, B allele diverged from the A allele with two critical amino acid substitutions in exon 7, and the major O allele diverged from the A allele with Δ261 in exon 6. However, a recent phylogenetic network analysis study showed that the A allele of humans emerged through a recombination between the B and O alleles. In the previous study, a restricted dataset from only two populations was used. In this study, therefore, we used a large single nucleotide polymorphism (SNP) dataset from the HapMap Project. The results indicated that the A101-A201-O09 haplogroup was a recombinant lineage between the B and O haplotypes, containing the intact exon 6 from the B allele and the two critical A type sites in exon 7 from the major O allele. Its recombination point was assumed to be located just behind Δ261 in exon 6.

  3. Analysis of a Larger SNP Dataset from the HapMap Project Confirmed That the Modern Human A Allele of the ABO Blood Group Genes Is a Descendant of a Recombinant between B and O Alleles

    Directory of Open Access Journals (Sweden)

    Masaya Itou

    2013-01-01

    Full Text Available The human ABO blood group gene consists of three main alleles (A, B, and O that encode a glycosyltransferase. The A and B alleles differ by two critical amino acids in exon 7, and the major O allele has a single nucleotide deletion (Δ261 in exon 6. Previous evolutionary studies have revealed that the A allele is the most ancient, B allele diverged from the A allele with two critical amino acid substitutions in exon 7, and the major O allele diverged from the A allele with Δ261 in exon 6. However, a recent phylogenetic network analysis study showed that the A allele of humans emerged through a recombination between the B and O alleles. In the previous study, a restricted dataset from only two populations was used. In this study, therefore, we used a large single nucleotide polymorphism (SNP dataset from the HapMap Project. The results indicated that the A101-A201-O09 haplogroup was a recombinant lineage between the B and O haplotypes, containing the intact exon 6 from the B allele and the two critical A type sites in exon 7 from the major O allele. Its recombination point was assumed to be located just behind Δ261 in exon 6.

  4. Integrated Transcriptome Map Highlights Structural and Functional Aspects of the Normal Human Heart.

    Science.gov (United States)

    Caracausi, Maria; Piovesan, Allison; Vitale, Lorenza; Pelleri, Maria Chiara

    2017-04-01

    A systematic meta-analysis of the available gene expression profiling datasets for the whole normal human heart generated a quantitative transcriptome reference map of this organ. Transcriptome Mapper (TRAM) software integrated 32 gene expression profile datasets from different sources returning a reference value of expression for each of the 43,360 known, mapped transcripts assayed by any of the experimental platforms used in this regard. Main findings include the visualization at the gene and chromosomal levels of the classical description of the basic histology and physiology of the heart, the identification of suitable housekeeping reference genes, the analysis of stoichiometry of gene products, and the focusing on chromosome 21 genes, which are present in one excess copy in Down syndrome subjects, presenting cardiovascular defects in 30-40% of cases. Independent in vitro validation showed an excellent correlation coefficient (r = 0.98) with the in silico data. Remarkably, heart/non-cardiac tissue expression ratio may also be used to anticipate that effects of mutations will most probably affect or not the heart. The quantitative reference global portrait of gene expression in the whole normal human heart illustrates the structural and functional aspects of the whole organ and is a general model to understand the mechanisms underlying heart pathophysiology. J. Cell. Physiol. 232: 759-770, 2017. © 2016 Wiley Periodicals, Inc.

  5. Comparing different stimulus configurations for population receptive field mapping in human fMRI

    Directory of Open Access Journals (Sweden)

    Ivan eAlvarez

    2015-02-01

    Full Text Available Population receptive field (pRF mapping is a widely used approach to measuring aggregate human visual receptive field properties by recording non-invasive signals using functional MRI. Despite growing interest, no study to date has systematically investigated the effects of different stimulus configurations on pRF estimates from human visual cortex. Here we compared the effects of three different stimulus configurations on a model-based approach to pRF estimation: size-invariant bars and eccentricity-scaled bars defined in Cartesian coordinates and traveling along the cardinal axes, and a novel simultaneous ‘wedge and ring’ stimulus defined in polar coordinates, systematically covering polar and eccentricity axes. We found that the presence or absence of eccentricity scaling had a significant effect on goodness of fit and pRF size estimates. Further, variability in pRF size estimates was directly influenced by stimulus configuration, particularly for higher visual areas including V5/MT+. Finally, we compared eccentricity estimation between phase-encoded and model-based pRF approaches. We observed a tendency for more peripheral eccentricity estimates using phase-encoded methods, independent of stimulus size. We conclude that both eccentricity scaling and polar rather than Cartesian stimulus configuration are important considerations for optimal experimental design in pRF mapping. While all stimulus configurations produce adequate estimates, simultaneous wedge and ring stimulation produced higher fit reliability, with a significant advantage in reduced acquisition time.

  6. Optical mapping of single-molecule human DNA in disposable, mass-produced all-polymer

    DEFF Research Database (Denmark)

    Østergaard, Peter Friis; Lopacinska-Jørgensen, Joanna; Pedersen, Jonas Nyvold

    2015-01-01

    We demonstrate all-polymer injection molded devices for optical mapping of denaturation–renaturation (DR) patterns on long, single DNA-molecules from the human genome. The devices have channels with ultra-low aspect ratio, only 110 nm deep while 20 μm wide, and are superior to the silica devices...... used previously in the field. With these polymer devices, we demonstrate on-chip recording of DR images of DNA-molecules stretched to more than 95% of their contour length. The stretching is done by opposing flows Marie et al (2013 Proc. Natl Acad. Sci. USA 110 4893–8). The performance is validated...... by mapping 20 out of 24 Mbp-long DNA fragments to the human reference genome. We optimized fabrication of the devices to a yield exceeding 95%. This permits a substantial economies-of-scale driven cost-reduction, leading to device costs as low as 3 USD per device, about a factor 70 lower than the cost...

  7. Human Collaborative Localization and Mapping in Indoor Environments with Non-Continuous Stereo

    Science.gov (United States)

    Guerra, Edmundo; Munguia, Rodrigo; Bolea, Yolanda; Grau, Antoni

    2016-01-01

    A new approach to the monocular simultaneous localization and mapping (SLAM) problem is presented in this work. Data obtained from additional bearing-only sensors deployed as wearable devices is fully fused into an Extended Kalman Filter (EKF). The wearable device is introduced in the context of a collaborative task within a human-robot interaction (HRI) paradigm, including the SLAM problem. Thus, based on the delayed inverse-depth feature initialization (DI-D) SLAM, data from the camera deployed on the human, capturing his/her field of view, is used to enhance the depth estimation of the robotic monocular sensor which maps and locates the device. The occurrence of overlapping between the views of both cameras is predicted through geometrical modelling, activating a pseudo-stereo methodology which allows to instantly measure the depth by stochastic triangulation of matched points found through SIFT/SURF. Experimental validation is provided through results from experiments, where real data is captured as synchronized sequences of video and other data (relative pose of secondary camera) and processed off-line. The sequences capture indoor trajectories representing the main challenges for a monocular SLAM approach, namely, singular trajectories and close turns with high angular velocities with respect to linear velocities. PMID:26927100

  8. Probabilistic map of critical functional regions of the human cerebral cortex: Broca's area revisited.

    Science.gov (United States)

    Tate, Matthew C; Herbet, Guillaume; Moritz-Gasser, Sylvie; Tate, Joseph E; Duffau, Hugues

    2014-10-01

    The organization of basic functions of the human brain, particularly in the right hemisphere, remains poorly understood. Recent advances in functional neuroimaging have improved our understanding of cortical organization but do not allow for direct interrogation or determination of essential (versus participatory) cortical regions. Direct cortical stimulation represents a unique opportunity to provide novel insights into the functional distribution of critical epicentres. Direct cortical stimulation (bipolar, 60 Hz, 1-ms pulse) was performed in 165 consecutive patients undergoing awake mapping for resection of low-grade gliomas. Tasks included motor, sensory, counting, and picture naming. Stimulation sites eliciting positive (sensory/motor) or negative (speech arrest, dysarthria, anomia, phonological and semantic paraphasias) findings were recorded and mapped onto a standard Montreal Neurological Institute brain atlas. Montreal Neurological Institute-space functional data were subjected to cluster analysis algorithms (K-means, partition around medioids, hierarchical Ward) to elucidate crucial network epicentres. Sensorimotor function was observed in the pre/post-central gyri as expected. Articulation epicentres were also found within the pre/post-central gyri. However, speech arrest localized to ventral premotor cortex, not the classical Broca's area. Anomia/paraphasia data demonstrated foci not only within classical Wernicke's area but also within the middle and inferior frontal gyri. We report the first bilateral probabilistic map for crucial cortical epicentres of human brain functions in the right and left hemispheres, including sensory, motor, and language (speech, articulation, phonology and semantics). These data challenge classical theories of brain organization (e.g. Broca's area as speech output region) and provide a distributed framework for future studies of neural networks.

  9. Retinal degeneration slow (rds) in mouse results from simple insertion of a t haplotype-specific element into protein-coding exon II

    Energy Technology Data Exchange (ETDEWEB)

    Ma, J.; Norton, J.C.; Allen, A.C.; Burns, J.L.; Travis, G.H. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)] [and others

    1995-07-20

    Retinal degeneration slow (rds) is a semidominant mutation of mice that causes dysplasia and degeneration of rod and cone photoreceptors. Mutations in RDS, the human ortholog of the rds gene, are responsible for several inherited retinal dystrophies including a subset of retinitis pigmentosa. The normal rds locus encodes rds/peripherin, an integral membrane glycoprotein present in outer segment discs. Genomic libraries form wildtype and rds/rds mice were screened with an rds cDNA, and phage {lambda} clones that span the normal and mutant loci were mapped. We show that in mice, rds is caused by the insertion into exon II of a 9.2-kb repetitive genomic element that is very similar to the t haplotype-specific element in the H-2 complex. The entire element is included in the RNA products of the mutant locus. We present evidence that rds in mice represents a null allele. 40 refs., 4 figs.

  10. Report mapping legal and policy instruments of the EU for human rights and democracy support, FRAME Deliverable 12.1

    NARCIS (Netherlands)

    Churruca Muguruza, C.; Isa, F. G.; San José, D. G.; Fernández Sánchez, P. A.; Márquez Carrasco, C.; Muñoz Nogal, E.; Nagore Casas, M.; Timmer, Alexandra

    2014-01-01

    This report is devoted to the mapping of legal and policy instruments of the EU for human rights and democracy support. In particular, it highlights the EU´s human rights priorities in terms of themes and vulnerable groups in its external action based on a review of EU policy documents and literatur

  11. Integrated map of the chromosome 8p12-p21 region, a region involved in human cancers and Werner syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Imbert, A.; Chaffanet, M.; Birnbaum, D.; Pebusque, M.J. [INSERM, Marseille (France)] [and others

    1996-02-15

    This article discusses the genetic mapping of the specific region on human chromosome 8, 8p12-p21, and its implications to human hereditary cancers and diseases. The localization of disease genes such as NEFL and FGFR1 are given, accomplished using contigs which span the region of deletion involved in these hereditary diseases. 59 refs., 4 figs., 3 tabs.

  12. Mapping cis-Regulatory Domains in the Human Genome UsingMulti-Species Conservation of Synteny

    Energy Technology Data Exchange (ETDEWEB)

    Ahituv, Nadav; Prabhakar, Shyam; Poulin, Francis; Rubin, EdwardM.; Couronne, Olivier

    2005-06-13

    Our inability to associate distant regulatory elements with the genes that they regulate has largely precluded their examination for sequence alterations contributing to human disease. One major obstacle is the large genomic space surrounding targeted genes in which such elements could potentially reside. In order to delineate gene regulatory boundaries we used whole-genome human-mouse-chicken (HMC) and human-mouse-frog (HMF) multiple alignments to compile conserved blocks of synteny (CBS), under the hypothesis that these blocks have been kept intact throughout evolution at least in part by the requirement of regulatory elements to stay linked to the genes that they regulate. A total of 2,116 and 1,942 CBS>200 kb were assembled for HMC and HMF respectively, encompassing 1.53 and 0.86 Gb of human sequence. To support the existence of complex long-range regulatory domains within these CBS we analyzed the prevalence and distribution of chromosomal aberrations leading to position effects (disruption of a genes regulatory environment), observing a clear bias not only for mapping onto CBS but also for longer CBS size. Our results provide a genome wide data set characterizing the regulatory domains of genes and the conserved regulatory elements within them.

  13. Mapping cocaine binding sites in human and baboon brain in vivo.

    Science.gov (United States)

    Fowler, J S; Volkow, N D; Wolf, A P; Dewey, S L; Schlyer, D J; Macgregor, R R; Hitzemann, R; Logan, J; Bendriem, B; Gatley, S J

    1989-01-01

    The first direct measurements of cocaine binding in the brain of normal human volunteers and baboons have been made by using positron emission tomography (PET) and tracer doses of [N-11C-methyl]-(-)-cocaine ([11C]cocaine). Cocaine's binding and release from brain are rapid with the highest regional uptake of carbon-11 occurring in the corpus striatum at 4-10 minutes after intravenous injection of labeled cocaine. This was followed by a clearance to half the peak value at about 25 minutes with the overall time course paralleling the previously documented time course of the euphoria experienced after intravenous cocaine administration. Blockade of the dopamine reuptake sites with nomifensine reduced the striatal but not the cerebellar uptake of [11C]cocaine in baboons indicating that cocaine binding is associated with the dopamine reuptake site in the corpus striatum. A comparison of labeled metabolites of cocaine in human and baboon plasma showed that while cocaine is rapidly metabolized in both species, the profile of labeled metabolites is different, with baboon plasma containing significant amounts of labeled carbon dioxide, and human plasma containing no significant labeled carbon dioxide. These studies demonstrate the feasibility of using [11C]cocaine and PET to map binding sites for cocaine in human brain, to monitor its kinetics, and to characterize its binding mechanism by using appropriate pharmacological challenges.

  14. Haplotyping using a combination of polymerase chain reaction-single-strand conformational polymorphism analysis and haplotype-specific PCR amplification.

    Science.gov (United States)

    Zhou, Huitong; Li, Shaobin; Liu, Xiu; Wang, Jiqing; Luo, Yuzhu; Hickford, Jon G H

    2014-12-01

    A single nucleotide polymorphism (SNP) may have an impact on phenotype, but it may also be influenced by multiple SNPs within a gene; hence, the haplotype or phase of multiple SNPs needs to be known. Various methods for haplotyping SNPs have been proposed, but a simple and cost-effective method is currently unavailable. Here we describe a haplotyping approach using two simple techniques: polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) and haplotype-specific PCR. In this approach, individual regions of a gene are analyzed by PCR-SSCP to identify variation that defines sub-haplotypes, and then extended haplotypes are assembled from the sub-haplotypes either directly or with the additional use of haplotype-specific PCR amplification. We demonstrate the utility of this approach by haplotyping ovine FABP4 across two variable regions that contain seven SNPs and one indel. The simplicity of this approach makes it suitable for large-scale studies and/or diagnostic screening.

  15. Modeling of identity-by-descent processes along a chromosome between haplotypes and their genotyped ancestors.

    Science.gov (United States)

    Druet, Tom; Farnir, Frederic Paul

    2011-06-01

    Identity-by-descent probabilities are important for many applications in genetics. Here we propose a method for modeling the transmission of the haplotypes from the closest genotyped relatives along an entire chromosome. The method relies on a hidden Markov model where hidden states correspond to the set of all possible origins of a haplotype within a given pedigree. Initial state probabilities are estimated from average genetic contribution of each origin to the modeled haplotype while transition probabilities are computed from recombination probabilities and pedigree relationships between the modeled haplotype and the various possible origins. The method was tested on three simulated scenarios based on real data sets from dairy cattle, Arabidopsis thaliana, and maize. The mean identity-by-descent probabilities estimated for the truly inherited parental chromosome ranged from 0.94 to 0.98 according to the design and the marker density. The lowest values were observed in regions close to crossing over or where the method was not able to discriminate between several origins due to their similarity. It is shown that the estimated probabilities were correctly calibrated. For marker imputation (or QTL allele prediction for fine mapping or genomic selection), the method was efficient, with 3.75% allelic imputation error rates on a dairy cattle data set with a low marker density map (1 SNP/Mb). The method should prove useful for situations we are facing now in experimental designs and in plant and animal breeding, where founders are genotyped with relatively high markers densities and last generation(s) genotyped with a lower-density panel.

  16. Functional Haplotypes in Interleukin 4 Gene Associated with Periodontitis

    Science.gov (United States)

    Mayer, Marcia Pinto Alves; Rossa, Carlos

    2017-01-01

    Chronic periodontitis (CP) is an infectious inflammatory disease that affects tooth-supporting structures and in which dental plaque bacteria, immune mechanisms and genetic predisposition play important roles. Interleukin 4 (IL-4) is a key anti-inflammatory cytokine with relevant action in imbalances in inflamed periodontal tissue. Individuals carrying the TCI/CCI genotype (S-haplotype) of the IL-4 gene are 5 times more susceptible to CP, whereas the CTI/TTD genotype (P-haplotype) confers protection against CP. Compared with the S-haplotype, subjects with the P-haplotype produce higher levels of the IL-4 protein after non-surgical periodontal therapy. The present in vitro study aimed to investigate the functionality of IL-4 haplotypes in immune cells to obtain insight into the influence of these genetic variations in regulating immune responses to CP-associated bacteria. Peripheral blood was collected from 6 subjects carrying each haplotype, and their immune cells were challenged with periodontopathogens to compare responses of the different haplotypes with regard to gene expression, protein secretion and the immunophenotype of T helper responses. We found higher IL-4 mRNA and protein levels in the P-haplotype, which also presented higher levels of anti-inflammatory cytokines. In contrast, cells from S-haplotype subjects responded with higher levels of pro-inflammatory cytokines. S-haplotype individuals exhibited significantly greater polarization toward the Th1 phenotype, whereas the P-haplotype was associated with an attenuated response to periodontopathogens, with suggestive skewing toward Th2/M2 phenotypes. In conclusion, IL-4 genetic variations associated with susceptibility to or protection against chronic periodontitis are directly associated with influencing the response of immune cells to periodontopathogens. PMID:28114408

  17. Haplotype analysis of DNA microsatellites tightly linked to the locus of Usher syndrome type I on chromosome 11q

    Energy Technology Data Exchange (ETDEWEB)

    Korostishevsky, M.; Kalinsky, H.; Seroussi, E. [Sackler Faculty of Medicine, Ramat-Aviv (Israel)] [and other

    1994-09-01

    Usher syndrome type I (USHI), an autosomal recessive disorder associated with congenital sensorineural deafness and progressive visual loss, is closely linked to the D11S533 locus. The availability of 7 other polymorphic markers within few centimorgans spanning the disease locus allowed us to identify a unique and single haplotype among all carriers of USHI gene in the Samaritan kindred. Occurrence of recombination in this small chromosomal interval is rare, hindering the detection of the mitotic recombination events needed for analysis by traditional linkage methods. Attempts to order the eight loci by linkage disequilibrium models proved to be problematic. However, our haplotype analysis implied that recombinations which had arisen in past generations may be utilized in fine mapping of the USHI gene and in resolving the conflicting linkage maps previously obtained for this region. We have developed a simple algorithm for predicting the order of the microsatellites on the basis of haplotype resemblance. The following chromosomal map in which the USHI gene is closest to D11S533 (location score of 31.0 by multipoint analysis) is suggested: D11S916, GARP, D11S527, D11S533, OMP, D11S906, D11S911, D11S937. Physical mapping efforts are currently directed to verify and to detail the map of this chromosomal region.

  18. Haplotype frequencies at the DRD2 locus in populations of the East European Plain

    Directory of Open Access Journals (Sweden)

    Mikulich Alexey I

    2009-09-01

    Full Text Available Abstract Background It was demonstrated previously that the three-locus RFLP haplotype, TaqI B-TaqI D-TaqI A (B-D-A, at the DRD2 locus constitutes a powerful genetic marker and probably reflects the most ancient dispersal of anatomically modern humans. Results We investigated TaqI B, BclI, MboI, TaqI D, and TaqI A RFLPs in 17 contemporary populations of the East European Plain and Siberia. Most of these populations belong to the Indo-European or Uralic language families. We identified three common haplotypes, which occurred in more than 90% of chromosomes investigated. The frequencies of the haplotypes differed according to linguistic and geographical affiliation. Conclusion Populations in the northwestern (Byelorussians from Mjadel', northern (Russians from Mezen' and Oshevensk, and eastern (Russians from Puchezh parts of the East European Plain had relatively high frequencies of haplotype B2-D2-A2, which may reflect admixture with Uralic-speaking populations that inhabited all of these regions in the Early Middle Ages.

  19. Major histocompatibility complex class II alleles and haplotypes associated with non-suppurative meningoencephalitis in greyhounds.

    Science.gov (United States)

    Shiel, R E; Kennedy, L J; Nolan, C M; Mooney, C T; Callanan, J J

    2014-09-01

    Non-suppurative meningoencephalitis is a breed-restricted canine neuroinflammatory disorder affecting young greyhounds in Ireland. A genetic risk factor is suspected because of the development of disease in multiple siblings and an inability to identify a causative infectious agent. The aim of this study was to examine potential associations between dog leucocyte antigen (DLA) class II haplotype and the presence of the disease. DLA three locus haplotypes were determined in 31 dogs with non-suppurative meningoencephalitis and in 115 healthy control dogs using sequence-based typing (SBT) methods. All dogs were unrelated at the parental level. Two haplotypes (DRB1*01802/DQA1*00101/DQB1*00802 and DRB1*01501/DQA1*00601/DQB1*02201) were significantly (P = 0.0099 and 0.037) associated with the presence of meningoencephalitis, with odds ratios (95% confidence interval) of 5.531 (1.168-26.19) and 3.736 (1.446-9.652), respectively. These results confirm that there is an association between DLA class II haplotype and greyhound meningoencephalitis, suggesting an immunogenetic risk factor for the development of the disease. Greyhound meningoencephalitis may be a suitable model for human neuroinflammatory diseases with an immunogenetic component. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Association between HLA-DQ genotypes and haplotypes vs Helicobacter pylori infection in an Indonesian population.

    Science.gov (United States)

    Zhao, Yang; Wang, Jingwen; Tanaka, Tsutomu; Hosono, Akihiro; Ando, Ryosuke; Soeripto, Soeripto; Ediati Triningsih, F X; Triono, Tegu; Sumoharjo, Suwignyo; Astuti, E Y Wenny; Gunawan, Stephanus; Tokudome, Shinkan

    2012-01-01

    Helicobacter pylori is an important gastrointestinal pathogen related to the development of not only atrophic gastritis and peptic ulcer, but also gastric cancer. Human leukocyte antigens (HLA) may play particular roles in host immune responses to bacterial antigens. This study aimed to investigate the association between HLA-DQA1 and DQB1 genotypes and haplotypes vs H. pylori infection in an Indonesian population. We selected 294 healthy participants in Mataram, Lombok Island, Indonesia. H. pylori infection was determined by urea breath test (UBT). We analyzed HLA-DQA1 and DQB1 genotypes by PCR-RFLP and constructed haplotypes of HLA-DQA1 and DQB1 genes. Multiple comparisons were conducted according to the Bonferroni method. The H. pylori infection rate was 11.2% in this Indonesian population. The DQB1*0401 genotype was noted to be associated with a high risk of H. pylori infection, compared with the DQB1*0301 genotype. None of the HLA-DQA1 or DQB1 haplotypes were related to the risk of H. pylori infection. The study suggests that HLADQB1 genes play important roles in H. pylori infection, but there was no statistically significant association between HLA-DQA1 or DQB1 haplotypes and H.pylori infection in our Lombok Indonesian population.

  1. Mapping the distinctive populations of lymphatic endothelial cells in different zones of human lymph nodes.

    Directory of Open Access Journals (Sweden)

    Saem Mul Park

    Full Text Available The lymphatic sinuses in human lymph nodes (LNs are crucial to LN function yet their structure remains poorly defined. Much of our current knowledge of lymphatic sinuses derives from rodent models, however human LNs differ substantially in their sinus structure, most notably due to the presence of trabeculae and trabecular lymphatic sinuses that rodent LNs lack. Lymphatic sinuses are bounded and traversed by lymphatic endothelial cells (LECs. A better understanding of LECs in human LNs is likely to improve our understanding of the regulation of cell trafficking within LNs, now an important therapeutic target, as well as disease processes that involve lymphatic sinuses. We therefore sought to map all the LECs within human LNs using multicolor immunofluorescence microscopy to visualize the distribution of a range of putative markers. PROX1 was the only marker that uniquely identified the LECs lining and traversing all the sinuses in human LNs. In contrast, LYVE1 and STAB2 were only expressed by LECs in the paracortical and medullary sinuses in the vast majority of LNs studied, whilst the subcapsular and trabecular sinuses lacked these molecules. These data highlight the existence of at least two distinctive populations of LECs within human LNs. Of the other LEC markers, we confirmed VEGFR3 was not specific for LECs, and CD144 and CD31 stained both LECs and blood vascular endothelial cells (BECs; in contrast, CD59 and CD105 stained BECs but not LECs. We also showed that antigen-presenting cells (APCs in the sinuses could be clearly distinguished from LECs by their expression of CD169, and their lack of expression of PROX1 and STAB2, or endothelial markers such as CD144. However, both LECs and sinus APCs were stained with DCN46, an antibody commonly used to detect CD209.

  2. Chromosomal mapping, gene structure and characterization of the human and murine RAB27B gene

    Directory of Open Access Journals (Sweden)

    Huxley Clare

    2001-02-01

    Full Text Available Abstract Background Rab GTPases are regulators of intracellular membrane traffic. The Rab27 subfamily consists of Rab27a and Rab27b. Rab27a has been recently implicated in Griscelli Disease, a disease combining partial albinism with severe immunodeficiency. Rab27a plays a key role in the function of lysosomal-like organelles such as melanosomes in melanocytes and lytic granules in cytotoxic T lymphocytes. Little is known about Rab27b. Results The human RAB27B gene is organised in six exons, spanning about 69 kb in the chromosome 18q21.1 region. Exon 1 is non-coding and is separated from the others by 49 kb of DNA and exon 6 contains a long 3' untranslated sequence (6.4 kb. The mouse Rab27b cDNA shows 95% identity with the human cDNA at the protein level and maps to mouse chromosome 18. The mouse mRNA was detected in stomach, large intestine, spleen and eye by RT-PCR, and in heart, brain, spleen and kidney by Northern blot. Transient over-expression of EGF-Rab27b fusion protein in cultured melanocytes revealed that Rab27b is associated with melanosomes, as observed for EGF-Rab27a. Conclusions Our results indicate that the Rab27 subfamily of Ras-like GTPases is highly conserved in mammals. There is high degree of conservation in sequence and gene structure between RAB27A and RAB27B genes. Exogenous expression of Rab27b in melanocytes results in melanosomal association as observed for Rab27a, suggesting the two Rab27 proteins are functional homologues. As with RAB27A in Griscelli Disease, RAB27B may be also associated with human disease mapping to chromosome 18.

  3. Mapping human health risks from exposure to trace metal contamination of drinking water sources in Pakistan

    Energy Technology Data Exchange (ETDEWEB)

    Bhowmik, Avit Kumar [Institute for Environmental Sciences, University of Koblenz-Landau, Fortstrasse 7, D-76829 Landau in der Pfalz (Germany); Alamdar, Ambreen [Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Katsoyiannis, Ioannis [Aristotle University of Thessaloniki, Department of Chemistry, Division of Chemical Technology, Box 116, Thessaloniki 54124 (Greece); Shen, Heqing [Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Ali, Nadeem [Department of Environmental Sciences, FBAS, International Islamic University, Islamabad (Pakistan); Ali, Syeda Maria [Center of Excellence in Environmental Studies, King Abdulaziz University, Jeddah (Saudi Arabia); Bokhari, Habib [Public Health and Environment Division, Department of Biosciences, COMSATS Institute of Information Technology, Islamabad (Pakistan); Schäfer, Ralf B. [Institute for Environmental Sciences, University of Koblenz-Landau, Fortstrasse 7, D-76829 Landau in der Pfalz (Germany); Eqani, Syed Ali Musstjab Akber Shah, E-mail: ali_ebl2@yahoo.com [Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Public Health and Environment Division, Department of Biosciences, COMSATS Institute of Information Technology, Islamabad (Pakistan)

    2015-12-15

    The consumption of contaminated drinking water is one of the major causes of mortality and many severe diseases in developing countries. The principal drinking water sources in Pakistan, i.e. ground and surface water, are subject to geogenic and anthropogenic trace metal contamination. However, water quality monitoring activities have been limited to a few administrative areas and a nationwide human health risk assessment from trace metal exposure is lacking. Using geographically weighted regression (GWR) and eight relevant spatial predictors, we calculated nationwide human health risk maps by predicting the concentration of 10 trace metals in the drinking water sources of Pakistan and comparing them to guideline values. GWR incorporated local variations of trace metal concentrations into prediction models and hence mitigated effects of large distances between sampled districts due to data scarcity. Predicted concentrations mostly exhibited high accuracy and low uncertainty, and were in good agreement with observed concentrations. Concentrations for Central Pakistan were predicted with higher accuracy than for the North and South. A maximum 150–200 fold exceedance of guideline values was observed for predicted cadmium concentrations in ground water and arsenic concentrations in surface water. In more than 53% (4 and 100% for the lower and upper boundaries of 95% confidence interval (CI)) of the total area of Pakistan, the drinking water was predicted to be at risk of contamination from arsenic, chromium, iron, nickel and lead. The area with elevated risks is inhabited by more than 74 million (8 and 172 million for the lower and upper boundaries of 95% CI) people. Although these predictions require further validation by field monitoring, the results can inform disease mitigation and water resources management regarding potential hot spots. - Highlights: • Predictions of trace metal concentration use geographically weighted regression • Human health risk

  4. Correlation of physical and genetic maps of human chromosome 16. Annual progress report, October 1, 1990--July 31, 1991

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, G.R.

    1991-12-31

    This project aimed to divide chromosome 16 into approximately 50 intervals of {approximately}2Mb in size by constructing a series of mouse/human somatic cell hybrids each containing a rearranged chromosome 16. Using these hybrids, DNA probes would be regionally mapped by Southern blot or PCR analysis. Preference would be given to mapping probes which demonstrated polymorphisms for which the CEPH panel of families had been typed. This would allow a correlation of the physical and linkage maps of this chromosome. The aims have been substantially achieved. 49 somatic cell hybrids have been constructed which have allowed definition of 46, and potentially 57, different physical intervals on the chromosome. 164 loci have been fully mapped into these intervals. A correlation of the physical and genetic maps of the chromosome is in an advanced stage of preparation. The somatic cell hybrids constructed have been widely distributed to groups working on chromosome 16 and other genome projects.

  5. Human cDNA mapping using fluorescence in situ hybridization. Progress report, April 1, 1992--December 31, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Korenberg, J.R.

    1993-03-04

    Genetic mapping is approached using the techniques of high resolution fluorescence in situ hybridization (FISH). This technology and the results of its application are designed to rapidly generate whole genome as tool box of expressed sequence to speed the identification of human disease genes. The results of this study are intended to dovetail with and to link the results of existing technologies for creating backbone YAC and genetic maps. In the first eight months, this approach generated 60--80% of the expressed sequence map, the remainder expected to be derived through more long-term, labor-intensive, regional chromosomal gene searches or sequencing. The laboratory has made significant progress in the set-up phase, in mapping fetal and adult brain and other cDNAs, in testing a model system for directly linking genetic and physical maps using FISH with small fragments, in setting up a database, and in establishing the validity and throughput of the system.

  6. Two-dimensional gel proteome reference map of human small intestine

    Directory of Open Access Journals (Sweden)

    Canzonieri Vincenzo

    2009-03-01

    Full Text Available Abstract Background The small intestine is an important human organ that plays a central role in many physiological functions including digestion, absorption, secretion and defense. Duodenal pathologies include, for instance, the ulcer associated to Helicobacter Pylori infection, adenoma and, in genetically predisposed individuals, celiac disease. Alterations in the bowel reduce its capability to absorb nutrients, minerals and fat-soluble vitamins. Anemia and osteopenia or osteoporosis may develop as a consequence of vitamins malabsorption. Adenoma is a benign tumor that has the potential to become cancerous. Adult celiac disease patients present an overall risk of cancer that is almost twice than that found in the general population. These disease processes are not completely known. To date, a two dimensional (2D reference map of proteins expressed in human duodenal tissue is not yet available: the aim of our study was to characterize the 2D protein map, and to identify proteins of duodenal mucosa of adult individuals without duodenal illness, to create a protein database. This approach, may be useful for comparing similar protein samples in different laboratories and for the molecular characterization of intestinal pathologies without recurring to the use of surgical material. Results The enrolled population comprised five selected samples (3 males and 2 females, aged 19 to 42, taken from 20 adult subjects, on their first visit at the gastroenterology unit for a suspected celiac disease, who did not turn to be affected by any duodenal pathology after gastrointestinal and histological evaluations. Proteins extracted from the five duodenal mucosal specimens were singly separated by 2D gel electrophoresis. After image analysis of each 2D gel, 179 protein spots, representing 145 unique proteins, from 218 spots tested, were successfully identified by MALDI-TOF ms analysis. Normalized volumes, for each protein, have been reported for every gel

  7. A 1.4-Mb interval RH map of horse chromosome 17 provides detailed comparison with human and mouse homologues.

    Science.gov (United States)

    Lee, Eun-Joon; Raudsepp, Terje; Kata, Srinivas R; Adelson, David; Womack, James E; Skow, Loren C; Chowdhary, Bhanu P

    2004-02-01

    Comparative genomics has served as a backbone for the rapid development of gene maps in domesticated animals. The integration of this approach with radiation hybrid (RH) analysis provides one of the most direct ways to obtain physically ordered comparative maps across evolutionarily diverged species. We herein report the development of a detailed RH and comparative map for horse chromosome 17 (ECA17). With markers distributed at an average interval of every 1.4 Mb, the map is currently the most informative among the equine chromosomes. It comprises 75 markers (56 genes and 19 microsatellites), of which 50 gene specific and 5 microsatellite markers were generated in this study and typed to our 5000-rad horse x hamster whole genome RH panel. The markers are dispersed over six RH linkage groups and span 825 cR(5000). The map is among the most comprehensive whole chromosome comparative maps currently available for domesticated animals. It finely aligns ECA17 to human and mouse homologues (HSA13 and MMU1, 3, 5, 8, and 14, respectively) and homologues in other domesticated animals. Comparisons provide insight into their relative organization and help to identify evolutionarily conserved segments. The new ECA17 map will serve as a template for the development of clusters of BAC contigs in regions containing genes of interest. Sequencing of these regions will help to initiate studies aimed at understanding the molecular mechanisms for various diseases and inherited disorders in horse as well as human.

  8. An overview of the haplotype problems and algorithms

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yuzhong; XU Yun; ZHANG Qiangfeng; CHEN Guoliang

    2007-01-01

    A single nucleotide polymorphism (SNP),as the most common form of genetic variation,has been widely studied to help analyze the possible association between diseases and genomes.To gain more information,SNPs on a single chromosome are usually studied together,which constitute a haplotype.Gaining haplotypes from biological experiments is usually very costly and time-consuming,which causes people to develop efficient methods to determine haplotypes from the computational angle.Many problems and algorithms about haplotypes have been proposed to reduce the cost of studies of disease association.In general,four categories of problems are widely researched:the haplotype assembly problem,the haplotype inference problem,the haplotype block partition problem,and the haplotype tagging SNP selection problem.The former two problems have been well reviewed by many researchers,whereas the latter two have not been comprehensively surveyed to our knowledge.In this paper,we try to make a detailed introduction to the four problems,especially the latter two.

  9. Restriction digestion method for haplotyping the potato psyllid, Bactericera cockerelli

    Science.gov (United States)

    A restriction digestion method has been developed for haplotyping the potato psyllid, Bactericera cockerelli Sulc., an economically important pest of solanaceous crops. This method differentiates the four known potato psyllid haplotypes by utilizing restriction enzyme digestion of a portion of the ...

  10. Retrieving quantifiable social media data from human sensor networks for disaster modeling and crisis mapping

    Science.gov (United States)

    Aulov, Oleg

    This dissertation presents a novel approach that utilizes quantifiable social media data as a human aware, near real-time observing system, coupled with geophysical predictive models for improved response to disasters and extreme events. It shows that social media data has the potential to significantly improve disaster management beyond informing the public, and emphasizes the importance of different roles that social media can play in management, monitoring, modeling and mitigation of natural and human-caused extreme disasters. In the proposed approach Social Media users are viewed as "human sensors" that are "deployed" in the field, and their posts are considered to be "sensor observations", thus different social media outlets all together form a Human Sensor Network. We utilized the "human sensor" observations, as boundary value forcings, to show improved geophysical model forecasts of extreme disaster events when combined with other scientific data such as satellite observations and sensor measurements. Several recent extreme disasters are presented as use case scenarios. In the case of the Deepwater Horizon oil spill disaster of 2010 that devastated the Gulf of Mexico, the research demonstrates how social media data from Flickr can be used as a boundary forcing condition of GNOME oil spill plume forecast model, and results in an order of magnitude forecast improvement. In the case of Hurricane Sandy NY/NJ landfall impact of 2012, we demonstrate how the model forecasts, when combined with social media data in a single framework, can be used for near real-time forecast validation, damage assessment and disaster management. Owing to inherent uncertainties in the weather forecasts, the NOAA operational surge model only forecasts the worst-case scenario for flooding from any given hurricane. Geolocated and time-stamped Instagram photos and tweets allow near real-time assessment of the surge levels at different locations, which can validate model forecasts, give

  11. Precision mapping of the human O-GalNAc glycoproteome through SimpleCell technology.

    Science.gov (United States)

    Steentoft, Catharina; Vakhrushev, Sergey Y; Joshi, Hiren J; Kong, Yun; Vester-Christensen, Malene B; Schjoldager, Katrine T-B G; Lavrsen, Kirstine; Dabelsteen, Sally; Pedersen, Nis B; Marcos-Silva, Lara; Gupta, Ramneek; Bennett, Eric Paul; Mandel, Ulla; Brunak, Søren; Wandall, Hans H; Levery, Steven B; Clausen, Henrik

    2013-05-15

    Glycosylation is the most abundant and diverse posttranslational modification of proteins. While several types of glycosylation can be predicted by the protein sequence context, and substantial knowledge of these glycoproteomes is available, our knowledge of the GalNAc-type O-glycosylation is highly limited. This type of glycosylation is unique in being regulated by 20 polypeptide GalNAc-transferases attaching the initiating GalNAc monosaccharides to Ser and Thr (and likely some Tyr) residues. We have developed a genetic engineering approach using human cell lines to simplify O-glycosylation (SimpleCells) that enables proteome-wide discovery of O-glycan sites using 'bottom-up' ETD-based mass spectrometric analysis. We implemented this on 12 human cell lines from different organs, and present a first map of the human O-glycoproteome with almost 3000 glycosites in over 600 O-glycoproteins as well as an improved NetOGlyc4.0 model for prediction of O-glycosylation. The finding of unique subsets of O-glycoproteins in each cell line provides evidence that the O-glycoproteome is differentially regulated and dynamic. The greatly expanded view of the O-glycoproteome should facilitate the exploration of how site-specific O-glycosylation regulates protein function.

  12. Active Site Mapping of Human Cathepsin F with Dipeptide Nitrile Inhibitors.

    Science.gov (United States)

    Schmitz, Janina; Furtmann, Norbert; Ponert, Moritz; Frizler, Maxim; Löser, Reik; Bartz, Ulrike; Bajorath, Jürgen; Gütschow, Michael

    2015-08-01

    Cleavage of the invariant chain is the key event in the trafficking pathway of major histocompatibility complex class II. Cathepsin S is the major processing enzyme of the invariant chain, but cathepsin F acts in macrophages as its functional synergist which is as potent as cathepsin S in invariant chain cleavage. Dedicated low-molecular-weight inhibitors for cathepsin F have not yet been developed. An active site mapping with 52 dipeptide nitriles, reacting as covalent-reversible inhibitors, was performed to draw structure-activity relationships for the non-primed binding region of human cathepsin F. In a stepwise process, new compounds with optimized fragment combinations were designed and synthesized. These dipeptide nitriles were evaluated on human cysteine cathepsins F, B, L, K and S. Compounds 10 (N-(4-phenylbenzoyl)-leucylglycine nitrile) and 12 (N-(4-phenylbenzoyl)leucylmethionine nitrile) were found to be potent inhibitors of human cathepsin F, with Ki values nitriles from our study, a 3D activity landscape was generated to visualize structure-activity relationships for this series of cathepsin F inhibitors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Single chain human interleukin 5 and its asymmetric mutagenesis for mapping receptor binding sites.

    Science.gov (United States)

    Li, J; Cook, R; Dede, K; Chaiken, I

    1996-01-26

    Wild type human (h) interleukin 5 (wt IL5) is composed of two identical peptide chains linked by disulfide bonds. A gene encoding a single chain form of hIL5 dimer was constructed by linking the two hIL5 chain coding regions with Gly-Gly linker. Expression of this gene in COS cells yielded a single chain IL5 protein (sc IL5) having biological activity similar to that of wt IL5, as judged by stimulation of human cell proliferation. Single chain and wt IL5 also had similar binding affinity for soluble IL5 receptor alpha chain, the specificity subunit of the IL5 receptor, as measured kinetically with an optical biosensor. The design of functionally active sc IL5 molecule. Such mutagenesis was exemplified by changes at residues Glu-13, Arg-91, Glu-110, and Trp-111. The receptor binding and bioactivity data obtained are consistent with a model in which residues from both IL5 monomers interact with the receptor alpha chain, while the interaction likely is asymmetric due to the intrinsic asymmetry of folded receptor. The results demonstrate a general route to the further mapping of receptor and other binding sites on the surface of human IL5.

  14. A Compendium of Chromatin Contact Maps Reveals Spatially Active Regions in the Human Genome.

    Science.gov (United States)

    Schmitt, Anthony D; Hu, Ming; Jung, Inkyung; Xu, Zheng; Qiu, Yunjiang; Tan, Catherine L; Li, Yun; Lin, Shin; Lin, Yiing; Barr, Cathy L; Ren, Bing

    2016-11-15

    The three-dimensional configuration of DNA is integral to all nuclear processes in eukaryotes, yet our knowledge of the chromosome architecture is still limited. Genome-wide chromosome conformation capture studies have uncovered features of chromatin organization in cultured cells, but genome architecture in human tissues has yet to be explored. Here, we report the most comprehensive survey to date of chromatin organization in human tissues. Through integrative analysis of chromatin contact maps in 21 primary human tissues and cell types, we find topologically associating domains highly conserved in different tissues. We also discover genomic regions that exhibit unusually high levels of local chromatin interactions. These frequently interacting regions (FIREs) are enriched for super-enhancers and are near tissue-specifically expressed genes. They display strong tissue-specificity in local chromatin interactions. Additionally, FIRE formation is partially dependent on CTCF and the Cohesin complex. We further show that FIREs can help annotate the function of non-coding sequence variants. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Conserved synteny between pig chromosome 8 and human chromosome 4 but rearranged and distorted linkage maps

    Energy Technology Data Exchange (ETDEWEB)

    Ellegren, H.; Edfors-Lilja, I.; Anderson, L. (Swedish Univ. of Agricultural Sciences, Uppsala (Sweden)); Wintero, A.K. (Royal Veterinary and Agricultural Univ., Fredriksberg (Denmark))

    1993-09-01

    The porcine genes encoding interleukin 2, alcohol dehydrogenase (class I) gamma polypeptide, and osteopontin were mapped to chromosome 8 by linkage analysis. Together with previous assignments to this chromosome (the albumin, platelet-derived growth factor receptor A, and fibrinogen genes), an extensive syntenic homology with human chromosome 4 was discovered. Loci from about three-quarters of the q arm of human chromosome 4 are on pig chromosome 8. However, the linear order of the markers is not identical in the two species, and there are several examples of interspecific differences in the recombination fractions between adjacent markers. The conserved synteny between man and the pig gives strong support to a previous suggestion that a synteny group present in the ancestor of mammalian species has been retained on human chromosome 4q. Since loci from this synteny group are found on two cattle chromosomes, the bovine rearrangement must have occurred after the split of Suidae and Bovidae within Artiodactyla. 29 refs., 3 figs., 1 tab.

  16. Genome-wide map of regulatory interactions in the human genome.

    Science.gov (United States)

    Heidari, Nastaran; Phanstiel, Douglas H; He, Chao; Grubert, Fabian; Jahanbani, Fereshteh; Kasowski, Maya; Zhang, Michael Q; Snyder, Michael P

    2014-12-01

    Increasing evidence suggests that interactions between regulatory genomic elements play an important role in regulating gene expression. We generated a genome-wide interaction map of regulatory elements in human cells (ENCODE tier 1 cells, K562, GM12878) using Chromatin Interaction Analysis by Paired-End Tag sequencing (ChIA-PET) experiments targeting six broadly distributed factors. Bound regions covered 80% of DNase I hypersensitive sites including 99.7% of TSS and 98% of enhancers. Correlating this map with ChIP-seq and RNA-seq data sets revealed cohesin, CTCF, and ZNF143 as key components of three-dimensional chromatin structure and revealed how the distal chromatin state affects gene transcription. Comparison of interactions between cell types revealed that enhancer-promoter interactions were highly cell-type-specific. Construction and comparison of distal and proximal regulatory networks revealed stark differences in structure and biological function. Proximal binding events are enriched at genes with housekeeping functions, while distal binding events interact with genes involved in dynamic biological processes including response to stimulus. This study reveals new mechanistic and functional insights into regulatory region organization in the nucleus. © 2014 Heidari et al.; Published by Cold Spring Harbor Laboratory Press.

  17. Magneto encephalography (MEG: perspectives of speech areas functional mapping in human subjects

    Directory of Open Access Journals (Sweden)

    Butorina A. V.

    2012-06-01

    Full Text Available One of the main problems in clinical practice and academic research is how to localize speech zones in the human brain. Two speech areas (Broca and Wernicke areas that are responsible for language production and for understanding of written and spoken language have been known since the past century. Their location and even hemispheric lateralization have a substantial inter-individual variability, especially in neurosurgery patients. Wada test is one of the most frequently used invasive methodology for speech hemispheric lateralization in neurosurgery patients. However, besides relatively high-risk of Wada test for patient's health, it has its own limitation, e. g. low reliability of Wada-based evidence of verbal memory brain lateralization. Therefore, there is an urgent need for non-invasive, reliable methods of speech zones mapping.The current review summarizes the recent experimental evidence from magnitoencephalographic (MEG research suggesting that speech areas are included in the speech processing within the first 200 ms after the word onset. The electro-magnetic response to deviant word, mismatch negativity wave with latency of 100—200 ms, can be recorded from auditory cortex within the oddball-paradigm. We provide the arguments that basic features of this brain response, such as its automatic, pre-attentive nature, high signal to noise ratio, source localization at superior temporal sulcus, make it a promising vehicle for non-invasive MEG-based speech areas mapping in neurosurgery.

  18. Physical map and one-megabase sequencing of the human immunoglobulin lambda locus

    Directory of Open Access Journals (Sweden)

    Geraldo A.S. Passos Jr.

    1998-06-01

    Full Text Available The human immunoglobulin lambda (IGL locus is located on chromosome 22q11.1-q11.2 and contains the genes responsible for the immunoglobulin lambda light chains. This locus was recently mapped (physical map and its 1-Mb DNA totally sequenced. In this review we focus on the characterization of the v-lambda genes, its chromosomal location, genomics and sequencing of the IGL locus.O locus IGL humano está localizado no cromosomo 22q11.1-q11.2 e contém os genes responsáveis pelas cadeias leves de imunoglobulina tipo lambda. Este locus foi recentemente mapeado (mapa físico e seu 1 Mb DNA totalmente sequenciado. Nesta revisão focamos os principais resultados de caracterização dos genes v-lambda, sua localização cromossômica, a genômica e seqüenciamento do locus IGL.

  19. Mapping and characterization of non-HLA multigene assemblages in the human MHC class I region

    Energy Technology Data Exchange (ETDEWEB)

    Venditti, C.P.; Harris, J.M.; Geraghty, D.E. [Pennsylvania State Univ. College of Medicine, Hershey, PA (United States)] [and others

    1994-07-15

    The major histocompatibility complex (MHC) class I region has been shown to be associated with a variety of immune and nonimmune disorders. In an effort to initiate steps designed to identify the idiopathic hemochromatosis disease gene (HFE), the authors have cloned and mapped two expressed messages using probes from the HLA-H subregion that lie immediately distal to the HLA-A9 breakpoint. Although the cDNA clones identify distinct multifragment families that are dispersed throughout the MHC, the gene sequences from which the two cDNA clones derive map centromeric to the HLA-B locus and are absent from the genomes of higher nonhuman primates. This suggests that a syntenic coding segment arose within a highly polymorphic region (TNF to HLA-B interval) as the result of an insertion event following the emergence of Homo sapiens. An additional syntenic cluster exists within a peak of linkage disequilibrium with the HFE gene and may define coding sequences that underlie the defect in genetic iron overload. These data generally support the concept that the class I region is potentially gene-rich and further highlight the possibility that these new coding sequences may play a role in the development of a variety of HLA-linked diseases. The observations presented suggest that interlocus exchanges have played a structural role in the genesis of the human class I region. 46 refs., 6 refs.

  20. Topological Data Analysis Generates High-Resolution, Genome-wide Maps of Human Recombination.

    Science.gov (United States)

    Camara, Pablo G; Rosenbloom, Daniel I S; Emmett, Kevin J; Levine, Arnold J; Rabadan, Raul

    2016-07-01

    Meiotic recombination is a fundamental evolutionary process driving diversity in eukaryotes. In mammals, recombination is known to occur preferentially at specific genomic regions. Using topological data analysis (TDA), a branch of applied topology that extracts global features from large data sets, we developed an efficient method for mapping recombination at fine scales. When compared to standard linkage-based methods, TDA can deal with a larger number of SNPs and genomes without incurring prohibitive computational costs. We applied TDA to 1,000 Genomes Project data and constructed high-resolution whole-genome recombination maps of seven human populations. Our analysis shows that recombination is generally under-represented within transcription start sites. However, the binding sites of specific transcription factors are enriched for sites of recombination. These include transcription factors that regulate the expression of meiosis- and gametogenesis-specific genes, cell cycle progression, and differentiation blockage. Additionally, our analysis identifies an enrichment for sites of recombination at repeat-derived loci matched by piwi-interacting RNAs.

  1. A 3D map of the islet routes throughout the healthy human pancreas

    Science.gov (United States)

    Ionescu-Tirgoviste, Constantin; Gagniuc, Paul A.; Gubceac, Elvira; Mardare, Liliana; Popescu, Irinel; Dima, Simona; Militaru, Manuella

    2015-01-01

    Islets of Langerhans are fundamental in understanding diabetes. A healthy human pancreas from a donor has been used to asses various islet parameters and their three-dimensional distribution. Here we show that islets are spread gradually from the head up to the tail section of the pancreas in the form of contracted or dilated islet routes. We also report a particular anatomical structure, namely the cluster of islets. Our observations revealed a total of 11 islet clusters which comprise of small islets that surround large blood vessels. Additional observations in the peripancreatic adipose tissue have shown lymphoid-like nodes and blood vessels captured in a local inflammatory process. Our observations are based on regional slice maps of the pancreas, comprising of 5,423 islets. We also devised an index of sphericity which briefly indicates various islet shapes that are dominant throughout the pancreas. PMID:26417671

  2. General Framework for Meta-Analysis of Haplotype Association Tests.

    Science.gov (United States)

    Wang, Shuai; Zhao, Jing Hua; An, Ping; Guo, Xiuqing; Jensen, Richard A; Marten, Jonathan; Huffman, Jennifer E; Meidtner, Karina; Boeing, Heiner; Campbell, Archie; Rice, Kenneth M; Scott, Robert A; Yao, Jie; Schulze, Matthias B; Wareham, Nicholas J; Borecki, Ingrid B; Province, Michael A; Rotter, Jerome I; Hayward, Caroline; Goodarzi, Mark O; Meigs, James B; Dupuis, Josée

    2016-04-01

    For complex traits, most associated single nucleotide variants (SNV) discovered to date have a small effect, and detection of association is only possible with large sample sizes. Because of patient confidentiality concerns, it is often not possible to pool genetic data from multiple cohorts, and meta-analysis has emerged as the method of choice to combine results from multiple studies. Many meta-analysis methods are available for single SNV analyses. As new approaches allow the capture of low frequency and rare genetic variation, it is of interest to jointly consider multiple variants to improve power. However, for the analysis of haplotypes formed by multiple SNVs, meta-analysis remains a challenge, because different haplotypes may be observed across studies. We propose a two-stage meta-analysis approach to combine haplotype analysis results. In the first stage, each cohort estimate haplotype effect sizes in a regression framework, accounting for relatedness among observations if appropriate. For the second stage, we use a multivariate generalized least square meta-analysis approach to combine haplotype effect estimates from multiple cohorts. Haplotype-specific association tests and a global test of independence between haplotypes and traits are obtained within our framework. We demonstrate through simulation studies that we control the type-I error rate, and our approach is more powerful than inverse variance weighted meta-analysis of single SNV analysis when haplotype effects are present. We replicate a published haplotype association between fasting glucose-associated locus (G6PC2) and fasting glucose in seven studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and we provide more precise haplotype effect estimates.

  3. Development of Time-Series Human Settlement Mapping System Using Historical Landsat Archive

    Science.gov (United States)

    Miyazaki, H.; Nagai, M.; Shibasaki, R.

    2016-06-01

    Methodology of automated human settlement mapping is highly needed for utilization of historical satellite data archives for urgent issues of urban growth in global scale, such as disaster risk management, public health, food security, and urban management. As development of global data with spatial resolution of 10-100 m was achieved by some initiatives using ASTER, Landsat, and TerraSAR-X, next goal has targeted to development of time-series data which can contribute to studies urban development with background context of socioeconomy, disaster risk management, public health, transport and other development issues. We developed an automated algorithm to detect human settlement by classification of built-up and non-built-up in time-series Landsat images. A machine learning algorithm, Local and Global Consistency (LLGC), was applied with improvements for remote sensing data. The algorithm enables to use MCD12Q1, a MODIS-based global land cover map with 500-m resolution, as training data so that any manual process is not required for preparation of training data. In addition, we designed the method to composite multiple results of LLGC into a single output to reduce uncertainty. The LLGC results has a confidence value ranging 0.0 to 1.0 representing probability of built-up and non-built-up. The median value of the confidence for a certain period around a target time was expected to be a robust output of confidence to identify built-up or non-built-up areas against uncertainties in satellite data quality, such as cloud and haze contamination. Four scenes of Landsat data for each target years, 1990, 2000, 2005, and 2010, were chosen among the Landsat archive data with cloud contamination less than 20%.We developed a system with the algorithms on the Data Integration and Analysis System (DIAS) in the University of Tokyo and processed 5200 scenes of Landsat data for cities with more than one million people worldwide.

  4. DEVELOPMENT OF TIME-SERIES HUMAN SETTLEMENT MAPPING SYSTEM USING HISTORICAL LANDSAT ARCHIVE

    Directory of Open Access Journals (Sweden)

    H. Miyazaki

    2016-06-01

    Full Text Available Methodology of automated human settlement mapping is highly needed for utilization of historical satellite data archives for urgent issues of urban growth in global scale, such as disaster risk management, public health, food security, and urban management. As development of global data with spatial resolution of 10-100 m was achieved by some initiatives using ASTER, Landsat, and TerraSAR-X, next goal has targeted to development of time-series data which can contribute to studies urban development with background context of socioeconomy, disaster risk management, public health, transport and other development issues. We developed an automated algorithm to detect human settlement by classification of built-up and non-built-up in time-series Landsat images. A machine learning algorithm, Local and Global Consistency (LLGC, was applied with improvements for remote sensing data. The algorithm enables to use MCD12Q1, a MODIS-based global land cover map with 500-m resolution, as training data so that any manual process is not required for preparation of training data. In addition, we designed the method to composite multiple results of LLGC into a single output to reduce uncertainty. The LLGC results has a confidence value ranging 0.0 to 1.0 representing probability of built-up and non-built-up. The median value of the confidence for a certain period around a target time was expected to be a robust output of confidence to identify built-up or non-built-up areas against uncertainties in satellite data quality, such as cloud and haze contamination. Four scenes of Landsat data for each target years, 1990, 2000, 2005, and 2010, were chosen among the Landsat archive data with cloud contamination less than 20%.We developed a system with the algorithms on the Data Integration and Analysis System (DIAS in the University of Tokyo and processed 5200 scenes of Landsat data for cities with more than one million people worldwide.

  5. Phasing for medical sequencing using rare variants and large haplotype reference panels

    Science.gov (United States)

    Sharp, Kevin; Kretzschmar, Warren; Delaneau, Olivier; Marchini, Jonathan

    2016-01-01

    Motivation: There is growing recognition that estimating haplotypes from high coverage sequencing of single samples in clinical settings is an important problem. At the same time very large datasets consisting of tens and hundreds of thousands of high-coverage sequenced samples will soon be available. We describe a method that takes advantage of these huge human genetic variation resources and rare variant sharing patterns to estimate haplotypes on single sequenced samples. Sharing rare variants between two individuals is more likely to arise from a recent common ancestor and, hence, also more likely to indicate similar shared haplotypes over a substantial flanking region of sequence. Results: Our method exploits this idea to select a small set of highly informative copying states within a Hidden Markov Model (HMM) phasing algorithm. Using rare variants in this way allows us to avoid iterative MCMC methods to infer haplotypes. Compared to other approaches that do not explicitly use rare variants we obtain significant gains in phasing accuracy, less variation over phasing runs and improvements in speed. For example, using a reference panel of 7420 haplotypes from the UK10K project, we are able to reduce switch error rates by up to 50% when phasing samples sequenced at high-coverage. In addition, a single step rephasing of the UK10K panel, using rare variant information, has a downstream impact on phasing performance. These results represent a proof of concept that rare variant sharing patterns can be utilized to phase large high-coverage sequencing studies such as the 100 000 Genomes Project dataset. Availability and implementation: A webserver that includes an implementation of this new method and allows phasing of high-coverage clinical samples is available at https://phasingserver.stats.ox.ac.uk/. Contact: marchini@stats.ox.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153703

  6. Chromosomal mapping of the human and murine orphan receptors ERRalpha (ESRRA) and ERRbeta (ESRRB) and identification of a novel human ERRalpha-related pseudogene.

    Science.gov (United States)

    Sladek, R; Beatty, B; Squire, J; Copeland, N G; Gilbert, D J; Jenkins, N A; Giguère, V

    1997-10-15

    The estrogen-related receptors ERRalpha and ERRbeta (formerly ERR1 and ERR2) form a subgroup of the steroid/thyroid/retinoid receptor family. ERRalpha and ERRbeta are homologous to the estrogen receptor and bind similar DNA targets; however, they are unable to activate gene transcription in response to estrogens. We have used interspecific backcross analysis to map the murine Estrra locus to chromosome 19 and Estrrb to mouse chromosome 12. Using fluorescence in situ hybridization, we have mapped the human ESRRA gene to chromosome 11q12-q13 and the human ESRRB gene to chromosome 14q24.3. In addition, we report the isolation of a processed human ERRalpha pseudogene mapping to chromosome 13q12.1. To our knowledge, this represents the first report of a pseudogene associated with a member of the nuclear receptor superfamily.

  7. The Atlas of human African trypanosomiasis: a contribution to global mapping of neglected tropical diseases

    Directory of Open Access Journals (Sweden)

    Courtin Fabrice

    2010-11-01

    Full Text Available Abstract Background Following World Health Assembly resolutions 50.36 in 1997 and 56.7 in 2003, the World Health Organization (WHO committed itself to supporting human African trypanosomiasis (HAT-endemic countries in their efforts to remove the disease as a public health problem. Mapping the distribution of HAT in time and space has a pivotal role to play if this objective is to be met. For this reason WHO launched the HAT Atlas initiative, jointly implemented with the Food and Agriculture Organization of the United Nations, in the framework of the Programme Against African Trypanosomosis. Results The distribution of HAT is presented for 23 out of 25 sub-Saharan countries having reported on the status of sleeping sickness in the period 2000 - 2009. For the two remaining countries, i.e. Angola and the Democratic Republic of the Congo, data processing is ongoing. Reports by National Sleeping Sickness Control Programmes (NSSCPs, Non-Governmental Organizations (NGOs and Research Institutes were collated and the relevant epidemiological data were entered in a database, thus incorporating (i the results of active screening of over 2.2 million people, and (ii cases detected in health care facilities engaged in passive surveillance. A total of over 42 000 cases of HAT and 6 000 different localities were included in the database. Various sources of geographic coordinates were used to locate the villages of epidemiological interest. The resulting average mapping accuracy is estimated at 900 m. Conclusions Full involvement of NSSCPs, NGOs and Research Institutes in building the Atlas of HAT contributes to the efficiency of the mapping process and it assures both the quality of the collated information and the accuracy of the outputs. Although efforts are still needed to reduce the number of undetected and unreported cases, the comprehensive, village-level mapping of HAT control activities over a ten-year period ensures a detailed and reliable

  8. Understanding the contrasting spatial haplotype patterns of malaria-protective β-globin polymorphisms

    OpenAIRE

    Hockham, Carinna; Piel, Frédéric B; Gupta, Sunetra; Penman, Bridget S.

    2015-01-01

    The malaria-protective β-globin polymorphisms, sickle-cell (βS) and β0-thalassaemia, are canonical examples of human adaptation to infectious disease. Occurring on distinct genetic backgrounds, they vary markedly in their patterns of linked genetic variation at the population level, suggesting different evolutionary histories. βS is associated with five classical restriction fragment length polymorphism haplotypes that exhibit remarkable specificity in their geographical distributions; by con...

  9. Identification of a major phosphopeptide in human tristetraprolin by phosphopeptide mapping and mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Heping Cao

    Full Text Available Tristetraprolin/zinc finger protein 36 (TTP/ZFP36 binds and destabilizes some pro-inflammatory cytokine mRNAs. TTP-deficient mice develop a profound inflammatory syndrome due to excessive production of pro-inflammatory cytokines. TTP expression is induced by various factors including insulin and extracts from cinnamon and green tea. TTP is highly phosphorylated in vivo and is a substrate for several protein kinases. Multiple phosphorylation sites are identified in human TTP, but it is difficult to assign major vs. minor phosphorylation sites. This study aimed to generate additional information on TTP phosphorylation using phosphopeptide mapping and mass spectrometry (MS. Wild-type and site-directed mutant TTP proteins were expressed in transfected human cells followed by in vivo radiolabeling with [32P]-orthophosphate. Histidine-tagged TTP proteins were purified with Ni-NTA affinity beads and digested with trypsin and lysyl endopeptidase. The digested peptides were separated by C18 column with high performance liquid chromatography. Wild-type and all mutant TTP proteins were localized in the cytosol, phosphorylated extensively in vivo and capable of binding to ARE-containing RNA probes. Mutant TTP with S90 and S93 mutations resulted in the disappearance of a major phosphopeptide peak. Mutant TTP with an S197 mutation resulted in another major phosphopeptide peak being eluted earlier than the wild-type. Additional mutations at S186, S296 and T271 exhibited little effect on phosphopeptide profiles. MS analysis identified the peptide that was missing in the S90 and S93 mutant protein as LGPELSPSPTSPTATSTTPSR (corresponding to amino acid residues 83-103 of human TTP. MS also identified a major phosphopeptide associated with the first zinc-finger region. These analyses suggest that the tryptic peptide containing S90 and S93 is a major phosphopeptide in human TTP.

  10. A genomic portrait of haplotype diversity and signatures of selection in indigenous southern African populations.

    Directory of Open Access Journals (Sweden)

    Emile R Chimusa

    2015-03-01

    Full Text Available We report a study of genome-wide, dense SNP (∼ 900K and copy number polymorphism data of indigenous southern Africans. We demonstrate the genetic contribution to southern and eastern African populations, which involved admixture between indigenous San, Niger-Congo-speaking and populations of Eurasian ancestry. This finding illustrates the need to account for stratification in genome-wide association studies, and that admixture mapping would likely be a successful approach in these populations. We developed a strategy to detect the signature of selection prior to and following putative admixture events. Several genomic regions show an unusual excess of Niger-Kordofanian, and unusual deficiency of both San and Eurasian ancestry, which were considered the footprints of selection after population admixture. Several SNPs with strong allele frequency differences were observed predominantly between the admixed indigenous southern African populations, and their ancestral Eurasian populations. Interestingly, many candidate genes, which were identified within the genomic regions showing signals for selection, were associated with southern African-specific high-risk, mostly communicable diseases, such as malaria, influenza, tuberculosis, and human immunodeficiency virus/AIDs. This observation suggests a potentially important role that these genes might have played in adapting to the environment. Additionally, our analyses of haplotype structure, linkage disequilibrium, recombination, copy number variation and genome-wide admixture highlight, and support the unique position of San relative to both African and non-African populations. This study contributes to a better understanding of population ancestry and selection in south-eastern African populations; and the data and results obtained will support research into the genetic contributions to infectious as well as non-communicable diseases in the region.

  11. Cytoarchitectonic identification and probabilistic mapping of two distinct areas within the anterior ventral bank of the human intraparietal sulcus.

    Science.gov (United States)

    Choi, Hi-Jae; Zilles, Karl; Mohlberg, Hartmut; Schleicher, Axel; Fink, Gereon R; Armstrong, Este; Amunts, Katrin

    2006-03-01

    Anatomical studies in the macaque cortex and functional imaging studies in humans have demonstrated the existence of different cortical areas within the intraparietal sulcus (IPS). Such functional segregation, however, does not correlate with presently available architectonic maps of the human brain. This is particularly true for the classical Brodmann map, which is still widely used as an anatomical reference in functional imaging studies. The aim of this cytoarchitectonic mapping study was to use previously defined algorithms to determine whether consistent regions and borders can be found within the cortex of the anterior IPS in a population of 10 post-mortem human brains. Two areas, the human intraparietal area 1 (hIP1) and the human intraparietal area 2 (hIP2), were delineated in serial histological sections of the anterior, lateral bank of the human IPS. The region hIP1 is located posterior and medial to hIP2, and the former is always within the depths of the IPS. The latter, on the other hand, sometimes reaches the free surface of the superior parietal lobule. The delineations were registered to standard reference space, and probabilistic maps were calculated, thereby quantifying the intersubject variability in location and extent of both areas. In the future, they can be a tool for analyzing structure-function relationships and a basis for determining degrees of homology in the IPS among anthropoid primates. We conclude that the human IPS has a more finely grained parcellation than shown in Brodmann's map. J. Comp. Neurol. 495:53-69, 2006. (c) 2006 Wiley-Liss, Inc.

  12. NotI linking clones as a tool for joining physical and genetic maps of the human genome.

    Science.gov (United States)

    Allikmets, R L; Kashuba, V I; Pettersson, B; Gizatullin, R; Lebedeva, T; Kholodnyuk, I D; Bannikov, V M; Petrov, N; Zakharyev, V M; Winberg, G

    1994-01-15

    To study the connection among NotI linking clones, CpG islands, and genes, the sequence surrounding 143 NotI sites was determined. These NotI linking clones were isolated from human chromosome 3-specific libraries and contain an average C + G content of 65%. These clones represent sequence-tagged sites that can be positioned onto chromosome maps and used for generating a long-range NotI map of the human genome. A majority (about 90%) of these clones contain transcribed sequences, as detected by Northern blot hybridization, providing an efficient link between physical and functional (genetic) maps. The GenBank nucleotide database was searched with sequences from these NotI linking clones. For many clones, homology was found to human and other vertebrate genes. About 20 clones contained various repeats in their sequences and may represent microsatellite loci. Most of these NotI linking clones therefore represent evolutionarily conserved DNA fragments and also can be used for comparative genome mapping of other mammalian species. In addition, approximately 20% of all sequenced human CpG island-containing genes and more than 12% of all well-characterized human genes were found to possess NotI restriction sites. This is at least 2-5 times more than has been previously estimated and suggests that NotI sites have a much stronger association with genes.

  13. NotL linking clones as a tool for joining physical and genetic maps of the human genome

    Energy Technology Data Exchange (ETDEWEB)

    Allikmets, R.L.; Dean, M.; Modi, W. (DynCorp National Cancer Institute, Frederick, MD (United States)); Kholodnyuk, I.D.; Winberg, G.; Klein, G. (Karolinska Institutet, Stockholm (Sweden)); Pettersson, B.; Uhlen, M. (Royal Institute of Technology, Stockholm (Sweden)); Gizatullin, R.; Bannikov, V.M. (and others)

    1994-01-15

    To study the connection among NotI linking clones, CpG islands, and genes, the sequence surrounding 143 NotI sites was determined. These NotI linking clones were isolated from human chromosome 3-specific libraries and contain an average C + G content of 65%. These clones represent sequence-tagged sites that can be positioned onto chromosome maps and used for generating a long-range NotI map of the human genome. A majority (about 90%) of these clones contain transcribed sequences, as detected by Northern blot hybridization, providing an efficient link between physical and functional (genetic) maps. The GenBank nucleotide database was searched with sequences from these NotI linking clones. For many clones, homology was found to human and other vertebrate genes. About 20 clones contained various repeats in their sequences and may represent microsatellite loci. Most of these NotI linking clones therefore represent evolutionarily conserved DNA fragments and also can be used for comparative genome mapping of other mammalian species. In addition, approximately 20% of all sequenced human CpG island-containing genes and more than 12% of all well-characterized human genes were found to possess NotI restriction sites. This is at least 2-5 times more than has been previously estimated and suggests that NotI sites have a much stronger association with genes. 41 refs., 3 figs., 2 tabs.

  14. DNA analysis of ancient dogs of the Americas: identifying possible founding haplotypes and reconstructing population histories.

    Science.gov (United States)

    Witt, Kelsey E; Judd, Kathleen; Kitchen, Andrew; Grier, Colin; Kohler, Timothy A; Ortman, Scott G; Kemp, Brian M; Malhi, Ripan S

    2015-02-01

    As dogs have traveled with humans to every continent, they can potentially serve as an excellent proxy when studying human migration history. Past genetic studies into the origins of Native American dogs have used portions of the hypervariable region (HVR) of mitochondrial DNA (mtDNA) to indicate that prior to European contact the dogs of Native Americans originated in Eurasia. In this study, we summarize past DNA studies of both humans and dogs to discuss their population histories in the Americas. We then sequenced a portion of the mtDNA HVR of 42 pre-Columbian dogs from three sites located in Illinois, coastal British Columbia, and Colorado, and identify four novel dog mtDNA haplotypes. Next, we analyzed a dataset comprised of all available ancient dog sequences from the Americas to infer the pre-Columbian population history of dogs in the Americas. Interestingly, we found low levels of genetic diversity for some populations consistent with the possibility of deliberate breeding practices. Furthermore, we identified multiple putative founding haplotypes in addition to dog haplotypes that closely resemble those of wolves, suggesting admixture with North American wolves or perhaps a second domestication of canids in the Americas. Notably, initial effective population size estimates suggest at least 1000 female dogs likely existed in the Americas at the time of the first known canid burial, and that population size increased gradually over time before stabilizing roughly 1200 years before present.

  15. Analysis of Amblyomma sculptum haplotypes in an area endemic for Brazilian spotted fever.

    Science.gov (United States)

    Bitencourth, K; Voloch, C M; Serra-Freire, N M; Machado-Ferreira, E; Amorim, M; Gazêta, G S

    2016-09-01

    Amblyomma sculptum (Ixodida: Ixodidae) Berlese, 1888, a member of the Amblyomma cajennense complex, is the major vector of Brazilian spotted fever (BSF) in southeastern Brazil. In this study, the genetic diversity of A. sculptum populations in the state of Rio de Janeiro (RJ), Brazil, was investigated because genetic variability in tick populations may be related to vector competence. Samples of A. sculptum from 19 municipalities in 7 regions of RJ were subjected to DNA extraction, amplification and sequencing of D-loop, cytochrome oxidase II and 12S rDNA mitochondrial genes. These sequences were used to map the genetic diversity of this tick. Amblyomma sculptum populations are genetically diverse in RJ, especially in the South Centre and Highland regions. Few unique haplotypes were observed in all populations, and the majority of genetic variation found was among ticks within each population. Phylogenetic reconstruction reinforced the assumption that all the haplotypes identified in RJ belong to A. sculptum. However, some RJ haplotypes are closer to A. sculptum from Argentina than to A. sculptum from elsewhere in Brazil. In RJ, A. sculptum has high genetic diversity, although little genetic differentiation. Observations also indicated a high level of gene flow among the studied populations and no evidence of population structure according to region in RJ.

  16. Forensic Spanish allele and haplotype database for a 17 X-STR panel.

    Science.gov (United States)

    Prieto-Fernández, Endika; Núñez, Carolina; Baeta, Miriam; Jiménez-Moreno, Susana; Martínez-Jarreta, Begoña; de Pancorbo, Marian M

    2016-09-01

    The currently developed 17 X-STR panel (DXS8378, DXS9898, DXS7133, GATA31E08, GATA172D05, DXS6801, DXS7423, DXS6809, DXS6799, DXS7132, DXS9902, DXS6800, DXS6789, DXS10075, DXS10079, DXS6807, and DXS6803) offers a highly discriminative tool for forensic identification and kinship testing. With the aim of providing a global Spanish population X-STR database, we present haplotype and allele frequencies and parameters of forensic interest for the 17 X-STR panel obtained from 593 unrelated individuals from Alicante, Aragon, the Basque Country, Andalusia, Galicia, Madrid, and Barcelona that represent the most populated regions of the Spanish Peninsular territory. The seven populations were compared to test possible population genetic substructures. The lack of significant differences among the studied Spanish populations supports the use of the allele and haplotype frequency database presented herein as a global Spanish population sample useful for statistical evaluation in forensic casework. After conducting the LD plots derived from HapMap and pairwise linkage disequilibrium tests, DXS7132, DXS10075, and DXS10079 markers were included in a cluster and haplotype frequencies were calculated. The improvement in the forensic parameters for the Spanish population using 17 X-STRs in comparison to the previous 10 X-STR allele frequencies database is also shown.

  17. Are molecular haplotypes worth the time and expense? A cost-effective method for applying molecular haplotypes.

    Directory of Open Access Journals (Sweden)

    Mark A Levenstien

    2006-08-01

    Full Text Available Because current molecular haplotyping methods are expensive and not amenable to automation, many researchers rely on statistical methods to infer haplotype pairs from multilocus genotypes, and subsequently treat these inferred haplotype pairs as observations. These procedures are prone to haplotype misclassification. We examine the effect of these misclassification errors on the false-positive rate and power for two association tests. These tests include the standard likelihood ratio test (LRTstd and a likelihood ratio test that employs a double-sampling approach to allow for the misclassification inherent in the haplotype inference procedure (LRTae. We aim to determine the cost-benefit relationship of increasing the proportion of individuals with molecular haplotype measurements in addition to genotypes to raise the power gain of the LRTae over the LRTstd. This analysis should provide a guideline for determining the minimum number of molecular haplotypes required for desired power. Our simulations under the null hypothesis of equal haplotype frequencies in cases and controls indicate that (1 for each statistic, permutation methods maintain the correct type I error; (2 specific multilocus genotypes that are misclassified as the incorrect haplotype pair are consistently misclassified throughout each entire dataset; and (3 our simulations under the alternative hypothesis showed a significant power gain for the LRTae over the LRTstd for a subset of the parameter settings. Permutation methods should be used exclusively to determine significance for each statistic. For fixed cost, the power gain of the LRTae over the LRTstd varied depending on the relative costs of genotyping, molecular haplotyping, and phenotyping. The LRTae showed the greatest benefit over the LRTstd when the cost of phenotyping was very high relative to the cost of genotyping. This situation is likely to occur in a replication study as opposed to a whole-genome association study.

  18. Human cDNA mapping using fluorescence in situ hybridization. Progress report, April 1--December 31, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Korenberg, J.R.

    1993-12-31

    The ultimate goal of this proposal is to create a cDNA map of the human genome. Mapping is approached using the techniques of high resolution fluorescence in situ hybridization (FISH). This technology and the results of its application are designed to rapidly generate whole genome as tool box of expressed sequence to speed the identification of human disease genes. The results of this study are intended to dovetail with and to link the results of existing technologies for creating backbone YAC and genetic maps. In the first eight months, this approach will generate 60--80% of the expressed sequence map, the remainder expected to be derived through more long-term, labor-intensive, regional chromosomal gene searches or sequencing. The laboratory has made significant progress in the set-up phase, in mapping fetal and adult brain and other cDNAs, in testing a model system for directly linking genetic and physical maps using FISH with small fragments, in setting up a database, and in establishing the validity and throughput of the system.

  19. [Retinotopic mapping of the human visual cortex with functional magnetic resonance imaging - basic principles, current developments and ophthalmological perspectives].

    Science.gov (United States)

    Hoffmann, M B; Kaule, F; Grzeschik, R; Behrens-Baumann, W; Wolynski, B

    2011-07-01

    Since its initial introduction in the mid-1990 s, retinotopic mapping of the human visual cortex, based on functional magnetic resonance imaging (fMRI), has contributed greatly to our understanding of the human visual system. Multiple cortical visual field representations have been demonstrated and thus numerous visual areas identified. The organisation of specific areas has been detailed and the impact of pathophysiologies of the visual system on the cortical organisation uncovered. These results are based on investigations at a magnetic field strength of 3 Tesla or less. In a field-strength comparison between 3 and 7 Tesla, it was demonstrated that retinotopic mapping benefits from a magnetic field strength of 7 Tesla. Specifically, the visual areas can be mapped with high spatial resolution for a detailed analysis of the visual field maps. Applications of fMRI-based retinotopic mapping in ophthalmological research hold promise to further our understanding of plasticity in the human visual cortex. This is highlighted by pioneering studies in patients with macular dysfunction or misrouted optic nerves.

  20. cDNA cloning, chromosome mapping and expression characterization of human geranylgeranyl pyrophosphate synthase

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Geranylgeranyl pyrophosphate (GGPP) mainly participates in post-translational modification for various proteins including Rho/Rac, Rap and Rab families, as well as in regulation for cell apoptosis. Geranylgeranyl pyrophosphate synthase (GGPPS), which catalyzes the condensation reaction between farnesyl diphosphate and isopentenyl diphosphate, is the key enzyme for synthesizing GGPP. We report the isolation of a gene transcript showing high homology with Drosophila GGPPS cDNA. The transcript is 1 466 bp in length and contains an intact open reading frame (ORF) ranging from nt 239 to 1 138. This ORF encodes a deduced protein of 300 residues with calculated molecular weight of 35 ku. The deduced protein shows 57.5% identity and 75% similarity with Drosophila GGPPS, and contains five characteristic domains of prenyltransferases. Northern hybridization revealed that human GGPPS was expressed highest in heart, and moderately in spleen, testis, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. No obvious bands were detected in other examined tissues. The GGPPS gene was located on human chromosome 1q43 by Radiation Hybrid mapping method. It was proved that there was a putative predisposing gene for prostate cancer in this region, and that analogs of GGPP can inhibit the geranylgeranylation of p21rap protein in PC-3 prostate cancer cell lines. These facts suggest that GGPPS may be one of the candidate genes for prostate cancer.

  1. MSV3d: database of human MisSense Variants mapped to 3D protein structure.

    Science.gov (United States)

    Luu, Tien-Dao; Rusu, Alin-Mihai; Walter, Vincent; Ripp, Raymond; Moulinier, Luc; Muller, Jean; Toursel, Thierry; Thompson, Julie D; Poch, Olivier; Nguyen, Hoan

    2012-01-01

    The elucidation of the complex relationships linking genotypic and phenotypic variations to protein structure is a major challenge in the post-genomic era. We present MSV3d (Database of human MisSense Variants mapped to 3D protein structure), a new database that contains detailed annotation of missense variants of all human proteins (20 199 proteins). The multi-level characterization includes details of the physico-chemical changes induced by amino acid modification, as well as information related to the conservation of the mutated residue and its position relative to functional features in the available or predicted 3D model. Major releases of the database are automatically generated and updated regularly in line with the dbSNP (database of Single Nucleotide Polymorphism) and SwissVar releases, by exploiting the extensive Décrypthon computational grid resources. The database (http://decrypthon.igbmc.fr/msv3d) is easily accessible through a simple web interface coupled to a powerful query engine and a standard web service. The content is completely or partially downloadable in XML or flat file formats. Database URL: http://decrypthon.igbmc.fr/msv3d.

  2. Cloning, mapping and mutation analysis of human gene GJB5 encoding gap junction protein b-5

    Institute of Scientific and Technical Information of China (English)

    XIA; Jiahui; (夏家辉); ZHENG; Duo; (郑多),; TANG; Dongsheng; (唐冬生); DAI; Heping; (戴和平); PAN; Qian; (潘乾); LONG; Zhigao; (龙志高); LIAO; Xiaodong; (廖晓东)

    2001-01-01

    By homologous EST searching and nested PCR a new human gene GJB5 encoding gap junction protein b-5 was identified. GJB5 was genetically mapped to human chromosome 1p33-p35 by FISH. RT-PCR revealed that it was expressed in skin, placenta and fetal skin. DNA sequencing of GJB5 was carried out in 142 patients with sensorineural hearing impairment and probands of 36 families with genetic diseases, including erythrokeratodermia (5 families), Charcot-Marie-Tooth disease (13), ptosis (4), and retinitis pigmentosa and deafness (14). Two missense mutations (686A→G, H229R; 25C→T, L9F) were detected in two sensorineural hearing impairment families. A heterologous deletion of 18 bp within intron was found in 3 families with heredity hearing impairment, and in one of the 3 families, a missense mutation (R265P) was identified also. But the deletion and missense mutation seemed not segregating with hearing impairment in the family. No abnormal mRNA or mRNA expression was detected in deletion carriers by RT-PCR analysis in skin tissue. Mutation analysis in 199 unaffected individuals revealed that two of them were carriers with the same 18 bp deletion.

  3. Cloning, mapping and mutation analysis of human gene GJB5 encoding gap junction protein b-5

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    By homologous EST searching and nested PCR a new human gene GJB5encoding gap junction protein b-5 was identified. GJB5 was genetically mapped to human chromosome 1p33-p35 by FISH. RT-PCR revealed that it was expressed in skin, placenta and fetal skin. DNA sequencing of GJB5 was carried out in 142 patients with sensorineural hearing impairment and probands of 36 families with genetic diseases, including erythrokeratodermia (5 families), Charcot-Marie-Tooth disease (13), ptosis (4), and retinitis pigmentosa and deafness (14). Two missense mutations (686A→G, H229R; 25C→T, L9F) were detected in two sensorineural hearing impairment families. A heterologous deletion of 18 bp within intron was found in 3 families with heredity hearing impairment, and in one of the 3 families, a missense mutation (R265P) was identified also. But the deletion and missense mutation seemed not segregating with hearing impairment in the family. No abnormal mRNA or mRNA expression was detected in deletion carriers by RT-PCR analysis in skin tissue. Mutation analysis in 199 unaffected individuals revealed that two of them were carriers with the same 18 bp deletion.

  4. Accounting for haplotype phase uncertainty in linkage disequilibrium estimation.

    Science.gov (United States)

    Kulle, B; Frigessi, A; Edvardsen, H; Kristensen, V; Wojnowski, L

    2008-02-01

    The characterization of linkage disequilibrium (LD) is applied in a variety of studies including the identification of molecular determinants of the local recombination rate, the migration and population history of populations, and the role of positive selection in adaptation. LD suffers from the phase uncertainty of the haplotypes used in its calculation, which reflects limitations of the algorithms used for haplotype estimation. We introduce a LD calculation method, which deals with phase uncertainty by weighting all possible haplotype pairs according to their estimated probabilities as evaluated by PHASE. In contrast to the expectation-maximization (EM) algorithm as implemented in the HAPLOVIEW and GENETICS packages, our method considers haplotypes based on the entire genetic information available for the candidate region. We tested the method using simulated and real genotyping data. The results show that, for all practical purposes, the new method is advantageous in comparison with algorithms that calculate LD using only the most probable haplotype or bilocus haplotypes based on the EM algorithm. The new method deals especially well with low LD regions, which contribute strongly to phase uncertainty. Altogether, the method is an attractive alternative to standard LD calculation procedures, including those based on the EM algorithm. We implemented the method in the software suite R, together with an interface to the popular haplotype calculation package PHASE.

  5. Association of Nrf2-encoding NFE2L2 haplotypes with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Nilsson Michael

    2010-03-01

    Full Text Available Abstract Background Oxidative stress is heavily implicated in the pathogenic process of Parkinson's disease. Varying capacity to detoxify radical oxygen species through induction of phase II antioxidant enzymes in substantia nigra may influence disease risk. Here, we hypothesize that variation in NFE2L2 and KEAP1, the genes encoding the two major regulators of the phase II response, may affect the risk of Parkinson's disease. Methods The study included a Swedish discovery case-control material (165 cases and 190 controls and a Polish replication case-control material (192 cases and 192 controls. Eight tag single nucleotide polymorphisms representing the variation in NFE2L2 and three representing the variation in KEAP1 were chosen using HapMap data and were genotyped using TaqMan Allelic Discrimination. Results We identified a protective NFE2L2 haplotype in both of our European case-control materials. Each haplotype allele was associated with five years later age at onset of the disease (p = 0.001 in the Swedish material, and decreased risk of PD (p = 2 × 10-6, with an odds ratio of 0.4 (95% CI 0.3-0.6 for heterozygous and 0.2 (95% CI 0.1-0.4 for homozygous carriers, in the Polish material. The identified haplotype includes a functional promoter haplotype previously associated with high transcriptional activity. Genetic variation in KEAP1 did not show any associations. Conclusion These data suggest that variation in NFE2L2 modifies the Parkinson's disease process and provide another link between oxidative stress and neurodegeneration.

  6. Fine-scale map of encyclopedia of DNA elements regions in the Korean population.

    Science.gov (United States)

    Yoo, Yeon-Kyeong; Ke, Xiayi; Hong, Sungwoo; Jang, Hye-Yoon; Park, Kyunghee; Kim, Sook; Ahn, TaeJin; Lee, Yeun-Du; Song, Okryeol; Rho, Na-Young; Lee, Moon Sue; Lee, Yeon-Su; Kim, Jaeheup; Kim, Young J; Yang, Jun-Mo; Song, Kyuyoung; Kimm, Kyuchan; Weir, Bruce; Cardon, Lon R; Lee, Jong-Eun; Hwang, Jung-Joo

    2006-09-01

    The International HapMap Project aims to generate detailed human genome variation maps by densely genotyping single-nucleotide polymorphisms (SNPs) in CEPH, Chinese, Japanese, and Yoruba samples. This will undoubtedly become an important facility for genetic studies of diseases and complex traits in the four populations. To address how the genetic information contained in such variation maps is transferable to other populations, the Korean government, industries, and academics have launched the Korean HapMap project to genotype high-density Encyclopedia of DNA Elements (ENCODE) regions in 90 Korean individuals. Here we show that the LD pattern, block structure, haplotype diversity, and recombination rate are highly concordant between Korean and the two HapMap Asian samples, particularly Japanese. The availability of information from both Chinese and Japanese samples helps to predict more accurately the possible performance of HapMap markers in Korean disease-gene studies. Tagging SNPs selected from the two HapMap Asian maps, especially the Japanese map, were shown to be very effective for Korean samples. These results demonstrate that the HapMap variation maps are robust in related populations and will serve as an important resource for the studies of the Korean population in particular.

  7. A comprehensive mapping of the current capacity for human nutrition training in Cameroon

    Directory of Open Access Journals (Sweden)

    Roger Sodjinou

    2016-01-01

    Full Text Available Background: There is consensus among stakeholders in Cameroon on the need to develop and strengthen human resource capacity for nutrition. This study was conducted to provide a comprehensive mapping of the current capacity for tertiary-level human nutrition training in Cameroon. Design: Participating institutions included university-level institutions offering dedicated nutrition degree programs or other programs in which nutrition courses were taught. A semi-structured questionnaire administered during in-person interviews was used to collect data on existing programs and content of training curricula. Nutrition curricula were reviewed against the following criteria: intended objectives, coverage of nutrition topics, and teaching methods. Results: In total, five nutrition degree programs (four undergraduate programs and one master's program were identified. Three additional programs were about to be launched at the time of data collection. We did not find any doctorate degree programs in nutrition. All the undergraduate programs only had little focus on public health nutrition whereas the master's program in our sample offered a good coverage of all dimensions of human nutrition including basic and applied nutrition. The predominant teaching method was didactic lecture in all the programs. We did not find any formal documentation outlining the competencies that students were expected to gain upon completion of these programs. Nutrition courses in agricultural and health schools were limited in terms of contact hours and scope. Public health nutrition was not covered in any of the health professional schools surveyed. We found no institution offering in-service nutrition training at the time of the study. Conclusions: Based on our findings, we recommend that nutrition training programs in Cameroon be redesigned to make them more responsive to the public health needs of the country.

  8. Towards Consistent Mapping of Urban Structures - Global Human Settlement Layer and Local Climate Zones

    Science.gov (United States)

    Bechtel, B.; Pesaresi, M.; See, L.; Mills, G.; Ching, J.; Alexander, P. J.; Feddema, J. J.; Florczyk, A. J.; Stewart, I.

    2016-06-01

    Although more than half of the Earth's population live in urban areas, we know remarkably little about most cities and what we do know is incomplete (lack of coverage) and inconsistent (varying definitions and scale). While there have been considerable advances in the derivation of a global urban mask using satellite information, the complexity of urban structures, the heterogeneity of materials, and the multiplicity of spectral properties have impeded the derivation of universal urban structural types (UST). Further, the variety of UST typologies severely limits the comparability of such studies and although a common and generic description of urban structures is an essential requirement for the universal mapping of urban structures, such a standard scheme is still lacking. More recently, there have been two developments in urban mapping that have the potential for providing a standard approach: the Local Climate Zone (LCZ) scheme (used by the World Urban Database and Access Portal Tools project) and the Global Human Settlement Layer (GHSL) methodology by JRC. In this paper the LCZ scheme and the GHSL LABEL product were compared for selected cities. The comparison between both datasets revealed a good agreement at city and coarse scale, while the contingency at pixel scale was limited due to the mismatch in grid resolution and typology. At a 1 km scale, built-up as well as open and compact classes showed very good agreement in terms of correlation coefficient and mean absolute distance, spatial pattern, and radial distribution as a function of distance from town, which indicates that a decomposition relevant for modelling applications could be derived from both. On the other hand, specific problems were found for both datasets, which are discussed along with their general advantages and disadvantages as a standard for UST classification in urban remote sensing.

  9. JAK3 maps to human chromosome 19p12 within a cluster of protooncogenes and transcription factors

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, S.M.G.; Gordon, L.A.; Mohrenweiser, H.W. [Lawrence Livermore National Lab., CA (United States); Lai, Koon Siew [Univ. of North Carolina, Chapel Hill, NC (United States)] [and others

    1997-07-01

    The gene for the most recently discoverd member of a family of cytoplasmic tyrosine kinases, JAK3, was mapped to human chromosome 19p12 using polymerase chain reaction. JAK3 plays a role in the interleukin (IL)-2 signaling pathway that regulates T and B lymphocyte development and proliferation. 20 refs., 1 fig.

  10. Background field removal using a region adaptive kernel for quantitative susceptibility mapping of human brain

    Science.gov (United States)

    Fang, Jinsheng; Bao, Lijun; Li, Xu; van Zijl, Peter C. M.; Chen, Zhong

    2017-08-01

    Background field removal is an important MR phase preprocessing step for quantitative susceptibility mapping (QSM). It separates the local field induced by tissue magnetic susceptibility sources from the background field generated by sources outside a region of interest, e.g. brain, such as air-tissue interface. In the vicinity of air-tissue boundary, e.g. skull and paranasal sinuses, where large susceptibility variations exist, present background field removal methods are usually insufficient and these regions often need to be excluded by brain mask erosion at the expense of losing information of local field and thus susceptibility measures in these regions. In this paper, we propose an extension to the variable-kernel sophisticated harmonic artifact reduction for phase data (V-SHARP) background field removal method using a region adaptive kernel (R-SHARP), in which a scalable spherical Gaussian kernel (SGK) is employed with its kernel radius and weights adjustable according to an energy ;functional; reflecting the magnitude of field variation. Such an energy functional is defined in terms of a contour and two fitting functions incorporating regularization terms, from which a curve evolution model in level set formation is derived for energy minimization. We utilize it to detect regions of with a large field gradient caused by strong susceptibility variation. In such regions, the SGK will have a small radius and high weight at the sphere center in a manner adaptive to the voxel energy of the field perturbation. Using the proposed method, the background field generated from external sources can be effectively removed to get a more accurate estimation of the local field and thus of the QSM dipole inversion to map local tissue susceptibility sources. Numerical simulation, phantom and in vivo human brain data demonstrate improved performance of R-SHARP compared to V-SHARP and RESHARP (regularization enabled SHARP) methods, even when the whole paranasal sinus regions

  11. Measuring the Uncertainty of Probabilistic Maps Representing Human Motion for Indoor Navigation

    Directory of Open Access Journals (Sweden)

    Susanna Kaiser

    2016-01-01

    Full Text Available Indoor navigation and mapping have recently become an important field of interest for researchers because global navigation satellite systems (GNSS are very often unavailable inside buildings. FootSLAM, a SLAM (Simultaneous Localization and Mapping algorithm for pedestrians based on step measurements, addresses the indoor mapping and positioning problem and can provide accurate positioning in many structured indoor environments. In this paper, we investigate how to compare FootSLAM maps via two entropy metrics. Since collaborative FootSLAM requires the alignment and combination of several individual FootSLAM maps, we also investigate measures that help to align maps that partially overlap. We distinguish between the map entropy conditioned on the sequence of pedestrian’s poses, which is a measure of the uncertainty of the estimated map, and the entropy rate of the pedestrian’s steps conditioned on the history of poses and conditioned on the estimated map. Because FootSLAM maps are built on a hexagon grid, the entropy and relative entropy metrics are derived for the special case of hexagonal transition maps. The entropy gives us a new insight on the performance of FootSLAM’s map estimation process.

  12. Mapping of interactions between human macrophages and Staphylococcus aureus reveals an involvement of MAP kinase signaling in the host defense.

    NARCIS (Netherlands)

    Miller, M.; Dreisbach, A.; Otto, A.; Becher, D.; Bernhardt, J.; Hecker, M.; Peppelenbosch, M.P.; Dijl, J.M. van

    2011-01-01

    Staphylococcus aureus is a dangerous opportunistic human pathogen that causes serious invasive diseases when it reaches the bloodstream. Recent studies have shown that S. aureus is highly resistant to killing by professional phagocytes and that such cells even provide a favorable environment for

  13. Preferred SLA class I/class II haplotype combinations in German Landrace pigs.

    Science.gov (United States)

    Gimsa, Ulrike; Ho, Chak-Sum; Hammer, Sabine E

    2017-01-01

    Major histocompatibility complex (MHC) molecules are responsible for the antigen presentation to T lymphocytes. High recombination rates in the MHC genes, as observed in humans, are believed to serve the evolutionary goal to achieve a high genetic diversity, allowing for a broad and efficient immune response. In a cohort of 155 pedigreed German Landrace pigs (65 founders and 90 piglets), we found that MHC genes occur in particular class I and class II haplotype combinations. This phenomenon has not been described before, probably because most of the earlier MHC studies in pigs were not pedigree-based. After comparing our data with published genotypes of different European pig breeds and Asian pigs, we hypothesise that the combination of particular but different haplotypes in different geographical regions may have developed under the evolutionary pressure of regionally endemic pathogens. This proposed mechanism ensures an efficient immune response despite low recombination rates.

  14. ICOS gene haplotypes correlate with IL10 secretion and multiple sclerosis evolution.

    Science.gov (United States)

    Castelli, Luca; Comi, Cristoforo; Chiocchetti, Annalisa; Nicola, Stefania; Mesturini, Riccardo; Giordano, Mara; D'Alfonso, Sandra; Cerutti, Elisa; Galimberti, Daniela; Fenoglio, Chiara; Tesser, Fabiana; Yagi, Junji; Rojo, José Maria; Perla, Franco; Leone, Maurizio; Scarpini, Elio; Monaco, Francesco; Dianzani, Umberto

    2007-05-01

    Human ICOS is a T cell costimulatory molecule supporting IL10 secretion. A pilot study investigating variations of the ICOS gene 3'UTR detected 8 polymorphisms forming three haplotypes (A, B, C). Haplotype-A and -C displayed the highest difference. Activated T cells from healthy AA homozygotes expressed significantly less ICOS and secreted more IL10 than AC heterozygotes, whereas AB heterozygotes displayed intermediate levels. Analysis of 441 multiple sclerosis patients and 793 controls showed that frequency of AA homozygosity was significantly lower in MS patients with relapsing-remitting onset (N=416) than in controls (OR=0.70). Moreover, AA patients with relapsing-remitting onset had lower relapse rate and multiple sclerosis severity score than non-AA patients.

  15. Inheritance of the 8.1 ancestral haplotype in recurrent pregnancy loss

    DEFF Research Database (Denmark)

    Kolte, Astrid M; Nielsen, Henriette S; Steffensen, Rudi

    2015-01-01

    BACKGROUND AND OBJECTIVES: The 8.1 ancestral haplotype (AH) (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2) is a remarkably long and conserved haplotype in the human major histocompatibility complex. It has been associated with both beneficial and detrimental effects, consistent with antagonistic....... The objective was to test the gestational drive theory for the 8.1AH in women with RPL and their live born children. METHODOLOGY: We investigated the inheritance of the 8.1AH from 82 heterozygous RPL women to 110 live born children. All participants were genotyped for HLA-A, -B and -DRB1 in DNA from EDTA...

  16. Maps on the basis of the Arts & Humanities Citation Index: the journals Leonardo and Art Journal versus "Digital Humanities" as a topic

    NARCIS (Netherlands)

    Leydesdorff, L.; Salah, A.A.A.

    2010-01-01

    The possibilities of using the Arts & Humanities Citation Index (A&HCI) for journal mapping have not been sufficiently recognized because of the absence of a Journal Citations Report (JCR) for this database. A quasi-JCR for the A&HCI (2008) was constructed from the data contained in theWeb of Scienc

  17. Maps on the basis of the Arts & Humanities Citation Index: the journals Leonardo and Art Journal versus "Digital Humanities" as a topic

    NARCIS (Netherlands)

    Leydesdorff, L.; Salah, A.A.A.

    2010-01-01

    The possibilities of using the Arts & Humanities Citation Index (A&HCI) for journal mapping have not been sufficiently recognized because of the absence of a Journal Citations Report (JCR) for this database. A quasi-JCR for the A&HCI (2008) was constructed from the data contained in theWeb of Scienc

  18. Tag SNP selection for Finnish individuals based on the CEPH Utah HapMap database.

    Science.gov (United States)

    Willer, Cristen J; Scott, Laura J; Bonnycastle, Lori L; Jackson, Anne U; Chines, Peter; Pruim, Randall; Bark, Craig W; Tsai, Ya-Yu; Pugh, Elizabeth W; Doheny, Kimberly F; Kinnunen, Leena; Mohlke, Karen L; Valle, Timo T; Bergman, Richard N; Tuomilehto, Jaakko; Collins, Francis S; Boehnke, Michael

    2006-02-01

    The pattern and nature of linkage disequilibrium in the human genome is being studied and catalogued as part of the International HapMap Project [:2003 Nature 426:789-796]. A key goal of the HapMap Project is to enable identification of tag single nucleotide polymorphisms (SNPs) that capture a substantial portion of common human genetic variability while requiring only a small fraction of SNPs to be genotyped [International HapMap Consortium, 2005: Nature 437:1299-1320]. In the current study, we examined the effectiveness of using the CEU HapMap database to select tag SNPs for a Finnish sample. We selected SNPs in a 17.9-Mb region of chromosome 14 based on pairwise linkage disequilibrium (r(2)) estimates from the HapMap CEU sample, and genotyped 956 of these SNPs in 1,425 Finnish individuals. An excess of SNPs showed significantly different allele frequencies between the HapMap CEU and the Finnish samples, consistent with population-specific differences. However, we observed strong correlations between the two samples for estimates of allele frequencies, r(2) values, and haplotype frequencies. Our results demonstrate that the HapMap CEU samples provide an adequate basis for tag SNP selection in Finnish individuals, without the need to create a map specifically for the Finnish population, and suggest that the four-population HapMap data will provide useful information for tag SNP selection beyond the specific populations from which they were sampled.

  19. Insights into HLA-G genetics provided by worldwide haplotype diversity

    Directory of Open Access Journals (Sweden)

    Erick C Castelli

    2014-10-01

    Full Text Available Human Leucocyte Antigen G (HLA-G belongs to the family of nonclassical HLA class I genes, located within the major histocompatibility complex (MHC. HLA-G has been the target of most recent research regarding the function of class I nonclassical genes. The main features that distinguish HLA-G from classical class I genes are: a limited protein variability; b alternative splicing generating several membrane bound and soluble isoforms; c short cytoplasmic tail; d modulation of immune response (immune tolerance; e restricted expression to certain tissues. In the present work, we describe the HLA-G gene structure and address the HLA-G variability and haplotype diversity among several populations around the world, considering each of its major segments (promoter, coding and 3’untranslated regions. For this purpose, we developed a pipeline to reevaluate the 1000Genomes data and recover miscalled or missing genotypes and haplotypes. It became clear that the overall structure of the HLA-G molecule has been maintained during the evolutionary process and that most of the variation sites found in the HLA-G coding region are either coding synonymous or intronic mutations. In addition, only a few frequent and divergent extended haplotypes are found when the promoter, coding and 3’ untranslated regions are evaluated together. The divergence is particularly evident for the regulatory regions. The population comparisons confirmed that most of the HLA-G variability has originated before human dispersion from Africa and that the allele and haplotype frequencies have probably been shaped by strong selective pressures.

  20. Molecular characterization of a long range haplotype affecting protein yield and mastitis susceptibility in Norwegian Red cattle

    Directory of Open Access Journals (Sweden)

    Hayes Ben J

    2011-08-01

    Full Text Available Abstract Background Previous fine mapping studies in Norwegian Red cattle (NRC in the region 86-90.4 Mb on Bos taurus chromosome 6 (BTA6 has revealed a quantitative trait locus (QTL for protein yield (PY around 88 Mb and a QTL for clinical mastitis (CM around 90 Mb. The close proximity of these QTLs may partly explain the unfavorable genetic correlation between these two traits in NRC. A long range haplotype covering this region was introduced into the NRC population through the importation of a Holstein-Friesian bull (1606 Frasse from Sweden in the 1970s. It has been suggested that this haplotype has a favorable effect on milk protein content but an unfavorable effect on mastitis susceptibility. Selective breeding for milk production traits is likely to have increased the frequency of this haplotype in the NRC population. Results Association mapping for PY and CM in NRC was performed using genotypes from 556 SNPs throughout the region 86-97 Mb on BTA6 and daughter-yield-deviations (DYDs from 2601 bulls made available from the Norwegian dairy herd recording system. Highest test scores for PY were found for single-nucleotide polymorphisms (SNPs within and surrounding the genes CSN2 and CSN1S2, coding for the β-casein and αS2-casein proteins. High coverage re-sequencing by high throughput sequencing technology enabled molecular characterization of a long range haplotype from 1606 Frasse encompassing these two genes. Haplotype analysis of a large number of descendants from this bull indicated that the haplotype was not markedly disrupted by recombination in this region. The haplotype was associated with both increased milk protein content and increased susceptibility to mastitis, which might explain parts of the observed genetic correlation between PY and CM in NRC. Plausible causal polymorphisms affecting PY were detected in the promoter region and in the 5'-flanking UTR of CSN1S2. These polymorphisms could affect transcription or translation of

  1. Power laws for heavy-tailed distributions: modeling allele and haplotype diversity for the national marrow donor program.

    Directory of Open Access Journals (Sweden)

    Noa Slater

    2015-04-01

    Full Text Available Measures of allele and haplotype diversity, which are fundamental properties in population genetics, often follow heavy tailed distributions. These measures are of particular interest in the field of hematopoietic stem cell transplant (HSCT. Donor/Recipient suitability for HSCT is determined by Human Leukocyte Antigen (HLA similarity. Match predictions rely upon a precise description of HLA diversity, yet classical estimates are inaccurate given the heavy-tailed nature of the distribution. This directly affects HSCT matching and diversity measures in broader fields such as species richness. We, therefore, have developed a power-law based estimator to measure allele and haplotype diversity that accommodates heavy tails using the concepts of regular variation and occupancy distributions. Application of our estimator to 6.59 million donors in the Be The Match Registry revealed that haplotypes follow a heavy tail distribution across all ethnicities: for example, 44.65% of the European American haplotypes are represented by only 1 individual. Indeed, our discovery rate of all U.S. European American haplotypes is estimated at 23.45% based upon sampling 3.97% of the population, leaving a large number of unobserved haplotypes. Population coverage, however, is much higher at 99.4% given that 90% of European Americans carry one of the 4.5% most frequent haplotypes. Alleles were found to be less diverse suggesting the current registry represents most alleles in the population. Thus, for HSCT registries, haplotype discovery will remain high with continued recruitment to a very deep level of sampling, but population coverage will not. Finally, we compared the convergence of our power-law versus classical diversity estimators such as Capture recapture, Chao, ACE and Jackknife methods. When fit to the haplotype data, our estimator displayed favorable properties in terms of convergence (with respect to sampling depth and accuracy (with respect to diversity

  2. Functional maps of human auditory cortex: effects of acoustic features and attention.

    Directory of Open Access Journals (Sweden)

    David L Woods

    , ARMs increased in amplitude throughout stimulus blocks. CONCLUSIONS/SIGNIFICANCE: The results are consistent with the view that medial regions of human auditory cortex contain tonotopically organized core and belt fields that map the basic acoustic features of sounds while surrounding higher-order parabelt regions are tuned to more abstract stimulus attributes. Intermodal selective attention enhances processing in neuronal populations that are partially distinct from those activated by unattended stimuli.

  3. Three-dimensional probabilistic maps of the occipital sulci of the human brain in standardized stereotaxic space.

    Science.gov (United States)

    Iaria, G; Robbins, S; Petrides, M

    2008-01-02

    Developments in functional neuroimaging in normal human subjects, such as functional magnetic resonance imaging (fMRI), have permitted the mapping of several visual areas of the human brain and have already provided provisional identification of some of the visual areas that were first described in nonhuman primates. However, the lack of a detailed description of the sulcal patterns of the human occipital lobe makes it difficult to establish clear relationships between sulcal landmarks and identified visual areas with functional neuroimaging. In the present study we used magnetic resonance images to investigate the morphological variation of the human occipital sulci in both the left and right hemispheres of 40 normal adult human brains. We identified 11 occipital sulci, the parieto-occipital fissure and the temporo-occipital incisure, and their corresponding gray matter voxels were marked in the magnetic resonance volumes which had been transformed into the Montreal Neurological Institute standard proportional stereotaxic space. Probability maps were then constructed for each occipital sulcus. These probability maps provide a quantitative measure of the variability of the occipital sulci in standard stereotaxic space and are a useful tool to identify the location of voxels of other magnetic resonance imaging images transformed in the same stereotaxic space.

  4. Modelling risk of tick exposure in southern Scandinavia using machine learning techniques, satellite imagery, and human population density maps

    DEFF Research Database (Denmark)

    Kjær, Lene Jung; Korslund, L.; Kjelland, V.

    Vector-borne diseases such as Lyme disease and tick-borne encephalitis have become more common in recent decades and present a real health problem in many parts of Europe. Risk assessment, control, and prevention of these diseases require a better understanding of vector abundance as well as risk...... factors determining human exposure to ticks. There is a great need for analyses and models that can predict how vectors and their associated diseases are distributed and how this relates to high risk areas for human exposure.As a part of the ScandTick Innovation project, we surveyed ticks at approximately...... distribution (probability of presence) in southern Scandinavia. Together with the predicted distribution maps, we used human density maps to determine areas with high risk of exposure to ticks. For nymphs, the predicted distribution found corresponded well with known distributions of ticks in Scandinavia...

  5. Mapping the Stability of Human Brain Asymmetry across Five Sex-Chromosome Aneuploidies

    Science.gov (United States)

    Lin, Amy; Clasen, Liv; Lee, Nancy Raitano; Wallace, Gregory L.; Lalonde, Francois; Blumenthal, Jonathan; Giedd, Jay N.

    2015-01-01

    The human brain displays stereotyped and early emerging patterns of cortical asymmetry in health. It is unclear if these asymmetries are highly sensitive to genetic and environmental variation or fundamental features of the brain that can survive severe developmental perturbations. To address this question, we mapped cortical thickness (CT) asymmetry in a group of genetically defined disorders known to impact CT development. Participants included 137 youth with one of five sex-chromosome aneuploidies [SCAs; XXX (n = 28), XXY (n = 58), XYY (n = 26), XXYY (n = 20), and XXXXY (n = 5)], and 169 age-matched typically developing controls (80 female). In controls, we replicated previously reported rightward inferior frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal CT asymmetries were broadly preserved in all five SCA groups. However, we also detected foci of shifting CT asymmetry with aneuploidy, which fell almost exclusively within regions of significant CT asymmetry in controls. Specifically, X-chromosome aneuploidy accentuated normative rightward inferior frontal asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial prefrontal and lateral temporal asymmetries. These findings indicate that (1) the stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from developmental mechanisms that can withstand gross chromosomal aneuploidy and (2) X and Y chromosomes can exert focal, nonoverlapping and directionally opposed influences on CT asymmetry within cortical regions of significant asymmetry in health. Our study attests to the resilience of developmental mechanisms that support the global patterning of CT asymmetry in humans, and motivates future research into the molecular bases and functional consequences of sex chromosome dosage effects on CT asymmetry. PMID:25568109

  6. Mapping the stability of human brain asymmetry across five sex-chromosome aneuploidies.

    Science.gov (United States)

    Lin, Amy; Clasen, Liv; Lee, Nancy Raitano; Wallace, Gregory L; Lalonde, Francois; Blumenthal, Jonathan; Giedd, Jay N; Raznahan, Armin

    2015-01-07

    The human brain displays stereotyped and early emerging patterns of cortical asymmetry in health. It is unclear if these asymmetries are highly sensitive to genetic and environmental variation or fundamental features of the brain that can survive severe developmental perturbations. To address this question, we mapped cortical thickness (CT) asymmetry in a group of genetically defined disorders known to impact CT development. Participants included 137 youth with one of five sex-chromosome aneuploidies [SCAs; XXX (n = 28), XXY (n = 58), XYY (n = 26), XXYY (n = 20), and XXXXY (n = 5)], and 169 age-matched typically developing controls (80 female). In controls, we replicated previously reported rightward inferior frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal CT asymmetries were broadly preserved in all five SCA groups. However, we also detected foci of shifting CT asymmetry with aneuploidy, which fell almost exclusively within regions of significant CT asymmetry in controls. Specifically, X-chromosome aneuploidy accentuated normative rightward inferior frontal asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial prefrontal and lateral temporal asymmetries. These findings indicate that (1) the stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from developmental mechanisms that can withstand gross chromosomal aneuploidy and (2) X and Y chromosomes can exert focal, nonoverlapping and directionally opposed influences on CT asymmetry within cortical regions of significant asymmetry in health. Our study attests to the resilience of developmental mechanisms that support the global patterning of CT asymmetry in humans, and motivates future research into the molecular bases and functional consequences of sex chromosome dosage effects on CT asymmetry.

  7. Mapping human health risks from exposure to trace metal contamination of drinking water sources in Pakistan.

    Science.gov (United States)

    Bhowmik, Avit Kumar; Alamdar, Ambreen; Katsoyiannis, Ioannis; Shen, Heqing; Ali, Nadeem; Ali, Syeda Maria; Bokhari, Habib; Schäfer, Ralf B; Eqani, Syed Ali Musstjab Akber Shah

    2015-12-15

    The consumption of contaminated drinking water is one of the major causes of mortality and many severe diseases in developing countries. The principal drinking water sources in Pakistan, i.e. ground and surface water, are subject to geogenic and anthropogenic trace metal contamination. However, water quality monitoring activities have been limited to a few administrative areas and a nationwide human health risk assessment from trace metal exposure is lacking. Using geographically weighted regression (GWR) and eight relevant spatial predictors, we calculated nationwide human health risk maps by predicting the concentration of 10 trace metals in the drinking water sources of Pakistan and comparing them to guideline values. GWR incorporated local variations of trace metal concentrations into prediction models and hence mitigated effects of large distances between sampled districts due to data scarcity. Predicted concentrations mostly exhibited high accuracy and low uncertainty, and were in good agreement with observed concentrations. Concentrations for Central Pakistan were predicted with higher accuracy than for the North and South. A maximum 150-200 fold exceedance of guideline values was observed for predicted cadmium concentrations in ground water and arsenic concentrations in surface water. In more than 53% (4 and 100% for the lower and upper boundaries of 95% confidence interval (CI)) of the total area of Pakistan, the drinking water was predicted to be at risk of contamination from arsenic, chromium, iron, nickel and lead. The area with elevated risks is inhabited by more than 74 million (8 and 172 million for the lower and upper boundaries of 95% CI) people. Although these predictions require further validation by field monitoring, the results can inform disease mitigation and water resources management regarding potential hot spots.

  8. Y-chromosome STR haplotypes in males from Greenland

    DEFF Research Database (Denmark)

    Hallenberg, Charlotte; Tomas Mas, Carmen; Simonsen, Bo;

    2009-01-01

    A total of 272 males from Greenland were typed for 11 Y-chromosome STRs DYS19, DYS385a/b, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439 with the PowerPlex Y System (Promega). A total of 146 different haplotypes were observed and the haplotype diversity was 0.9887....

  9. Novel methods for physical mapping of the human genome applied to the long arm of chromosome 5. Final report

    Energy Technology Data Exchange (ETDEWEB)

    McClelland, M.

    1991-12-01

    The object of our current grant is to develop novel methods for mapping of the human genome. The techniques to be assessed were: (1) three methods for the production of unique sequence clones from the region of interest; (2) novel methods for the production and separation of multi-megabase DNA fragments; (3) methods for the production of ``physical linking clones`` that contain rare restriction sites; (4) application of these methods and available resources to map the region of interest. Progress includes: In the first two years methods were developed for physical mapping and the production of arrayed clones; We have concentrated on developing rare- cleavage tools based or restriction endonucleases and methylases; We studied the effect of methylation on enzymes used for PFE mapping of the human genome; we characterized two new isoschizomers of rare cutting endonucleases; we developed a reliable way to produce partial digests of DNA in agarose plugs and applied it to the human genome; and we applied a method to double the apparent specificity of the ``rare-cutter`` endonucleases.

  10. Novel methods for physical mapping of the human genome applied to the long arm of chromosome 5

    Energy Technology Data Exchange (ETDEWEB)

    McClelland, M.

    1991-12-01

    The object of our current grant is to develop novel methods for mapping of the human genome. The techniques to be assessed were: (1) three methods for the production of unique sequence clones from the region of interest; (2) novel methods for the production and separation of multi-megabase DNA fragments; (3) methods for the production of physical linking clones'' that contain rare restriction sites; (4) application of these methods and available resources to map the region of interest. Progress includes: In the first two years methods were developed for physical mapping and the production of arrayed clones; We have concentrated on developing rare- cleavage tools based or restriction endonucleases and methylases; We studied the effect of methylation on enzymes used for PFE mapping of the human genome; we characterized two new isoschizomers of rare cutting endonucleases; we developed a reliable way to produce partial digests of DNA in agarose plugs and applied it to the human genome; and we applied a method to double the apparent specificity of the rare-cutter'' endonucleases.

  11. Mapping of guanylin to murine chromosome 4 and human chromosome 1p34-p35

    Energy Technology Data Exchange (ETDEWEB)

    Sciaky, D.; Cohen, M.B. [Univ. of Cincinnati, OH (United States); Jenkins, N.A. [Mammalian Genetics Lab., Frederick, MD (United States)] [and others

    1995-03-20

    Guanylin is a 15-amino-acid peptide similar in structure and in function to ST{sub a}, the heat stable enterotoxin of enterotoxigenic Escherichia coli (4). Both guanylin and ST{sub a} bind guanylyl cyclase-C (GC-C), resulting in increased levels of intracellular cGMP and induction of Cl- secretion (4) via the cystic fibrosis transmembrane regulator (CFM) (2). Guanylin is a highly regulated intestinal gene that is differentially expressed along the duodenal-to-colonic and villus-to-crypt axes. Guanylin mRNA abundance is maximal in the distal small intestine and proximal colon, where the mRNA is detected mainly in differentiated villus epithelial cells and superficial colonic epithelial cells, respectively. The murine guanylin gene (Guca2) has been isolated and sequenced; the gene is 1.7 kb and consists of 3 exons. We report here the mapping of Guca2 to mouse chromosome 4 by linkage analysis and to human chromosome region 1p34-p35 using fluorescence in situ hybridization (FISH). 20 refs., 2 figs.

  12. Cloning, structural organization, and chromosomal mapping of the human phenol sulfotransferase STP2 gene

    Energy Technology Data Exchange (ETDEWEB)

    Gaedigk, A.; Beatty, B.G.; Grant, D.M. [Hospital for Sick Children, Toronto, Ontario (Canada)

    1997-03-01

    Phenol- and monoamine-metabolizing sulfotransferases (STP and STM, respectively) are members of a superfamily of enzymes that add sulfate to a variety of xenobiotics and endobiotics containing hydroxyl or amino functional groups. To characterize related sulfotransferase genes further, we used extra-long PCR (XL-PCR) to generate three distinct sizes of amplification products from human genomic DNA or from genomic phage library clones, each of which contained sulfotransferase gene sequences. One of the PCR fragments contained a new sulfotransferase gene, STP2, corresponding to a recently published cDNA clone that encodes a sulfotransferase with catalytic specificity distinct from that of the previously described STP1 and STM. Additional upstream sequence information was obtained using a second STP2-specific XL-PCR-based approach. The STP2 gene is composed of eight exons and seven introns, with exon sizes ranging from 95 to 181 bp. Protein-coding exon lengths and locations of the splice junctions were identical to those in both the STM gene and an STP2 gene published independently by another group recently. The STP2 gene maps to a chromosomal location (16p11.2-p1.2) that is the same as that previously determined for both STP1 and STM. The characterization of the STP2 gene provides further insight into the organization, regulation, and multiplicity of the sulfotransferase supergene family. 27 refs., 3 figs.

  13. Data for a comprehensive map and functional annotation of the human cerebrospinal fluid proteome

    Directory of Open Access Journals (Sweden)

    Yang Zhang

    2015-06-01

    Full Text Available Knowledge about the normal human cerebrospinal fluid (CSF proteome serves as a baseline reference for CSF biomarker discovery and provides insight into CSF physiology. In this study, high-pH reverse-phase liquid chromatography (hp-RPLC was first integrated with a TripleTOF 5600 mass spectrometer to comprehensively profile the normal CSF proteome. A total of 49,836 unique peptides and 3256 non-redundant proteins were identified. To obtain high-confidence results, 2513 proteins with at least 2 unique peptides were further selected as bona fide CSF proteins. Nearly 30% of the identified CSF proteins have not been previously reported in the normal CSF proteome. More than 25% of the CSF proteins were components of CNS cell microenvironments, and network analyses indicated their roles in the pathogenesis of neurological diseases. The top canonical pathway in which the CSF proteins participated was axon guidance signaling. More than one-third of the CSF proteins (788 proteins were related to neurological diseases, and these proteins constitute potential CSF biomarker candidates. The mapping results can be freely downloaded at http://122.70.220.102:8088/csf/, which can be used to navigate the CSF proteome. For more information about the data, please refer to the related original article [1], which has been recently accepted by Journal of Proteomics.

  14. Functional mapping of human dynamin-1-like GTPase domain based on x-ray structure analyses.

    Directory of Open Access Journals (Sweden)

    Julia Wenger

    Full Text Available Human dynamin-1-like protein (DNM1L is a GTP-driven molecular machine that segregates mitochondria and peroxisomes. To obtain insights into its catalytic mechanism, we determined crystal structures of a construct comprising the GTPase domain and the bundle signaling element (BSE in the nucleotide-free and GTP-analogue-bound states. The GTPase domain of DNM1L is structurally related to that of dynamin and binds the nucleotide 5'-Guanylyl-imidodiphosphate (GMP-PNP via five highly conserved motifs, whereas the BSE folds into a pocket at the opposite side. Based on these structures, the GTPase center was systematically mapped by alanine mutagenesis and kinetic measurements. Thus, residues essential for the GTPase reaction were characterized, among them Lys38, Ser39 and Ser40 in the phosphate binding loop, Thr59 from switch I, Asp146 and Gly149 from switch II, Lys216 and Asp218 in the G4 element, as well as Asn246 in the G5 element. Also, mutated Glu81 and Glu82 in the unique 16-residue insertion of DNM1L influence the activity significantly. Mutations of Gln34, Ser35, and Asp190 in the predicted assembly interface interfered with dimerization of the GTPase domain induced by a transition state analogue and led to a loss of the lipid-stimulated GTPase activity. Our data point to related catalytic mechanisms of DNM1L and dynamin involving dimerization of their GTPase domains.

  15. Functional Topography of Human Corpus Callosum: An fMRI Mapping Study

    Directory of Open Access Journals (Sweden)

    Mara Fabri

    2013-01-01

    Full Text Available The concept of a topographical map of the corpus callosum (CC has emerged from human lesion studies and from electrophysiological and anatomical tracing investigations in other mammals. Over the last few years a rising number of researchers have been reporting functional magnetic resonance imaging (fMRI activation in white matter, particularly the CC. In this study the scope for describing CC topography with fMRI was explored by evoking activation through simple sensory stimulation and motor tasks. We reviewed our published and unpublished fMRI and diffusion tensor imaging data on the cortical representation of tactile, gustatory, auditory, and visual sensitivity and of motor activation, obtained in 36 normal volunteers and in 6 patients with partial callosotomy. Activation foci were consistently detected in discrete CC regions: anterior (taste stimuli, central (motor tasks, central and posterior (tactile stimuli, and splenium (auditory and visual stimuli. Reconstruction of callosal fibers connecting activated primary gustatory, motor, somatosensory, auditory, and visual cortices by diffusion tensor tracking showed bundles crossing, respectively, through the genu, anterior and posterior body, and splenium, at sites harboring fMRI foci. These data confirm that the CC commissure has a topographical organization and demonstrate that its functional topography can be explored with fMRI.

  16. Comparative sequence analysis of the potato cyst nematode resistance locus H1 reveals a ma