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Sample records for ancestry highly correlated

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

    PubMed Central

    Gompert, Zachariah

    2016-01-01

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

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

    PubMed

    Gompert, Zachariah

    2016-01-01

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

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

    PubMed

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

    2014-12-01

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

  4. The correlation between ancestry and color in two cities of Northeast Brazil with contrasting ethnic compositions

    PubMed Central

    Magalhães da Silva, Thiago; Sandhya Rani, M R; de Oliveira Costa, Gustavo Nunes; Figueiredo, Maria A; Melo, Paulo S; Nascimento, João F; Molyneaux, Neil D; Barreto, Maurício L; Reis, Mitermayer G; Teixeira, M Glória; Blanton, Ronald E

    2015-01-01

    The degree of admixture in Brazil between historically isolated populations is complex and geographically variable. Studies differ as to what the genetic and phenotypic consequences of this mixing have been. In Northeastern Brazil, we enrolled 522 residents of Salvador and 620 of Fortaleza whose distributions of self-declared color were comparable to those in the national census. Using the program Structure and principal components analysis there was a clear correlation between biogeographic ancestry and categories of skin color. This correlation with African ancestry was stronger in Salvador (r=0.585; P<0.001) than in Fortaleza (r=0.236; P<0.001). In Fortaleza, although self-declared blacks had a greater proportion of European ancestry, they had more African ancestry than the other categories. When the populations were analyzed without pseudoancestors, as in some studies, the relationship of ‘race' to genetic ancestry tended to diffuse or disappear. The inclusion of different African populations also influenced ancestry estimates. The percentage of unlinked ancestry informative markers in linkage disequilibrium, a measure of population structure, was 3–5 times higher in both Brazilian populations than expected by chance. We propose that certain methods, ascertainment bias and population history of the specific populations surveyed can result in failure to demonstrate a correlation between skin color and genetic ancestry. Population structure in Brazil has important implications for genetic studies, but genetic ancestry is irrelevant for how individuals are treated in society, their health, their income or their inclusion. These track more closely with perceived skin color than genetic ancestry. PMID:25293718

  5. The correlation between ancestry and color in two cities of Northeast Brazil with contrasting ethnic compositions.

    PubMed

    Magalhães da Silva, Thiago; Sandhya Rani, M R; de Oliveira Costa, Gustavo Nunes; Figueiredo, Maria A; Melo, Paulo S; Nascimento, João F; Molyneaux, Neil D; Barreto, Maurício L; Reis, Mitermayer G; Teixeira, M Glória; Blanton, Ronald E

    2015-07-01

    The degree of admixture in Brazil between historically isolated populations is complex and geographically variable. Studies differ as to what the genetic and phenotypic consequences of this mixing have been. In Northeastern Brazil, we enrolled 522 residents of Salvador and 620 of Fortaleza whose distributions of self-declared color were comparable to those in the national census. Using the program Structure and principal components analysis there was a clear correlation between biogeographic ancestry and categories of skin color. This correlation with African ancestry was stronger in Salvador (r=0.585; P<0.001) than in Fortaleza (r=0.236; P<0.001). In Fortaleza, although self-declared blacks had a greater proportion of European ancestry, they had more African ancestry than the other categories. When the populations were analyzed without pseudoancestors, as in some studies, the relationship of 'race' to genetic ancestry tended to diffuse or disappear. The inclusion of different African populations also influenced ancestry estimates. The percentage of unlinked ancestry informative markers in linkage disequilibrium, a measure of population structure, was 3-5 times higher in both Brazilian populations than expected by chance. We propose that certain methods, ascertainment bias and population history of the specific populations surveyed can result in failure to demonstrate a correlation between skin color and genetic ancestry. Population structure in Brazil has important implications for genetic studies, but genetic ancestry is irrelevant for how individuals are treated in society, their health, their income or their inclusion. These track more closely with perceived skin color than genetic ancestry.

  6. Genetically Determined Amerindian Ancestry Correlates with Increased Frequency of Risk Alleles for Systemic Lupus Erythematosus

    PubMed Central

    Sanchez, E; Webb, R; Rasmussen, A.; Kelly, J.A; Riba, L.; Kaufman, K.M.; Garcia-de la Torre, I.; Moctezuma, J.F.; Maradiaga-Ceceña, M.A.; Cardiel, M.; Acevedo, E.; Cucho-Venegas, M.; Garcia, M.A.; Gamron, S.; Pons-Estel, B.A.; Vasconcelos, C.; Martin, J.; Tusié-Luna, T.; Harley, J.B.; Richardson, B.; Sawalha, A.H.; Alarcón-Riquelme, M.E.

    2011-01-01

    Objectives To analyze if genetically determined Amerindian ancestry predicts the increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus. Methods Single nucleotide polymorphisms within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo normal healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation of the presence of risk alleles with ancestry was done using linear regression. Results A meta-analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4, STAT4, PDCD1, ITGAM, and IRF5 were associated with lupus in a Hispanic-Mestizo cohort enriched for European and Amerindian ancestry. In addition, two SNPs within the MHC region, previously associated in a genome-wide association study in Europeans, were also associated in Mestizos. Using linear regression we predict an average increase of 2.34 risk alleles when comparing a lupus patient with 100% Amerindian ancestry to an SLE patient with 0% American Indian Ancestry (p<0.0001). SLE patients with 43% more Amerindian ancestry are predicted to carry one additional risk allele. Conclusion Amerindian ancestry increased the number of risk alleles for lupus. PMID:20848568

  7. Optimization of a pentaplex panel for MSI analysis without control DNA in a Brazilian population: correlation with ancestry markers.

    PubMed

    Campanella, Nathália C; Berardinelli, Gustavo N; Scapulatempo-Neto, Cristovam; Viana, Danilo; Palmero, Edenir I; Pereira, Rui; Reis, Rui M

    2014-07-01

    Microsatellite instability (MSI) testing has been advocated for all newly diagnosed colorectal cancer patients. One of the most common tests is composed by a pentaplex panel of mononucleotides markers (NR-27, NR-21, NR-24, BAT-25, and BAT-26), which allows the analysis of MSI in tumors without the need of reference DNA. For that, it is fundamental to establish a quasi-monomorphic variation range (QMVR) for each marker. Herein, we aimed to establish the QMVR in a Brazilian healthy population, to evaluate the feasibility of MSI determination of tumors, without the matching normal DNA. Furthermore, we intend to assess their ancestry using specific ancestry-informative markers (AIMs) and correlate with QMVR. The QMVR was assessed in 214 individuals, through a pentaplex PCR followed by fragment analysis. The ancestry analysis was done by 46 AIMs in a single multiplex PCR followed by capillary electrophoresis. Following QMVR establishment, we observed 23 individuals with alleles outside the QMVR. Importantly, none of them exhibited more than one marker outside the range. Therefore, individuals with instability at ≥2 markers would be accurately classified as MSI. The European ancestry proportion was the most frequent (67.5%), followed by the African (19.6%). The comparison of the individuals with alleles within (n=191) and outside (n=23) the QMVR showed statistical difference in the proportions of European and African alleles, confirming the higher polymorphic nature of African ancestry. In conclusion, the present study reports an accurate methodology to assess MSI status without matched-normal DNA and independently of the ethnicity, even in the highly admixed population of Brazil.

  8. Optimization of a pentaplex panel for MSI analysis without control DNA in a Brazilian population: correlation with ancestry markers

    PubMed Central

    Campanella, Nathália C; Berardinelli, Gustavo N; Scapulatempo-Neto, Cristovam; Viana, Danilo; Palmero, Edenir I; Pereira, Rui; Reis, Rui M

    2014-01-01

    Microsatellite instability (MSI) testing has been advocated for all newly diagnosed colorectal cancer patients. One of the most common tests is composed by a pentaplex panel of mononucleotides markers (NR-27, NR-21, NR-24, BAT-25, and BAT-26), which allows the analysis of MSI in tumors without the need of reference DNA. For that, it is fundamental to establish a quasi-monomorphic variation range (QMVR) for each marker. Herein, we aimed to establish the QMVR in a Brazilian healthy population, to evaluate the feasibility of MSI determination of tumors, without the matching normal DNA. Furthermore, we intend to assess their ancestry using specific ancestry-informative markers (AIMs) and correlate with QMVR. The QMVR was assessed in 214 individuals, through a pentaplex PCR followed by fragment analysis. The ancestry analysis was done by 46 AIMs in a single multiplex PCR followed by capillary electrophoresis. Following QMVR establishment, we observed 23 individuals with alleles outside the QMVR. Importantly, none of them exhibited more than one marker outside the range. Therefore, individuals with instability at ≥2 markers would be accurately classified as MSI. The European ancestry proportion was the most frequent (67.5%), followed by the African (19.6%). The comparison of the individuals with alleles within (n=191) and outside (n=23) the QMVR showed statistical difference in the proportions of European and African alleles, confirming the higher polymorphic nature of African ancestry. In conclusion, the present study reports an accurate methodology to assess MSI status without matched-normal DNA and independently of the ethnicity, even in the highly admixed population of Brazil. PMID:24193342

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    PubMed Central

    Lu, Yingchang; Justice, Anne E.; Mudgal, Poorva; Liu, Ching-Ti; Young, Kristin; Feitosa, Mary F.; Rand, Kristin; Dimitrov, Latchezar; Duan, Qing; Guo, Xiuqing; Lange, Leslie A.; Nalls, Michael A.; Okut, Hayrettin; Tayo, Bamidele O.; Vedantam, Sailaja; Bradfield, Jonathan P.; Chen, Guanjie; Chesi, Alessandra; Irvin, Marguerite R.; Padhukasahasram, Badri; Zheng, Wei; Allison, Matthew A.; Ambrosone, Christine B.; Bandera, Elisa V.; Berndt, Sonja I.; Blot, William J.; Bottinger, Erwin P.; Carpten, John; Chanock, Stephen J.; Chen, Yii-Der Ida; Conti, David V.; Cooper, Richard S.; Fornage, Myriam; Freedman, Barry I.; Garcia, Melissa; Goodman, Phyllis J.; Hsu, Yu-Han H.; Hu, Jennifer; Huff, Chad D.; Ingles, Sue A.; John, Esther M.; Kittles, Rick; Klein, Eric; Li, Jin; McKnight, Barbara; Nayak, Uma; Nemesure, Barbara; Olshan, Andrew; Salako, Babatunde; Sanderson, Maureen; Shao, Yaming; Siscovick, David S.; Stanford, Janet L.; Strom, Sara S.; Witte, John S.; Yao, Jie; Zhu, Xiaofeng; Ziegler, Regina G.; Zonderman, Alan B.; Ambs, Stefan; Cushman, Mary; Faul, Jessica D.; Hakonarson, Hakon; Levin, Albert M.; Nathanson, Katherine L.; Weir, David R.; Zhi, Degui; Arnett, Donna K.; Kardia, Sharon L. R.; Oloapde, Olufunmilayo I.; Rao, D. C.; Williams, L. Keoki; Becker, Diane M.; Borecki, Ingrid B.; Evans, Michele K.; Harris, Tamara B.; Hirschhorn, Joel N.; Psaty, Bruce M.; Wilson, James G.; Bowden, Donald W.; Cupples, L. Adrienne; Haiman, Christopher A.; Loos, Ruth J. F.; North, Kari E.

    2017-01-01

    Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10−8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in

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

    PubMed

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

    2017-04-01

    Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10-8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in

  12. Genomic ancestry and somatic alterations correlate with age at diagnosis in Hispanic children with B-cell acute lymphoblastic leukemia.

    PubMed

    Walsh, Kyle M; de Smith, Adam J; Welch, Tara C; Smirnov, Ivan; Cunningham, Marc J; Ma, Xiaomei; Chokkalingam, Anand P; Dahl, Gary V; Roberts, William; Barcellos, Lisa F; Buffler, Patricia A; Metayer, Catherine; Wiemels, Joseph L

    2014-07-01

    Hispanic children have a higher incidence of acute lymphoblastic leukemia (ALL) than non-Hispanic whites but tend to be diagnosed at older ages. In genome-wide association studies, Native American ancestry and polymorphisms in six genes have been associated with ALL risk. In multivariable regression models, we investigated whether genomic ancestry, inherited risk SNPs, or acquired somatic alterations were associated with differences in age at diagnosis in Hispanic children with B-cell ALL. Genome-wide array data were used to estimate each participant's percent membership in the three Hispanic ancestral populations: Native American, African, and European. Each 20% increase in European ancestry was associated with a six month younger age at diagnosis (95% CI = 0.36-11.6 months, P = 0.037). Correspondingly, each 20% increase in Native American ancestry was associated with a six-month older age at diagnosis (P = 0.037). Both the TEL-AML1 translocation and high-hyperdiploidy were associated with younger age at diagnosis (24.4 months, P = 2.0 x 10(-4) and 12.4 months, P = 0.011, respectively), while CDKN2A and IKZF1 deletions were associated with older age at diagnosis (19.7 months, P = 7.0 x 10(-4) and 18.1 months, P = 0.012, respectively). No associations with age at diagnosis were observed for RAS mutation, PAX5 deletion or for known heritable risk alleles in IKZF1, CDKN2A, PIP4K2A, GATA3, ARID5B, or CEBPE. Because younger age at diagnosis is associated with improved treatment outcomes for children with ALL, the effect of European ancestry on ALL survival may be mediated by its effect on age at diagnosis, or by proxy, its association with more treatable molecular subtypes of ALL.

  13. Kaiso is highly expressed in TNBC tissues of women of African ancestry compared to Caucasian women.

    PubMed

    Bassey-Archibong, Blessing I; Hercules, Shawn M; Rayner, Lyndsay G A; Skeete, Desiree H A; Smith Connell, Suzanne P; Brain, Ian; Daramola, Adetola; Banjo, Adekunbiola A F; Byun, Jung S; Gardner, Kevin; Dushoff, Jonathan; Daniel, Juliet M

    2017-09-08

    Triple-negative breast cancer (TNBC) is most prevalent in young women of African ancestry (WAA) compared to women of other ethnicities. Recent studies found a correlation between high expression of the transcription factor Kaiso, TNBC aggressiveness, and ethnicity. However, little is known about Kaiso expression and localization patterns in TNBC tissues of WAA. Herein, we analyze Kaiso expression patterns in TNBC tissues of African (Nigerian), Caribbean (Barbados), African American (AA), and Caucasian American (CA) women. Formalin-fixed and paraffin embedded (FFPE) TNBC tissue blocks from Nigeria and Barbados were utilized to construct a Nigerian/Barbadian tissue microarray (NB-TMA). This NB-TMA and a commercially available TMA comprising AA and CA TNBC tissues (AA-CA-YTMA) were subjected to immunohistochemistry to assess Kaiso expression and subcellular localization patterns, and correlate Kaiso expression with TNBC clinical features. Nigerian and Barbadian women in our study were diagnosed with TNBC at a younger age than AA and CA women. Nuclear and cytoplasmic Kaiso expression was observed in all tissues analyzed. Analysis of Kaiso expression in the NB-TMA and AA-CA-YTMA revealed that nuclear Kaiso H scores were significantly higher in Nigerian, Barbadian, and AA women compared with CA women. However, there was no statistically significant difference in nuclear Kaiso expression between Nigerian versus Barbadian women, or Barbadian versus AA women. High levels of nuclear Kaiso expression were detected in patients with a higher degree of African heritage compared to their Caucasian counterparts, suggesting a role for Kaiso in TNBC racial disparity.

  14. African ancestry is a risk factor for asthma and high total IgE levels in African admixed populations.

    PubMed

    Vergara, Candelaria; Murray, Tanda; Rafaels, Nicholas; Lewis, Rachel; Campbell, Monica; Foster, Cassandra; Gao, Li; Faruque, Mezbah; Oliveira, Ricardo Riccio; Carvalho, Edgar; Araujo, Maria Ilma; Cruz, Alvaro A; Watson, Harold; Mercado, Dilia; Knight-Madden, Jennifer; Ruczinski, Ingo; Dunston, Georgia; Ford, Jean; Caraballo, Luis; Beaty, Terri H; Mathias, Rasika A; Barnes, Kathleen C

    2013-05-01

    Characterization of genetic admixture of populations in the Americas and the Caribbean is of interest for anthropological, epidemiological, and historical reasons. Asthma has a higher prevalence and is more severe in populations with a high African component. Association of African ancestry with asthma has been demonstrated. We estimated admixture proportions of samples from six trihybrid populations of African descent and determined the relationship between African ancestry and asthma and total serum IgE levels (tIgE). We genotyped 237 ancestry informative markers in asthmatics and nonasthmatic controls from Barbados (190/277), Jamaica (177/529), Brazil (40/220), Colombia (508/625), African Americans from New York (207/171), and African Americans from Baltimore/Washington, D.C. (625/757). We estimated individual ancestries and evaluated genetic stratification using Structure and principal component analysis. Association of African ancestry and asthma and tIgE was evaluated by regression analysis. Mean ± SD African ancestry ranged from 0.76 ± 0.10 among Barbadians to 0.33 ± 0.13 in Colombians. The European component varied from 0.14 ± 0.05 among Jamaicans and Barbadians to 0.26 ± 0.08 among Colombians. African ancestry was associated with risk for asthma in Colombians (odds ratio (OR) = 4.5, P = 0.001) Brazilians (OR = 136.5, P = 0.003), and African Americans of New York (OR: 4.7; P = 0.040). African ancestry was also associated with higher tIgE levels among Colombians (β = 1.3, P = 0.04), Barbadians (β = 3.8, P = 0.03), and Brazilians (β = 1.6, P = 0.03). Our findings indicate that African ancestry can account for, at least in part, the association between asthma and its associated trait, tIgE levels. © 2013 Wiley Periodicals, Inc.

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

    PubMed Central

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

    2014-01-01

    Introduction In a North American, HIV-positive, highly active antiretroviral therapy (HAART)-treated, adherent cohort of self-identified white and black patients, we previously observed that chemokine (C-C motif) receptor 5 (CCR5) –2459G>A genotype had a strong association with time to achieve virologic success (TVLS) in black but not in white patients. Methods Using 128 genome-wide ancestry informative markers, we performed a quantitative assessment of ancestry in these patients (n = 310) to determine (1) whether CCR5 –2459G>A genotype is still associated with TVLS of HAART when ancestry, not self-identified race, is considered and (2) whether this association is influenced by varying African ancestry. Results We found that the interaction between CCR5 –2459G>A genotype and African ancestry (≤0.125 vs. ≥0.425 and <0.71 vs. ≥0.71) was significantly associated with TVLS (GG compared with AA, P = 0.044 and 0.018, respectively). Furthermore, the association between CCR5 –2459G>A genotype and TVLS was stronger in patients with African ancestry ≥0.71 than in patients with African ancestry ≥0.452, in both Kaplan-Meier (log-rank P = 0.039 and 0.057, respectively, for AA, GA, and GG) and Cox proportional hazards regression (relative hazard for GG compared with AA 2.59 [95% CI, 1.27–5.22; P = 0.01] and 2.26 [95% CI, 1.18–4.32; P = 0.01], respectively) analyses. Conclusions We observed that the association between CCR5 –2459G>A genotype and TVLS of HAART increased with stronger African ancestry. Understanding the genomic mechanisms by which African ancestry influences this association is critical, and requires further studies. PMID:24714069

  16. African Ancestry is a Risk Factor for Asthma and High Total IgE Levels in African Admixed Populations

    PubMed Central

    Vergara, Candelaria; Murray, Tanda; Rafaels, Nicholas; Lewis, Rachel; Campbell, Monica; Foster, Cassandra; Gao, Li; Faruque, Mezbah; Oliveira, Ricardo Riccio; Carvalho, Edgar; Araujo, Maria Ilma; Cruz, Alvaro A.; Watson, Harold; Mercado, Dilia; Knight-Madden, Jennifer; Ruczinski, Ingo; Dunston, Georgia; Ford, Jean; Caraballo, Luis; Beaty, Terri H.; Mathias, Rasika A.; Barnes, Kathleen C.

    2014-01-01

    Characterization of genetic admixture of populations in the Americas and the Caribbean is of interest for anthropological, epidemiological, and historical reasons. Asthma has a higher prevalence and is more severe in populations with a high African component. Association of African ancestry with asthma has been demonstrated. We estimated admixture proportions of samples from six trihybrid populations of African descent and determined the relationship between African ancestry and asthma and total serum IgE levels (tIgE). We genotyped 237 ancestry informative markers in asthmatics and nonasthmatic controls from Barbados (190/277), Jamaica (177/529), Brazil (40/220), Colombia (508/625), African Americans from New York (207/171), and African Americans from Baltimore/Washington, D.C. (625/757). We estimated individual ancestries and evaluated genetic stratification using Structure and principal component analysis. Association of African ancestry and asthma and tIgE was evaluated by regression analysis. Mean SD African ancestry ranged from 0.76 ± 0.10 among Barbadians to 0.33 ± 0.13 in Colombians. The European component varied from 0.14 ± 0.05 among Jamaicans and Barbadians to 0.26 ± 0.08 among Colombians. African ancestry was associated with risk for asthma in Colombians (odds ratio (OR) = 4.5, P = 0.001) Brazilians (OR = 136.5, P = 0.003), and African Americans of New York (OR: 4.7; P = 0.040). African ancestry was also associated with higher tIgE levels among Colombians (β = 1.3, P = 0.04), Barbadians (β = 3.8, P = 0.03), and Brazilians (β = 1.6, P = 0.03). Our findings indicate that African ancestry can account for, at least in part, the association between asthma and its associated trait, tIgE levels. PMID:23554133

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

    PubMed

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

    2015-10-01

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

  18. Skin pigmentation, biogeographical ancestry and admixture mapping.

    PubMed

    Shriver, Mark D; Parra, Esteban J; Dios, Sonia; Bonilla, Carolina; Norton, Heather; Jovel, Celina; Pfaff, Carrie; Jones, Cecily; Massac, Aisha; Cameron, Neil; Baron, Archie; Jackson, Tabitha; Argyropoulos, George; Jin, Li; Hoggart, Clive J; McKeigue, Paul M; Kittles, Rick A

    2003-04-01

    Ancestry informative markers (AIMs) are genetic loci showing alleles with large frequency differences between populations. AIMs can be used to estimate biogeographical ancestry at the level of the population, subgroup (e.g. cases and controls) and individual. Ancestry estimates at both the subgroup and individual level can be directly instructive regarding the genetics of the phenotypes that differ qualitatively or in frequency between populations. These estimates can provide a compelling foundation for the use of admixture mapping (AM) methods to identify the genes underlying these traits. We present details of a panel of 34 AIMs and demonstrate how such studies can proceed, by using skin pigmentation as a model phenotype. We have genotyped these markers in two population samples with primarily African ancestry, viz. African Americans from Washington D.C. and an African Caribbean sample from Britain, and in a sample of European Americans from Pennsylvania. In the two African population samples, we observed significant correlations between estimates of individual ancestry and skin pigmentation as measured by reflectometry (R(2)=0.21, P<0.0001 for the African-American sample and R(2)=0.16, P<0.0001 for the British African-Caribbean sample). These correlations confirm the validity of the ancestry estimates and also indicate the high level of population structure related to admixture, a level that characterizes these populations and that is detectable by using other tests to identify genetic structure. We have also applied two methods of admixture mapping to test for the effects of three candidate genes (TYR, OCA2, MC1R) on pigmentation. We show that TYR and OCA2 have measurable effects on skin pigmentation differences between the west African and west European parental populations. This work indicates that it is possible to estimate the individual ancestry of a person based on DNA analysis with a reasonable number of well-defined genetic markers. The implications and

  19. Inference of human continental origin and admixture proportions using a highly discriminative ancestry informative 41-SNP panel

    PubMed Central

    2013-01-01

    Background Accurate determination of genetic ancestry is of high interest for many areas such as biomedical research, personal genomics and forensics. It remains an important topic in genetic association studies, as it has been shown that population stratification, if not appropriately considered, can lead to false-positive and -negative results. While large association studies typically extract ancestry information from available genome-wide SNP genotypes, many important clinical data sets on rare phenotypes and historical collections assembled before the GWAS area are in need of a feasible method (i.e., ease of genotyping, small number of markers) to infer the geographic origin and potential admixture of the study subjects. Here we report on the development, application and limitations of a small, multiplexable ancestry informative marker (AIM) panel of SNPs (or AISNP) developed specifically for this purpose. Results Based on worldwide populations from the HGDP, a 41-AIM AISNP panel for multiplex application with the ABI SNPlex and a subset with 31 AIMs for the Sequenome iPLEX system were selected and found to be highly informative for inferring ancestry among the seven continental regions Africa, the Middle East, Europe, Central/South Asia, East Asia, the Americas and Oceania. The panel was found to be least informative for Eurasian populations, and additional AIMs for a higher resolution are suggested. A large reference set including over 4,000 subjects collected from 120 global populations was assembled to facilitate accurate ancestry determination. We show practical applications of this AIM panel, discuss its limitations for admixed individuals and suggest ways to incorporate ancestry information into genetic association studies. Conclusion We demonstrated the utility of a small AISNP panel specifically developed to discern global ancestry. We believe that it will find wide application because of its feasibility and potential for a wide range of applications

  20. Correlates of Bone Mineral Density among Postmenopausal Women of African Caribbean Ancestry: Tobago Women’s Health Study

    PubMed Central

    Hill, Deanna D.; Cauley, Jane A.; Bunker, Clareann H.; Baker, Carol E.; Patrick, Alan L.; Beckles, Gloria L. A.; Wheeler, Victor W.; Zmuda, Joseph M.

    2008-01-01

    Population dynamics predict a drastic growth in the number of older minority women, and resultant increases in the number of fractures. Low bone mineral density (BMD) is an important risk factor for fracture. Many studies have identified the lifestyle and health related factors that correlate with BMD in Whites. Few studies have focused on non-Whites. The objective of the current analyses is to examine the lifestyle, anthropometric and health related factors that are correlated with BMD in a population based cohort of Caribbean women of West African ancestry. We enrolled 340 postmenopausal women residing on the Caribbean Island of Tobago. Participants completed a questionnaire and had anthropometric measures taken. Hip BMD was measured by DXA. We estimated volumetric BMD by calculating bone mineral apparent density (BMAD). BMD was 10% and 20% higher across all age groups in Tobagonian women compared to US non-Hispanic Black and White women, respectively. In multiple linear regression models, 35–36% of the variability in femoral neck and total hip BMD respectively was predicted. Each 16 kilogram (one standard deviation (SD)) increase in weight was associated with 7% higher BMD; and weight explained over 10% of the variability of BMD. Each eight year (1 SD) increase in age was associated with 6% lower BMD. Current use of both thiazide diuretics and oral hypoglycemic medication were associated with 4–5% higher BMD. For femoral neck BMAD, 26% of the variability was explained by a multiple linear regression model. Current statin use was associated with 5% higher BMAD and a history of breast feeding or coronary heart disease were associated with 1–1.5% of higher BMAD. In conclusion, African Caribbean women have the highest BMD on a population level reported to date for women. This may reflect low European admixture. Correlates of BMD among Caribbean women of West African ancestry were similar to those reported for U.S. Black and White women. PMID:18448413

  1. Correlation of E-selectin concentrations with carotid intima-media thickness and cardio-metabolic profile of mixed ancestry South Africans: a cross-sectional study.

    PubMed

    Zemlin, Annalise E; Matsha, Tandi E; Kengne, Andre P; Hon, Gloudina M; Erasmus, Rajiv T

    2017-01-01

    Background E-selectin, an adhesion molecule, is a specific marker of endothelial dysfunction. High concentrations have been reported in type 2 diabetes and disorders with high risk of cardiovascular disease (CVD). Measurement of carotid intima-media thickness (CIMT) is a surrogate marker of early atherosclerosis. We examined the relationship between E-selectin concentrations, CIMT and cardio-metabolic traits in normo- and hyperglycaemic mixed ancestry South Africans. Methods E-selectin concentrations were determined in 308 subjects from the Cape Town Bellville South Community-based study on a mixed ancestry population. Their correlation with CIMT and cardio-metabolic profile used robust correlations and linear regression models. Results E-selectin concentrations were significantly higher in the hyperglycaemic (median 139.8 µg/L) compared to the normoglycaemic group (median 118.8 µg/L), ( p = 0.0007). Significant differences between the two groups were found for markers of glycaemia and adiposity, but not for CIMT. Significant correlations were found between E-selectin and age, markers of glycaemia and inflammation, central obesity and lipid variables. Associations remained significant only with age, hyperglycaemia and C-reactive protein in robust linear regression models. In similar regressions models, age and gender were the main predictors of CIMT, which was not associated with E-selectin. Conclusions E-selectin concentrations in this study were associated with hyperglycaemia, possibly reflecting early endothelial damage. However, E-selectin was not useful to assess CIMT, a marker of subclinical atherosclerosis, which appeared to be determined by ageing and male gender.

  2. Chromosome 8q24 Variants Are Associated With Prostate Cancer Risk in a High Risk Population of African Ancestry

    PubMed Central

    Okobia, Michael N.; Zmuda, Joseph M.; Ferrell, Robert E.; Patrick, Alan L.; Bunker, Clareann H.

    2015-01-01

    BACKGROUND Earlier studies on the role of germline variations in the disproportionate higher burden of prostate cancer in men of African ancestry have been largely unrewarding. However, the successful replication of recent genome-wide association findings implicating some regions of chromosome 8q24 in the disparate prostate cancer susceptibility in men of European and African ancestry have been encouraging. This case–control study was designed to evaluate the association between germline variations in chromosome 8q24 and prostate cancer risk in Afro-Caribbean Tobago men, a population of predominantly West African ancestry. METHODS High molecular weight genomic DNA was isolated from blood clots using Qiagen kits. Genotyping was performed on genomic DNA using a pre-designed TaqMan SNP assay according to the manufacture’s protocol on a 7900HT Fast Real-Time PCR system (Applied Biosystems, Foster City, CA). RESULTS SNP rs16901979 in region 2 was associated with significantly increased risk of prostate cancer (OR = 1.41, 95% confidence interval [CI] 1.02–1.95, P = 0.04) with the risk stronger in men with early-onset prostate cancer (OR = 2.37, 95% CI 1.40–3.99, P = 0.001). There was a tendency towards significantly increased risk for SNPs rs1447295 and rs6983267 in men with early-onset prostate cancer. CONCLUSIONS The replication of the association of chromosome 8q24 variants with increased prostate cancer risk in Tobago men and the higher frequency of the risk alleles in controls in populations of African ancestry further strengthens the possible role of this genomic region in the disproportionate higher burden of prostate cancer in men of African ancestry. PMID:21557270

  3. Chromosome 8q24 variants are associated with prostate cancer risk in a high risk population of African ancestry.

    PubMed

    Okobia, Michael N; Zmuda, Joseph M; Ferrell, Robert E; Patrick, Alan L; Bunker, Clareann H

    2011-07-01

    Earlier studies on the role of germline variations in the disproportionate higher burden of prostate cancer in men of African ancestry have been largely unrewarding. However, the successful replication of recent genome-wide association findings implicating some regions of chromosome 8q24 in the disparate prostate cancer susceptibility in men of European and African ancestry have been encouraging. This case-control study was designed to evaluate the association between germline variations in chromosome 8q24 and prostate cancer risk in Afro-Caribbean Tobago men, a population of predominantly West African ancestry. High molecular weight genomic DNA was isolated from blood clots using Qiagen kits. Genotyping was performed on genomic DNA using a pre-designed TaqMan SNP assay according to the manufacture's protocol on a 7900HT Fast Real-Time PCR system (Applied Biosystems, Foster City, CA). SNP rs16901979 in region 2 was associated with significantly increased risk of prostate cancer (OR = 1.41, 95% confidence interval [CI] 1.02-1.95, P = 0.04) with the risk stronger in men with early-onset prostate cancer (OR = 2.37, 95% CI 1.40-3.99, P = 0.001). There was a tendency towards significantly increased risk for SNPs rs1447295 and rs6983267 in men with early-onset prostate cancer. The replication of the association of chromosome 8q24 variants with increased prostate cancer risk in Tobago men and the higher frequency of the risk alleles in controls in populations of African ancestry further strengthens the possible role of this genomic region in the disproportionate higher burden of prostate cancer in men of African ancestry. Copyright © 2011 Wiley-Liss, Inc.

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

    Previous studies in dementia epidemiology have reported higher Alzheimer's disease rates in African-Americans when compared with White Americans. To determine whether genetically determined African ancestry is associated with neuropathological changes commonly associated with dementia, we analyzed a population-based brain bank in the highly admixed city of São Paulo, Brazil. African ancestry was estimated through the use of previously described ancestry-informative markers. Risk of presence of neuritic plaques, neurofibrillary tangles, small vessel disease, brain infarcts and Lewy bodies in subjects with significant African ancestry versus those without was determined. Results were adjusted for multiple environmental risk factors, demographic variables and apolipoprotein E genotype. African ancestry was inversely correlated with neuritic plaques (P=0.03). Subjects with significant African ancestry (n=112, 55.4%) showed lower prevalence of neuritic plaques in the univariate analysis (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.55–0.95, P=0.01) and when adjusted for age, sex, APOE genotype and environmental risk factors (OR 0.43, 95% CI 0.21–0.89, P=0.02). There were no significant differences for the presence of other neuropathological alterations. We show for the first time, using genetically determined ancestry, that African ancestry may be highly protective of Alzheimer's disease neuropathology, functioning through either genetic variants or unknown environmental factors. Epidemiological studies correlating African-American race/ethnicity with increased Alzheimer's disease rates should not be interpreted as surrogates of genetic ancestry or considered to represent African-derived populations from the developing nations such as Brazil. PMID:22064377

  6. Breast cancer disparities: high-risk breast cancer and African ancestry.

    PubMed

    Newman, Lisa A

    2014-07-01

    African American women have a lower lifetime incidence of breast cancer than white/Caucasian Americans yet have a higher risk of breast cancer mortality. African American women are also more likely to be diagnosed with breast cancer at young ages, and they have higher risk for the biologically more aggressive triple-negative breast cancers. These features are also more common among women from western, sub-Saharan Africa who share ancestry with African Americans, and this prompts questions regarding an association between African ancestry and inherited susceptibility for certain patterns of mammary carcinogenesis.

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

    PubMed

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

    2015-01-01

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

  8. Surname‐Inferred andean ancestry is associated with child stature and limb lengths at high altitude in Peru, but not at sea level

    PubMed Central

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

    2015-01-01

    Abstract Objectives Native Andean ancestry gives partial protection from reduced birthweight at high altitude in the Andes compared with European ancestry. Whether Andean ancestry is also associated with body proportions and greater postnatal body size at altitude is unknown. Therefore, we tested whether a greater proportion of Andean ancestry is associated with stature and body proportions among Peruvian children at high and low altitude. Methods Height, head circumference, head‐trunk height, upper and lower limb lengths, and tibia, ulna, hand and foot lengths, were measured in 133 highland and 169 lowland children aged 6 months to 8.5 years. For highland and lowland groups separately, age‐sex‐adjusted anthropometry z scores were regressed on the number of indigenous parental surnames as a proxy for Andean ancestry, adjusting for potential confounders (maternal age and education, parity, altitude [highlands only]). Results Among highland children, greater Andean ancestry was negatively associated with stature and tibia, ulna, and lower limb lengths, independent of negative associations with greater altitude for these measurements. Relationships were strongest for tibia length: each additional Andean surname or 1,000 m increase at altitude among highland children was associated with 0.18 and 0.65 z score decreases in tibia length, respectively. Anthropometry was not significantly associated with ancestry among lowland children. Conclusions Greater Andean ancestry is associated with shorter stature and limb measurements at high but not low altitude. Gene‐environment interactions between high altitude and Andean ancestry may exacerbate the trade‐off between chest dimensions and stature that was proposed previously, though we could not test this directly. Am. J. Hum. Biol. 27:798–806, 2015. © 2015 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc. PMID:25960137

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

    PubMed

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

    2015-01-01

    Higher body mass index (BMI) is a well-established risk factor for type 2 diabetes, and rates of obesity and type 2 diabetes are substantially higher among Mexican-Americans relative to non-Hispanic European Americans. Mexican-Americans are genetically diverse, with a highly variable distribution of Native American, European, and African ancestries. Here, we evaluate the role of Native American ancestry on BMI and diabetes risk in a well-defined Mexican-American population. Participants were randomly selected among individuals residing in the Houston area who are enrolled in the Mexican-American Cohort study. Using a custom Illumina GoldenGate Panel, we genotyped DNA from 4,662 cohort participants for 87 Ancestry-Informative Markers. On average, the participants were of 50.2% Native American ancestry, 42.7% European ancestry and 7.1% African ancestry. Using multivariate linear regression, we found BMI and Native American ancestry were inversely correlated; individuals with <20% Native American ancestry were 2.5 times more likely to be severely obese compared to those with >80% Native American ancestry. Furthermore, we demonstrated an interaction between BMI and Native American ancestry in diabetes risk among women; Native American ancestry was a strong risk factor for diabetes only among overweight and obese women (OR = 1.190 for each 10% increase in Native American ancestry). This study offers new insight into the complex relationship between obesity, genetic ancestry, and their respective effects on diabetes risk. Findings from this study may improve the diabetes risk prediction among Mexican-American individuals thereby facilitating targeted prevention strategies.

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

    PubMed Central

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

    2015-01-01

    Higher body mass index (BMI) is a well-established risk factor for type 2 diabetes, and rates of obesity and type 2 diabetes are substantially higher among Mexican-Americans relative to non-Hispanic European Americans. Mexican-Americans are genetically diverse, with a highly variable distribution of Native American, European, and African ancestries. Here, we evaluate the role of Native American ancestry on BMI and diabetes risk in a well-defined Mexican-American population. Participants were randomly selected among individuals residing in the Houston area who are enrolled in the Mexican-American Cohort study. Using a custom Illumina GoldenGate Panel, we genotyped DNA from 4,662 cohort participants for 87 Ancestry-Informative Markers. On average, the participants were of 50.2% Native American ancestry, 42.7% European ancestry and 7.1% African ancestry. Using multivariate linear regression, we found BMI and Native American ancestry were inversely correlated; individuals with <20% Native American ancestry were 2.5 times more likely to be severely obese compared to those with >80% Native American ancestry. Furthermore, we demonstrated an interaction between BMI and Native American ancestry in diabetes risk among women; Native American ancestry was a strong risk factor for diabetes only among overweight and obese women (OR = 1.190 for each 10% increase in Native American ancestry). This study offers new insight into the complex relationship between obesity, genetic ancestry, and their respective effects on diabetes risk. Findings from this study may improve the diabetes risk prediction among Mexican-American individuals thereby facilitating targeted prevention strategies. PMID:26501420

  11. Race, genetic West African ancestry, and prostate cancer prediction by prostate-specific antigen in prospectively screened high-risk men.

    PubMed

    Giri, Veda N; Egleston, Brian; Ruth, Karen; Uzzo, Robert G; Chen, David Y T; Buyyounouski, Mark; Raysor, Susan; Hooker, Stanley; Torres, Jada Benn; Ramike, Teniel; Mastalski, Kathleen; Kim, Taylor Y; Kittles, Rick

    2009-03-01

    "Race-specific" prostate-specific antigen (PSA) needs evaluation in men at high risk for prostate cancer for optimizing early detection. Baseline PSA and longitudinal prediction for prostate cancer were examined by self-reported race and genetic West African (WA) ancestry in the Prostate Cancer Risk Assessment Program, a prospective high-risk cohort. Eligibility criteria were age 35 to 69 years, family history of prostate cancer, African American race, or BRCA1/2 mutations. Biopsies were done at low PSA values (<4.0 ng/mL). WA ancestry was discerned by genotyping 100 ancestry informative markers. Cox proportional hazards models evaluated baseline PSA, self-reported race, and genetic WA ancestry. Cox models were used for 3-year predictions for prostate cancer. Six hundred forty-six men (63% African American) were analyzed. Individual WA ancestry estimates varied widely among self-reported African American men. Race-specific differences in baseline PSA were not found by self-reported race or genetic WA ancestry. Among men with > or =1 follow-up visit (405 total, 54% African American), 3-year prediction for prostate cancer with a PSA of 1.5 to 4.0 ng/mL was higher in African American men with age in the model (P = 0.025) compared with European American men. Hazard ratios of PSA for prostate cancer were also higher by self-reported race (1.59 for African American versus 1.32 for European American, P = 0.04). There was a trend for increasing prediction for prostate cancer with increasing genetic WA ancestry. "Race-specific" PSA may need to be redefined as higher prediction for prostate cancer at any given PSA in African American men. Large-scale studies are needed to confirm if genetic WA ancestry explains these findings to make progress in personalizing prostate cancer early detection.

  12. Denisovan Ancestry in East Eurasian and Native American Populations.

    PubMed

    Qin, Pengfei; Stoneking, Mark

    2015-10-01

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

  13. Ancestry-related assortative mating in Latino populations.

    PubMed

    Risch, Neil; Choudhry, Shweta; Via, Marc; Basu, Analabha; Sebro, Ronnie; Eng, Celeste; Beckman, Kenneth; Thyne, Shannon; Chapela, Rocio; Rodriguez-Santana, Jose R; Rodriguez-Cintron, William; Avila, Pedro C; Ziv, Elad; Gonzalez Burchard, Esteban

    2009-01-01

    While spouse correlations have been documented for numerous traits, no prior studies have assessed assortative mating for genetic ancestry in admixed populations. Using 104 ancestry informative markers, we examined spouse correlations in genetic ancestry for Mexican spouse pairs recruited from Mexico City and the San Francisco Bay Area, and Puerto Rican spouse pairs recruited from Puerto Rico and New York City. In the Mexican pairs, we found strong spouse correlations for European and Native American ancestry, but no correlation in African ancestry. In the Puerto Rican pairs, we found significant spouse correlations for African ancestry and European ancestry but not Native American ancestry. Correlations were not attributable to variation in socioeconomic status or geographic heterogeneity. Past evidence of spouse correlation was also seen in the strong evidence of linkage disequilibrium between unlinked markers, which was accounted for in regression analysis by ancestral allele frequency difference at the pair of markers (European versus Native American for Mexicans, European versus African for Puerto Ricans). We also observed an excess of homozygosity at individual markers within the spouses, but this provided weaker evidence, as expected, of spouse correlation. Ancestry variance is predicted to decline in each generation, but less so under assortative mating. We used the current observed variances of ancestry to infer even stronger patterns of spouse ancestry correlation in previous generations. Assortative mating related to genetic ancestry persists in Latino populations to the current day, and has impacted on the genomic structure in these populations.

  14. Ancestry-related assortative mating in Latino populations

    PubMed Central

    2009-01-01

    Background While spouse correlations have been documented for numerous traits, no prior studies have assessed assortative mating for genetic ancestry in admixed populations. Results Using 104 ancestry informative markers, we examined spouse correlations in genetic ancestry for Mexican spouse pairs recruited from Mexico City and the San Francisco Bay Area, and Puerto Rican spouse pairs recruited from Puerto Rico and New York City. In the Mexican pairs, we found strong spouse correlations for European and Native American ancestry, but no correlation in African ancestry. In the Puerto Rican pairs, we found significant spouse correlations for African ancestry and European ancestry but not Native American ancestry. Correlations were not attributable to variation in socioeconomic status or geographic heterogeneity. Past evidence of spouse correlation was also seen in the strong evidence of linkage disequilibrium between unlinked markers, which was accounted for in regression analysis by ancestral allele frequency difference at the pair of markers (European versus Native American for Mexicans, European versus African for Puerto Ricans). We also observed an excess of homozygosity at individual markers within the spouses, but this provided weaker evidence, as expected, of spouse correlation. Ancestry variance is predicted to decline in each generation, but less so under assortative mating. We used the current observed variances of ancestry to infer even stronger patterns of spouse ancestry correlation in previous generations. Conclusions Assortative mating related to genetic ancestry persists in Latino populations to the current day, and has impacted on the genomic structure in these populations. PMID:19930545

  15. High interpopulation homogeneity in Central Argentina as assessed by Ancestry Informative Markers (AIMs).

    PubMed

    García, Angelina; Dermarchi, Darío A; Tovo-Rodrigues, Luciana; Pauro, Maia; Callegari-Jacques, Sidia M; Salzano, Francisco M; Hutz, Mara H

    2015-01-01

    The population of Argentina has already been studied with regard to several genetic markers, but much more data are needed for the appropriate definition of its genetic profile. This study aimed at investigating the admixture patterns and genetic structure in Central Argentina, using biparental markers and comparing the results with those previously obtained by us with mitochondrial DNA (mtDNA) in the same samples. A total of 521 healthy unrelated individuals living in 13 villages of the Córdoba and San Luis provinces were tested. The individuals were genotyped for ten autosomal ancestry informative markers (AIMs). Allele frequencies were compared with those of African, European and Native American populations, chosen to represent parental contributions. The AIM estimates indicated a greater influence of the Native American ancestry as compared to previous studies in the same or other Argentinean regions, but smaller than that observed with the mtDNA tests. These differences can be explained, respectively, by different genetic contributions between rural and urban areas, and asymmetric gene flow occurred in the past. But a most unexpected finding was the marked interpopulation genetic homogeneity found in villages located in diverse geographic environments across a wide territory, suggesting considerable gene flow.

  16. High interpopulation homogeneity in Central Argentina as assessed by Ancestry Informative Markers (AIMs)

    PubMed Central

    García, Angelina; Dermarchi, Darío A.; Tovo-Rodrigues, Luciana; Pauro, Maia; Callegari-Jacques, Sidia M.; Salzano, Francisco M.; Hutz, Mara H.

    2015-01-01

    The population of Argentina has already been studied with regard to several genetic markers, but much more data are needed for the appropriate definition of its genetic profile. This study aimed at investigating the admixture patterns and genetic structure in Central Argentina, using biparental markers and comparing the results with those previously obtained by us with mitochondrial DNA (mtDNA) in the same samples. A total of 521 healthy unrelated individuals living in 13 villages of the Córdoba and San Luis provinces were tested. The individuals were genotyped for ten autosomal ancestry informative markers (AIMs). Allele frequencies were compared with those of African, European and Native American populations, chosen to represent parental contributions. The AIM estimates indicated a greater influence of the Native American ancestry as compared to previous studies in the same or other Argentinean regions, but smaller than that observed with the mtDNA tests. These differences can be explained, respectively, by different genetic contributions between rural and urban areas, and asymmetric gene flow occurred in the past. But a most unexpected finding was the marked interpopulation genetic homogeneity found in villages located in diverse geographic environments across a wide territory, suggesting considerable gene flow. PMID:26500436

  17. Examination of ancestry and ethnic affiliation using highly informative diallelic DNA markers: application to diverse and admixed populations and implications for clinical epidemiology and forensic medicine.

    PubMed

    Yang, Nan; Li, Hongzhe; Criswell, Lindsey A; Gregersen, Peter K; Alarcon-Riquelme, Marta E; Kittles, Rick; Shigeta, Russell; Silva, Gabriel; Patel, Pragna I; Belmont, John W; Seldin, Michael F

    2005-12-01

    We and others have identified several hundred ancestry informative markers (AIMs) with large allele frequency differences between different major ancestral groups. For this study, a panel of 199 widely distributed AIMs was used to examine a diverse set of 796 DNA samples including self-identified European Americans, West Africans, East Asians, Amerindians, African Americans, Mexicans, Mexican Americans, Puerto Ricans and South Asians. Analysis using a Bayesian clustering algorithm (STRUCTURE) showed grouping of individuals with similar ethnic identity without any identifier other than the AIMs genotyping and showed admixture proportions that clearly distinguished different individuals of mixed ancestry. Additional analyses showed that, for the majority of samples, the predicted ethnic identity corresponded with the self-identified ethnicity at high probability (P > 0.99). Overall, the study demonstrates that AIMs can provide a useful adjunct to forensic medicine, pharmacogenomics and disease studies in which major ancestry or ethnic affiliation might be linked to specific outcomes.

  18. High-altitude ancestry and hypoxia acclimation have distinct effects on exercise capacity and muscle phenotype in deer mice.

    PubMed

    Lui, Mikaela A; Mahalingam, Sajeni; Patel, Paras; Connaty, Alex D; Ivy, Catherine M; Cheviron, Zachary A; Storz, Jay F; McClelland, Grant B; Scott, Graham R

    2015-05-01

    The hypoxic and cold environment at high altitudes requires that small mammals sustain high rates of O2 transport for exercise and thermogenesis while facing a diminished O2 availability. We used laboratory-born and -raised deer mice (Peromyscus maniculatus) from highland and lowland populations to determine the interactive effects of ancestry and hypoxia acclimation on exercise performance. Maximal O₂consumption (V̇o(2max)) during exercise in hypoxia increased after hypoxia acclimation (equivalent to the hypoxia at ∼4,300 m elevation for 6-8 wk) and was consistently greater in highlanders than in lowlanders. V̇o(2max) during exercise in normoxia was not affected by ancestry or acclimation. Highlanders also had consistently greater capillarity, oxidative fiber density, and maximal activities of oxidative enzymes (cytochrome c oxidase and citrate synthase) in the gastrocnemius muscle, lower lactate dehydrogenase activity in the gastrocnemius, and greater cytochrome c oxidase activity in the diaphragm. Hypoxia acclimation did not affect any of these muscle traits. The unique gastrocnemius phenotype of highlanders was associated with higher mRNA and protein abundances of peroxisome proliferator-activated receptor γ (PPARγ). Vascular endothelial growth factor (VEGFA) transcript abundance was lower in highlanders, and hypoxia acclimation reduced the expression of numerous genes that regulate angiogenesis and energy metabolism, in contrast to the observed population differences in muscle phenotype. Lowlanders exhibited greater increases in blood hemoglobin content, hematocrit, and wet lung mass (but not dry lung mass) than highlanders after hypoxia acclimation. Genotypic adaptation to high altitude, therefore, improves exercise performance in hypoxia by mechanisms that are at least partially distinct from those underlying hypoxia acclimation.

  19. High-altitude ancestry and hypoxia acclimation have distinct effects on exercise capacity and muscle phenotype in deer mice

    PubMed Central

    Lui, Mikaela A.; Mahalingam, Sajeni; Patel, Paras; Connaty, Alex D.; Ivy, Catherine M.; Cheviron, Zachary A.; Storz, Jay F.; McClelland, Grant B.

    2015-01-01

    The hypoxic and cold environment at high altitudes requires that small mammals sustain high rates of O2 transport for exercise and thermogenesis while facing a diminished O2 availability. We used laboratory-born and -raised deer mice (Peromyscus maniculatus) from highland and lowland populations to determine the interactive effects of ancestry and hypoxia acclimation on exercise performance. Maximal O2 consumption (V̇o2max) during exercise in hypoxia increased after hypoxia acclimation (equivalent to the hypoxia at ∼4,300 m elevation for 6–8 wk) and was consistently greater in highlanders than in lowlanders. V̇o2max during exercise in normoxia was not affected by ancestry or acclimation. Highlanders also had consistently greater capillarity, oxidative fiber density, and maximal activities of oxidative enzymes (cytochrome c oxidase and citrate synthase) in the gastrocnemius muscle, lower lactate dehydrogenase activity in the gastrocnemius, and greater cytochrome c oxidase activity in the diaphragm. Hypoxia acclimation did not affect any of these muscle traits. The unique gastrocnemius phenotype of highlanders was associated with higher mRNA and protein abundances of peroxisome proliferator-activated receptor γ (PPARγ). Vascular endothelial growth factor (VEGFA) transcript abundance was lower in highlanders, and hypoxia acclimation reduced the expression of numerous genes that regulate angiogenesis and energy metabolism, in contrast to the observed population differences in muscle phenotype. Lowlanders exhibited greater increases in blood hemoglobin content, hematocrit, and wet lung mass (but not dry lung mass) than highlanders after hypoxia acclimation. Genotypic adaptation to high altitude, therefore, improves exercise performance in hypoxia by mechanisms that are at least partially distinct from those underlying hypoxia acclimation. PMID:25695288

  20. African ancestry is associated with risk of asthma and high total serum IgE in a population from the Caribbean Coast of Colombia.

    PubMed

    Vergara, Candelaria; Caraballo, Luis; Mercado, Dilia; Jimenez, Silvia; Rojas, Winston; Rafaels, Nicholas; Hand, Tracey; Campbell, Monica; Tsai, Yuhjung J; Gao, Li; Duque, Constanza; Lopez, Sergio; Bedoya, Gabriel; Ruiz-Linares, Andrés; Barnes, Kathleen C

    2009-06-01

    African descended populations exhibit an increased prevalence of asthma and allergies compared to Europeans. One approach to distinguish between environmental and genetic explanations for this difference is to study relationships of asthma risk to individual admixture. We aimed to determine the admixture proportions of a case-control sample from the Caribbean Coast of Colombia currently participating in genetic studies for asthma, and to test for population stratification and association between African ancestry and asthma and total serum IgE levels (tIgE). We genotyped 368 asthmatics and 365 non-asthmatics for 52 autosomal ancestry informative markers, six mtDNA haplogroups and nine haplogroups and five microsatellites in Y chromosome. Autosomal admixture proportions, population stratification, and associations between ancestry and the phenotypes were estimated by ADMIXMAP. The average admixture proportions among asthmatics were 42.8% European, 39.9% African and 17.2% Native American and among non-asthmatics they were 44.2% (P = 0.068), 37.6% (P = 0.007) and 18.1% (P = 0.050), respectively. In the total sample, the paternal contributions were 71% European, 25% African and 4.0% Native American and the maternal lineages were 56.8% Native American, and 20.2% African; 22.9% of the individuals carried other non-Native American mtDNA haplogroups. African ancestry was significantly associated with asthma (OR: 2.97; 95% CI: 1.08-8.08), high tIgE (OR: 1.9; 95% CI: 1.17-3.12) and socioeconomic status (OR = 0.64; 95% CI: 0.47-0.87). Significant population stratification was observed in this sample. Our findings indicate that genetic factors can explain the association between asthma and African ancestry and suggest that this sample is a useful resource for performing admixture mapping for asthma.

  1. Genetic Ancestry, Serum Interferon-α Activity, and Autoantibodies in Systemic Lupus Erythematosus

    PubMed Central

    Ko, Kichul; Franek, Beverly S.; Marion, Miranda; Kaufman, Kenneth M.; Langefeld, Carl D.; Harley, John B.; Niewold, Timothy B.

    2012-01-01

    Objective To investigate and refine the relationships among systemic lupus erythematosus (SLE) and related autoantibodies, interferon-α (IFN-α), and various ancestral backgrounds. Methods We investigated quantitatively defined genetic ancestry through principal component analysis in place of self-reported ancestry. Results African ancestry was found to be associated with presence of anti-RNP antibody (p = 0.0026), and anti-RNP was correlated with high levels of IFN-α (p = 2.8 × 10−5). Conclusion Our data support a model in which African ancestry increases the likelihood of SLE-associated autoantibody formation, which subsequently results in higher levels of serum IFN-α. PMID:22505704

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

    PubMed

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

    2017-08-01

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

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

    PubMed

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

    2014-12-12

    Criollo-type cacao trees are an important pool of genes with potential to be used in cacao breeding and selection programs. For that reason, we assessed the diversity and population structure of Criollo-type trees (108 cultivars with Criollo phenotypic characteristics and 10 Criollo references) using 12 simple sequence repeat (SSR) markers. Cultivars were selected from 7 demes in the Soconusco region of southern Mexico. SSRs amplified 74 alleles with an average of 3.6 alleles per population. The overall populations showed an average observed heterozygosity of 0.28, indicating heterozygote deficiency (average fixation index F = 0.50). However, moderate allelic diversity was found within populations (Shannon index for all populations I = 0.97). Bayesian method analysis determined 2 genetic clusters (K = 2) within individuals. In concordance, an assignment test grouped 37 multilocus genotypes (including 10 references) into a first cluster (Criollo), 54 into a second (presumably Amelonado), and 27 admixed individuals unassigned at the 90% threshold likely corresponding to the Trinitario genotype. This classification was supported by the principal coordinate analysis and analysis of molecular variance, which showed 12% of variation among populations (FST = 0.123, P < 0.0001). Sampled demes sites (1- 7) in the Soconusco region did not show any evidence of clustering by geographic location, and this was supported by the Mantel test (Rxy = 0.54, P = 0.120). Individuals with high Criollo lineage planted in Soconusco farms could be an important reservoir of genes for future breeding programs searching for fine, taste, flavor, and aroma cocoa.

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

    PubMed Central

    Nielsen, Rasmus

    2017-01-01

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

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

    PubMed Central

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

    2016-01-01

    The Brazilian population is considered to be highly admixed. The main contributing ancestral populations were European and African, with Amerindians contributing to a lesser extent. The aims of this study were to provide a resource for determining and quantifying individual continental ancestry using the smallest number of SNPs possible, thus allowing for a cost- and time-efficient strategy for genomic ancestry determination. We identified and validated a minimum set of 192 ancestry informative markers (AIMs) for the genetic ancestry determination of Brazilian populations. These markers were selected on the basis of their distribution throughout the human genome, and their capacity of being genotyped on widely available commercial platforms. We analyzed genotyping data from 6487 individuals belonging to three Brazilian cohorts. Estimates of individual admixture using this 192 AIM panels were highly correlated with estimates using ~370 000 genome-wide SNPs: 91%, 92%, and 74% of, respectively, African, European, and Native American ancestry components. Besides that, 192 AIMs are well distributed among populations from these ancestral continents, allowing greater freedom in future studies with this panel regarding the choice of reference populations. We also observed that genetic ancestry inferred by AIMs provides similar association results to the one obtained using ancestry inferred by genomic data (370 K SNPs) in a simple regression model with rs1426654, related to skin pigmentation, genotypes as dependent variable. In conclusion, these markers can be used to identify and accurately quantify ancestry of Latin Americans or US Hispanics/Latino individuals, in particular in the context of fine-mapping strategies that require the quantification of continental ancestry in thousands of individuals. PMID:26395555

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

    PubMed

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

    2016-05-01

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

  7. Do Anti-angiogenic or Angiogenic Factors Contribute to the Protection of Birth Weight at High Altitude Afforded by Andean Ancestry?

    PubMed Central

    Dávila, R. Daniela; Julian, Colleen G.; Wilson, Megan J.; Browne, Vaughn A.; Rodriguez, Carmelo; Bigham, Abigail W.; Shriver, Mark D.; Vargas, Enrique; Moore, Lorna G.

    2011-01-01

    Objective This prospective study was designed to determine whether variation in angiogenic (placental growth factor [PlGF]) and/or anti-angiogenic (soluble fms-like tyrosine kinase [sFlt-1]) factors contribute to the protective effect of highland ancestry (Andean) from altitude-associated reductions in fetal growth. Study design Plasma sFlt-1 and PlGF levels, uterine artery (UA) blood flow, and fetal biometry were determined in low-altitude (400 m; Andean n = 27, European n = 28) and high-altitude (3600 m; Andean n = 51, European n = 44) residents during pregnancy (20 and 36 weeks) and 4 months postpartum. Results High-altitude decreased sFlt-1 levels in both groups, Andeans had lower sFlt-1, comparable PlGF, lower sFlt-1/PlGF ratios, and higher UA blood flow throughout pregnancy relative to Europeans. Altitude decreased birth weight in Europeans but not Andeans. In high-altitude Europeans sFlt-1/PlGF and sFlt-1 levels were negatively associated with UA diameter and birth weight, respectively. Conclusions Lower sFlt-1 and sFlt-1/PLGF ratio may contribute to or result from variations in maternal vascular adaptation to pregnancy between Andean and Europeans at high altitude. Subsequently, these effects could potentially influence ancestry-associated differences in birth weight. PMID:20601535

  8. African Ancestry and Its Correlation to Type 2 Diabetes in African Americans: A Genetic Admixture Analysis in Three U.S. Population Cohorts

    PubMed Central

    Cheng, Ching-Yu; Reich, David; Haiman, Christopher A.; Tandon, Arti; Patterson, Nick; Elizabeth, Selvin; Akylbekova, Ermeg L.; Brancati, Frederick L.; Coresh, Josef; Boerwinkle, Eric; Altshuler, David; Taylor, Herman A.; Henderson, Brian E.; Wilson, James G.; Kao, W. H. Linda

    2012-01-01

    The risk of type 2 diabetes is approximately 2-fold higher in African Americans than in European Americans even after adjusting for known environmental risk factors, including socioeconomic status (SES), suggesting that genetic factors may explain some of this population difference in disease risk. However, relatively few genetic studies have examined this hypothesis in a large sample of African Americans with and without diabetes. Therefore, we performed an admixture analysis using 2,189 ancestry-informative markers in 7,021 African Americans (2,373 with type 2 diabetes and 4,648 without) from the Atherosclerosis Risk in Communities Study, the Jackson Heart Study, and the Multiethnic Cohort to 1) determine the association of type 2 diabetes and its related quantitative traits with African ancestry controlling for measures of SES and 2) identify genetic loci for type 2 diabetes through a genome-wide admixture mapping scan. The median percentage of African ancestry of diabetic participants was slightly greater than that of non-diabetic participants (study-adjusted difference = 1.6%, P<0.001). The odds ratio for diabetes comparing participants in the highest vs. lowest tertile of African ancestry was 1.33 (95% confidence interval 1.13–1.55), after adjustment for age, sex, study, body mass index (BMI), and SES. Admixture scans identified two potential loci for diabetes at 12p13.31 (LOD = 4.0) and 13q14.3 (Z score = 4.5, P = 6.6×10−6). In conclusion, genetic ancestry has a significant association with type 2 diabetes above and beyond its association with non-genetic risk factors for type 2 diabetes in African Americans, but no single gene with a major effect is sufficient to explain a large portion of the observed population difference in risk of diabetes. There undoubtedly is a complex interplay among specific genetic loci and non-genetic factors, which may both be associated with overall admixture, leading to the observed ethnic differences in

  9. African ancestry and its correlation to type 2 diabetes in African Americans: a genetic admixture analysis in three U.S. population cohorts.

    PubMed

    Cheng, Ching-Yu; Reich, David; Haiman, Christopher A; Tandon, Arti; Patterson, Nick; Selvin, Elizabeth; Elizabeth, Selvin; Akylbekova, Ermeg L; Brancati, Frederick L; Coresh, Josef; Boerwinkle, Eric; Altshuler, David; Taylor, Herman A; Henderson, Brian E; Wilson, James G; Kao, W H Linda

    2012-01-01

    The risk of type 2 diabetes is approximately 2-fold higher in African Americans than in European Americans even after adjusting for known environmental risk factors, including socioeconomic status (SES), suggesting that genetic factors may explain some of this population difference in disease risk. However, relatively few genetic studies have examined this hypothesis in a large sample of African Americans with and without diabetes. Therefore, we performed an admixture analysis using 2,189 ancestry-informative markers in 7,021 African Americans (2,373 with type 2 diabetes and 4,648 without) from the Atherosclerosis Risk in Communities Study, the Jackson Heart Study, and the Multiethnic Cohort to 1) determine the association of type 2 diabetes and its related quantitative traits with African ancestry controlling for measures of SES and 2) identify genetic loci for type 2 diabetes through a genome-wide admixture mapping scan. The median percentage of African ancestry of diabetic participants was slightly greater than that of non-diabetic participants (study-adjusted difference = 1.6%, P<0.001). The odds ratio for diabetes comparing participants in the highest vs. lowest tertile of African ancestry was 1.33 (95% confidence interval 1.13-1.55), after adjustment for age, sex, study, body mass index (BMI), and SES. Admixture scans identified two potential loci for diabetes at 12p13.31 (LOD = 4.0) and 13q14.3 (Z score = 4.5, P = 6.6 × 10(-6)). In conclusion, genetic ancestry has a significant association with type 2 diabetes above and beyond its association with non-genetic risk factors for type 2 diabetes in African Americans, but no single gene with a major effect is sufficient to explain a large portion of the observed population difference in risk of diabetes. There undoubtedly is a complex interplay among specific genetic loci and non-genetic factors, which may both be associated with overall admixture, leading to the observed ethnic differences in diabetes risk.

  10. Genomics Assisted Ancestry Deconvolution in Grape

    PubMed Central

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

    2013-01-01

    The genus Vitis (the grapevine) is a group of highly diverse, diploid woody perennial vines consisting of approximately 60 species from across the northern hemisphere. It is the world’s most valuable horticultural crop with ~8 million hectares planted, most of which is processed into wine. To gain insights into the use of wild Vitis species during the past century of interspecific grape breeding and to provide a foundation for marker-assisted breeding programmes, we present a principal components analysis (PCA) based ancestry estimation method to calculate admixture proportions of hybrid grapes in the United States Department of Agriculture grape germplasm collection using genome-wide polymorphism data. We find that grape breeders have backcrossed to both the domesticated V. vinifera and wild Vitis species and that reasonably accurate genome-wide ancestry estimation can be performed on interspecific Vitis hybrids using a panel of fewer than 50 ancestry informative markers (AIMs). We compare measures of ancestry informativeness used in selecting SNP panels for two-way admixture estimation, and verify the accuracy of our method on simulated populations of admixed offspring. Our method of ancestry deconvolution provides a first step towards selection at the seed or seedling stage for desirable admixture profiles, which will facilitate marker-assisted breeding that aims to introgress traits from wild Vitis species while retaining the desirable characteristics of elite V. vinifera cultivars. PMID:24244717

  11. Ancestry-environment interactions and asthma risk among Puerto Ricans.

    PubMed

    Choudhry, Shweta; Burchard, Esteban González; Borrell, Luisa N; Tang, Hua; Gomez, Ivan; Naqvi, Mariam; Nazario, Sylvette; Torres, Alphonso; Casal, Jesus; Martinez-Cruzado, Juan Carlos; Ziv, Elad; Avila, Pedro C; Rodriguez-Cintron, William; Risch, Neil J

    2006-11-15

    Puerto Ricans, an admixed population of African, European, and Native American ancestries, have the highest asthma prevalence, morbidity, and mortality rates of any United States' population. Although socioeconomic status (SES) is negatively correlated with asthma incidence in most populations, no such relationship has been identified among Puerto Ricans. We hypothesized that, in this admixed population, the association between SES and asthma may interact with genetic ancestry. We analyzed 135 Puerto Rican subjects with asthma and 156 control subjects recruited from six different recruitment centers in Puerto Rico. Individual ancestry for each subject was estimated using 44 ancestry informative markers. SES was assigned using the census tracts' median family income. Analyses of SES were based on the SES of the clinic site from which the subjects were recruited and on a subset of individuals on whom home address-based SES was available. In the two (independent) analyses, we found a significant interaction between SES, ancestry, and asthma disease status. At lower SES, European ancestry was associated with increased risk of asthma, whereas African ancestry was associated with decreased risk. The opposite was true for their higher SES counterparts. The observed interaction may help to explain the unique pattern of risk for asthma in Puerto Ricans and the lack of association with SES observed in previous studies when not accounting for varying proportions of ancestry.

  12. Cattle ancestry in bison: explanations for higher mtDNA than autosomal ancestry.

    PubMed

    Hedrick, Philip W

    2010-08-01

    Understanding and documenting the process of hybridization and introgression between related species is a major focus of recent evolutionary research using molecular techniques. Many North American bison herds have cattle ancestry introduced by crossbreeding over a century ago. Molecular estimates of this ancestry have shown much higher levels for cattle mtDNA than for autosomal cattle genes. A large part of this difference appears to be the result of partial reproductive isolation between the two species where only bison bull x domestic cow crosses are successful, and all the surviving progeny are females. In addition, selection against autosomal cattle genes in bison may have contributed to differential levels of cattle ancestry. The impact of selection against cattle mtDNA and gene flow of bison mtDNA are examined to explain particular combinations of mtDNA and autosomal cattle ancestry. A bottleneck, after the level of cattle ancestry in bison was reduced to a low level, is consistent with the high variance over autosomal loci observed for cattle ancestry, and differential selection among cattle loci in bison does not need to be invoked. Further examination of the cattle genome in bison may shed light on whether these markers, or their associated regions, are indeed neutral.

  13. European ancestry and polymorphisms in DNA repair genes modify the risk of melanoma: a case-control study in a high UV index region in Brazil.

    PubMed

    Gonçalves, Fernanda T; Francisco, Guilherme; de Souza, Sonia P; Luiz, Olinda C; Festa-Neto, Cyro; Sanches, José A; Chammas, Roger; Gattas, Gilka J F; Eluf-Neto, José

    2011-10-01

    UV radiation is the major environmental factor related to development of cutaneous melanoma. Besides sun exposure and the influence of latitude, some host characteristics such as skin phototype and hair and eye color are also risk factors for melanoma. Polymorphisms in DNA repair genes could be good candidates for susceptibility genes, mainly in geographical regions exposed to high solar radiation. Evaluate the role of host characteristics and DNA repair polymorphism in melanoma risk in Brazil. We carried out a hospital-based case-control study in Brazil to evaluate the contribution of host factors and polymorphisms in DNA repair to melanoma risk. A total of 412 patients (202 with melanoma and 210 controls) were analyzed regarding host characteristics for melanoma risk as well as for 11 polymorphisms in DNA repair genes. We found an association of host characteristics with melanoma development, such as eye and hair color, fair skin, history of pigmented lesions removed, sunburns in childhood and adolescence, and also European ancestry. Regarding DNA repair gene polymorphisms, we found protection for the XPG 1104 His/His genotype (OR 0.32; 95% CI 0.13-0.75), and increased risk for three polymorphisms in the XPC gene (PAT+; IV-6A and 939Gln), which represent a haplotype for XPC. Melanoma risk was higher in individuals carrying the complete XPC haplotype than each individual polymorphism (OR 3.64; 95% CI 1.77-7.48). Our data indicate that the host factors European ancestry and XPC polymorphisms contributed to melanoma risk in a region exposed to high sun radiation. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  14. Characterizing the admixed African ancestry of African Americans.

    PubMed

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

    2009-01-01

    Accurate, high-throughput genotyping allows the fine characterization of genetic ancestry. Here we applied recently developed statistical and computational techniques to the question of African ancestry in African Americans by using data on more than 450,000 single-nucleotide polymorphisms (SNPs) genotyped in 94 Africans of diverse geographic origins included in the HGDP, as well as 136 African Americans and 38 European Americans participating in the Atherosclerotic Disease Vascular Function and Genetic Epidemiology (ADVANCE) study. To focus on African ancestry, we reduced the data to include only those genotypes in each African American determined statistically to be African in origin. From cluster analysis, we found that all the African Americans are admixed in their African components of ancestry, with the majority contributions being from West and West-Central Africa, and only modest variation in these African-ancestry proportions among individuals. Furthermore, by principal components analysis, we found little evidence of genetic structure within the African component of ancestry in African Americans. These results are consistent with historic mating patterns among African Americans that are largely uncorrelated to African ancestral origins, and they cast doubt on the general utility of mtDNA or Y-chromosome markers alone to delineate the full African ancestry of African Americans. Our results also indicate that the genetic architecture of African Americans is distinct from that of Africans, and that the greatest source of potential genetic stratification bias in case-control studies of African Americans derives from the proportion of European ancestry.

  15. Pairing Correlations at High Spins

    NASA Astrophysics Data System (ADS)

    Ma, Hai-Liang; Dong, Bao-Guo; Zhang, Yan; Fan, Ping; Yuan, Da-Qing; Zhu, Shen-Yun; Zhang, Huan-Qiao; Petrache, C. M.; Ragnarsson, I.; Carlsson, B. G.

    The pairing correcting energies at high spins in 161Lu and 138Nd are studied by comparing the results of the cranked-Nilsson-Strutinsky (CNS) and cranked-Nilsson-Strutinsky-Bogoliubov (CNSB) models. It is concluded that the Coriolis effect rather than the rotational alignment effect plays a major role in the reduction of the pairing correlations in the high spin region. Then we proposed an average pairing correction method which not only better reproduces the experimental data comparing with the CNS model but also enables a clean-cut tracing of the configurations thus the full-spin-range discussion on the various rotating bands.

  16. Comparative Analysis of Breast Cancer Phenotypes in African American, White American, and West Versus East African patients: Correlation Between African Ancestry and Triple-Negative Breast Cancer.

    PubMed

    Jiagge, Evelyn; Jibril, Aisha Souleiman; Chitale, Dhananjay; Bensenhaver, Jessica M; Awuah, Baffour; Hoenerhoff, Mark; Adjei, Ernest; Bekele, Mahteme; Abebe, Engida; Nathanson, S David; Gyan, Kofi; Salem, Barbara; Oppong, Joseph; Aitpillah, Francis; Kyei, Ishmael; Bonsu, Ernest Osei; Proctor, Erica; Merajver, Sofia D; Wicha, Max; Stark, Azadeh; Newman, Lisa A

    2016-11-01

    Triple-negative breast cancer (TNBC) is more common among African American (AA) and western sub-Saharan African breast cancer (BC) patients compared with White/Caucasian Americans (WA) and Europeans. Little is known about TNBC in east Africa. Invasive BC diagnosed 1998-2014 were evaluated: WA and AA patients from the Henry Ford Health System in Detroit, Michigan; Ghanaian/west Africans from the Komfo Anokye Teaching Hospital in Kumasi, Ghana; and Ethiopian/east Africans from the St. Paul's Hospital Millennium Medical College in Addis Ababa, Ethiopia. Histopathology and immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), and HER2/neu expression was performed in Michigan on formalin-fixed, paraffin-embedded samples from all cases. A total of 234 Ghanaian (mean age 49 years), 94 Ethiopian (mean age 43 years), 272 AA (mean age 60 years), and 321 WA (mean age 62 years; p = 0.001) patients were compared. ER-negative and TNBC were more common among Ghanaian and AA compared with WA and Ethiopian cases (frequency ER-negativity 71.1 and 37.1 % vs. 19.8 and 28.6 % respectively, p < 0.0001; frequency TNBC 53.2 and 29.8 % vs. 15.5 and 15.0 %, respectively, p < 0.0001). Among patients younger than 50 years, prevalence of TNBC remained highest among Ghanaians (50.8 %) and AA (34.3 %) compared with WA and Ethiopians (approximately 16 % in each; p = 0.0002). This study confirms an association between TNBC and West African ancestry; TNBC frequency among AA patients is intermediate between WA and Ghanaian/West Africans consistent with genetic admixture following the west Africa-based trans-Atlantic slave trade. TNBC frequency was low among Ethiopians/East Africans; this may reflect less shared ancestry between AA and Ethiopians.

  17. African Ancestry Is Associated with Asthma Risk in African Americans

    PubMed Central

    Pino-Yanes, María; Wade, Michael S.; Pérez-Méndez, Lina; Kittles, Rick A.; Wang, Deli; Papaiahgari, Srinivas; Ford, Jean G.; Kumar, Rajesh; Garcia, Joe G. N.

    2012-01-01

    Background Asthma is a common complex condition with clear racial and ethnic differences in both prevalence and severity. Asthma consultation rates, mortality, and severe symptoms are greatly increased in African descent populations of developed countries. African ancestry has been associated with asthma, total serum IgE and lower pulmonary function in African-admixed populations. To replicate previous findings, here we aimed to examine whether African ancestry was associated with asthma susceptibility in African Americans. In addition, we examined for the first time whether African ancestry was associated with asthma exacerbations. Methodology/Principal Findings After filtering for self-reported ancestry and genotype data quality, samples from 1,117 self-reported African-American individuals from New York and Baltimore (394 cases, 481 controls), and Chicago (321 cases followed for asthma exacerbations) were analyzed. Genetic ancestry was estimated based on ancestry informative markers (AIMs) selected for being highly divergent among European and West African populations (95 AIMs for New York and Baltimore, and 66 independent AIMs for Chicago). Among case-control samples, the mean African ancestry was significantly higher in asthmatics than in non-asthmatics (82.0±14.0% vs. 77.8±18.1%, mean difference 4.2% [95% confidence interval (CI):2.0–6.4], p<0.0001). This association remained significant after adjusting for potential confounders (odds ratio: 4.55, 95% CI: 1.69–12.29, p = 0.003). African ancestry failed to show an association with asthma exacerbations (p = 0.965) using a model based on longitudinal data of the number of exacerbations followed over 1.5 years. Conclusions/Significance These data replicate previous findings indicating that African ancestry constitutes a risk factor for asthma and suggest that elevated asthma rates in African Americans can be partially attributed to African genetic ancestry. PMID:22235241

  18. African ancestry is associated with asthma risk in African Americans.

    PubMed

    Flores, Carlos; Ma, Shwu-Fan; Pino-Yanes, María; Wade, Michael S; Pérez-Méndez, Lina; Kittles, Rick A; Wang, Deli; Papaiahgari, Srinivas; Ford, Jean G; Kumar, Rajesh; Garcia, Joe G N

    2012-01-01

    Asthma is a common complex condition with clear racial and ethnic differences in both prevalence and severity. Asthma consultation rates, mortality, and severe symptoms are greatly increased in African descent populations of developed countries. African ancestry has been associated with asthma, total serum IgE and lower pulmonary function in African-admixed populations. To replicate previous findings, here we aimed to examine whether African ancestry was associated with asthma susceptibility in African Americans. In addition, we examined for the first time whether African ancestry was associated with asthma exacerbations. After filtering for self-reported ancestry and genotype data quality, samples from 1,117 self-reported African-American individuals from New York and Baltimore (394 cases, 481 controls), and Chicago (321 cases followed for asthma exacerbations) were analyzed. Genetic ancestry was estimated based on ancestry informative markers (AIMs) selected for being highly divergent among European and West African populations (95 AIMs for New York and Baltimore, and 66 independent AIMs for Chicago). Among case-control samples, the mean African ancestry was significantly higher in asthmatics than in non-asthmatics (82.0±14.0% vs. 77.8±18.1%, mean difference 4.2% [95% confidence interval (CI):2.0-6.4], p<0.0001). This association remained significant after adjusting for potential confounders (odds ratio: 4.55, 95% CI: 1.69-12.29, p = 0.003). African ancestry failed to show an association with asthma exacerbations (p = 0.965) using a model based on longitudinal data of the number of exacerbations followed over 1.5 years. These data replicate previous findings indicating that African ancestry constitutes a risk factor for asthma and suggest that elevated asthma rates in African Americans can be partially attributed to African genetic ancestry.

  19. Exploring iris colour prediction and ancestry inference in admixed populations of South America.

    PubMed

    Freire-Aradas, A; Ruiz, Y; Phillips, C; Maroñas, O; Söchtig, J; Tato, A Gómez; Dios, J Álvarez; de Cal, M Casares; Silbiger, V N; Luchessi, A D; Luchessi, A D; Chiurillo, M A; Carracedo, Á; Lareu, M V

    2014-11-01

    New DNA-based predictive tests for physical characteristics and inference of ancestry are highly informative tools that are being increasingly used in forensic genetic analysis. Two eye colour prediction models: a Bayesian classifier - Snipper and a multinomial logistic regression (MLR) system for the Irisplex assay, have been described for the analysis of unadmixed European populations. Since multiple SNPs in combination contribute in varying degrees to eye colour predictability in Europeans, it is likely that these predictive tests will perform in different ways amongst admixed populations that have European co-ancestry, compared to unadmixed Europeans. In this study we examined 99 individuals from two admixed South American populations comparing eye colour versus ancestry in order to reveal a direct correlation of light eye colour phenotypes with European co-ancestry in admixed individuals. Additionally, eye colour prediction following six prediction models, using varying numbers of SNPs and based on Snipper and MLR, were applied to the study populations. Furthermore, patterns of eye colour prediction have been inferred for a set of publicly available admixed and globally distributed populations from the HGDP-CEPH panel and 1000 Genomes databases with a special emphasis on admixed American populations similar to those of the study samples.

  20. Effect of genetic ancestry on leukocyte global DNA methylation in cancer patients.

    PubMed

    Cappetta, Mónica; Berdasco, María; Hochmann, Jimena; Bonilla, Carolina; Sans, Mónica; Hidalgo, Pedro C; Artagaveytia, Nora; Kittles, Rick; Martínez, Miguel; Esteller, Manel; Bertoni, Bernardo

    2015-05-27

    The study of genetic variants alone is not enough to explain a complex disease like cancer. Alterations in DNA methylation patterns have been associated with different types of tumor. In order to detect markers of susceptibility for the development of cutaneous melanoma and breast cancer in the Uruguayan population, we integrated genetic and epigenetic information of patients and controls. We performed two case-control studies that included 49 individuals with sporadic cutaneous melanoma and 73 unaffected controls, and 179 women with sporadic breast cancer and 209 women controls. We determined the level of global leukocyte DNA methylation using relative quantification of 5mdC by HPLC, and we compared methylation levels between cases and controls with nonparametric statistical tests. Since the Uruguayan population is admixed and both melanoma and breast cancer have very high incidences in Uruguay compared to other populations, we examined whether individual ancestry influences global leucocyte DNA methylation status. We carried out a correlation analysis between the percentage of African, European and Native American individual ancestries, determined using 59 ancestry informative markers, and global DNA methylation in all participants. We detected global DNA hypomethylation in leukocytes of melanoma and breast cancer patients compared with healthy controls (p < 0.001). Additionally, we found a negative correlation between African ancestry and global DNA methylation in cancer patients (p <0.005). These results support the potential use of global DNA methylation as a biomarker for cancer risk. In addition, our findings suggest that the ancestral genome structure generated by the admixture process influences DNA methylation patterns, and underscore the importance of considering genetic ancestry as a modifying factor in epigenetic association studies in admixed populations such as Latino ones.

  1. Cis-Regulatory Variants Affect CHRNA5 mRNA Expression in Populations of African and European Ancestry

    PubMed Central

    Wang, Jen-Chyong; Spiegel, Noah; Bertelsen, Sarah; Le, Nhung; McKenna, Nicholas; Budde, John P.; Harari, Oscar; Kapoor, Manav; Brooks, Andrew; Hancock, Dana; Tischfield, Jay; Foroud, Tatiana; Bierut, Laura J.; Steinbach, Joe Henry; Edenberg, Howard J.; Traynor, Bryan J.; Goate, Alison M.

    2013-01-01

    Variants within the gene cluster encoding α3, α5, and β4 nicotinic receptor subunits are major risk factors for substance dependence. The strongest impact on risk is associated with variation in the CHRNA5 gene, where at least two mechanisms are at work: amino acid variation and altered mRNA expression levels. The risk allele of the non-synonymous variant (rs16969968; D398N) primarily occurs on the haplotype containing the low mRNA expression allele. In populations of European ancestry, there are approximately 50 highly correlated variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster and the adjacent PSMA4 gene region that are associated with CHRNA5 mRNA levels. It is not clear which of these variants contribute to the changes in CHRNA5 transcript level. Because populations of African ancestry have reduced linkage disequilibrium among variants spanning this gene cluster, eQTL mapping in subjects of African ancestry could potentially aid in defining the functional variants that affect CHRNA5 mRNA levels. We performed quantitative allele specific gene expression using frontal cortices derived from 49 subjects of African ancestry and 111 subjects of European ancestry. This method measures allele-specific transcript levels in the same individual, which eliminates other biological variation that occurs when comparing expression levels between different samples. This analysis confirmed that substance dependence associated variants have a direct cis-regulatory effect on CHRNA5 transcript levels in human frontal cortices of African and European ancestry and identified 10 highly correlated variants, located in a 9 kb region, that are potential functional variants modifying CHRNA5 mRNA expression levels. PMID:24303001

  2. Cis-regulatory variants affect CHRNA5 mRNA expression in populations of African and European ancestry.

    PubMed

    Wang, Jen-Chyong; Spiegel, Noah; Bertelsen, Sarah; Le, Nhung; McKenna, Nicholas; Budde, John P; Harari, Oscar; Kapoor, Manav; Brooks, Andrew; Hancock, Dana; Tischfield, Jay; Foroud, Tatiana; Bierut, Laura J; Steinbach, Joe Henry; Edenberg, Howard J; Traynor, Bryan J; Goate, Alison M

    2013-01-01

    Variants within the gene cluster encoding α3, α5, and β4 nicotinic receptor subunits are major risk factors for substance dependence. The strongest impact on risk is associated with variation in the CHRNA5 gene, where at least two mechanisms are at work: amino acid variation and altered mRNA expression levels. The risk allele of the non-synonymous variant (rs16969968; D398N) primarily occurs on the haplotype containing the low mRNA expression allele. In populations of European ancestry, there are approximately 50 highly correlated variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster and the adjacent PSMA4 gene region that are associated with CHRNA5 mRNA levels. It is not clear which of these variants contribute to the changes in CHRNA5 transcript level. Because populations of African ancestry have reduced linkage disequilibrium among variants spanning this gene cluster, eQTL mapping in subjects of African ancestry could potentially aid in defining the functional variants that affect CHRNA5 mRNA levels. We performed quantitative allele specific gene expression using frontal cortices derived from 49 subjects of African ancestry and 111 subjects of European ancestry. This method measures allele-specific transcript levels in the same individual, which eliminates other biological variation that occurs when comparing expression levels between different samples. This analysis confirmed that substance dependence associated variants have a direct cis-regulatory effect on CHRNA5 transcript levels in human frontal cortices of African and European ancestry and identified 10 highly correlated variants, located in a 9 kb region, that are potential functional variants modifying CHRNA5 mRNA expression levels.

  3. African Ancestry and Lung Function in Puerto Rican Children

    PubMed Central

    Brehm, John M.; Acosta-Pérez, Edna; Klei, Lambertus; Roeder, Kathryn; Barmada, Michael; Boutaoui, Nadia; Forno, Erick; Cloutier, Michelle; Datta, Soma; Kelly, Roxanne; Paul, Kathryn; Sylvia, Jody; Calvert, Deanna; Thornton-Thompson, Sherell; Wakefield, Dorothy; Litonjua, Augusto A.; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C.

    2012-01-01

    Background Puerto Ricans and African Americans share a significant proportion of African ancestry. Recent findings suggest that African ancestry influences lung function in African American adults. Objective To examine whether a greater proportion of African ancestry is associated with lower FEV1 and FVC in Puerto Rican children, independently of socioeconomic status (SES), healthcare access or key environmental/lifestyle (EL) factors. Methods Cross-sectional case-control study of 943 Puerto Rican children ages 6 to 14 years with (n=520) and without (n=423) asthma (defined as physician-diagnosed asthma and wheeze in the prior year) living in Hartford (CT, n=383) and San Juan (PR, n=560). We estimated the percentage of African racial ancestry in study participants using genome-wide genotypic data. We tested whether African ancestry is associated with FEV1 and FVC using linear regression. Multivariate models were adjusted for indicators of SES and healthcare, and selected EL exposures. Results After adjustment for household income and other covariates, each 20% increment in African ancestry was significantly associated with lower pre-bronchodilator(BD) FEV1 (−105 ml, 95% confidence interval [CI] = −159 ml to −51 ml, P <0.001) and FVC (−133 ml, 95% CI −197 ml to −69 ml, P <0.001), and post-BD FEV1 (−152 ml, 95% CI=−210 ml to −94 ml, P <0.001) and FVC (−145 ml, 95% CI= −211 to −79 ml, P <0.001) in children with asthma. Similar but weaker associations were found for pre- and post-BD FEV1 (change for each 20% increment in African ancestry= −78 ml, 95% CI= −131 to −25 ml, P=0.004), and for post-BD FVC among children without asthma. Conclusions Genetic and/or EL factors correlated with African ancestry may influence childhood lung function in Puerto Ricans. PMID:22560959

  4. Biogeographical ancestry and race.

    PubMed

    Gannett, Lisa

    2014-09-01

    The use of racial and ethnic categories in biological and biomedical research is controversial-for example, in the comparison of disease risk in different groups or as a means of making use of or controlling for population structure in the mapping of genes to chromosomes. Biogeographical ancestry (BGA) has been recommended as a more accurate and appropriate category. BGA is a product of the collaboration between biological anthropologist Mark Shriver from Pennsylvania State University and molecular biologist Tony Frudakis from the now-defunct biotechnology start-up company DNAPrint genomics, Inc. Shriver and Frudakis portray BGA as a measure of the 'biological', 'genetic', 'natural', and 'objective' components of race and ethnicity, what philosophers of science would call a natural kind. This paper argues that BGA is not a natural kind that escapes social and political connotations of race and ethnicity, as Shriver and Frudakis and other proponents believe, but a construction that is built upon race-as race has been socially constructed in the European scientific and philosophical traditions. More specifically, BGA is not a global category of biological and anthropological classification but a local category shaped by the U.S. context of its production, especially the forensic aim of being able to predict the race or ethnicity of an unknown suspect based on DNA found at the crime scene. Therefore, caution needs to be exercised in the embrace of BGA as an alternative to the use of racial and ethnic categories in biological and biomedical research.

  5. Discerning the Ancestry of European Americans in Genetic Association Studies

    PubMed Central

    Price, Alkes L; Butler, Johannah; Patterson, Nick; Capelli, Cristian; Pascali, Vincenzo L; Scarnicci, Francesca; Ruiz-Linares, Andres; Groop, Leif; Saetta, Angelica A; Korkolopoulou, Penelope; Seligsohn, Uri; Waliszewska, Alicja; Schirmer, Christine; Ardlie, Kristin; Ramos, Alexis; Nemesh, James; Arbeitman, Lori; Goldstein, David B

    2008-01-01

    European Americans are often treated as a homogeneous group, but in fact form a structured population due to historical immigration of diverse source populations. Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false-positive or false-negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries. Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European, and Ashkenazi Jewish ancestry are the main sources of European American population structure. Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries. We demonstrate that this panel of markers can be used to correct for stratification in association studies that do not generate dense genotype data. PMID:18208327

  6. Maternal oxygen delivery is not related to altitude- and ancestry-associated differences in human fetal growth

    PubMed Central

    Zamudio, Stacy; Postigo, Lucrecia; Illsley, Nicholas P; Rodriguez, Carmelo; Heredia, Gladys; Brimacombe, Michael; Echalar, Lourdes; Torricos, Tatiana; Tellez, Wilma; Maldonado, Ivan; Balanza, Elfride; Alvarez, Tatiana; Ameller, Julio; Vargas, Enrique

    2007-01-01

    Fetal growth is reduced at high altitude, but the decrease is less among long-resident populations. We hypothesized that greater maternal uteroplacental O2 delivery would explain increased fetal growth in Andean natives versus European migrants to high altitude. O2 delivery was measured with ultrasound, Doppler and haematological techniques. Participants (n= 180) were pregnant women of self-professed European or Andean ancestry living at 3600 m or 400 m in Bolivia. Ancestry was quantified using ancestry-informative single nucleotide polymorphims. The altitude-associated decrement in birth weight was 418 g in European versus 236 g in Andean women (P < 0.005). Altitude was associated with decreased uterine artery diameter, volumetric blood flow and O2 delivery regardless of ancestry. But the hypothesis was rejected as O2 delivery was similar between ancestry groups at their respective altitudes of residence. Instead, Andean neonates were larger and heavier per unit of O2 delivery, regardless of altitude (P < 0.001). European admixture among Andeans was negatively correlated with birth weight at both altitudes (P < 0.01), but admixture was not related to any of the O2 transport variables. Genetically mediated differences in maternal O2 delivery are thus unlikely to explain the Andean advantage in fetal growth. Of the other independent variables, only placental weight and gestational age explained significant variation in birth weight. Thus greater placental efficiency in O2 and nutrient transport, and/or greater fetal efficiency in substrate utilization may contribute to ancestry- and altitude-related differences in fetal growth. Uterine artery O2 delivery in these pregnancies was 99 ± 3 ml min−1, ∼5-fold greater than near-term fetal O2 consumption. Deficits in maternal O2 transport in third trimester normal pregnancy are unlikely to be causally associated with variation in fetal growth. PMID:17510190

  7. Ancestry, Temporality, and Potentiality

    PubMed Central

    Gibbon, Sahra

    2014-01-01

    In this paper I examine the variety of ways potential is articulated, entailed, and produced in how the field of cancer genetics is being constituted as a domain of transnational research and an emerging site of health-care intervention in southern Brazil. Drawing on analysis of fieldwork in Brazilian cancer-genetics clinics, I explore how different expressions of potential come to inform dynamically the pursuit of prevention, care, and research as diversely scaled investments for those working and living with cancer-genetics knowledge and technologies. It illustrates how specific temporalities help to constitute and “abductively” frame the meaning of these different potentials particularly as this relates to a focus on ancestry. Colonial histories of migration, the embodied effects of dietary habits, or the moral failings of near and distant ancestors as well as promissory futures and the contingency of lived lives become at different times templates for identifying, materializing, and transforming how the potential of cancer genetics in Brazil is articulated. Potential is also expressed through an idiom of “choice” in different efforts to situate participation in cancer-genetics research as prevention or to negotiate access to basic public health. I explore how these expressions of cancer genetics as potential powerfully yet unevenly work to sustain knowledge practices as well as propel patients and their families into fledgling domains of clinical practice and scientific research. At the same time there is always an “excess of meaning” in these endeavors that make visible lines of fracture and disjuncture in collective efforts to make future histories of and from the pursuit of cancer genetics in southern Brazil. PMID:25018561

  8. Structural reconstruction of protein ancestry.

    PubMed

    Rouet, Romain; Langley, David B; Schofield, Peter; Christie, Mary; Roome, Brendan; Porebski, Benjamin T; Buckle, Ashley M; Clifton, Ben E; Jackson, Colin J; Stock, Daniela; Christ, Daniel

    2017-03-29

    Ancestral protein reconstruction allows the resurrection and characterization of ancient proteins based on computational analyses of sequences of modern-day proteins. Unfortunately, many protein families are highly divergent and not suitable for sequence-based reconstruction approaches. This limitation is exemplified by the antigen receptors of jawed vertebrates (B- and T-cell receptors), heterodimers formed by pairs of Ig domains. These receptors are believed to have evolved from an extinct homodimeric ancestor through a process of gene duplication and diversification; however molecular evidence has so far remained elusive. Here, we use a structural approach and laboratory evolution to reconstruct such molecules and characterize their interaction with antigen. High-resolution crystal structures of reconstructed homodimeric receptors in complex with hen-egg white lysozyme demonstrate how nanomolar affinity binding of asymmetrical antigen is enabled through selective recruitment and structural plasticity within the receptor-binding site. Our results provide structural evidence in support of long-held theories concerning the evolution of antigen receptors, and provide a blueprint for the experimental reconstruction of protein ancestry in the absence of phylogenetic evidence.

  9. Characterizing the admixed African ancestry of African Americans

    PubMed Central

    2009-01-01

    Background Accurate, high-throughput genotyping allows the fine characterization of genetic ancestry. Here we applied recently developed statistical and computational techniques to the question of African ancestry in African Americans by using data on more than 450,000 single-nucleotide polymorphisms (SNPs) genotyped in 94 Africans of diverse geographic origins included in the HGDP, as well as 136 African Americans and 38 European Americans participating in the Atherosclerotic Disease Vascular Function and Genetic Epidemiology (ADVANCE) study. To focus on African ancestry, we reduced the data to include only those genotypes in each African American determined statistically to be African in origin. Results From cluster analysis, we found that all the African Americans are admixed in their African components of ancestry, with the majority contributions being from West and West-Central Africa, and only modest variation in these African-ancestry proportions among individuals. Furthermore, by principal components analysis, we found little evidence of genetic structure within the African component of ancestry in African Americans. Conclusions These results are consistent with historic mating patterns among African Americans that are largely uncorrelated to African ancestral origins, and they cast doubt on the general utility of mtDNA or Y-chromosome markers alone to delineate the full African ancestry of African Americans. Our results also indicate that the genetic architecture of African Americans is distinct from that of Africans, and that the greatest source of potential genetic stratification bias in case-control studies of African Americans derives from the proportion of European ancestry. PMID:20025784

  10. Straightforward Inference of Ancestry and Admixture Proportions through Ancestry-Informative Insertion Deletion Multiplexing

    PubMed Central

    Pereira, Rui; Phillips, Christopher; Pinto, Nádia; Santos, Carla; dos Santos, Sidney Emanuel Batista; Amorim, António; Carracedo, Ángel; Gusmão, Leonor

    2012-01-01

    Ancestry-informative markers (AIMs) show high allele frequency divergence between different ancestral or geographically distant populations. These genetic markers are especially useful in inferring the likely ancestral origin of an individual or estimating the apportionment of ancestry components in admixed individuals or populations. The study of AIMs is of great interest in clinical genetics research, particularly to detect and correct for population substructure effects in case-control association studies, but also in population and forensic genetics studies. This work presents a set of 46 ancestry-informative insertion deletion polymorphisms selected to efficiently measure population admixture proportions of four different origins (African, European, East Asian and Native American). All markers are analyzed in short fragments (under 230 basepairs) through a single PCR followed by capillary electrophoresis (CE) allowing a very simple one tube PCR-to-CE approach. HGDP-CEPH diversity panel samples from the four groups, together with Oceanians, were genotyped to evaluate the efficiency of the assay in clustering populations from different continental origins and to establish reference databases. In addition, other populations from diverse geographic origins were tested using the HGDP-CEPH samples as reference data. The results revealed that the AIM-INDEL set developed is highly efficient at inferring the ancestry of individuals and provides good estimates of ancestry proportions at the population level. In conclusion, we have optimized the multiplexed genotyping of 46 AIM-INDELs in a simple and informative assay, enabling a more straightforward alternative to the commonly available AIM-SNP typing methods dependent on complex, multi-step protocols or implementation of large-scale genotyping technologies. PMID:22272242

  11. Straightforward inference of ancestry and admixture proportions through ancestry-informative insertion deletion multiplexing.

    PubMed

    Pereira, Rui; Phillips, Christopher; Pinto, Nádia; Santos, Carla; dos Santos, Sidney Emanuel Batista; Amorim, António; Carracedo, Ángel; Gusmão, Leonor

    2012-01-01

    Ancestry-informative markers (AIMs) show high allele frequency divergence between different ancestral or geographically distant populations. These genetic markers are especially useful in inferring the likely ancestral origin of an individual or estimating the apportionment of ancestry components in admixed individuals or populations. The study of AIMs is of great interest in clinical genetics research, particularly to detect and correct for population substructure effects in case-control association studies, but also in population and forensic genetics studies. This work presents a set of 46 ancestry-informative insertion deletion polymorphisms selected to efficiently measure population admixture proportions of four different origins (African, European, East Asian and Native American). All markers are analyzed in short fragments (under 230 basepairs) through a single PCR followed by capillary electrophoresis (CE) allowing a very simple one tube PCR-to-CE approach. HGDP-CEPH diversity panel samples from the four groups, together with Oceanians, were genotyped to evaluate the efficiency of the assay in clustering populations from different continental origins and to establish reference databases. In addition, other populations from diverse geographic origins were tested using the HGDP-CEPH samples as reference data. The results revealed that the AIM-INDEL set developed is highly efficient at inferring the ancestry of individuals and provides good estimates of ancestry proportions at the population level. In conclusion, we have optimized the multiplexed genotyping of 46 AIM-INDELs in a simple and informative assay, enabling a more straightforward alternative to the commonly available AIM-SNP typing methods dependent on complex, multi-step protocols or implementation of large-scale genotyping technologies.

  12. Attitudes on DNA ancestry tests.

    PubMed

    Wagner, Jennifer K; Weiss, Kenneth M

    2012-01-01

    The DNA ancestry testing industry is more than a decade old, yet details about it remain a mystery: there remain no reliable, empirical data on the number, motivations, and attitudes of customers to date, the number of products available and their characteristics, or the industry customs and standard practices that have emerged in the absence of specific governmental regulations. Here, we provide preliminary data collected in 2009 through indirect and direct participant observation, namely blog post analysis, generalized survey analysis, and targeted survey analysis. The attitudes include the first available data on attitudes of those of individuals who have and have not had their own DNA ancestry tested as well as individuals who are members of DNA ancestry-related social networking groups. In a new and fluid landscape, the results highlight the need for empirical data to guide policy discussions and should be interpreted collectively as an invitation for additional investigation of (1) the opinions of individuals purchasing these tests, individuals obtaining these tests through research participation, and individuals not obtaining these tests; (2) the psychosocial and behavioral reactions of individuals obtaining their DNA ancestry information with attention given both to expectations prior to testing and the sociotechnical architecture of the test used; and (3) the applications of DNA ancestry information in varying contexts.

  13. Genetic heterogeneity of self-reported ancestry groups in an admixed Brazilian population.

    PubMed

    Lins, Tulio C; Vieira, Rodrigo G; Abreu, Breno S; Gentil, Paulo; Moreno-Lima, Ricardo; Oliveira, Ricardo J; Pereira, Rinaldo W

    2011-01-01

    Population stratification is the main source of spurious results and poor reproducibility in genetic association findings. Population heterogeneity can be controlled for by grouping individuals in ethnic clusters; however, in admixed populations, there is evidence that such proxies do not provide efficient stratification control. The aim of this study was to evaluate the relation of self-reported with genetic ancestry and the statistical risk of grouping an admixed sample based on self-reported ancestry. A questionnaire that included an item on self-reported ancestry was completed by 189 female volunteers from an admixed Brazilian population. Individual genetic ancestry was then determined by genotyping ancestry informative markers. Self-reported ancestry was classified as white, intermediate, and black. The mean difference among self-reported groups was significant for European and African, but not Amerindian, genetic ancestry. Pairwise fixation index analysis revealed a significant difference among groups. However, the increase in the chance of type 1 error was estimated to be 14%. Self-reporting of ancestry was not an appropriate methodology to cluster groups in a Brazilian population, due to high variance at the individual level. Ancestry informative markers are more useful for quantitative measurement of biological ancestry.

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

    PubMed

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

    2017-04-04

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

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

    PubMed

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

    2014-09-01

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

  16. Ethnic characterization of a population of children exposed to high doses of arsenic via drinking water and a possible correlation with metabolic processes.

    PubMed

    Bobillo, Cecilia; Navoni, Julio A; Olmos, Valentina; Merini, Luciano J; Villaamil Lepori, Edda; Corach, Daniel

    2014-01-01

    Because the ratio between the two major arsenic metabolites is related to the adverse health effects of arsenic, numerous studies have been performed to establish a relationship between the ability to metabolically detoxify arsenic and other variables, including exposure level, gender, age and ethnicity. Because ethnicity may play a key role and provide relevant information for heterogeneous populations, we characterized a group of 70 children from rural schools in the Argentinean provinces of Chaco and Santiago del Estero who were exposed to high levels of arsenic. We used genetic markers for maternal, paternal and bi-parental ancestry to achieve this goal. Our results demonstrate that the Amerindian maternal linages are present in 100% of the samples, whereas the Amerindian component transmitted through the paternal line is less than 10%. Informative markers for autosomal ancestry show a predominantly European ancestry, in which 37% of the samples contained between 90 and 99% European ancestry. The native American component ranged from 50 to 80% in 15.7% of the samples, and in all but four samples, the African component was less than 10%. Correlation analysis demonstrated that the ethnicity and the ratio of the excreted arsenic metabolites monomethyl arsenic and dimethyl arsenic are not associated, dismissing a relationship between ethnic origin and differential metabolism.

  17. Ethnic characterization of a population of children exposed to high doses of arsenic via drinking water and a possible correlation with metabolic processes

    PubMed Central

    Bobillo, Cecilia; Navoni, Julio A; Olmos, Valentina; Merini, Luciano J; Villaamil Lepori, Edda; Corach, Daniel

    2014-01-01

    Because the ratio between the two major arsenic metabolites is related to the adverse health effects of arsenic, numerous studies have been performed to establish a relationship between the ability to metabolically detoxify arsenic and other variables, including exposure level, gender, age and ethnicity. Because ethnicity may play a key role and provide relevant information for heterogeneous populations, we characterized a group of 70 children from rural schools in the Argentinean provinces of Chaco and Santiago del Estero who were exposed to high levels of arsenic. We used genetic markers for maternal, paternal and bi-parental ancestry to achieve this goal. Our results demonstrate that the Amerindian maternal linages are present in 100% of the samples, whereas the Amerindian component transmitted through the paternal line is less than 10%. Informative markers for autosomal ancestry show a predominantly European ancestry, in which 37% of the samples contained between 90 and 99% European ancestry. The native American component ranged from 50 to 80% in 15.7% of the samples, and in all but four samples, the African component was less than 10%. Correlation analysis demonstrated that the ethnicity and the ratio of the excreted arsenic metabolites monomethyl arsenic and dimethyl arsenic are not associated, dismissing a relationship between ethnic origin and differential metabolism. PMID:24596592

  18. What Is Genetic Ancestry Testing?

    MedlinePlus

    ... from one provider to another. Also, because most human populations have migrated many times throughout their history and ... used by scientists to explore the history of populations as they arose, migrated, and mixed with ... American Society of Human Genetics (ASHG) developed a position paper on ancestry ...

  19. Evidence for common ancestry among viruses isolated from wild birds in Beringia and highly pathogenic intercontinental reassortant H5N1 and H5N2 influenza A viruses

    USGS Publications Warehouse

    Ramey, Andy M.; Reeves, Andrew; Teslaa, Joshua L.; Nashold, Sean W.; Donnelly, Tyrone F.; Bahl, Justin; Hall, Jeffrey S.

    2016-01-01

    Highly pathogenic clade 2.3.4.4 H5N8, H5N2, and H5N1 influenza A viruses were first detected in wild, captive, and domestic birds in North America in November–December 2014. In this study, we used wild waterbird samples collected in Alaska prior to the initial detection of clade 2.3.4.4 H5 influenza A viruses in North America to assess the evidence for: (1) dispersal of highly pathogenic influenza A viruses from East Asia to North America by migratory birds via Alaska and (2) ancestral origins of clade 2.3.4.4 H5 reassortant viruses in Beringia. Although we did not detect highly pathogenic influenza A viruses in our sample collection from western Alaska, we did identify viruses that contained gene segments sharing recent common ancestry with intercontinental reassortant H5N2 and H5N1 viruses. Results of phylogenetic analyses and estimates for times of most recent common ancestry support migratory birds sampled in Beringia as maintaining viral diversity closely related to novel highly pathogenic influenza A virus genotypes detected in North America. Although our results do not elucidate the route by which highly pathogenic influenza A viruses were introduced into North America, genetic evidence is consistent with the hypothesized trans-Beringian route of introduction via migratory birds.

  20. Evidence for common ancestry among viruses isolated from wild birds in Beringia and highly pathogenic intercontinental reassortant H5N1 and H5N2 influenza A viruses.

    PubMed

    Ramey, Andrew M; Reeves, Andrew B; TeSlaa, Joshua L; Nashold, Sean; Donnelly, Tyrone; Bahl, Justin; Hall, Jeffrey S

    2016-06-01

    Highly pathogenic clade 2.3.4.4 H5N8, H5N2, and H5N1 influenza A viruses were first detected in wild, captive, and domestic birds in North America in November-December 2014. In this study, we used wild waterbird samples collected in Alaska prior to the initial detection of clade 2.3.4.4 H5 influenza A viruses in North America to assess the evidence for: (1) dispersal of highly pathogenic influenza A viruses from East Asia to North America by migratory birds via Alaska and (2) ancestral origins of clade 2.3.4.4 H5 reassortant viruses in Beringia. Although we did not detect highly pathogenic influenza A viruses in our sample collection from western Alaska, we did identify viruses that contained gene segments sharing recent common ancestry with intercontinental reassortant H5N2 and H5N1 viruses. Results of phylogenetic analyses and estimates for times of most recent common ancestry support migratory birds sampled in Beringia as maintaining viral diversity closely related to novel highly pathogenic influenza A virus genotypes detected in North America. Although our results do not elucidate the route by which highly pathogenic influenza A viruses were introduced into North America, genetic evidence is consistent with the hypothesized trans-Beringian route of introduction via migratory birds. Published by Elsevier B.V.

  1. Blood vitamin d levels in relation to genetic estimation of African ancestry.

    PubMed

    Signorello, Lisa B; Williams, Scott M; Zheng, Wei; Smith, Jeffrey R; Long, Jirong; Cai, Qiuyin; Hargreaves, Margaret K; Hollis, Bruce W; Blot, William J

    2010-09-01

    African-Americans generally have lower circulating levels of 25 hydroxyvitamin D [25(OH)D] than Whites, attributed to skin pigmentation and dietary habits. Little is known about the genetic determinants of 25(OH)D levels nor whether the degree of African ancestry associates with circulating 25(OH)D. With the use of a panel of 276 ancestry informative genetic markers, we estimated African and European admixture for a sample of 758 African-American and non-Hispanic White Southern Community Cohort Study participants. For African-Americans, cut points of <85%, 85% to 95%, and >or=95% defined low, medium, and high African ancestry, respectively. We estimated the association between African ancestry and 25(OH)D and also explored whether vitamin D exposure (sunlight, diet) had varying effects on 25(OH)D levels dependent on ancestry level. The mean serum 25(OH)D levels among Whites and among African-Americans of low, medium, and high African ancestry were 27.2, 19.5, 18.3, and 16.5 ng/mL, respectively. Serum 25(OH)D was estimated to decrease by 1.0 to 1.1 ng/mL per 10% increase in African ancestry. The effect of high vitamin D exposure from sunlight and diet was 46% lower among African-Americans with high African ancestry than among those with low/medium ancestry. We found novel evidence that the level of African ancestry may play a role in clinical vitamin D status. This is the first study to describe how 25(OH)D levels vary in relation to genetic estimation of African ancestry. Further study is warranted to replicate these findings and uncover the potential pathways involved. (c)2010 AACR.

  2. The landscape of Neandertal ancestry in present-day humans

    PubMed Central

    Sankararaman, Sriram; Mallick, Swapan; Dannemann, Michael; Prüfer, Kay; Kelso, Janet; Pääbo, Svante; Patterson, Nick; Reich, David

    2014-01-01

    Analyses of Neandertal genomes have revealed that Neandertals have contributed genetic variants to modern humans1–2. The antiquity of Neandertal gene flow into modern humans means that regions that derive from Neandertals in any one human today are usually less than a hundred kilobases in size. However, Neandertal haplotypes are also distinctive enough that several studies have been able to detect Neandertal ancestry at specific loci1,3–8. Here, we have systematically inferred Neandertal haplotypes in the genomes of 1,004 present-day humans12. Regions that harbor a high frequency of Neandertal alleles in modern humans are enriched for genes affecting keratin filaments suggesting that Neandertal alleles may have helped modern humans adapt to non-African environments. Neandertal alleles also continue to shape human biology, as we identify multiple Neandertal-derived alleles that confer risk for disease. We also identify regions of millions of base pairs that are nearly devoid of Neandertal ancestry and enriched in genes, implying selection to remove genetic material derived from Neandertals. Neandertal ancestry is significantly reduced in genes specifically expressed in testis, and there is an approximately 5-fold reduction of Neandertal ancestry on chromosome X, which is known to harbor a disproportionate fraction of male hybrid sterility genes20–22. These results suggest that part of the reduction in Neandertal ancestry near genes is due to Neandertal alleles that reduced fertility in males when moved to a modern human genetic background. PMID:24476815

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

    PubMed

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

    2017-01-01

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

  4. The role of ancestry in TB susceptibility of an admixed South African population.

    PubMed

    Daya, Michelle; van der Merwe, Lize; van Helden, Paul D; Möller, Marlo; Hoal, Eileen G

    2014-07-01

    Genetic susceptibility to tuberculosis (TB) has been well established and this, taken together with variation in susceptibility observed between different geographic and ethnic populations, implies that susceptibility to TB may in part be affected by ethnicity. In a previous genome-wide TB case-control study (642 cases and 91 controls) of the admixed South African Coloured (SAC) population, we found a positive correlation between African San ancestry and TB susceptibility, and negative correlations with European and Asian ancestries. Since genome-wide data was available for only a small number of controls in the previous study, we endeavored to validate this finding by genotyping a panel of ancestry informative markers (AIMs) in additional individuals, yielding a data set of 918 cases and 507 controls. Ancestry proportions were estimated using the AIMs for each of the source populations of the SAC (African San, African non-San, European, South Asian and East Asian). Using logistic regression models to test for association between TB and ancestry, we confirmed the substantial effect of ancestry on TB susceptibility. We also investigated the effect of adjusting for ancestry in candidate gene TB association studies of the SAC. We report a polymorphism that is no longer significantly associated with TB after adjustment for ancestry, a polymorphism that is significantly associated with TB only after adjustment for ancestry, and a polymorphism where the association significance remains unchanged. By comparing the allele frequencies of these polymorphisms in the source populations of the SAC, we demonstrate that association results are likely to be affected by adjustment for ancestry if allele frequencies differ markedly in the source populations of the SAC.

  5. Inferring Genetic Ancestry: Opportunities, Challenges, and Implications

    PubMed Central

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

    2010-01-01

    Increasing public interest in direct-to-consumer (DTC) genetic ancestry testing has been accompanied by growing concern about issues ranging from the personal and societal implications of the testing to the scientific validity of ancestry inference. The very concept of “ancestry” is subject to misunderstanding in both the general and scientific communities. What do we mean by ancestry? How exactly is ancestry measured? How far back can such ancestry be defined and by which genetic tools? How do we validate inferences about ancestry in genetic research? What are the data that demonstrate our ability to do this correctly? What can we say and what can we not say from our research findings and the test results that we generate? This white paper from the American Society of Human Genetics (ASHG) Ancestry and Ancestry Testing Task Force builds upon the 2008 ASHG Ancestry Testing Summary Statement in providing a more in-depth analysis of key scientific and non-scientific aspects of genetic ancestry inference in academia and industry. It culminates with recommendations for advancing the current debate and facilitating the development of scientifically based, ethically sound, and socially attentive guidelines concerning the use of these continually evolving technologies. PMID:20466090

  6. Angular correlations and high energy evolution

    SciTech Connect

    Kovner, Alex; Lublinsky, Michael

    2011-11-01

    We address the question of to what extent JIMWLK evolution is capable of taking into account angular correlations in a high energy hadronic wave function. Our conclusion is that angular (and indeed other) correlations in the wave function cannot be reliably calculated without taking into account Pomeron loops in the evolution. As an example we study numerically the energy evolution of angular correlations between dipole scattering amplitudes in the framework of the large N{sub c} approximation to JIMWLK evolution (the 'projectile dipole model'). Target correlations are introduced via averaging over an (isotropic) ensemble of anisotropic initial conditions. We find that correlations disappear very quickly with rapidity even inside the saturation radius. This is in accordance with our physical picture of JIMWLK evolution. The actual correlations inside the saturation radius in the target QCD wave function, on the other hand, should remain sizable at any rapidity.

  7. African ancestry and lung function in Puerto Rican children.

    PubMed

    Brehm, John M; Acosta-Pérez, Edna; Klei, Lambertus; Roeder, Kathryn; Barmada, Michael M; Boutaoui, Nadia; Forno, Erick; Cloutier, Michelle M; Datta, Soma; Kelly, Roxanne; Paul, Kathryn; Sylvia, Jody; Calvert, Deanna; Thornton-Thompson, Sherell; Wakefield, Dorothy; Litonjua, Augusto A; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C

    2012-06-01

    Puerto Rican and African American subjects share a significant proportion of African ancestry. Recent findings suggest that African ancestry influences lung function in African American adults. We sought to examine whether a greater proportion of African ancestry is associated with lower FEV(1) and forced vital capacity (FVC) in Puerto Rican children independently of socioeconomic status, health care access, or key environmental/lifestyle factors. We performed a cross-sectional case-control study of 943 Puerto Rican children aged 6 to 14 years with (n= 520) and without (n= 423) asthma (defined as physician-diagnosed asthma and wheeze in the prior year) living in Hartford, Connecticut (n= 383), and San Juan, Puerto Rico (n= 560). We estimated the percentage of African racial ancestry in study participants using genome-wide genotypic data. We tested whether African ancestry is associated with FEV(1) and FVC using linear regression. Multivariate models were adjusted for indicators of socioeconomic status and health care and selected environmental/lifestyle exposures. After adjustment for household income and other covariates, each 20% increment in African ancestry was significantly associated with lower prebronchodilator FEV(1) (-105 mL; 95% CI, -159 to -51 mL; P< .001) and FVC (-133 mL; 95% CI, -197 to -69 mL; P< .001) and postbronchodilator FEV(1) (-152 mL; 95% CI, -210 to -94 mL; P< .001) and FVC (-145 mL; 95% CI, -211 to -79 mL; P< .001) in children with asthma. Similar but weaker associations were found for prebronchodilator and postbronchodilator FEV(1) (change for each 20% increment in African ancestry, -78 mL; 95% CI, -131 to -25 mL; P= .004) and for postbronchodilator FVC among children without asthma. Genetic factors, environmental/lifestyle factors, or both correlated with African ancestry might influence childhood lung function in Puerto Rican subjects. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights

  8. Uniparental ancestry markers in Chilean populations

    PubMed Central

    Vieira-Machado, Camilla Dutra; Tostes, Maluah; Alves, Gabrielle; Nazer, Julio; Martinez, Liliana; Wettig, Elisabeth; Pizarro Rivadeneira, Oscar; Diaz Caamaño, Marcela; Larenas Ascui, Jessica; Pavez, Pedro; Dutra, Maria da Graça; Castilla, Eduardo Enrique; Orioli, Ieda Maria

    2016-01-01

    Abstract The presence of Native Americans, Europeans, and Africans has led to the development of a multi-ethnic, admixed population in Chile. This study aimed to contribute to the characterization of the uniparental genetic structure of three Chilean regions. Newborns from seven hospitals in Independencia, Providencia, Santiago, Curicó, Cauquenes, Valdívia, and Puerto Montt communes, belonging to the Chilean regions of Santiago, Maule, and Los Lagos, were studied. The presence of Native American mitochondrial DNA (mtDNA) haplogroups and two markers present in the non-recombinant region of the Y chromosome, DYS199 and DYS287, indicative of Native American and African ancestry, respectively, was determined. A high Native American matrilineal contribution and a low Native American and African patrilineal contributions were found in all three studied regions. As previously found in Chilean admixed populations, the Native American matrilineal contribution was lower in Santiago than in the other studied regions. However, there was an unexpectedly higher contribution of Native American ancestry in one of the studied communes in Santiago, probably due to the high rate of immigration from other regions of the country. The population genetic sub-structure we detected in Santiago using few uniparental markers requires further confirmation, owing to possible stratification for autosomal and X-chromosome markers. PMID:27561109

  9. HGDP and HapMap Analysis by Ancestry Mapper Reveals Local and Global Population Relationships

    PubMed Central

    Magalhães, Tiago R.; Casey, Jillian P.; Conroy, Judith; Regan, Regina; Fitzpatrick, Darren J.; Shah, Naisha; Sobral, João; Ennis, Sean

    2012-01-01

    Knowledge of human origins, migrations, and expansions is greatly enhanced by the availability of large datasets of genetic information from different populations and by the development of bioinformatic tools used to analyze the data. We present Ancestry Mapper, which we believe improves on existing methods, for the assignment of genetic ancestry to an individual and to study the relationships between local and global populations. The principle function of the method, named Ancestry Mapper, is to give each individual analyzed a genetic identifier, made up of just 51 genetic coordinates, that corresponds to its relationship to the HGDP reference population. As a consequence, the Ancestry Mapper Id (AMid) has intrinsic biological meaning and provides a tool to measure similarity between world populations. We applied Ancestry Mapper to a dataset comprised of the HGDP and HapMap data. The results show distinctions at the continental level, while simultaneously giving details at the population level. We clustered AMids of HGDP/HapMap and observe a recapitulation of human migrations: for a small number of clusters, individuals are grouped according to continental origins; for a larger number of clusters, regional and population distinctions are evident. Calculating distances between AMids allows us to infer ancestry. The number of coordinates is expandable, increasing the power of Ancestry Mapper. An R package called Ancestry Mapper is available to apply this method to any high density genomic data set. PMID:23189146

  10. HGDP and HapMap analysis by Ancestry Mapper reveals local and global population relationships.

    PubMed

    Magalhães, Tiago R; Casey, Jillian P; Conroy, Judith; Regan, Regina; Fitzpatrick, Darren J; Shah, Naisha; Sobral, João; Ennis, Sean

    2012-01-01

    Knowledge of human origins, migrations, and expansions is greatly enhanced by the availability of large datasets of genetic information from different populations and by the development of bioinformatic tools used to analyze the data. We present Ancestry Mapper, which we believe improves on existing methods, for the assignment of genetic ancestry to an individual and to study the relationships between local and global populations. The principle function of the method, named Ancestry Mapper, is to give each individual analyzed a genetic identifier, made up of just 51 genetic coordinates, that corresponds to its relationship to the HGDP reference population. As a consequence, the Ancestry Mapper Id (AMid) has intrinsic biological meaning and provides a tool to measure similarity between world populations. We applied Ancestry Mapper to a dataset comprised of the HGDP and HapMap data. The results show distinctions at the continental level, while simultaneously giving details at the population level. We clustered AMids of HGDP/HapMap and observe a recapitulation of human migrations: for a small number of clusters, individuals are grouped according to continental origins; for a larger number of clusters, regional and population distinctions are evident. Calculating distances between AMids allows us to infer ancestry. The number of coordinates is expandable, increasing the power of Ancestry Mapper. An R package called Ancestry Mapper is available to apply this method to any high density genomic data set.

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

    PubMed

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

    2015-11-01

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

  12. Pairing correlations in high-spin isomers

    SciTech Connect

    Odahara, A.; Gono, Y.; Fukuchi, T.; Wakabayashi, Y.; Sagawa, H.; Satula, W.; Nazarewicz, W.

    2005-12-15

    High-spin isomers with J{sup {pi}}=49/2{sup +} and 27{sup +} have been systematically observed in a number of N=83 isotones with 60{<=}Z{<=}67 at excitation energies {approx}9 MeV. Based on experimental excitation energies, an odd-even binding energy staggering has been extracted for the first time for these multi-quasiparticle states. Surprisingly, the magnitude of the odd-even effect in high-spin isomers turned out to be very close to that in ground states, thus challenging conventional wisdom that pairing correlations are reduced in highly excited states. Theoretical analysis based on mean-field theory explains the observed proton number dependence of the odd-even effect as a manifestation of strong pairing correlations in the highly excited states. Mean-field effects and the proton-neutron residual interaction on the odd-even staggering are also examined.

  13. Explicit modeling of ancestry improves polygenic risk scores and BLUP prediction

    PubMed Central

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

    2016-01-01

    Polygenic prediction using genome-wide SNPs can provide high prediction accuracy for complex traits. Here, we investigate the question of how to account for genetic ancestry when conducting polygenic prediction. We show that the accuracy of polygenic prediction in structured populations may be partly due to genetic ancestry. However, we hypothesized that explicitly modeling ancestry could improve polygenic prediction accuracy. We analyzed three GWAS of hair color, tanning ability and basal cell carcinoma (BCC) in European Americans (sample size from 7,440 to 9,822) and considered two widely used polygenic prediction approaches: polygenic risk scores (PRS) and Best Linear Unbiased Prediction (BLUP). We compared polygenic prediction without correction for ancestry to polygenic prediction with ancestry as a separate component in the model. In 10-fold cross-validation using the PRS approach, the R2 for hair color increased by 66% (0.0456 to 0.0755; p<10−16), the R2 for tanning ability increased by 123% (0.0154 to 0.0344; p<10−16) and the liability-scale R2 for BCC increased by 68% (0.0138 to 0.0232; p<10−16) when explicitly modeling ancestry, which prevents ancestry effects from entering into each SNP effect and being over-weighted. Surprisingly, explicitly modeling ancestry produces a similar improvement when using the BLUP approach, which fits all SNPs simultaneously in a single variance component and causes ancestry to be underweighted. We validate our findings via simulations, which show that the differences in prediction accuracy will increase in magnitude as sample sizes increase. In summary, our results show that explicitly modeling ancestry can be important in both PRS and BLUP prediction. PMID:25995153

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

    PubMed Central

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

    2015-01-01

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

  15. Improved ancestry estimation for both genotyping and sequencing data using projection procrustes analysis and genotype imputation.

    PubMed

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

    2015-06-04

    Accurate estimation of individual ancestry is important in genetic association studies, especially when a large number of samples are collected from multiple sources. However, existing approaches developed for genome-wide SNP data do not work well with modest amounts of genetic data, such as in targeted sequencing or exome chip genotyping experiments. We propose a statistical framework to estimate individual ancestry in a principal component ancestry map generated by a reference set of individuals. This framework extends and improves upon our previous method for estimating ancestry using low-coverage sequence reads (LASER 1.0) to analyze either genotyping or sequencing data. In particular, we introduce a projection Procrustes analysis approach that uses high-dimensional principal components to estimate ancestry in a low-dimensional reference space. Using extensive simulations and empirical data examples, we show that our new method (LASER 2.0), combined with genotype imputation on the reference individuals, can substantially outperform LASER 1.0 in estimating fine-scale genetic ancestry. Specifically, LASER 2.0 can accurately estimate fine-scale ancestry within Europe using either exome chip genotypes or targeted sequencing data with off-target coverage as low as 0.05×. Under the framework of LASER 2.0, we can estimate individual ancestry in a shared reference space for samples assayed at different loci or by different techniques. Therefore, our ancestry estimation method will accelerate discovery in disease association studies not only by helping model ancestry within individual studies but also by facilitating combined analysis of genetic data from multiple sources. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. Higher percent body fat in young women with lower physical activity level and greater proportion Pacific Islander ancestry.

    PubMed

    Black, Nate; Nabokov, Vanessa; Vijayadeva, Vinutha; Novotny, Rachel

    2011-11-01

    Samoan women exhibit high rates of obesity, which can possibly be attenuated through diet and physical activity. Obesity, and body fatness in particular, is associated with increased risk for chronic diseases. Ancestry, physical activity, and dietary patterns have been associated with body composition. Using a cross-sectional design, the relative importance of proportion of Pacific Islander (PI) ancestry, level of physical activity, and macronutrients among healthy women in Honolulu, Hawai'i, ages 18 to 28 years was examined. All data were collected between January 2003 and December 2004. Percent body fat (%BF) was determined by whole body dual energy x-ray absorptiometry (DXA). Nutrient data were derived from a three-day food record. Means and standard deviations were computed for all variables of interest. Bivariate correlation analysis was used to determine correlates of %BF. Multiple regression analysis was used to determine relative contribution of variables significantly associated with %BF. Proportion of PI ancestry was significantly positively associated with %BF (P=0.0001). Physical activity level was significantly negatively associated with %BF (P=0.0006). Intervention to increase physical activity level of young Samoan women may be effective to decrease body fat and improve health. CRC-NIH grant: 0216.

  17. Higher Percent Body Fat in Young Women with Lower Physical Activity Level and Greater Proportion Pacific Islander Ancestry

    PubMed Central

    Nabokov, Vanessa; Vijayadeva, Vinutha; Novotny, Rachel

    2011-01-01

    Samoan women exhibit high rates of obesity, which can possibly be attenuated through diet and physical activity. Obesity, and body fatness in particular, is associated with increased risk for chronic diseases. Ancestry, physical activity, and dietary patterns have been associated with body composition. Using a cross-sectional design, the relative importance of proportion of Pacific Islander (PI) ancestry, level of physical activity, and macronutrients among healthy women in Honolulu, Hawai‘i, ages 18 to 28 years was examined. All data were collected between January 2003 and December 2004. Percent body fat (%BF) was determined by whole body dual energy x-ray absorptiometry (DXA). Nutrient data were derived from a three-day food record. Means and standard deviations were computed for all variables of interest. Bivariate correlation analysis was used to determine correlates of %BF. Multiple regression analysis was used to determine relative contribution of variables significantly associated with %BF. Proportion of PI ancestry was significantly positively associated with %BF (P=0.0001). Physical activity level was significantly negatively associated with %BF (P=0.0006). Intervention to increase physical activity level of young Samoan women may be effective to decrease body fat and improve health. CRC-NIH grant: 0216. PMID:22235159

  18. LAIT: a local ancestry inference toolkit.

    PubMed

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

    2017-09-06

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

  19. Population genetics models of local ancestry.

    PubMed

    Gravel, Simon

    2012-06-01

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

  20. Population genetic inference from personal genome data: impact of ancestry and admixture on human genomic variation.

    PubMed

    Kidd, Jeffrey M; Gravel, Simon; Byrnes, Jake; Moreno-Estrada, Andres; Musharoff, Shaila; Bryc, Katarzyna; Degenhardt, Jeremiah D; Brisbin, Abra; Sheth, Vrunda; Chen, Rong; McLaughlin, Stephen F; Peckham, Heather E; Omberg, Larsson; Bormann Chung, Christina A; Stanley, Sarah; Pearlstein, Kevin; Levandowsky, Elizabeth; Acevedo-Acevedo, Suehelay; Auton, Adam; Keinan, Alon; Acuña-Alonzo, Victor; Barquera-Lozano, Rodrigo; Canizales-Quinteros, Samuel; Eng, Celeste; Burchard, Esteban G; Russell, Archie; Reynolds, Andy; Clark, Andrew G; Reese, Martin G; Lincoln, Stephen E; Butte, Atul J; De La Vega, Francisco M; Bustamante, Carlos D

    2012-10-05

    Full sequencing of individual human genomes has greatly expanded our understanding of human genetic variation and population history. Here, we present a systematic analysis of 50 human genomes from 11 diverse global populations sequenced at high coverage. Our sample includes 12 individuals who have admixed ancestry and who have varying degrees of recent (within the last 500 years) African, Native American, and European ancestry. We found over 21 million single-nucleotide variants that contribute to a 1.75-fold range in nucleotide heterozygosity across diverse human genomes. This heterozygosity ranged from a high of one heterozygous site per kilobase in west African genomes to a low of 0.57 heterozygous sites per kilobase in segments inferred to have diploid Native American ancestry from the genomes of Mexican and Puerto Rican individuals. We show evidence of all three continental ancestries in the genomes of Mexican, Puerto Rican, and African American populations, and the genome-wide statistics are highly consistent across individuals from a population once ancestry proportions have been accounted for. Using a generalized linear model, we identified subtle variations across populations in the proportion of neutral versus deleterious variation and found that genome-wide statistics vary in admixed populations even once ancestry proportions have been factored in. We further infer that multiple periods of gene flow shaped the diversity of admixed populations in the Americas-70% of the European ancestry in today's African Americans dates back to European gene flow happening only 7-8 generations ago.

  1. Population Genetic Inference from Personal Genome Data: Impact of Ancestry and Admixture on Human Genomic Variation

    PubMed Central

    Kidd, Jeffrey M.; Gravel, Simon; Byrnes, Jake; Moreno-Estrada, Andres; Musharoff, Shaila; Bryc, Katarzyna; Degenhardt, Jeremiah D.; Brisbin, Abra; Sheth, Vrunda; Chen, Rong; McLaughlin, Stephen F.; Peckham, Heather E.; Omberg, Larsson; Bormann Chung, Christina A.; Stanley, Sarah; Pearlstein, Kevin; Levandowsky, Elizabeth; Acevedo-Acevedo, Suehelay; Auton, Adam; Keinan, Alon; Acuña-Alonzo, Victor; Barquera-Lozano, Rodrigo; Canizales-Quinteros, Samuel; Eng, Celeste; Burchard, Esteban G.; Russell, Archie; Reynolds, Andy; Clark, Andrew G.; Reese, Martin G.; Lincoln, Stephen E.; Butte, Atul J.; De La Vega, Francisco M.; Bustamante, Carlos D.

    2012-01-01

    Full sequencing of individual human genomes has greatly expanded our understanding of human genetic variation and population history. Here, we present a systematic analysis of 50 human genomes from 11 diverse global populations sequenced at high coverage. Our sample includes 12 individuals who have admixed ancestry and who have varying degrees of recent (within the last 500 years) African, Native American, and European ancestry. We found over 21 million single-nucleotide variants that contribute to a 1.75-fold range in nucleotide heterozygosity across diverse human genomes. This heterozygosity ranged from a high of one heterozygous site per kilobase in west African genomes to a low of 0.57 heterozygous sites per kilobase in segments inferred to have diploid Native American ancestry from the genomes of Mexican and Puerto Rican individuals. We show evidence of all three continental ancestries in the genomes of Mexican, Puerto Rican, and African American populations, and the genome-wide statistics are highly consistent across individuals from a population once ancestry proportions have been accounted for. Using a generalized linear model, we identified subtle variations across populations in the proportion of neutral versus deleterious variation and found that genome-wide statistics vary in admixed populations even once ancestry proportions have been factored in. We further infer that multiple periods of gene flow shaped the diversity of admixed populations in the Americas—70% of the European ancestry in today’s African Americans dates back to European gene flow happening only 7–8 generations ago. PMID:23040495

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

    PubMed Central

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

    2016-01-01

    Objective The aim of this study is to assess the association between genetic ancestry, self-declared race and haemodynamic parameters in patients with chronic heart failure (HF). Methods Observational, cross-sectional study. Eligible participants were aged between 18 and 80 years; ejection fraction was ≤50%. Patients underwent genetic analysis of ancestry informative markers, echocardiography and impedance cardiography (ICG). Race was determined by self-classification into two groups: white and non-white. Genomic ancestry was estimated using a panel of 101 348 polymorphic markers and three continental reference populations (European, African and Native American). Results Our study included 362 patients with HF between August 2012 and August 2014. 123 patients with HF declared themselves as white and 234 patients declared themselves as non-white. No statistically significant differences were found regarding the ICG parameters according to self-declared race. The Amerindian ancestry was positively correlated with systolic time ratio (r=0.109, p<0.05). The thoracic fluid content index (r=0.124. p<0.05), E wave peak (r=0.127. p<0.05) and E/e′ ratio (r=0.197. p<0.01) were correlated positively with African ancestry. In multiple linear regression, African ancestry remained associated with the E/e′ ratio, even after adjustment to risk factors. Conclusions The African genetic ancestry was associated with worse parameters of diastolic function; the Amerindian ancestry correlated with a worse pattern of ventricular contractility, while self-declared colour was not helpful to infer haemodynamic profiles in HF. Trials registration number NTC02043431. PMID:27547430

  3. Association of serum lipid components and obesity with genetic ancestry in an admixed population of elderly women

    PubMed Central

    Lins, Tulio C.; Pires, Alause S.; Paula, Roberta S.; Moraes, Clayton F.; Vieira, Rodrigo G.; Vianna, Lucy G.; Nobrega, Otávio T.; Pereira, Rinaldo W.

    2012-01-01

    The prevalence of metabolic disorders varies among ethnic populations and these disorders represent a critical health care issue for elderly women. This study investigated the correlation between genetic ancestry and body composition, metabolic traits and clinical status in a sample of elderly women. Clinical, nutritional and anthropometric data were collected from 176 volunteers. Genetic ancestry was estimated using 23 ancestry-informative markers. Pearsons correlation test was used to examine the relationship between continuous variables and an independent samples t-test was used to compare the means of continuous traits within categorical variables. Overall ancestry was a combination of European (57.49%), Native American (25.78%) and African (16.73%). Significant correlations were found for European ancestry with body mass index (r = 0.165; p = 0.037) and obesity (mean difference (MD) = 5.3%; p = 0.042). African ancestry showed a significant correlation with LDL (r = 0.159, p = 0.035), VLDL (r = −0.185; p = 0.014), hypertriglyceridemia (MD = 6.4%; p = 0.003) and hyperlipidemia (MD = 4.8%; p = 0.026). Amerindian ancestry showed a significant correlation with triglyceride levels (r = 0.150; p = 0.047) and hypertriglyceridemia (MD = 4.5%; p = 0.039). These findings suggest that genetic admixture may influence the etiology of lipid metabolism-related diseases and obesity in elderly women. PMID:23055794

  4. Inference of biogeographical ancestry across central regions of Eurasia.

    PubMed

    Bulbul, O; Filoglu, G; Zorlu, T; Altuncul, H; Freire-Aradas, A; Söchtig, J; Ruiz, Y; Klintschar, M; Triki-Fendri, S; Rebai, A; Phillips, C; Lareu, M V; Carracedo, Á; Schneider, P M

    2016-01-01

    The inference of biogeographical ancestry (BGA) can provide useful information for forensic investigators when there are no suspects to be compared with DNA collected at the crime scene or when no DNA database matches exist. Although public databases are increasing in size and population scope, there is a lack of information regarding genetic variation in Eurasian populations, especially in central regions such as the Middle East. Inhabitants of these regions show a high degree of genetic admixture, characterized by an allele frequency cline running from NW Europe to East Asia. Although a proper differentiation has been established between the cline extremes of western Europe and South Asia, populations geographically located in between, i.e, Middle East and Mediterranean populations, require more detailed study in order to characterize their genetic background as well as to further understand their demographic histories. To initiate these studies, three ancestry informative SNP (AI-SNP) multiplex panels: the SNPforID 34-plex, Eurasiaplex and a novel 33-plex assay were used to describe the ancestry patterns of a total of 24 populations ranging across the longitudinal axis from NW Europe to East Asia. Different ancestry inference approaches, including STRUCTURE, PCA, DAPC and Snipper Bayes analysis, were applied to determine relationships among populations. The structure results show differentiation between continental groups and a NW to SE allele frequency cline running across Eurasian populations. This study adds useful population data that could be used as reference genotypes for future ancestry investigations in forensic cases. The 33-plex assay also includes pigmentation predictive SNPs, but this study primarily focused on Eurasian population differentiation using 33-plex and its combination with the other two AI-SNP sets.

  5. Dissecting the Within-Africa Ancestry of Populations of African Descent in the Americas

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2011-01-06

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

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

    PubMed Central

    Colangelo, Laura A.; Williams, L. Keoki; Sen, Saunak; Kritchevsky, Stephen B.; Meibohm, Bernd; Galanter, Joshua; Hu, Donglei; Gignoux, Christopher R.; Liu, Yongmei; Harris, Tamara B.; Ziv, Elad; Zmuda, Joseph; Garcia, Melissa; Leak, Tennille S.; Foreman, Marilyn G.; Smith, Lewis J.; Fornage, Myriam; Liu, Kiang; Burchard, Esteban G.

    2012-01-01

    Background Smoking tobacco reduces lung function. African Americans have both lower lung function and decreased metabolism of tobacco smoke compared to European Americans. African ancestry is also associated with lower pulmonary function in African Americans. We aimed to determine whether African ancestry modifies the association between smoking and lung function and its rate of decline in African Americans. Methodology/Principal Findings We evaluated a prospective ongoing cohort of 1,281 African Americans participating in the Health, Aging, and Body Composition (Health ABC) Study initiated in 1997. We also examined an ongoing prospective cohort initiated in 1985 of 1,223 African Americans in the Coronary Artery Disease in Young Adults (CARDIA) Study. Pulmonary function and tobacco smoking exposure were measured at baseline and repeatedly over the follow-up period. Individual genetic ancestry proportions were estimated using ancestry informative markers selected to distinguish European and West African ancestry. African Americans with a high proportion of African ancestry had lower baseline forced expiratory volume in one second (FEV1) per pack-year of smoking (−5.7 ml FEV1/ smoking pack-year) compared with smokers with lower African ancestry (−4.6 ml in FEV1/ smoking pack-year) (interaction P value  = 0.17). Longitudinal analyses revealed a suggestive interaction between smoking, and African ancestry on the rate of FEV1 decline in Health ABC and independently replicated in CARDIA. Conclusions/Significance African American individuals with a high proportion of African ancestry are at greater risk for losing lung function while smoking. PMID:22737244

  8. Genetic Ancestry in Lung-Function Predictions

    PubMed Central

    Kumar, Rajesh; Seibold, Max A.; Aldrich, Melinda C.; Williams, L. Keoki; Reiner, Alex P.; Colangelo, Laura; Galanter, Joshua; Gignoux, Christopher; Hu, Donglei; Sen, Saunak; Choudhry, Shweta; Peterson, Edward L.; Rodriguez-Santana, Jose; Rodriguez-Cintron, William; Nalls, Michael A.; Leak, Tennille S.; O’Meara, Ellen; Meibohm, Bernd; Kritchevsky, Stephen B.; Li, Rongling; Harris, Tamara B.; Nickerson, Deborah A.; Fornage, Myriam; Enright, Paul; Ziv, Elad; Smith, Lewis J.; Liu, Kiang; Burchard, Esteban González

    2010-01-01

    BACKGROUND Self-identified race or ethnic group is used to determine normal reference standards in the prediction of pulmonary function. We conducted a study to determine whether the genetically determined percentage of African ancestry is associated with lung function and whether its use could improve predictions of lung function among persons who identified themselves as African American. METHODS We assessed the ancestry of 777 participants self-identified as African American in the Coronary Artery Risk Development in Young Adults (CARDIA) study and evaluated the relation between pulmonary function and ancestry by means of linear regression. We performed similar analyses of data for two independent cohorts of subjects identifying themselves as African American: 813 participants in the Health, Aging, and Body Composition (HABC) study and 579 participants in the Cardiovascular Health Study (CHS). We compared the fit of two types of models to lung-function measurements: models based on the covariates used in standard prediction equations and models incorporating ancestry. We also evaluated the effect of the ancestry-based models on the classification of disease severity in two asthma-study populations. RESULTS African ancestry was inversely related to forced expiratory volume in 1 second (FEV1) and forced vital capacity in the CARDIA cohort. These relations were also seen in the HABC and CHS cohorts. In predicting lung function, the ancestry-based model fit the data better than standard models. Ancestry-based models resulted in the reclassification of asthma severity (based on the percentage of the predicted FEV1) in 4 to 5% of participants. CONCLUSIONS Current predictive equations, which rely on self-identified race alone, may misestimate lung function among subjects who identify themselves as African American. Incorporating ancestry into normative equations may improve lung-function estimates and more accurately categorize disease severity. (Funded by the National

  9. Impact of ancestry and common genetic variants on QT interval in African Americans.

    PubMed

    Smith, J Gustav; Avery, Christy L; Evans, Daniel S; Nalls, Michael A; Meng, Yan A; Smith, Erin N; Palmer, Cameron; Tanaka, Toshiko; Mehra, Reena; Butler, Anne M; Young, Taylor; Buxbaum, Sarah G; Kerr, Kathleen F; Berenson, Gerald S; Schnabel, Renate B; Li, Guo; Ellinor, Patrick T; Magnani, Jared W; Chen, Wei; Bis, Joshua C; Curb, J David; Hsueh, Wen-Chi; Rotter, Jerome I; Liu, Yongmei; Newman, Anne B; Limacher, Marian C; North, Kari E; Reiner, Alexander P; Quibrera, P Miguel; Schork, Nicholas J; Singleton, Andrew B; Psaty, Bruce M; Soliman, Elsayed Z; Solomon, Allen J; Srinivasan, Sathanur R; Alonso, Alvaro; Wallace, Robert; Redline, Susan; Zhang, Zhu-Ming; Post, Wendy S; Zonderman, Alan B; Taylor, Herman A; Murray, Sarah S; Ferrucci, Luigi; Arking, Dan E; Evans, Michele K; Fox, Ervin R; Sotoodehnia, Nona; Heckbert, Susan R; Whitsel, Eric A; Newton-Cheh, Christopher

    2012-12-01

    Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval. First, individual estimates of African and European ancestry were inferred from genome-wide single-nucleotide polymorphism (SNP) data in 7 population-based cohorts of African Americans (n=12,097) and regressed on measured QT interval from ECGs. Second, imputation was performed for 2.8 million SNPs, and a genome-wide association study of QT interval was performed in 10 cohorts (n=13,105). There was no evidence of association between genetic ancestry and QT interval (P=0.94). Genome-wide significant associations (P<2.5 × 10(-8)) were identified with SNPs at 2 loci, upstream of the genes NOS1AP (rs12143842, P=2 × 10(-15)) and ATP1B1 (rs1320976, P=2 × 10(-10)). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low probability values (P<10(-5)) were observed for SNPs at several other loci previously identified in genome-wide association studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF, and PLN. We observed no difference in duration of cardiac repolarization with global genetic indices of African American ancestry. In addition, our genome-wide association study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include individuals of African ancestry.

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

    PubMed

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

    2016-10-17

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

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

    PubMed

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

    2017-01-01

    Hispanic/Latino populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. The molecular profile of breast cancer has been widely described in non-Hispanic Whites but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian women was Luminal B as defined by St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. We found 5 genes potentially modulated by genetic ancestry: ERBB2 (log2FC = 2.367, padj<0.01), GRB7 (log2FC = 2.327, padj<0.01), GSDMB (log2FC = 1.723, padj<0.01, MIEN1 (log2FC = 2.195, padj<0.01 and ONECUT2 (log2FC = 2.204, padj<0.01). In the replication set we found a statistical significant association between ERBB2 expression with Indigenous American ancestry (p = 0.02, B = 3.11). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value.

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

    PubMed Central

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

    2017-01-01

    Background Hispanic/Latino populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. The molecular profile of breast cancer has been widely described in non-Hispanic Whites but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian women was Luminal B as defined by St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. Methods We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. Results We found 5 genes potentially modulated by genetic ancestry: ERBB2 (log2FC = 2.367, padj<0.01), GRB7 (log2FC = 2.327, padj<0.01), GSDMB (log2FC = 1.723, padj<0.01, MIEN1 (log2FC = 2.195, padj<0.01 and ONECUT2 (log2FC = 2.204, padj<0.01). In the replication set we found a statistical significant association between ERBB2 expression with Indigenous American ancestry (p = 0.02, B = 3.11). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. Conclusions Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value. PMID:28832682

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

    PubMed

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

    2017-09-06

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

  14. Diffraction Correlation to Reconstruct Highly Strained Particles

    NASA Astrophysics Data System (ADS)

    Brown, Douglas; Harder, Ross; Clark, Jesse; Kim, J. W.; Kiefer, Boris; Fullerton, Eric; Shpyrko, Oleg; Fohtung, Edwin

    2015-03-01

    Through the use of coherent x-ray diffraction a three-dimensional diffraction pattern of a highly strained nano-crystal can be recorded in reciprocal space by a detector. Only the intensities are recorded, resulting in a loss of the complex phase. The recorded diffraction pattern therefore requires computational processing to reconstruct the density and complex distribution of the diffracted nano-crystal. For highly strained crystals, standard methods using HIO and ER algorithms are no longer sufficient to reconstruct the diffraction pattern. Our solution is to correlate the symmetry in reciprocal space to generate an a priori shape constraint to guide the computational reconstruction of the diffraction pattern. This approach has improved the ability to accurately reconstruct highly strained nano-crystals.

  15. Disorder and Transport in Highly Correlated Systems

    DTIC Science & Technology

    1992-03-31

    Denr Dow. Vlease find included 1th100 copies of the Annu at [rport for my Grant NOOO 14- 1 j- 14󈧪, entitled " Disorder and Transport in I licility...of N ava1l Research for your support. 1Ian K. Sch~ilter Fnclosures Appr~I ~ir k~ll~ereleae;\\ t)Is~i I gm~U itedl ONR GRANT N00014-91J-1438 " Disorder ...001 i92-11805 ’ Introduction This grant was a new start dedicated to studies of disorder and transport in highly correlated electron systems, mostly

  16. Amerindian genetic ancestry protects against Alzheimer's disease.

    PubMed

    Benedet, Andrea L; Moraes, Clayton F; Camargos, Einstein F; Oliveira, Larissa F; Souza, Vinícius C; Lins, Túlio C; Henriques, Adriane D; Carmo, Dayanne G S; Machado-Silva, Wilcelly; Araújo, Carla Nunes; Córdova, Cláudio; Pereira, Rinaldo W; Nóbrega, Otávio T

    2012-01-01

    Alzheimer's disease (AD) is the most common form of dementia worldwide, and bears remarkable evidence for a differential prevalence among continental populations. In this scenario, estimating ancestry proportions in recently admixed populations is a strategy that can help increasing knowledge about the genetic structure of this complex trait. Our purpose was to assess mean ancestry estimates for the three main parental contributors to the Brazilian contingent (European, African and Amerindian) using a panel of 12 ancestry informative markers. Outpatients with the late-onset form of AD (n = 120) were compared for ancestry levels with non-cognitively impaired subjects (n = 412) in the Midwest Brazil, controlling for classic clinical, social and anthropometric risk factors. Our findings show a 3-fold greater genetic Amerindian content among control subjects compared to AD patients (p < 0.001). Our results suggest that the allelic architecture of Native Americans can confer protection against the onset of the disease. Copyright © 2012 S. Karger AG, Basel.

  17. Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry

    PubMed Central

    Kessler, Michael D.; Yerges-Armstrong, Laura; Taub, Margaret A.; Shetty, Amol C.; Maloney, Kristin; Jeng, Linda Jo Bone; Ruczinski, Ingo; Levin, Albert M.; Williams, L. Keoki; Beaty, Terri H.; Mathias, Rasika A.; Barnes, Kathleen C.; Boorgula, Meher Preethi; Campbell, Monica; Chavan, Sameer; Ford, Jean G.; Foster, Cassandra; Gao, Li; Hansel, Nadia N.; Horowitz, Edward; Huang, Lili; Ortiz, Romina; Potee, Joseph; Rafaels, Nicholas; Scott, Alan F.; Vergara, Candelaria; Gao, Jingjing; Hu, Yijuan; Johnston, Henry Richard; Qin, Zhaohui S.; Padhukasahasram, Badri; Dunston, Georgia M.; Faruque, Mezbah U.; Kenny, Eimear E.; Gietzen, Kimberly; Hansen, Mark; Genuario, Rob; Bullis, Dave; Lawley, Cindy; Deshpande, Aniket; Grus, Wendy E.; Locke, Devin P.; Foreman, Marilyn G.; Avila, Pedro C.; Grammer, Leslie; Kim, Kwang-YounA; Kumar, Rajesh; Schleimer, Robert; Bustamante, Carlos; De La Vega, Francisco M.; Gignoux, Chris R.; Shringarpure, Suyash S.; Musharoff, Shaila; Wojcik, Genevieve; Burchard, Esteban G.; Eng, Celeste; Gourraud, Pierre-Antoine; Hernandez, Ryan D.; Lizee, Antoine; Pino-Yanes, Maria; Torgerson, Dara G.; Szpiech, Zachary A.; Torres, Raul; Nicolae, Dan L.; Ober, Carole; Olopade, Christopher O.; Olopade, Olufunmilayo; Oluwole, Oluwafemi; Arinola, Ganiyu; Song, Wei; Abecasis, Goncalo; Correa, Adolfo; Musani, Solomon; Wilson, James G.; Lange, Leslie A.; Akey, Joshua; Bamshad, Michael; Chong, Jessica; Fu, Wenqing; Nickerson, Deborah; Reiner, Alexander; Hartert, Tina; Ware, Lorraine B.; Bleecker, Eugene; Meyers, Deborah; Ortega, Victor E.; Pissamai, Maul R. N.; Trevor, Maul R. N.; Watson, Harold; Araujo, Maria Ilma; Oliveira, Ricardo Riccio; Caraballo, Luis; Marrugo, Javier; Martinez, Beatriz; Meza, Catherine; Ayestas, Gerardo; Herrera-Paz, Edwin Francisco; Landaverde-Torres, Pamela; Erazo, Said Omar Leiva; Martinez, Rosella; Mayorga, Alvaro; Mayorga, Luis F.; Mejia-Mejia, Delmy-Aracely; Ramos, Hector; Saenz, Allan; Varela, Gloria; Vasquez, Olga Marina; Ferguson, Trevor; Knight-Madden, Jennifer; Samms-Vaughan, Maureen; Wilks, Rainford J.; Adegnika, Akim; Ateba-Ngoa, Ulysse; Yazdanbakhsh, Maria; O'Connor, Timothy D.

    2016-01-01

    To characterize the extent and impact of ancestry-related biases in precision genomic medicine, we use 642 whole-genome sequences from the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) project to evaluate typical filters and databases. We find significant correlations between estimated African ancestry proportions and the number of variants per individual in all variant classification sets but one. The source of these correlations is highlighted in more detail by looking at the interaction between filtering criteria and the ClinVar and Human Gene Mutation databases. ClinVar's correlation, representing African ancestry-related bias, has changed over time amidst monthly updates, with the most extreme switch happening between March and April of 2014 (r=0.733 to r=−0.683). We identify 68 SNPs as the major drivers of this change in correlation. As long as ancestry-related bias when using these clinical databases is minimally recognized, the genetics community will face challenges with implementation, interpretation and cost-effectiveness when treating minority populations. PMID:27725664

  18. Genetic Population Structure Analysis in New Hampshire Reveals Eastern European Ancestry

    PubMed Central

    Sloan, Chantel D.; Andrew, Angeline D.; Duell, Eric J.; Williams, Scott M.; Karagas, Margaret R.; Moore, Jason H.

    2009-01-01

    Genetic structure due to ancestry has been well documented among many divergent human populations. However, the ability to associate ancestry with genetic substructure without using supervised clustering has not been explored in more presumably homogeneous and admixed US populations. The goal of this study was to determine if genetic structure could be detected in a United States population from a single state where the individuals have mixed European ancestry. Using Bayesian clustering with a set of 960 single nucleotide polymorphisms (SNPs) we found evidence of population stratification in 864 individuals from New Hampshire that can be used to differentiate the population into six distinct genetic subgroups. We then correlated self-reported ancestry of the individuals with the Bayesian clustering results. Finnish and Russian/Polish/Lithuanian ancestries were most notably found to be associated with genetic substructure. The ancestral results were further explained and substantiated using New Hampshire census data from 1870 to 1930 when the largest waves of European immigrants came to the area. We also discerned distinct patterns of linkage disequilibrium (LD) between the genetic groups in the growth hormone receptor gene (GHR). To our knowledge, this is the first time such an investigation has uncovered a strong link between genetic structure and ancestry in what would otherwise be considered a homogenous US population. PMID:19738909

  19. Genetic population structure analysis in New Hampshire reveals Eastern European ancestry.

    PubMed

    Sloan, Chantel D; Andrew, Angeline D; Duell, Eric J; Williams, Scott M; Karagas, Margaret R; Moore, Jason H

    2009-09-07

    Genetic structure due to ancestry has been well documented among many divergent human populations. However, the ability to associate ancestry with genetic substructure without using supervised clustering has not been explored in more presumably homogeneous and admixed US populations. The goal of this study was to determine if genetic structure could be detected in a United States population from a single state where the individuals have mixed European ancestry. Using Bayesian clustering with a set of 960 single nucleotide polymorphisms (SNPs) we found evidence of population stratification in 864 individuals from New Hampshire that can be used to differentiate the population into six distinct genetic subgroups. We then correlated self-reported ancestry of the individuals with the Bayesian clustering results. Finnish and Russian/Polish/Lithuanian ancestries were most notably found to be associated with genetic substructure. The ancestral results were further explained and substantiated using New Hampshire census data from 1870 to 1930 when the largest waves of European immigrants came to the area. We also discerned distinct patterns of linkage disequilibrium (LD) between the genetic groups in the growth hormone receptor gene (GHR). To our knowledge, this is the first time such an investigation has uncovered a strong link between genetic structure and ancestry in what would otherwise be considered a homogenous US population.

  20. The Genomic Ancestry of Individuals from Different Geographical Regions of Brazil Is More Uniform Than Expected

    PubMed Central

    Pena, Sérgio D. J.; Di Pietro, Giuliano; Fuchshuber-Moraes, Mateus; Genro, Julia Pasqualini; Hutz, Mara H.; Kehdy, Fernanda de Souza Gomes; Kohlrausch, Fabiana; Magno, Luiz Alexandre Viana; Montenegro, Raquel Carvalho; Moraes, Manoel Odorico; de Moraes, Maria Elisabete Amaral; de Moraes, Milene Raiol; Ojopi, Élida B.; Perini, Jamila A.; Racciopi, Clarice; Ribeiro-dos-Santos, Ândrea Kely Campos; Rios-Santos, Fabrício; Romano-Silva, Marco A.; Sortica, Vinicius A.; Suarez-Kurtz, Guilherme

    2011-01-01

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

  1. A rapid screening of ancestry for genetic association studies in an admixed population from Pernambuco, Brazil.

    PubMed

    Coelho, A V C; Moura, R R; Cavalcanti, C A J; Guimarães, R L; Sandrin-Garcia, P; Crovella, S; Brandão, L A C

    2015-03-31

    Genetic association studies determine how genes influence traits. However, non-detected population substructure may bias the analysis, resulting in spurious results. One method to detect substructure is to genotype ancestry informative markers (AIMs) besides the candidate variants, quantifying how much ancestral populations contribute to the samples' genetic background. The present study aimed to use a minimum quantity of markers, while retaining full potential to estimate ancestries. We tested the feasibility of a subset of the 12 most informative markers from a previously established study to estimate influence from three ancestral populations: European, African and Amerindian. The results showed that in a sample with a diverse ethnicity (N = 822) derived from 1000 Genomes database, the 12 AIMs had the same capacity to estimate ancestries when compared to the original set of 128 AIMs, since estimates from the two panels were closely correlated. Thus, these 12 SNPs were used to estimate ancestry in a new sample (N = 192) from an admixed population in Recife, Northeast Brazil. The ancestry estimates from Recife subjects were in accordance with previous studies, showing that Northeastern Brazilian populations show great influence from European ancestry (59.7%), followed by African (23.0%) and Amerindian (17.3%) ancestries. Ethnicity self-classification according to skin-color was confirmed to be a poor indicator of population substructure in Brazilians, since ancestry estimates overlapped between classifications. Thus, our streamlined panel of 12 markers may substitute panels with more markers, while retaining the capacity to control for population substructure and admixture, thereby reducing sample processing time.

  2. A substantial prehistoric European ancestry amongst Ashkenazi maternal lineages.

    PubMed

    Costa, Marta D; Pereira, Joana B; Pala, Maria; Fernandes, Verónica; Olivieri, Anna; Achilli, Alessandro; Perego, Ugo A; Rychkov, Sergei; Naumova, Oksana; Hatina, Jiři; Woodward, Scott R; Eng, Ken Khong; Macaulay, Vincent; Carr, Martin; Soares, Pedro; Pereira, Luísa; Richards, Martin B

    2013-01-01

    The origins of Ashkenazi Jews remain highly controversial. Like Judaism, mitochondrial DNA is passed along the maternal line. Its variation in the Ashkenazim is highly distinctive, with four major and numerous minor founders. However, due to their rarity in the general population, these founders have been difficult to trace to a source. Here we show that all four major founders, ~40% of Ashkenazi mtDNA variation, have ancestry in prehistoric Europe, rather than the Near East or Caucasus. Furthermore, most of the remaining minor founders share a similar deep European ancestry. Thus the great majority of Ashkenazi maternal lineages were not brought from the Levant, as commonly supposed, nor recruited in the Caucasus, as sometimes suggested, but assimilated within Europe. These results point to a significant role for the conversion of women in the formation of Ashkenazi communities, and provide the foundation for a detailed reconstruction of Ashkenazi genealogical history.

  3. A substantial prehistoric European ancestry amongst Ashkenazi maternal lineages

    PubMed Central

    Costa, Marta D.; Pereira, Joana B.; Pala, Maria; Fernandes, Verónica; Olivieri, Anna; Achilli, Alessandro; Perego, Ugo A.; Rychkov, Sergei; Naumova, Oksana; Hatina, Jiři; Woodward, Scott R.; Eng, Ken Khong; Macaulay, Vincent; Carr, Martin; Soares, Pedro; Pereira, Luísa; Richards, Martin B.

    2013-01-01

    The origins of Ashkenazi Jews remain highly controversial. Like Judaism, mitochondrial DNA is passed along the maternal line. Its variation in the Ashkenazim is highly distinctive, with four major and numerous minor founders. However, due to their rarity in the general population, these founders have been difficult to trace to a source. Here we show that all four major founders, ~40% of Ashkenazi mtDNA variation, have ancestry in prehistoric Europe, rather than the Near East or Caucasus. Furthermore, most of the remaining minor founders share a similar deep European ancestry. Thus the great majority of Ashkenazi maternal lineages were not brought from the Levant, as commonly supposed, nor recruited in the Caucasus, as sometimes suggested, but assimilated within Europe. These results point to a significant role for the conversion of women in the formation of Ashkenazi communities, and provide the foundation for a detailed reconstruction of Ashkenazi genealogical history. PMID:24104924

  4. Ancestry, admixture and fitness in Colombian genomes.

    PubMed

    Rishishwar, Lavanya; Conley, Andrew B; Wigington, Charles H; Wang, Lu; Valderrama-Aguirre, Augusto; Jordan, I King

    2015-07-21

    The human dimension of the Columbian Exchange entailed substantial genetic admixture between ancestral source populations from Africa, the Americas and Europe, which had evolved separately for many thousands of years. We sought to address the implications of the creation of admixed American genomes, containing novel allelic combinations, for human health and fitness via analysis of an admixed Colombian population from Medellin. Colombian genomes from Medellin show a wide range of three-way admixture contributions from ancestral source populations. The primary ancestry component for the population is European (average = 74.6%, range = 45.0%-96.7%), followed by Native American (average = 18.1%, range = 2.1%-33.3%) and African (average = 7.3%, range = 0.2%-38.6%). Locus-specific patterns of ancestry were evaluated to search for genomic regions that are enriched across the population for particular ancestry contributions. Adaptive and innate immune system related genes and pathways are particularly over-represented among ancestry-enriched segments, including genes (HLA-B and MAPK10) that are involved in defense against endemic pathogens such as malaria. Genes that encode functions related to skin pigmentation (SCL4A5) and cutaneous glands (EDAR) are also found in regions with anomalous ancestry patterns. These results suggest the possibility that ancestry-specific loci were differentially retained in the modern admixed Colombian population based on their utility in the New World environment.

  5. Ancestry Dependent DNA Methylation and Influence of Maternal Nutrition

    PubMed Central

    Mozhui, Khyobeni; Smith, Alicia K.; Tylavsky, Frances A.

    2015-01-01

    There is extensive variation in DNA methylation between individuals and ethnic groups. These differences arise from a combination of genetic and non-genetic influences and potential modifiers include nutritional cues, early life experience, and social and physical environments. Here we compare genome-wide DNA methylation in neonatal cord blood from African American (AA; N = 112) and European American (EA; N = 91) participants of the CANDLE Study (Conditions Affecting Neurocognitive Development and Learning in Early Childhood). Our goal is to determine if there are replicable ancestry-specific methylation patterns that may implicate risk factors for diseases that have differential prevalence between populations. To identify the most robust ancestry-specific CpG sites, we replicate our results in lymphoblastoid cell lines from Yoruba African and CEPH European panels of HapMap. We also evaluate the influence of maternal nutrition—specifically, plasma levels of vitamin D and folate during pregnancy—on methylation in newborns. We define stable ancestry-dependent methylation of genes that include tumor suppressors and cell cycle regulators (e.g., APC, BRCA1, MCC). Overall, there is lower global methylation in African ancestral groups. Plasma levels of 25-hydroxy vitamin D are also considerably lower among AA mothers and about 60% of AA and 40% of EA mothers have concentrations below 20 ng/ml. Using a weighted correlation analysis, we define a network of CpG sites that is jointly modulated by ancestry and maternal vitamin D. Our results show that differences in DNA methylation patterns are remarkably stable and maternal micronutrients can exert an influence on the child epigenome. PMID:25742137

  6. The Combined Landscape of Denisovan and Neanderthal Ancestry in Present-Day Humans.

    PubMed

    Sankararaman, Sriram; Mallick, Swapan; Patterson, Nick; Reich, David

    2016-05-09

    Some present-day humans derive up to ∼5% [1] of their ancestry from archaic Denisovans, an even larger proportion than the ∼2% from Neanderthals [2]. We developed methods that can disambiguate the locations of segments of Denisovan and Neanderthal ancestry in present-day humans and applied them to 257 high-coverage genomes from 120 diverse populations, among which were 20 individual Oceanians with high Denisovan ancestry [3]. In Oceanians, the average size of Denisovan fragments is larger than Neanderthal fragments, implying a more recent average date of Denisovan admixture in the history of these populations (p = 0.00004). We document more Denisovan ancestry in South Asia than is expected based on existing models of history, reflecting a previously undocumented mixture related to archaic humans (p = 0.0013). Denisovan ancestry, just like Neanderthal ancestry, has been deleterious on a modern human genetic background, as reflected by its depletion near genes. Finally, the reduction of both archaic ancestries is especially pronounced on chromosome X and near genes more highly expressed in testes than other tissues (p = 1.2 × 10(-7) to 3.2 × 10(-7) for Denisovan and 2.2 × 10(-3) to 2.9 × 10(-3) for Neanderthal ancestry even after controlling for differences in level of selective constraint across gene classes). This suggests that reduced male fertility may be a general feature of mixtures of human populations diverged by >500,000 years.

  7. Determining Ancestry Proportions in Complex Admixture Scenarios in South Africa Using a Novel Proxy Ancestry Selection Method

    PubMed Central

    Chimusa, Emile R.; Daya, Michelle; Möller, Marlo; Ramesar, Raj; Henn, Brenna M.; van Helden, Paul D.; Mulder, Nicola J.; Hoal, Eileen G.

    2013-01-01

    Admixed populations can make an important contribution to the discovery of disease susceptibility genes if the parental populations exhibit substantial variation in susceptibility. Admixture mapping has been used successfully, but is not designed to cope with populations that have more than two or three ancestral populations. The inference of admixture proportions and local ancestry and the imputation of missing genotypes in admixed populations are crucial in both understanding variation in disease and identifying novel disease loci. These inferences make use of reference populations, and accuracy depends on the choice of ancestral populations. Using an insufficient or inaccurate ancestral panel can result in erroneously inferred ancestry and affect the detection power of GWAS and meta-analysis when using imputation. Current algorithms are inadequate for multi-way admixed populations. To address these challenges we developed PROXYANC, an approach to select the best proxy ancestral populations. From the simulation of a multi-way admixed population we demonstrate the capability and accuracy of PROXYANC and illustrate the importance of the choice of ancestry in both estimating admixture proportions and imputing missing genotypes. We applied this approach to a complex, uniquely admixed South African population. Using genome-wide SNP data from over 764 individuals, we accurately estimate the genetic contributions from the best ancestral populations: isiXhosa , ‡Khomani SAN , European , Indian , and Chinese . We also demonstrate that the ancestral allele frequency differences correlate with increased linkage disequilibrium in the South African population, which originates from admixture events rather than population bottlenecks. Nomenclature The collective term for people of mixed ancestry in southern Africa is “Coloured,” and this is officially recognized in South Africa as a census term, and for self-classification. Whilst we acknowledge that some cultures may

  8. On universal common ancestry, sequence similarity, and phylogenetic structure: the sins of P-values and the virtues of Bayesian evidence

    PubMed Central

    2011-01-01

    Background The universal common ancestry (UCA) of all known life is a fundamental component of modern evolutionary theory, supported by a wide range of qualitative molecular evidence. Nevertheless, recently both the status and nature of UCA has been questioned. In earlier work I presented a formal, quantitative test of UCA in which model selection criteria overwhelmingly choose common ancestry over independent ancestry, based on a dataset of universally conserved proteins. These model-based tests are founded in likelihoodist and Bayesian probability theory, in opposition to classical frequentist null hypothesis tests such as Karlin-Altschul E-values for sequence similarity. In a recent comment, Koonin and Wolf (K&W) claim that the model preference for UCA is "a trivial consequence of significant sequence similarity". They support this claim with a computational simulation, derived from universally conserved proteins, which produces similar sequences lacking phylogenetic structure. The model selection tests prefer common ancestry for this artificial data set. Results For the real universal protein sequences, hierarchical phylogenetic structure (induced by genealogical history) is the overriding reason for why the tests choose UCA; sequence similarity is a relatively minor factor. First, for cases of conflicting phylogenetic structure, the tests choose independent ancestry even with highly similar sequences. Second, certain models, like star trees and K&W's profile model (corresponding to their simulation), readily explain sequence similarity yet lack phylogenetic structure. However, these are extremely poor models for the real proteins, even worse than independent ancestry models, though they explain K&W's artificial data well. Finally, K&W's simulation is an implementation of a well-known phylogenetic model, and it produces sequences that mimic homologous proteins. Therefore the model selection tests work appropriately with the artificial data. Conclusions For K

  9. On universal common ancestry, sequence similarity, and phylogenetic structure: the sins of P-values and the virtues of Bayesian evidence.

    PubMed

    Theobald, Douglas L

    2011-11-24

    The universal common ancestry (UCA) of all known life is a fundamental component of modern evolutionary theory, supported by a wide range of qualitative molecular evidence. Nevertheless, recently both the status and nature of UCA has been questioned. In earlier work I presented a formal, quantitative test of UCA in which model selection criteria overwhelmingly choose common ancestry over independent ancestry, based on a dataset of universally conserved proteins. These model-based tests are founded in likelihoodist and Bayesian probability theory, in opposition to classical frequentist null hypothesis tests such as Karlin-Altschul E-values for sequence similarity. In a recent comment, Koonin and Wolf (K&W) claim that the model preference for UCA is "a trivial consequence of significant sequence similarity". They support this claim with a computational simulation, derived from universally conserved proteins, which produces similar sequences lacking phylogenetic structure. The model selection tests prefer common ancestry for this artificial data set. For the real universal protein sequences, hierarchical phylogenetic structure (induced by genealogical history) is the overriding reason for why the tests choose UCA; sequence similarity is a relatively minor factor. First, for cases of conflicting phylogenetic structure, the tests choose independent ancestry even with highly similar sequences. Second, certain models, like star trees and K&W's profile model (corresponding to their simulation), readily explain sequence similarity yet lack phylogenetic structure. However, these are extremely poor models for the real proteins, even worse than independent ancestry models, though they explain K&W's artificial data well. Finally, K&W's simulation is an implementation of a well-known phylogenetic model, and it produces sequences that mimic homologous proteins. Therefore the model selection tests work appropriately with the artificial data. For K&W's artificial protein data

  10. High speed image correlation for vibration analysis

    NASA Astrophysics Data System (ADS)

    Siebert, T.; Wood, R.; Splitthof, K.

    2009-08-01

    Digital speckle correlation techniques have already been successfully proven to be an accurate displacement analysis tool for a wide range of applications. With the use of two cameras, three dimensional measurements of contours and displacements can be carried out. With a simple setup it opens a wide range of applications. Rapid new developments in the field of digital imaging and computer technology opens further applications for these measurement methods to high speed deformation and strain analysis, e.g. in the fields of material testing, fracture mechanics, advanced materials and component testing. The high resolution of the deformation measurements in space and time opens a wide range of applications for vibration analysis of objects. Since the system determines the absolute position and displacements of the object in space, it is capable of measuring high amplitudes and even objects with rigid body movements. The absolute resolution depends on the field of view and is scalable. Calibration of the optical setup is a crucial point which will be discussed in detail. Examples of the analysis of harmonic vibration and transient events from material research and industrial applications are presented. The results show typical features of the system.

  11. Association of DXA-derived Bone Mineral Density and Fat Mass With African Ancestry

    PubMed Central

    Preus, Leah; Wactawski-Wende, Jean; Nie, Jing; Johnson, Nicholas A.; Zakharia, Fouad; Tang, Hua; Carlson, Chris; Carty, Cara; Chen, Zhao; Hoffman, Thomas; Hutter, Carolyn M.; Jackson, Rebecca D.; Kaplan, Robert C.; Li, Li; Liu, Song; Neuhouser, Marian L.; Peters, Ulrike; Robbins, John; Seldin, Michael F.; Thornton, Timothy A.; Thompson, Cheryl L.; Kooperberg, Charles

    2013-01-01

    Context: Both genes and environment have been implicated in determining the complex body composition phenotypes in individuals of European ancestry; however, few studies have been conducted in other race/ethnic groups. Objective: We conducted a genome-wide admixture mapping study in an attempt to localize novel genomic regions associated with genetic ancestry. Setting/Participants: We selected a sample of 842 African-American women from the Women's Health Initiative single nucleotide polymorphism (SNP) Health Association Resource for whom several dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) and fat mass phenotypes were available. Methods: We derived both global and local ancestry estimates for each individual from Affymetrix 6.0 data and analyzed the correlation of DXA phenotypes with global African ancestry. For each phenotype, we examined the association of local genetic ancestry (number of African ancestral alleles at each marker) and each DXA phenotype at 570 282 markers across the genome in additive models with adjustment for important covariates. Results: We identified statistically significant correlations of whole-body fat mass, trunk fat mass, and all 6 measures of BMD with a proportion of African ancestry. Genome-wide (admixture) significance for femoral neck BMD was achieved across 2 regions ∼3.7 MB and 0.3 MB on chromosome 19q13; similarly, total hip and intertrochanter BMD were associated with local ancestry in these regions. Trunk fat was the most significant fat mass phenotype showing strong, but not genomewide significant associations on chromosome Xp22. Conclusions: Our results suggest that genomic regions in postmenopausal African-American women contribute to variance in BMD and fat mass existence and warrant further study. PMID:23436924

  12. Association of DXA-derived bone mineral density and fat mass with African ancestry.

    PubMed

    Ochs-Balcom, Heather M; Preus, Leah; Wactawski-Wende, Jean; Nie, Jing; Johnson, Nicholas A; Zakharia, Fouad; Tang, Hua; Carlson, Chris; Carty, Cara; Chen, Zhao; Hoffman, Thomas; Hutter, Carolyn M; Jackson, Rebecca D; Kaplan, Robert C; Li, Li; Liu, Song; Neuhouser, Marian L; Peters, Ulrike; Robbins, John; Seldin, Michael F; Thornton, Timothy A; Thompson, Cheryl L; Kooperberg, Charles; Sucheston, Lara E

    2013-04-01

    Both genes and environment have been implicated in determining the complex body composition phenotypes in individuals of European ancestry; however, few studies have been conducted in other race/ethnic groups. We conducted a genome-wide admixture mapping study in an attempt to localize novel genomic regions associated with genetic ancestry. We selected a sample of 842 African-American women from the Women's Health Initiative single nucleotide polymorphism (SNP) Health Association Resource for whom several dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) and fat mass phenotypes were available. We derived both global and local ancestry estimates for each individual from Affymetrix 6.0 data and analyzed the correlation of DXA phenotypes with global African ancestry. For each phenotype, we examined the association of local genetic ancestry (number of African ancestral alleles at each marker) and each DXA phenotype at 570 282 markers across the genome in additive models with adjustment for important covariates. We identified statistically significant correlations of whole-body fat mass, trunk fat mass, and all 6 measures of BMD with a proportion of African ancestry. Genome-wide (admixture) significance for femoral neck BMD was achieved across 2 regions ∼3.7 MB and 0.3 MB on chromosome 19q13; similarly, total hip and intertrochanter BMD were associated with local ancestry in these regions. Trunk fat was the most significant fat mass phenotype showing strong, but not genomewide significant associations on chromosome Xp22. Our results suggest that genomic regions in postmenopausal African-American women contribute to variance in BMD and fat mass existence and warrant further study.

  13. The Impact of Ancestry and Common Genetic Variants on QT Interval in African Americans

    PubMed Central

    Smith, J. Gustav; Avery, Christy L.; Evans, Daniel S.; Nalls, Michael A.; Meng, Yan A.; Smith, Erin N.; Palmer, Cameron; Tanaka, Toshiko; Mehra, Reena; Butler, Anne M.; Young, Taylor; Buxbaum, Sarah G.; Kerr, Kathleen F.; Berenson, Gerald S.; Schnabel, Renate B.; Li, Guo; Ellinor, Patrick T.; Magnani, Jared W.; Chen, Wei; Bis, Joshua C.; Curb, J. David; Hsueh, Wen-Chi; Rotter, Jerome I.; Liu, Yongmei; Newman, Anne B.; Limacher, Marian C.; North, Kari E.; Reiner, Alexander P.; Quibrera, P. Miguel; Schork, Nicholas J.; Singleton, Andrew B.; Psaty, Bruce M.; Soliman, Elsayed Z.; Solomon, Allen J.; Srinivasan, Sathanur R.; Alonso, Alvaro; Wallace, Robert; Redline, Susan; Zhang, Zhu-Ming; Post, Wendy S.; Zonderman, Alan B.; Taylor, Herman A.; Murray, Sarah S.; Ferrucci, Luigi; Arking, Dan E.; Evans, Michele K.; Fox, Ervin R.; Sotoodehnia, Nona; Heckbert, Susan R.; Whitsel, Eric A.; Newton-Cheh, Christopher

    2013-01-01

    Background Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death (SCD) and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval. Methods and Results First, individual estimates of African and European ancestry were inferred from genome-wide single nucleotide polymorphism (SNP) data in seven population-based cohorts of African Americans (n=12 097) and regressed on measured QT interval from electrocardiograms. Second, imputation was performed for 2.8 million SNPs and a genome-wide association (GWA) study of QT interval performed in ten cohorts (n=13 105). There was no evidence of association between genetic ancestry and QT interval (p=0.94). Genome-wide significant associations (p<2.5×10−8) were identified with SNPs at two loci, upstream of the genes NOS1AP (rs12143842, p=2×10−15) and ATP1B1 (rs1320976, p=2×10−10). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low p-values (p<10−5) were observed for SNPs at several other loci previously identified in GWA studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF and PLN. Conclusions We observed no difference in duration of cardiac repolarization with global genetic indices of African ancestry. In addition, our GWA study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include African Americans. PMID:23166209

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

    PubMed

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

    2016-06-01

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

  15. Fast and accurate inference of local ancestry in Latino populations

    PubMed Central

    Baran, Yael; Pasaniuc, Bogdan; Sankararaman, Sriram; Torgerson, Dara G.; Gignoux, Christopher; Eng, Celeste; Rodriguez-Cintron, William; Chapela, Rocio; Ford, Jean G.; Avila, Pedro C.; Rodriguez-Santana, Jose; Burchard, Esteban Gonzàlez; Halperin, Eran

    2012-01-01

    Motivation: It is becoming increasingly evident that the analysis of genotype data from recently admixed populations is providing important insights into medical genetics and population history. Such analyses have been used to identify novel disease loci, to understand recombination rate variation and to detect recent selection events. The utility of such studies crucially depends on accurate and unbiased estimation of the ancestry at every genomic locus in recently admixed populations. Although various methods have been proposed and shown to be extremely accurate in two-way admixtures (e.g. African Americans), only a few approaches have been proposed and thoroughly benchmarked on multi-way admixtures (e.g. Latino populations of the Americas). Results: To address these challenges we introduce here methods for local ancestry inference which leverage the structure of linkage disequilibrium in the ancestral population (LAMP-LD), and incorporate the constraint of Mendelian segregation when inferring local ancestry in nuclear family trios (LAMP-HAP). Our algorithms uniquely combine hidden Markov models (HMMs) of haplotype diversity within a novel window-based framework to achieve superior accuracy as compared with published methods. Further, unlike previous methods, the structure of our HMM does not depend on the number of reference haplotypes but on a fixed constant, and it is thereby capable of utilizing large datasets while remaining highly efficient and robust to over-fitting. Through simulations and analysis of real data from 489 nuclear trio families from the mainland US, Puerto Rico and Mexico, we demonstrate that our methods achieve superior accuracy compared with published methods for local ancestry inference in Latinos. Availability: http://lamp.icsi.berkeley.edu/lamp/lampld/ Contact: bpasaniu@hsph.harvard.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:22495753

  16. Fast and accurate inference of local ancestry in Latino populations.

    PubMed

    Baran, Yael; Pasaniuc, Bogdan; Sankararaman, Sriram; Torgerson, Dara G; Gignoux, Christopher; Eng, Celeste; Rodriguez-Cintron, William; Chapela, Rocio; Ford, Jean G; Avila, Pedro C; Rodriguez-Santana, Jose; Burchard, Esteban Gonzàlez; Halperin, Eran

    2012-05-15

    It is becoming increasingly evident that the analysis of genotype data from recently admixed populations is providing important insights into medical genetics and population history. Such analyses have been used to identify novel disease loci, to understand recombination rate variation and to detect recent selection events. The utility of such studies crucially depends on accurate and unbiased estimation of the ancestry at every genomic locus in recently admixed populations. Although various methods have been proposed and shown to be extremely accurate in two-way admixtures (e.g. African Americans), only a few approaches have been proposed and thoroughly benchmarked on multi-way admixtures (e.g. Latino populations of the Americas). To address these challenges we introduce here methods for local ancestry inference which leverage the structure of linkage disequilibrium in the ancestral population (LAMP-LD), and incorporate the constraint of Mendelian segregation when inferring local ancestry in nuclear family trios (LAMP-HAP). Our algorithms uniquely combine hidden Markov models (HMMs) of haplotype diversity within a novel window-based framework to achieve superior accuracy as compared with published methods. Further, unlike previous methods, the structure of our HMM does not depend on the number of reference haplotypes but on a fixed constant, and it is thereby capable of utilizing large datasets while remaining highly efficient and robust to over-fitting. Through simulations and analysis of real data from 489 nuclear trio families from the mainland US, Puerto Rico and Mexico, we demonstrate that our methods achieve superior accuracy compared with published methods for local ancestry inference in Latinos.

  17. Analysis of genetic ancestry in the admixed Brazilian population from Rio de Janeiro using 46 autosomal ancestry-informative indel markers.

    PubMed

    Manta, Fernanda Saloum Neves; Pereira, Rui; Caiafa, Alexandre; Silva, Dayse Aparecida; Gusmão, Leonor; Carvalho, Elizeu Fagundes

    2013-01-01

    The Brazilian population is highly heterogeneous as a result of five centuries of inter-ethnic mating between native Amerindians, European colonizers and Africans arrived during slavery. This study aimed to assess the proportions of inter-ethnic admixture in the Brazilian population of Rio de Janeiro using autosomal Ancestry-Informative Markers (AIMs). The autosomal data were also compared to the results expected from uniparental genetic markers. A total of 413 individuals were genotyped for 46 AIM-Indels and ancestry estimates were then assessed using HGDP-CEPH samples as ancestral reference. Individuals from Rio de Janeiro presented highly diverse admixture patterns. The global admixture estimates showed a predominantly European ancestry, above 55%, followed by African and Amerindian contributions. A separate self-declared Afro-descendant group also included in this study revealed an increased African ancestry, from ∼30% to ∼50%. The inter-ethnic admixture landscape of Rio de Janeiro captured by autosomal AIM-Indels is in agreement with historical records and similar to that expected from uniparental mtDNA and Y-chromosome information. The AIM-Indel panel proved to be a rapid strategy to estimate autosomal genetic ancestry at individual and population levels in Rio de Janeiro, which is useful in population genetics and in case-control association studies.

  18. Development of a novel forensic STR multiplex for ancestry analysis and extended identity testing.

    PubMed

    Phillips, Chris; Fernandez-Formoso, Luis; Gelabert-Besada, Miguel; Garcia-Magariños, Manuel; Santos, Carla; Fondevila, Manuel; Carracedo, Angel; Lareu, Maria Victoria

    2013-04-01

    There is growing interest in developing additional DNA typing techniques to provide better investigative leads in forensic analysis. These include inference of genetic ancestry and prediction of common physical characteristics of DNA donors. To date, forensic ancestry analysis has centered on population-divergent SNPs but these binary loci cannot reliably detect DNA mixtures, common in forensic samples. Furthermore, STR genotypes, forming the principal DNA profiling system, are not routinely combined with forensic SNPs to strengthen frequency data available for ancestry inference. We report development of a 12-STR multiplex composed of ancestry informative marker STRs (AIM-STRs) selected from 434 tetranucleotide repeat loci. We adapted our online Bayesian classifier for AIM-SNPs: Snipper, to handle multiallele STR data using frequency-based training sets. We assessed the ability of the 12-plex AIM-STRs to differentiate CEPH Human Genome Diversity Panel populations, plus their informativeness combined with established forensic STRs and AIM-SNPs. We found combining STRs and SNPs improves the success rate of ancestry assignments while providing a reliable mixture detection system lacking from SNP analysis alone. As the 12 STRs generally show a broad range of alleles in all populations, they provide highly informative supplementary STRs for extended relationship testing and identification of missing persons with incomplete reference pedigrees. Lastly, mixed marker approaches (combining STRs with binary loci) for simple ancestry inference tests beyond forensic analysis bring advantages and we discuss the genotyping options available.

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

    PubMed Central

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

    2011-01-01

    Accurate estimation of recent shared ancestry is important for genetics, evolution, medicine, conservation biology, and forensics. Established methods estimate kinship accurately for first-degree through third-degree relatives. We demonstrate that chromosomal segments shared by two individuals due to identity by descent (IBD) provide much additional information about shared ancestry. We developed a maximum-likelihood method for the estimation of recent shared ancestry (ERSA) from the number and lengths of IBD segments derived from high-density SNP or whole-genome sequence data. We used ERSA to estimate relationships from SNP genotypes in 169 individuals from three large, well-defined human pedigrees. ERSA is accurate to within one degree of relationship for 97% of first-degree through fifth-degree relatives and 80% of sixth-degree and seventh-degree relatives. We demonstrate that ERSA's statistical power approaches the maximum theoretical limit imposed by the fact that distant relatives frequently share no DNA through a common ancestor. ERSA greatly expands the range of relationships that can be estimated from genetic data and is implemented in a freely available software package. PMID:21324875

  20. A small number of candidate gene SNPs reveal continental ancestry in African Americans

    PubMed Central

    KODAMAN, NURI; ALDRICH, MELINDA C.; SMITH, JEFFREY R.; SIGNORELLO, LISA B.; BRADLEY, KEVIN; BREYER, JOAN; COHEN, SARAH S.; LONG, JIRONG; CAI, QIUYIN; GILES, JUSTIN; BUSH, WILLIAM S.; BLOT, WILLIAM J.; MATTHEWS, CHARLES E.; WILLIAMS, SCOTT M.

    2013-01-01

    SUMMARY Using genetic data from an obesity candidate gene study of self-reported African Americans and European Americans, we investigated the number of Ancestry Informative Markers (AIMs) and candidate gene SNPs necessary to infer continental ancestry. Proportions of African and European ancestry were assessed with STRUCTURE (K=2), using 276 AIMs. These reference values were compared to estimates derived using 120, 60, 30, and 15 SNP subsets randomly chosen from the 276 AIMs and from 1144 SNPs in 44 candidate genes. All subsets generated estimates of ancestry consistent with the reference estimates, with mean correlations greater than 0.99 for all subsets of AIMs, and mean correlations of 0.99±0.003; 0.98± 0.01; 0.93±0.03; and 0.81± 0.11 for subsets of 120, 60, 30, and 15 candidate gene SNPs, respectively. Among African Americans, the median absolute difference from reference African ancestry values ranged from 0.01 to 0.03 for the four AIMs subsets and from 0.03 to 0.09 for the four candidate gene SNP subsets. Furthermore, YRI/CEU Fst values provided a metric to predict the performance of candidate gene SNPs. Our results demonstrate that a small number of SNPs randomly selected from candidate genes can be used to estimate admixture proportions in African Americans reliably. PMID:23278390

  1. A small number of candidate gene SNPs reveal continental ancestry in African Americans.

    PubMed

    Kodaman, Nuri; Aldrich, Melinda C; Smith, Jeffrey R; Signorello, Lisa B; Bradley, Kevin; Breyer, Joan; Cohen, Sarah S; Long, Jirong; Cai, Qiuyin; Giles, Justin; Bush, William S; Blot, William J; Matthews, Charles E; Williams, Scott M

    2013-01-01

    Using genetic data from an obesity candidate gene study of self-reported African Americans and European Americans, we investigated the number of Ancestry Informative Markers (AIMs) and candidate gene SNPs necessary to infer continental ancestry. Proportions of African and European ancestry were assessed with STRUCTURE (K = 2), using 276 AIMs. These reference values were compared to estimates derived using 120, 60, 30, and 15 SNP subsets randomly chosen from the 276 AIMs and from 1144 SNPs in 44 candidate genes. All subsets generated estimates of ancestry consistent with the reference estimates, with mean correlations greater than 0.99 for all subsets of AIMs, and mean correlations of 0.99 ± 0.003; 0.98 ± 0.01; 0.93 ± 0.03; and 0.81 ± 0.11 for subsets of 120, 60, 30, and 15 candidate gene SNPs, respectively. Among African Americans, the median absolute difference from reference African ancestry values ranged from 0.01 to 0.03 for the four AIMs subsets and from 0.03 to 0.09 for the four candidate gene SNP subsets. Furthermore, YRI/CEU Fst values provided a metric to predict the performance of candidate gene SNPs. Our results demonstrate that a small number of SNPs randomly selected from candidate genes can be used to estimate admixture proportions in African Americans reliably. © 2012 Blackwell Publishing Ltd/University College London.

  2. Ancestry, admixture and fitness in Colombian genomes

    PubMed Central

    Rishishwar, Lavanya; Conley, Andrew B.; Wigington, Charles H.; Wang, Lu; Valderrama-Aguirre, Augusto; King Jordan, I.

    2015-01-01

    The human dimension of the Columbian Exchange entailed substantial genetic admixture between ancestral source populations from Africa, the Americas and Europe, which had evolved separately for many thousands of years. We sought to address the implications of the creation of admixed American genomes, containing novel allelic combinations, for human health and fitness via analysis of an admixed Colombian population from Medellin. Colombian genomes from Medellin show a wide range of three-way admixture contributions from ancestral source populations. The primary ancestry component for the population is European (average = 74.6%, range = 45.0%–96.7%), followed by Native American (average = 18.1%, range = 2.1%–33.3%) and African (average = 7.3%, range = 0.2%–38.6%). Locus-specific patterns of ancestry were evaluated to search for genomic regions that are enriched across the population for particular ancestry contributions. Adaptive and innate immune system related genes and pathways are particularly over-represented among ancestry-enriched segments, including genes (HLA-B and MAPK10) that are involved in defense against endemic pathogens such as malaria. Genes that encode functions related to skin pigmentation (SCL4A5) and cutaneous glands (EDAR) are also found in regions with anomalous ancestry patterns. These results suggest the possibility that ancestry-specific loci were differentially retained in the modern admixed Colombian population based on their utility in the New World environment. PMID:26197429

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

    PubMed Central

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

    2014-01-01

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

  4. High-Fidelity Coding with Correlated Neurons

    PubMed Central

    da Silveira, Rava Azeredo; Berry, Michael J.

    2014-01-01

    Positive correlations in the activity of neurons are widely observed in the brain. Previous studies have shown these correlations to be detrimental to the fidelity of population codes, or at best marginally favorable compared to independent codes. Here, we show that positive correlations can enhance coding performance by astronomical factors. Specifically, the probability of discrimination error can be suppressed by many orders of magnitude. Likewise, the number of stimuli encoded—the capacity—can be enhanced more than tenfold. These effects do not necessitate unrealistic correlation values, and can occur for populations with a few tens of neurons. We further show that both effects benefit from heterogeneity commonly seen in population activity. Error suppression and capacity enhancement rest upon a pattern of correlation. Tuning of one or several effective parameters can yield a limit of perfect coding: the corresponding pattern of positive correlation leads to a ‘lock-in’ of response probabilities that eliminates variability in the subspace relevant for stimulus discrimination. We discuss the nature of this pattern and we suggest experimental tests to identify it. PMID:25412463

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

    PubMed

    Gayevskiy, Velimir; Klaere, Steffen; Knight, Sarah; Goddard, Matthew R

    2014-01-01

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

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

    PubMed Central

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

    2009-01-01

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

  7. Revisiting the Genetic Ancestry of Brazilians Using Autosomal AIM-Indels

    PubMed Central

    Saloum de Neves Manta, Fernanda; Pereira, Rui; Vianna, Romulo; Rodolfo Beuttenmüller de Araújo, Alfredo; Leite Góes Gitaí, Daniel; Aparecida da Silva, Dayse; de Vargas Wolfgramm, Eldamária; da Mota Pontes, Isabel; Ivan Aguiar, José; Ozório Moraes, Milton; Fagundes de Carvalho, Elizeu; Gusmão, Leonor

    2013-01-01

    There are many different studies that contribute to the global picture of the ethnic heterogeneity in Brazilian populations. These studies use different types of genetic markers and are focused on the comparison of populations at different levels. In some of them, each geographical region is treated as a single homogeneous population, whereas other studies create different subdivisions: political (e.g., pooling populations by State), demographic (e.g., urban and rural), or ethnic (e.g., culture, self-declaration, or skin colour). In this study, we performed an enhanced reassessment of the genetic ancestry of ~ 1,300 Brazilians characterised for 46 autosomal Ancestry Informative Markers (AIMs). In addition, 798 individuals from twelve Brazilian populations representing the five geographical macro-regions of Brazil were newly genotyped, including a Native American community and a rural Amazonian community. Following an increasing North to South gradient, European ancestry was the most prevalent in all urban populations (with values up to 74%). The populations in the North consisted of a significant proportion of Native American ancestry that was about two times higher than the African contribution. Conversely, in the Northeast, Center-West and Southeast, African ancestry was the second most prevalent. At an intrapopulation level, all urban populations were highly admixed, and most of the variation in ancestry proportions was observed between individuals within each population rather than among population. Nevertheless, individuals with a high proportion of Native American ancestry are only found in the samples from Terena and Santa Isabel. Our results allowed us to further refine the genetic landscape of Brazilians while establishing the basis for the effective application of an autosomal AIM panel in forensic casework and clinical association studies within the highly admixed Brazilian populations. PMID:24073242

  8. The 'stolen generations' of mothers and daughters: child apprehension and enhanced HIV vulnerabilities for sex workers of Aboriginal ancestry.

    PubMed

    Duff, Putu; Bingham, Brittany; Simo, Annick; Jury, Delores; Reading, Charlotte; Shannon, Kate

    2014-01-01

    The number of children in care of the state continues to grow in BC, Canada with a historical legacy of child apprehension among criminalized and marginalized populations, particularly women of Aboriginal ancestry and sex workers. However, there is a paucity of research investigating child apprehension experiences among marginalized mothers. The objective of the current analysis is to examine the prevalence and correlates of child apprehensions among female sex workers in Vancouver, Canada. Analyses were drawn from the AESHA (An Evaluation of Sex Workers Health Access, 2010-present), a prospective cohort of street and off-street SWs, through outreach and semi-annual visits to the research office. Bivariate and multivariate logistic regression were used to examine correlates of child apprehension. Of a total of 510 SWs, 350 women who had given birth to at least one child were included in the analyses (median age = 37 yrs: IQR: 31-44 yrs). The prevalence of child apprehension among mothers was 38.3%, with 37.4% reporting having been apprehended themselves by child welfare services. In multivariable analysis, servicing clients in outdoor public spaces (versus formal sex work establishments or informal indoor settings) (adjusted odds ratio, (aOR) = 2.73; 95%CI 1.27-5.90), history of injecting drugs (aOR  = 2.53; 95%CI 1.42-4.49), Aboriginal ancestry (aOR = 1.66; 95%CI 1.01-2.74) were associated with increased odds of child apprehension. Child apprehension rates are high, particularly among the most marginalized sex workers, including sex workers who use drugs and sex workers of Aboriginal ancestry. Structural reforms to child protection are urgently needed, that support family-based care address the historical legacy of colonization affecting Aboriginal peoples.

  9. Ancestry of the Population by State: 1980. Supplementary Report.

    ERIC Educational Resources Information Center

    Bureau of the Census (DOC), Suitland, MD. Population Div.

    Information from the 1980 U.S. Census concerning population size and geographic distribution of more than 100 ancestry groups in the United States is presented in this unique reference report. The general ancestry question was based on self-identification, provided no prelisted categories, and allowed for one or more ancestry responses. This was…

  10. Analysis of iris surface features in populations of diverse ancestry

    PubMed Central

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

    2016-01-01

    There are many textural elements that can be found in the human eye, including Fuchs’ crypts, Wolfflin nodules, pigment spots, contraction furrows and conjunctival melanosis. Although iris surface features have been well-studied in populations of European ancestry, the worldwide distribution of these traits is poorly understood. In this paper, we develop a new method of characterizing iris features from photographs of the iris. We then apply this method to a diverse sample of East Asian, European and South Asian ancestry. All five iris features showed significant differences in frequency between the three populations, indicating that iris features are largely population dependent. Although none of the features were correlated with each other in the East and South Asian groups, Fuchs’ crypts were significantly correlated with contraction furrows and pigment spots and contraction furrows were significantly associated with pigment spots in the European group. The genetic marker SEMA3A rs10235789 was significantly associated with Fuchs’ crypt grade in the European, East Asian and South Asian samples and a borderline association between TRAF3IP1 rs3739070 and contraction furrow grade was found in the European sample. The study of iris surface features in diverse populations may provide valuable information of forensic, biomedical and ophthalmological interest. PMID:26909168

  11. Discovering genetic ancestry using spectral graph theory.

    PubMed

    Lee, Ann B; Luca, Diana; Klei, Lambertus; Devlin, Bernie; Roeder, Kathryn

    2010-01-01

    As one approach to uncovering the genetic underpinnings of complex disease, individuals are measured at a large number of genetic variants (usually SNPs) across the genome and these SNP genotypes are assessed for association with disease status. We propose a new statistical method called Spectral-GEM for the analysis of genome-wide association studies; the goal of Spectral-GEM is to quantify the ancestry of the sample from such genotypic data. Ignoring structure due to differential ancestry can lead to an excess of spurious findings and reduce power. Ancestry is commonly estimated using the eigenvectors derived from principal component analysis (PCA). To develop an alternative to PCA we draw on connections between multidimensional scaling and spectral graph theory. Our approach, based on a spectral embedding derived from the normalized Laplacian of a graph, can produce more meaningful delineation of ancestry than by using PCA. Often the results from Spectral-GEM are straightforward to interpret and therefore useful in association analysis. We illustrate the new algorithm with an analysis of the POPRES data [Nelson et al., 2008].

  12. Chromosome Connections: Compelling Clues to Common Ancestry

    ERIC Educational Resources Information Center

    Flammer, Larry

    2013-01-01

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

  13. Proving universal common ancestry with similar sequences

    PubMed Central

    Martins, Leonardo de Oliveira; Posada, David

    2013-01-01

    Douglas Theobald recently developed an interesting test putatively capable of quantifying the evidence for a Universal Common Ancestry uniting the three domains of life (Eukarya, Archaea and Bacteria) against hypotheses of Independent Origins for some of these domains. We review here his model, in particular in relation to the treatment of Horizontal Gene Transfer (HGT) and to the quality of sequence alignment. PMID:23814665

  14. Chromosome Connections: Compelling Clues to Common Ancestry

    ERIC Educational Resources Information Center

    Flammer, Larry

    2013-01-01

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

  15. Unravelling the distinct strains of Tharu ancestry

    PubMed Central

    Chaubey, Gyaneshwer; Singh, Manvendra; Crivellaro, Federica; Tamang, Rakesh; Nandan, Amrita; Singh, Kamayani; Sharma, Varun Kumar; Pathak, Ajai Kumar; Shah, Anish M; Sharma, Vishwas; Singh, Vipin Kumar; Selvi Rani, Deepa; Rai, Niraj; Kushniarevich, Alena; Ilumäe, Anne-Mai; Karmin, Monika; Phillip, Anand; Verma, Abhilasha; Prank, Erik; Singh, Vijay Kumar; Li, Blaise; Govindaraj, Periyasamy; Chaubey, Akhilesh Kumar; Dubey, Pavan Kumar; Reddy, Alla G; Premkumar, Kumpati; Vishnupriya, Satti; Pande, Veena; Parik, Jüri; Rootsi, Siiri; Endicott, Phillip; Metspalu, Mait; Lahr, Marta Mirazon; van Driem, George; Villems, Richard; Kivisild, Toomas; Singh, Lalji; Thangaraj, Kumarasamy

    2014-01-01

    The northern region of the Indian subcontinent is a vast landscape interlaced by diverse ecologies, for example, the Gangetic Plain and the Himalayas. A great number of ethnic groups are found there, displaying a multitude of languages and cultures. The Tharu is one of the largest and most linguistically diverse of such groups, scattered across the Tarai region of Nepal and bordering Indian states. Their origins are uncertain. Hypotheses have been advanced postulating shared ancestry with Austroasiatic, or Tibeto-Burman-speaking populations as well as aboriginal roots in the Tarai. Several Tharu groups speak a variety of Indo-Aryan languages, but have traditionally been described by ethnographers as representing East Asian phenotype. Their ancestry and intra-population diversity has previously been tested only for haploid (mitochondrial DNA and Y-chromosome) markers in a small portion of the population. This study presents the first systematic genetic survey of the Tharu from both Nepal and two Indian states of Uttarakhand and Uttar Pradesh, using genome-wide SNPs and haploid markers. We show that the Tharu have dual genetic ancestry as up to one-half of their gene pool is of East Asian origin. Within the South Asian proportion of the Tharu genetic ancestry, we see vestiges of their common origin in the north of the South Asian Subcontinent manifested by mitochondrial DNA haplogroup M43. PMID:24667789

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

    PubMed Central

    González Silos, Rosa; Marcelain, Katherine; Baez Benavides, Pablo; Barahona Ponce, Carol; Fischer, Christine; Peil, Barbara; Sinsheimer, Janet; Barajas, Olga; Gonzalez-Jose, Rolando; Cátira Bortolini, Maria; Canizales-Quinteros, Samuel; Gallo, Carla; Ruiz Linares, Andres; Rothhammer, Francisco

    2017-01-01

    Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1–4.3%, P = 6×10−27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data. PMID:28542165

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

    PubMed

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

    2017-05-01

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

  18. MESON CORRELATION FUNCTIONS AT HIGH TEMPERATURES.

    SciTech Connect

    WISSEL, S.; DATTA, S.; KARSCH, F.; LAERMANN, E.; SHCHEREDIN, S.

    2005-07-25

    We present preliminary results for the correlation- and spectral functions of different meson channels on the lattice. The main focus lies on gaining control over cut-off as well as on the finite-volume effects. Extrapolations of screening masses above the deconfining temperature are guided by the result of the free (T = {infinity}) case on the lattice and in the continuum. We study the quenched non-perturbatively improved Wilson-clover fermion as well as the hypercube fermion action which might show less cut-off effects.

  19. Sequence similarity network reveals common ancestry of multidomain proteins.

    PubMed

    Song, Nan; Joseph, Jacob M; Davis, George B; Durand, Dannie

    2008-05-16

    We address the problem of homology identification in complex multidomain families with varied domain architectures. The challenge is to distinguish sequence pairs that share common ancestry from pairs that share an inserted domain but are otherwise unrelated. This distinction is essential for accuracy in gene annotation, function prediction, and comparative genomics. There are two major obstacles to multidomain homology identification: lack of a formal definition and lack of curated benchmarks for evaluating the performance of new methods. We offer preliminary solutions to both problems: 1) an extension of the traditional model of homology to include domain insertions; and 2) a manually curated benchmark of well-studied families in mouse and human. We further present Neighborhood Correlation, a novel method that exploits the local structure of the sequence similarity network to identify homologs with great accuracy based on the observation that gene duplication and domain shuffling leave distinct patterns in the sequence similarity network. In a rigorous, empirical comparison using our curated data, Neighborhood Correlation outperforms sequence similarity, alignment length, and domain architecture comparison. Neighborhood Correlation is well suited for automated, genome-scale analyses. It is easy to compute, does not require explicit knowledge of domain architecture, and classifies both single and multidomain homologs with high accuracy. Homolog predictions obtained with our method, as well as our manually curated benchmark and a web-based visualization tool for exploratory analysis of the network neighborhood structure, are available at http://www.neighborhoodcorrelation.org. Our work represents a departure from the prevailing view that the concept of homology cannot be applied to genes that have undergone domain shuffling. In contrast to current approaches that either focus on the homology of individual domains or consider only families with identical domain

  20. A 34-plex autosomal SNP single base extension assay for ancestry investigations.

    PubMed

    Phillips, C; Fondevila, M; Lareau, Maria Victoria

    2012-01-01

    Ancestry inference based on autosomal markers remains a niche approach in forensic analysis: most laboratories feel more secure with a review of the cumulative STR profile frequencies in a range of relevant populations with the possible additional analysis of mitochondrial and/or Y-chromosome variability. However, a proportion of autosomal single nucleotide polymorphisms (SNPs) show very well-differentiated allele frequencies among global population-groups. Furthermore, such ancestry informative marker SNPs (AIM-SNPs) lend themselves to relatively straightforward typing with short-amplicon PCR and multiplexed single base extension reactions using the same capillary electrophoresis detectors required for the sequencing and STR genotyping of mainstream forensic markers. In this chapter, we describe a 34 AIM-SNP multiplex that is robust enough for the analysis of challenging, often highly degraded DNA typical of much of routine forensic casework. We also outline in detail the in-silico procedures necessary for collecting parental population reference data from the SPSmart SNP databases and performing ancestry inference of single AIM-SNP profiles or large-scale population data using the companion ancestry analysis website of Snipper. Two casework examples are described that show, in both cases, that an inference of likely ancestry using AIM-SNPs helped the identification of highly degraded skeletal material.

  1. The genomic landscape of Neanderthal ancestry in present-day humans.

    PubMed

    Sankararaman, Sriram; Mallick, Swapan; Dannemann, Michael; Prüfer, Kay; Kelso, Janet; Pääbo, Svante; Patterson, Nick; Reich, David

    2014-03-20

    Genomic studies have shown that Neanderthals interbred with modern humans, and that non-Africans today are the products of this mixture. The antiquity of Neanderthal gene flow into modern humans means that genomic regions that derive from Neanderthals in any one human today are usually less than a hundred kilobases in size. However, Neanderthal haplotypes are also distinctive enough that several studies have been able to detect Neanderthal ancestry at specific loci. We systematically infer Neanderthal haplotypes in the genomes of 1,004 present-day humans. Regions that harbour a high frequency of Neanderthal alleles are enriched for genes affecting keratin filaments, suggesting that Neanderthal alleles may have helped modern humans to adapt to non-African environments. We identify multiple Neanderthal-derived alleles that confer risk for disease, suggesting that Neanderthal alleles continue to shape human biology. An unexpected finding is that regions with reduced Neanderthal ancestry are enriched in genes, implying selection to remove genetic material derived from Neanderthals. Genes that are more highly expressed in testes than in any other tissue are especially reduced in Neanderthal ancestry, and there is an approximately fivefold reduction of Neanderthal ancestry on the X chromosome, which is known from studies of diverse species to be especially dense in male hybrid sterility genes. These results suggest that part of the explanation for genomic regions of reduced Neanderthal ancestry is Neanderthal alleles that caused decreased fertility in males when moved to a modern human genetic background.

  2. High-order correlation of chaotic bosons and fermions

    NASA Astrophysics Data System (ADS)

    Liu, Hong-Chao

    2016-08-01

    We theoretically study the high-order correlation functions of chaotic bosons and fermions. Based on the different parity of the Stirling number, the products of the first-order correlation functions are well classified and employed to represent the high-order correlation function. The correlation of bosons conduces a bunching effect, which will be enhanced as order N increases. Different from bosons, the anticommutation relation of fermions leads to the parity of the Stirling number, which thereby results in a mixture of bunching and antibunching behaviors in high-order correlation. By further investigating third-order ghost diffraction and ghost imaging, the differences between the high-order correlations of bosons and fermions are discussed in detail. A larger N will dramatically improve the ghost image quality for bosons, but a good strategy should be carefully chosen for the fermionic ghost imaging process due to its complex correlation components.

  3. Neighborhood socio-economic characteristics, African ancestry, and Helicobacter pylori sero-prevalence

    PubMed Central

    Cohen, Sarah S.; Sonderman, Jennifer S.; Zheng, Wei; Williams, Scott M.; Blot, William J.; Signorello, Lisa B.

    2012-01-01

    Purpose The authors recently reported high Helicobacter pylori sero-prevalence among African-Americans of high African ancestry. We sought to determine whether neighborhood-level socio-economic characteristics are associated with H. pylori prevalence and whether this helps explain the link between African ancestry and H. pylori. Methods Antibodies to H. pylori proteins were assessed in the serum of 336 African-American and 329 white Southern Community Cohort Study participants. Prevalence odds ratios (ORs) and 95 % confidence intervals (CIs) for CagA+ and CagA− H. pylori were calculated using polytomous logistic regression in relation to 10 Census block group-level measures of socio-economic status. Results After adjusting for individual-level characteristics, three neighborhood-level factors were significantly inversely related to CagA+ H. pylori: percent completed high school; median house values; and percent employed (comparing highest to lowest tertile, OR, 0.47, 95 % CI, 0.26–0.85; OR, 0.56, 95 % CI, 0.32–0.99; and OR, 0.59, 95 % CI, 0.34–1.03, respectively). However, accounting for these measures did not attenuate the association between African ancestry and CagA+ H. pylori, with African-Americans of low, medium, and high African ancestry maintaining two-, seven-, and ninefold increased odds, respectively, compared to whites. Conclusions Neighborhood-level measures of education, employment, and house values are associated with CagA+ H. pylori sero-prevalence, but do not explain the persistent strong relationship between African ancestry level and CagA+ H. pylori. The findings suggest that neighborhood socio-economic status can help to highlight high-risk areas for prevention and screening efforts and that the link between African ancestry and H. pylori may have a biological basis. PMID:22527167

  4. Neighborhood socio-economic characteristics, African ancestry, and Helicobacter pylori sero-prevalence.

    PubMed

    Epplein, Meira; Cohen, Sarah S; Sonderman, Jennifer S; Zheng, Wei; Williams, Scott M; Blot, William J; Signorello, Lisa B

    2012-06-01

    The authors recently reported high Helicobacter pylori sero-prevalence among African-Americans of high African ancestry. We sought to determine whether neighborhood-level socio-economic characteristics are associated with H. pylori prevalence and whether this helps explain the link between African ancestry and H. pylori. Antibodies to H. pylori proteins were assessed in the serum of 336 African-American and 329 white Southern Community Cohort Study participants. Prevalence odds ratios (ORs) and 95 % confidence intervals (CIs) for CagA+ and CagA- H. pylori were calculated using polytomous logistic regression in relation to 10 Census block group-level measures of socio-economic status. After adjusting for individual-level characteristics, three neighborhood-level factors were significantly inversely related to CagA+ H. pylori: percent completed high school; median house values; and percent employed (comparing highest to lowest tertile, OR, 0.47, 95 % CI, 0.26-0.85; OR, 0.56, 95 % CI, 0.32-0.99; and OR, 0.59, 95 % CI, 0.34-1.03, respectively). However, accounting for these measures did not attenuate the association between African ancestry and CagA+ H. pylori, with African-Americans of low, medium, and high African ancestry maintaining two-, seven-, and ninefold increased odds, respectively, compared to whites. Neighborhood-level measures of education, employment, and house values are associated with CagA+ H. pylori sero-prevalence, but do not explain the persistent strong relationship between African ancestry level and CagA+ H. pylori. The findings suggest that neighborhood socio-economic status can help to highlight high-risk areas for prevention and screening efforts and that the link between African ancestry and H. pylori may have a biological basis.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-01-03

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

  7. Towards a phenome-wide catalog of human clinical traits impacted by genetic ancestry.

    PubMed

    Dumitrescu, Logan; Restrepo, Nicole A; Goodloe, Robert; Boston, Jonathan; Farber-Eger, Eric; Pendergrass, Sarah A; Bush, William S; Crawford, Dana C

    2015-01-01

    Racial/ethnic differences for commonly measured clinical variables are well documented, and it has been postulated that population-specific genetic factors may play a role. The genetic heterogeneity of admixed populations, such as African Americans, provides a unique opportunity to identify genomic regions and variants associated with the clinical variability observed for diseases and traits across populations. To begin a systematic search for these population-specific genomic regions at the phenome-wide scale, we determined the relationship between global genetic ancestry, specifically European and African ancestry, and clinical variables measured in a population of African Americans from BioVU, Vanderbilt University's biorepository linked to de-identified electronic medical records (EMRs) as part of the Epidemiologic Architecture using Genomics and Epidemiology (EAGLE) study. Through billing (ICD-9) codes, procedure codes, labs, and clinical notes, 36 common clinical and laboratory variables were mined from the EMR, including body mass index (BMI), kidney traits, lipid levels, blood pressure, and electrocardiographic measurements. A total of 15,863 DNA samples from non-European Americans were genotyped on the Illumina Metabochip containing ~200,000 variants, of which 11,166 were from African Americans. Tests of association were performed to examine associations between global ancestry and the phenotype of interest. Increased European ancestry, and conversely decreased African ancestry, was most strongly correlated with an increase in QRS duration, consistent with previous observations that African Americans tend to have shorter a QRS duration compared with European Americans. Despite known racial/ethnic disparities in blood pressure, European and African ancestry was neither associated with diastolic nor systolic blood pressure measurements. Collectively, these results suggest that this clinical population can be used to identify traits in which population

  8. Does Genetic Ancestry Explain Higher Values of Glycated Hemoglobin in African Americans?

    PubMed Central

    Maruthur, Nisa M.; Kao, W.H. Linda; Clark, Jeanne M.; Brancati, Frederick L.; Cheng, Ching-Yu; Pankow, James S.; Selvin, Elizabeth

    2011-01-01

    OBJECTIVE Glycated hemoglobin (HbA1c) values are higher in African Americans than whites, raising the question of whether classification of diabetes status by HbA1c should differ for African Americans. We investigated the relative contribution of genetic ancestry and nongenetic factors to HbA1c values and the effect of genetic ancestry on diabetes classification by HbA1c in African Americans. RESEARCH DESIGN AND METHODS We performed a cross-sectional analysis of data from the community-based Atherosclerosis Risk in Communities (ARIC) Study. We estimated percentage of European genetic ancestry (PEA) for each of the 2,294 African Americans without known diabetes using 1,350 ancestry-informative markers. HbA1c was measured from whole-blood samples and categorized using American Diabetes Association diagnostic cut points (<5.7, 5.7–6.4, and ≥6.5%). RESULTS PEA was inversely correlated with HbA1c (adjusted r = −0.07; P < 0.001) but explained <1% of its variance. Age and socioeconomic and metabolic factors, including fasting glucose, explained 13.8% of HbA1c variability. Eleven percent of participants were classified as having diabetes; adjustment for fasting glucose decreased this to 4.4%. Additional adjustment for PEA did not significantly reclassify diabetes status (net reclassification index = 0.034; P = 0.94) nor did further adjustment for demographic, socioeconomic, and metabolic risk factors. CONCLUSIONS The relative contribution of demographic and metabolic factors far outweighs the contribution of genetic ancestry to HbA1c values in African Americans. Moreover, the impact of adjusting for genetic ancestry when classifying diabetes by HbA1c is minimal after taking into account fasting glucose levels, thus supporting the use of currently recommended HbA1c categories for diagnosis of diabetes in African Americans. PMID:21788574

  9. Does genetic ancestry explain higher values of glycated hemoglobin in African Americans?

    PubMed

    Maruthur, Nisa M; Kao, W H Linda; Clark, Jeanne M; Brancati, Frederick L; Cheng, Ching-Yu; Pankow, James S; Selvin, Elizabeth

    2011-09-01

    Glycated hemoglobin (HbA(1c)) values are higher in African Americans than whites, raising the question of whether classification of diabetes status by HbA(1c) should differ for African Americans. We investigated the relative contribution of genetic ancestry and nongenetic factors to HbA(1c) values and the effect of genetic ancestry on diabetes classification by HbA(1c) in African Americans. We performed a cross-sectional analysis of data from the community-based Atherosclerosis Risk in Communities (ARIC) Study. We estimated percentage of European genetic ancestry (PEA) for each of the 2,294 African Americans without known diabetes using 1,350 ancestry-informative markers. HbA(1c) was measured from whole-blood samples and categorized using American Diabetes Association diagnostic cut points (<5.7, 5.7-6.4, and ≥6.5%). PEA was inversely correlated with HbA(1c) (adjusted r = -0.07; P < 0.001) but explained <1% of its variance. Age and socioeconomic and metabolic factors, including fasting glucose, explained 13.8% of HbA(1c) variability. Eleven percent of participants were classified as having diabetes; adjustment for fasting glucose decreased this to 4.4%. Additional adjustment for PEA did not significantly reclassify diabetes status (net reclassification index = 0.034; P = 0.94) nor did further adjustment for demographic, socioeconomic, and metabolic risk factors. The relative contribution of demographic and metabolic factors far outweighs the contribution of genetic ancestry to HbA(1c) values in African Americans. Moreover, the impact of adjusting for genetic ancestry when classifying diabetes by HbA(1c) is minimal after taking into account fasting glucose levels, thus supporting the use of currently recommended HbA(1c) categories for diagnosis of diabetes in African Americans.

  10. Highly noise resistant multiqubit quantum correlations

    NASA Astrophysics Data System (ADS)

    Laskowski, Wiesław; Vértesi, Tamás; Wieśniak, Marcin

    2015-11-01

    We analyze robustness of correlations of the N-qubit GHZ and Dicke states against white noise admixture. For sufficiently large N, the Dicke states (for any number of excitations) lead to more robust violation of local realism than the GHZ states (e.g. for N > 8 for the W state). We also identify states that are the most resistant to white noise. Surprisingly, it turns out that these states are the GHZ states augmented with fully product states. Based on our numerical analysis conducted up to N = 8, and an analytical formula derived for any N parties, we conjecture that the three-qubit GHZ state augmented with a product of (N - 3) pure qubits is the most robust against white noise admixture among any N-qubit state. As a by-product, we derive a single Bell inequality and show that it is violated by all pure entangled states of a given number of parties. This gives an alternative proof of Gisin’s theorem.

  11. Evaluation of Group Genetic Ancestry of Populations from Philadelphia and Dakar in the Context of Sex-Biased Admixture in the Americas

    PubMed Central

    Stefflova, Klara; Dulik, Matthew C.; Pai, Athma A.; Walker, Amy H.; Zeigler-Johnson, Charnita M.; Gueye, Serigne M.; Schurr, Theodore G.; Rebbeck, Timothy R.

    2009-01-01

    Background Population history can be reflected in group genetic ancestry, where genomic variation captured by the mitochondrial DNA (mtDNA) and non-recombining portion of the Y chromosome (NRY) can separate female- and male-specific admixture processes. Genetic ancestry may influence genetic association studies due to differences in individual admixture within recently admixed populations like African Americans. Principal Findings We evaluated the genetic ancestry of Senegalese as well as European Americans and African Americans from Philadelphia. Senegalese mtDNA consisted of ∼12% U haplotypes (U6 and U5b1b haplotypes, common in North Africa) while the NRY haplotypes belonged solely to haplogroup E. In Philadelphia, we observed varying degrees of admixture. While African Americans have 9–10% mtDNAs and ∼31% NRYs of European origin, these results are not mirrored in the mtDNA/NRY pools of European Americans: they have less than 7% mtDNAs and less than 2% NRYs from non-European sources. Additionally, there is <2% Native American contribution to Philadelphian African American ancestry and the admixture from combined mtDNA/NRY estimates is consistent with the admixture derived from autosomal genetic data. To further dissect these estimates, we have analyzed our samples in the context of different demographic groups in the Americas. Conclusions We found that sex-biased admixture in African-derived populations is present throughout the Americas, with continual influence of European males, while Native American females contribute mainly to populations of the Caribbean and South America. The high non-European female contribution to the pool of European-derived populations is consistently characteristic of Iberian colonization. These data suggest that genomic data correlate well with historical records of colonization in the Americas. PMID:19946364

  12. The Geography of Recent Genetic Ancestry across Europe

    PubMed Central

    Ralph, Peter; Coop, Graham

    2013-01-01

    The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (in the Population Reference Sample [POPRES] dataset) to conduct one of the first surveys of recent genealogical ancestry over the past 3,000 years at a continental scale. We detected 1.9 million shared long genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 2–12 genetic common ancestors from the last 1,500 years, and upwards of 100 genetic ancestors from the previous 1,000 years. These numbers drop off exponentially with geographic distance, but since these genetic ancestors are a tiny fraction of common genealogical ancestors, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1,000 years. There is also substantial regional variation in the number of shared genetic ancestors. For example, there are especially high numbers of common ancestors shared between many eastern populations that date roughly to the migration period (which includes the Slavic and Hunnic expansions into that region). Some of the lowest levels of common ancestry are seen in the Italian and Iberian peninsulas, which may indicate different effects of historical population expansions in these areas and/or more stably structured populations. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world. PMID:23667324

  13. The geography of recent genetic ancestry across Europe.

    PubMed

    Ralph, Peter; Coop, Graham

    2013-01-01

    The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (in the Population Reference Sample [POPRES] dataset) to conduct one of the first surveys of recent genealogical ancestry over the past 3,000 years at a continental scale. We detected 1.9 million shared long genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 2-12 genetic common ancestors from the last 1,500 years, and upwards of 100 genetic ancestors from the previous 1,000 years. These numbers drop off exponentially with geographic distance, but since these genetic ancestors are a tiny fraction of common genealogical ancestors, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1,000 years. There is also substantial regional variation in the number of shared genetic ancestors. For example, there are especially high numbers of common ancestors shared between many eastern populations that date roughly to the migration period (which includes the Slavic and Hunnic expansions into that region). Some of the lowest levels of common ancestry are seen in the Italian and Iberian peninsulas, which may indicate different effects of historical population expansions in these areas and/or more stably structured populations. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.

  14. Anthropologists' views on race, ancestry, and genetics.

    PubMed

    Wagner, Jennifer K; Yu, Joon-Ho; Ifekwunigwe, Jayne O; Harrell, Tanya M; Bamshad, Michael J; Royal, Charmaine D

    2017-02-01

    Controversies over race conceptualizations have been ongoing for centuries and have been shaped, in part, by anthropologists. To assess anthropologists' views on race, genetics, and ancestry. In 2012 a broad national survey of anthropologists examined prevailing views on race, ancestry, and genetics. Results demonstrate consensus that there are no human biological races and recognition that race exists as lived social experiences that can have important effects on health. Racial privilege affects anthropologists' views on race, underscoring the importance that anthropologists be vigilant of biases in the profession and practice. Anthropologists must mitigate racial biases in society wherever they might be lurking and quash any sociopolitical attempts to normalize or promote racist rhetoric, sentiment, and behavior. © 2016 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.

  15. Anthropologists' views on race, ancestry, and genetics

    PubMed Central

    Yu, Joon‐Ho; Ifekwunigwe, Jayne O.; Harrell, Tanya M.; Bamshad, Michael J.; Royal, Charmaine D.

    2016-01-01

    Abstract Controversies over race conceptualizations have been ongoing for centuries and have been shaped, in part, by anthropologists. Objective To assess anthropologists' views on race, genetics, and ancestry. Methods In 2012 a broad national survey of anthropologists examined prevailing views on race, ancestry, and genetics. Results Results demonstrate consensus that there are no human biological races and recognition that race exists as lived social experiences that can have important effects on health. Discussion Racial privilege affects anthropologists' views on race, underscoring the importance that anthropologists be vigilant of biases in the profession and practice. Anthropologists must mitigate racial biases in society wherever they might be lurking and quash any sociopolitical attempts to normalize or promote racist rhetoric, sentiment, and behavior. PMID:27874171

  16. PCAdmix: Principal Components-Based Assignment of Ancestry along Each Chromosome in Individuals with Admixed Ancestry from Two or More Populations

    PubMed Central

    Brisbin, Abra; Bryc, Katarzyna; Byrnes, Jake; Zakharia, Fouad; Omberg, Larsson; Degenhardt, Jeremiah; Reynolds, Andrew; Ostrer, Harry; Mezey, Jason G.; Bustamante, Carlos D.

    2013-01-01

    Identifying ancestry along each chromosome in admixed individuals provides a wealth of information for understanding the population genetic history of admixture events and is valuable for admixture mapping and identifying recent targets of selection. We present PCAdmix (available at https://sites.google.com/site/pcadmix/home), a Principal Components-based algorithm for determining ancestry along each chromosome from a high-density, genome-wide set of phased single-nucleotide polymorphism (SNP) genotypes of admixed individuals. We compare our method to HAPMIX on simulated data from two ancestral populations, and we find high concordance between the methods. Our method also has better accuracy than LAMP when applied to three-population admixture, a situation as yet unaddressed by HAPMIX. Finally, we apply our method to a data set of four Latino populations with European, African, and Native American ancestry. We find evidence of assortative mating in each of the four populations, and we identify regions of shared ancestry that may be recent targets of selection and could serve as candidate regions for admixture-based association mapping. PMID:23249312

  17. High-speed optical correlator with coaxial holographic system

    NASA Astrophysics Data System (ADS)

    Ikeda, Kanami; Watanabe, Eriko

    2015-09-01

    A high-speed volume holographic optical correlator is developed, which takes advantage of a coaxial holographic system. We have realized this high-speed correlator using an optimal design of the signal pattern, which improves the shift multiplex recording shift pitch. The speed of this correlator was further improved by increasing the number of pixels in the spatial light modulator and using a high speed rotating actuator. This correlation system successfully achieved an equal error rate of 0% by performing optical correlation over 900 times. It also achieved optical correlation experiment, at a shift pitch of 2.45 µm and a disk rotation speed of 900 rpm. In terms of optical correlation calculation speed, it yielded a peak interval of 542 ns, which corresponds to 1.846 × 106 frames per second.

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

    PubMed Central

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

    2015-01-01

    Background Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified single nucleotide polymorphisms (SNPs) among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population. Methods We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions. Results We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele odds ratio (OR): 0.94 (95% confidence interval 0.74–1.20), 1.20 (0.94–1.53) and 1.49 (1.28–1.75) for current, former and never hormone therapy users, respectively, P-interaction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72–1.42), 1.19 (0.98–1.45) and 1.69 (1.26–2.26) for never, <12 months, and >12 months breastfeeding, respectively, P-interaction 0.014]. Conclusions The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women. Impact These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and non-genetic risk factors and their contribution to breast cancer risk. PMID:26364163

  19. AncestrySNPminer: A bioinformatics tool to retrieve and develop ancestry informative SNP panels

    PubMed Central

    Amirisetty, Sushil; Khurana Hershey, Gurjit K.; Baye, Tesfaye M.

    2012-01-01

    A wealth of genomic information is available in public and private databases. However, this information is underutilized for uncovering population specific and functionally relevant markers underlying complex human traits. Given the huge amount of SNP data available from the annotation of human genetic variation, data mining is a faster and cost effective approach for investigating the number of SNPs that are informative for ancestry. In this study, we present AncestrySNPminer, the first web-based bioinformatics tool specifically designed to retrieve Ancestry Informative Markers (AIMs) from genomic data sets and link these informative markers to genes and ontological annotation classes. The tool includes an automated and simple “scripting at the click of a button” functionality that enables researchers to perform various population genomics statistical analyses methods with user friendly querying and filtering of data sets across various populations through a single web interface. AncestrySNPminer can be freely accessed at https://research.cchmc.org/mershalab/AncestrySNPminer/login.php. PMID:22584067

  20. Color and genomic ancestry in Brazilians.

    PubMed

    Parra, Flavia C; Amado, Roberto C; Lambertucci, José R; Rocha, Jorge; Antunes, Carlos M; Pena, Sérgio D J

    2003-01-07

    This work was undertaken to ascertain to what degree the physical appearance of a Brazilian individual was predictive of genomic African ancestry. Using a panel of 10 population-specific alleles, we assigned to each person an African ancestry index (AAI). The procedure was able to tell apart, with no overlaps, 20 males from northern Portugal from 20 males from São Tomé Island on the west coast of Africa. We also tested 10 Brazilian Amerindians and observed that their AAI values fell in the same range as the Europeans. Finally, we studied two different Brazilian population samples. The first consisted of 173 individuals from a rural Southeastern community, clinically classified according to their Color (white, black, or intermediate) with a multivariate evaluation based on skin pigmentation in the medial part of the arm, hair color and texture, and the shape of the nose and lips. In contrast to the clear-cut results with the African and European samples, our results showed large variances and extensive overlaps among the three Color categories. We next embarked on a study of 200 unrelated Brazilian white males who originated from cosmopolitan centers of the four major geographic regions of the country. The results showed AAI values intermediate between Europeans and Africans, even in southern Brazil, a region predominantly peopled by European immigrants. Our data suggest that in Brazil, at an individual level, color, as determined by physical evaluation, is a poor predictor of genomic African ancestry, estimated by molecular markers.

  1. Color and genomic ancestry in Brazilians

    PubMed Central

    Parra, Flavia C.; Amado, Roberto C.; Lambertucci, José R.; Rocha, Jorge; Antunes, Carlos M.; Pena, Sérgio D. J.

    2003-01-01

    This work was undertaken to ascertain to what degree the physical appearance of a Brazilian individual was predictive of genomic African ancestry. Using a panel of 10 population-specific alleles, we assigned to each person an African ancestry index (AAI). The procedure was able to tell apart, with no overlaps, 20 males from northern Portugal from 20 males from São Tomé Island on the west coast of Africa. We also tested 10 Brazilian Amerindians and observed that their AAI values fell in the same range as the Europeans. Finally, we studied two different Brazilian population samples. The first consisted of 173 individuals from a rural Southeastern community, clinically classified according to their Color (white, black, or intermediate) with a multivariate evaluation based on skin pigmentation in the medial part of the arm, hair color and texture, and the shape of the nose and lips. In contrast to the clear-cut results with the African and European samples, our results showed large variances and extensive overlaps among the three Color categories. We next embarked on a study of 200 unrelated Brazilian white males who originated from cosmopolitan centers of the four major geographic regions of the country. The results showed AAI values intermediate between Europeans and Africans, even in southern Brazil, a region predominantly peopled by European immigrants. Our data suggest that in Brazil, at an individual level, color, as determined by physical evaluation, is a poor predictor of genomic African ancestry, estimated by molecular markers. PMID:12509516

  2. Morphological assessment of ancestry using cranial macromorphoscopics.

    PubMed

    Klales, Alexandra R; Kenyhercz, Michael W

    2015-01-01

    Ancestry estimation is essential for biological profile estimation in forensic anthropology. Hefner (2009) and Osteoware (Smithsonian Institution, 2011) presented 16 macromorphoscopic traits that can be scored for standardized data collection and can also be used within a statistical framework to estimate ancestry. The primary purpose of this research was to examine the utility of these traits for assessing ancestry. Tests of observer agreement and the range of variation in trait expression were evaluated. A sample of 208 American whites and blacks from the Hamann-Todd Collection were scored, and several classification methods were utilized in accordance with Hefner (2009). Correct classifications for the pooled sex analyses ranged from 73.3% to 86.6% and from 46.7% to 64.3% when the sexes were analyzed independently. Interobserver agreement was variable and was found to be lower than that presented in Hefner (2009). Trait expression was variable in both groups and was generally consistent with Hefner's findings. © 2014 American Academy of Forensic Sciences.

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

    PubMed

    Watkins, W Scott; Xing, Jinchuan; Huff, Chad; Witherspoon, David J; Zhang, Yuhua; Perego, Ugo A; Woodward, Scott R; Jorde, Lynn B

    2012-05-20

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

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

    PubMed Central

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

    2013-01-01

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

  5. RFMix: a discriminative modeling approach for rapid and robust local-ancestry inference.

    PubMed

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

    2013-08-08

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

  6. Race, African ancestry, and Helicobacter pylori infection in a low-income United States population.

    PubMed

    Epplein, Meira; Signorello, Lisa B; Zheng, Wei; Peek, Richard M; Michel, Angelika; Williams, Scott M; Pawlita, Michael; Correa, Pelayo; Cai, Qiuyin; Blot, William J

    2011-05-01

    Gastric cancer incidence in African Americans is twice that of whites, and differing prevalence of Helicobacter pylori strain-specific isolates may help explain the disparity. Serum levels of antibodies to each of 15 H. pylori proteins were assessed using multiplex serology for a sample of 689 African American and white participants from the Southern Community Cohort Study. African and European admixture was estimated using a panel of 276 ancestry genetic markers, with "low," "medium," and "high" categories of African ancestry defined as <85%, 85% to 95%, and ≥95%. The majority (79%) of our study population were sero-positive for H. pylori. African American race was associated with a two- to sixfold increased odds for sero-positivity to eight H. pylori proteins, including the cancer-associated virulence constituents CagA [odds ratio (OR), 6.4; 95% CI, 4.5-9.1], and VacA (OR, 2.3; 95% CI, 1.5-3.5). Compared to whites, African Americans of low, medium, and high African ancestry had 1.6-, 4.1-, and 5.2-fold increased odds of sero-positivity to H. pylori, primarily related to CagA sero-positive strains, for which increasing African ancestry led to 2.5-, 9.6-, and 13.1-fold increased odds. Among African Americans alone, compared to those of low African ancestry, African Americans of medium and high African ancestry had 2.5- and 3.4-fold increased odds of sero-positivity to H. pylori, and 3.5- and 4.9-fold increased odds of CagA sero-positive H. pylori strains. Host genetic variation and/or lifestyle factors associated with African ancestry contribute to the likelihood of infection with H. pylori, particularly its virulent strains, in this low-income U.S. southern population. Our findings that low-income African Americans of high African ancestry have a particularly high prevalence of antibodies against H. pylori provides a framework for further research into better detection and prevention of gastric cancer in this population. ©2011 AACR.

  7. African Ancestry and Higher Prevalence of Triple-Negative Breast Cancer

    PubMed Central

    Stark, Azadeh; Kleer, Celina G.; Martin, Iman; Awuah, Baffour; Nsiah-Asare, Anthony; Takyi, Valerie; Braman, Maria; Quayson, Solomon E.; Zarbo, Richard; Wicha, Max; Newman, Lisa

    2011-01-01

    BACKGROUND The study of breast cancer in women with African ancestry offers the promise of identifying markers for risk assessment and treatment of triple-negative disease. METHODS African American and white American women with invasive cancer diagnosed at the Henry Ford Health System comprised the primary study population, and Ghanaian patients diagnosed and/or treated at the Komfo Anokye Teaching Hospital in Kumasi, Ghana constituted the comparison group. Formalin-fixed, paraffin-embedded specimens were transported to the University of Michigan for histopathology confirmation, and assessment of estrogen and progesterone receptors and HER-2/neu expression. RESULTS The study population included 1008 white Americans, 581 African Americans, and 75 Ghanaians. Mean age at diagnosis was 48.0 years for Ghanaian, 60.8 years for African American, and 62.4 for white American cases (P =.002). Proportions of Ghanaian, African American, and white American cases with estrogen receptor-negative tumors were 76%, 36%, and 22%, respectively (P < .001), and proportions with triple-negative disease were 82%, 26%, and 16%, respectively (P < .001). All Ghanaian cases were palpable, locally advanced cancers; 57 (76%) were grade 3. A total of 147 American women were diagnosed as stage III or IV; of these, 67.5% (n =46) of African Americans and 44.6% (n = 29) of white Americans were grade 3. Among palpable, grade 3 cancers, Ghanaians had the highest prevalence of triple-negative tumors (82.2%), followed by African Americans (32.8%) and white Americans (10.2%). CONCLUSIONS Our study demonstrates progressively increasing frequency of estrogen receptor-negative and triple-negative tumors among breast cancer patients with white American, African American, and Ghanaian/African backgrounds. This pattern indicates a need for additional investigations correlating the extent of African ancestry and high-risk breast cancer subtypes. PMID:20629078

  8. Race, African ancestry, and Helicobacter pylori infection in a low-income United States population

    PubMed Central

    Epplein, Meira; Signorello, Lisa B.; Zheng, Wei; Peek, Richard M.; Michel, Angelika; Williams, Scott M.; Pawlita, Michael; Correa, Pelayo; Cai, Qiuyin; Blot, William J.

    2011-01-01

    Background Gastric cancer incidence in African Americans is twice that of whites, and differing prevalence of Helicobacter pylori strain-specific isolates may help explain the disparity. Methods Serum levels of antibodies to each of 15 Helicobacter pylori proteins were assessed using multiplex serology for a sample of 689 African American and white participants from the Southern Community Cohort Study. African and European admixture was estimated using a panel of 276 ancestry genetic markers, with “low”, “medium”, and “high” categories of African ancestry defined as <85%, 85-95%, and ≥95%. Results The majority (79%) of our study population were sero-positive for Helicobacter pylori. African American race was associated with a 2- to 6-fold increased odds for sero-positivity to 8 Helicobacter pylori proteins, including the cancer-associated virulence constituents CagA (odds ratio, 6.4; 95% confidence interval, 4.5-9.1), and VacA (odds ratio, 2.3; 95% confidence interval, 1.5-3.5). Compared to whites, African Americans of low, medium, and high African ancestry had 1.6-, 4.1-, and 5.2-fold increased odds of sero-positivity to Helicobacter pylori, primarily related to CagA sero-positive strains, for which increasing African ancestry led to 2.5-, 9.6-, and 13.1-fold increased odds. Among African Americans alone, compared to those of low African ancestry, African Americans of medium and high African ancestry had 2.5- and 3.4-fold increased odds of sero-positivity to Helicobacter pylori, and 3.5-and 4.9-fold increased odds of CagA sero-positive Helicobacter pylori strains. Conclusions Host genetic variation and/or lifestyle factors associated with African ancestry contribute to the likelihood of infection with Helicobacter pylori, particularly its virulent strains, in this low-income U.S. southern population. Impact Our findings that low-income African Americans of high African ancestry have a particularly high prevalence of antibodies against Helicobacter

  9. Differentiation of African Components of Ancestry to Stratify Groups in a Case–Control Study of a Brazilian Urban Population

    PubMed Central

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

    2012-01-01

    Background: Balancing the subject composition of case and control groups to create homogenous ancestries between each group is essential for medical association studies. Methods: We explored the applicability of single-tube 34-plex ancestry informative markers (AIM) single nucleotide polymorphisms (SNPs) to estimate the African Component of Ancestry (ACA) to design a future case–control association study of a Brazilian urban sample. Results: One hundred eighty individuals (107 case group; 73 control group) self-described as white, brown-intermediate or black were selected. The proportions of the relative contribution of a variable number of ancestral population components were similar between case and control groups. Moreover, the case and control groups demonstrated similar distributions for ACA <0.25 and >0.50 categories. Notably a high number of outlier values (23 samples) were observed among individuals with ACA <0.25. These individuals presented a high probability of Native American and East Asian ancestral components; however, no individuals originally giving these self-described ancestries were observed in this study. Conclusions: The strategy proposed for the assessment of ancestry and adjustment of case and control groups for an association study is an important step for the proper construction of the study, particularly when subjects are taken from a complex urban population. This can be achieved using a straight forward multiplexed AIM-SNPs assay of highly discriminatory ancestry markers. PMID:22288895

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

    PubMed

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

    2012-06-01

    Balancing the subject composition of case and control groups to create homogenous ancestries between each group is essential for medical association studies. We explored the applicability of single-tube 34-plex ancestry informative markers (AIM) single nucleotide polymorphisms (SNPs) to estimate the African Component of Ancestry (ACA) to design a future case-control association study of a Brazilian urban sample. One hundred eighty individuals (107 case group; 73 control group) self-described as white, brown-intermediate or black were selected. The proportions of the relative contribution of a variable number of ancestral population components were similar between case and control groups. Moreover, the case and control groups demonstrated similar distributions for ACA <0.25 and >0.50 categories. Notably a high number of outlier values (23 samples) were observed among individuals with ACA <0.25. These individuals presented a high probability of Native American and East Asian ancestral components; however, no individuals originally giving these self-described ancestries were observed in this study. The strategy proposed for the assessment of ancestry and adjustment of case and control groups for an association study is an important step for the proper construction of the study, particularly when subjects are taken from a complex urban population. This can be achieved using a straight forward multiplexed AIM-SNPs assay of highly discriminatory ancestry markers.

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

    PubMed

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

    2016-05-04

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

  12. Ultraconserved words point to deep language ancestry across Eurasia

    PubMed Central

    Pagel, Mark; Atkinson, Quentin D.; S. Calude, Andreea; Meade, Andrew

    2013-01-01

    The search for ever deeper relationships among the World’s languages is bedeviled by the fact that most words evolve too rapidly to preserve evidence of their ancestry beyond 5,000 to 9,000 y. On the other hand, quantitative modeling indicates that some “ultraconserved” words exist that might be used to find evidence for deep linguistic relationships beyond that time barrier. Here we use a statistical model, which takes into account the frequency with which words are used in common everyday speech, to predict the existence of a set of such highly conserved words among seven language families of Eurasia postulated to form a linguistic superfamily that evolved from a common ancestor around 15,000 y ago. We derive a dated phylogenetic tree of this proposed superfamily with a time-depth of ∼14,450 y, implying that some frequently used words have been retained in related forms since the end of the last ice age. Words used more than once per 1,000 in everyday speech were 7- to 10-times more likely to show deep ancestry on this tree. Our results suggest a remarkable fidelity in the transmission of some words and give theoretical justification to the search for features of language that might be preserved across wide spans of time and geography. PMID:23650390

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

    PubMed

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

    2017-02-17

    Melasma is a chronic acquired focal hypermelanosis affecting photoexposed areas, especially for women during fertile age. Several factors contribute to its development: sun exposure, sex steroids, medicines, and family history. Melanic pigmentation pathway discloses several SNPs in different populations. Here, we evaluated the association between genetic ancestry and facial melasma. A cross-sectional study involving women with melasma and an age-matched control group from outpatients at FMB-Unesp, Botucatu-SP, Brazil was performed. DNA was extracted from oral mucosa swabs and ancestry determined by studying 61 INDELs. The genetic ancestry components were adjusted by other known risk factors by multiple logistic regression. We evaluated 119 women with facial melasma and 119 controls. Mean age was 39 ± 9 years. Mean age at beginning of disease was 27 ± 8 years. Pregnancy (40%), sun exposure (37%), and hormonal oral contraception (22%) were the most frequently reported melasma triggers. All subjects presented admixed ancestry, African and European genetic contributions were significantly different between cases and controls (respectively 10% vs 6%; 77% vs 82%; p < 0.05). African ancestry (OR = 1.04; 95% CI 1.01 to 1.07), first generation family history (OR = 3.04; 95% CI 1.56 to 5.94), low education level (OR = 4.04; 95% CI 1.56 to 5.94), and use of antidepressants by individuals with affected family members (OR = 6.15; 95% CI 1.13 to 33.37) were associated with melasma, independently of other known risk factors. Facial melasma was independently associated with African ancestry in a highly admixed population.

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

    PubMed

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

    2016-01-01

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

  15. Modification of Multiple Sclerosis Phenotypes by African Ancestry at HLA

    PubMed Central

    Cree, Bruce A. C.; Reich, David E.; Khan, Omar; De Jager, Philip L.; Nakashima, Ichiro; Takahashi, Toshiyuki; Bar-Or, Amit; Tong, Christine; Hauser, Stephen L.; Oksenberg, Jorge R.

    2015-01-01

    Background In those with multiple sclerosis (MS), African American individuals have a more severe disease course, an older age at onset, and more often have clinical manifestations restricted to the optic nerves and spinal cord (opticospinal MS) than white persons. Objective To determine whether genetic variation influences clinical MS patterns. Design Retrospective multicenter cohort study. Participants Six hundred seventy-three African American and 717 white patients with MS. Main Outcome Measures Patients with MS were geno-typed for HLA-DRB1 and HLA-DQB1 alleles. The proportion of European ancestry at HLA was estimated by genotyping single-nucleotide polymorphisms with known significant frequency differences in West African and European populations. These genotypes were correlated with the opticospinal disease phenotype, disability measures, and age at onset. Results Subjects with DRB1*15 alleles were twice as likely to have typical MS rather than opticospinal MS (P = .001). Of the subjects with opticospinal MS or a history of recurrent transverse myelitis who were seropositive for anti–aquaporin 4 antibodies (approximately 5%), none carried DRB1*15 alleles (P = .008). Independently of DRB1* 15, African ancestry at HLA correlated with disability as measured by the Multiple Sclerosis Severity Score (P < .001) andriskof cane dependency (hazard ratio, 1.36; P < .001); DRB1*15 alleles were associated with a 2.1-year earlier age at onset (P < .001). Conclusions These data indicate that the role of HLA in MS is not limited to disease susceptibility but that genes embedded in this locus also influence clinical outcomes. PMID:19204159

  16. Modification of Multiple Sclerosis Phenotypes by African Ancestry at HLA.

    PubMed

    Cree, Bruce A C; Reich, David E; Khan, Omar; De Jager, Philip L; Nakashima, Ichiro; Takahashi, Toshiyuki; Bar-Or, Amit; Tong, Christine; Hauser, Stephen L; Oksenberg, Jorge R

    2009-02-01

    In those with multiple sclerosis (MS), African American individuals have a more severe disease course, an older age at onset, and more often have clinical manifestations restricted to the optic nerves and spinal cord (opticospinal MS) than white persons. To determine whether genetic variation influences clinical MS patterns. Retrospective multicenter cohort study. Six hundred seventy-three African American and 717 white patients with MS. Patients with MS were genotyped for HLA-DRB1 and HLA-DQB1 alleles. The proportion of European ancestry at HLA was estimated by genotyping single-nucleotide polymorphisms with known significant frequency differences in West African and European populations. These genotypes were correlated with the opticospinal disease phenotype, disability measures, and age at onset. Subjects with DRB1*15 alleles were twice as likely to have typical MS rather than opticospinal MS (P = .001). Of the subjects with opticospinal MS or a history of recurrent transverse myelitis who were seropositive for anti-aquaporin 4 antibodies (approximately 5%), none carried DRB1*15 alleles (P = .008). Independently of DRB1*15, African ancestry at HLA correlated with disability as measured by the Multiple Sclerosis Severity Score (P < .001) and risk of cane dependency (hazard ratio, 1.36; P < .001); DRB1*15 alleles were associated with a 2.1-year earlier age at onset (P < .001). These data indicate that the role of HLA in MS is not limited to disease susceptibility but that genes embedded in this locus also influence clinical outcomes.

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

    PubMed

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

    2017-01-09

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

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

    PubMed

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

    2016-01-01

    A single-tube multiplex assay of a small set of ancestry-informative markers (AIMs) for effectively estimating individual ancestry and admixture is an ideal forensic tool to trace the population origin of an unknown DNA sample. We present a newly developed 27-plex single nucleotide polymorphism (SNP) panel with highly robust and balanced differential power to perfectly assign individuals to African, European, and East Asian ancestries. Evaluating 968 previously described intercontinental AIMs from three HapMap population genotyping datasets (Yoruban in Ibadan, Nigeria (YRI); Utah residents with Northern and Western European ancestry from the Centre de'Etude du Polymorphism Humain (CEPH) collection (CEU); and Han Chinese in Beijing, China (CHB)), the best set of markers was selected on the basis of Hardy-Weinberg equilibrium (p > 0.00001), population-specific allele frequency (two of three δ values >0.5), according to linkage disequilibrium (r (2) < 0.2), and capable of being multiplexed in one tube and detected by capillary electrophoresis. The 27-SNP panel was first validated by assigning the ancestry of the 11 populations in the HapMap project. Then, we tested the 27-plex SNP assay with 1164 individuals from 17 additional populations. The results demonstrated that the SNP panel was successful for ancestry inference of individuals with African, European, and East Asian ancestry. Furthermore, the system performed well when inferring the admixture of Eurasians (EUR/EAS) after analyzing admixed populations from Xinjiang (Central Asian) as follows: Tajik (68:27), Uyghur (49:46), Kirgiz (40:57), and Kazak (36:60). For individual analyses, we interpreted each sample with a three-ancestry component percentage and a population match probability sequence. This multiplex assay is a convenient and cost-effective tool to assist in criminal investigations, as well as to correct for the effects of population stratification for case-control studies.

  19. Genomic variation associated with mortality among adults of European and African ancestry with heart failure: the CHARGE Consortium

    PubMed Central

    Morrison, Alanna C.; Felix, Janine F.; Cupples, L. Adrienne; Glazer, Nicole L.; Loehr, Laura R.; Dehghan, Abbas; Demissie, Serkalem; Bis, Joshua C.; Rosamond, Wayne D.; Aulchenko, Yurii S.; Wang, Ying A.; Haritunians, Talin; Folsom, Aaron R.; Rivadeneira, Fernando; Benjamin, Emelia J.; Lumley, Thomas; Couper, David; Stricker, Bruno H.; O'Donnell, Christopher J.; Rice, Kenneth M.; Chang, Patricia P.; Hofman, Albert; Levy, Daniel; Rotter, Jerome I.; Fox, Ervin R.; Uitterlinden, Andre G.; Wang, Thomas J.; Psaty, Bruce M.; Willerson, James T.; van Duijn, Cornelia M.; Boerwinkle, Eric; Witteman, Jacqueline C. M.; Vasan, Ramachandran S.; Smith, Nicholas L.

    2011-01-01

    Background Prognosis and survival are significant concerns for individuals with heart failure (HF). In order to better understand the pathophysiology of HF prognosis, the association between 2,366,858 single nucleotide polymorphisms (SNPs) and all-cause mortality was evaluated among individuals with incident HF from four community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. Methods and Results Participants were 2,526 individuals of European ancestry and 466 individuals of African ancestry who suffered an incident HF event during follow-up in the respective cohorts. Within each study, the association between genetic variants and time to mortality among individuals with HF was assessed by Cox proportional hazards models that included adjustment for sex and age at the time of the HF event. Prospective fixed-effect meta-analyses were conducted for the four study populations of European ancestry (N=1,645 deaths) and for the two populations of African ancestry (N=281 deaths). Genome-wide significance was set at P=5.0×10-7. Meta-analytic findings among individuals of European ancestry revealed one genome-wide significant locus on chromosome 3p22 in an intron of CKLF-like MARVEL transmembrane domain containing 7 (CMTM7, p = 3.2×10-7). Eight additional loci in individuals of European ancestry and four loci in individuals of African ancestry were identified by high-signal SNPs (p < 1.0×10-5), but did not meet genome-wide significance. Conclusions This study identified a novel locus associated with all-cause mortality among individuals of European ancestry with HF. This finding warrants additional investigation, including replication, in other studies of HF. PMID:20400778

  20. A Genome-wide Admixture Scan for Ancestry-linked Genes Predisposing to Sarcoidosis in African Americans

    PubMed Central

    Rybicki, Benjamin A.; Levin, Albert M.; McKeigue, Paul; Datta, Indrani; Gray-McGuire, Courtney; Colombo, Marco; Reich, David; Burke, Robert R.; Iannuzzi, Michael C.

    2010-01-01

    Genome-wide linkage and association studies have uncovered variants associated with sarcoidosis, a multi-organ granulomatous inflammatory disease. African ancestry may influence disease pathogenesis since African Americans are more commonly affected by sarcoidosis. Therefore, we conducted the first sarcoidosis genome-wide ancestry scan using a map of 1,384 highly ancestry informative single nucleotide polymorphisms genotyped on 1,357 sarcoidosis cases and 703 unaffected controls self-identified as African American. The most significant ancestry association was at marker rs11966463 on chromosome 6p22.3 (ancestry association risk ratio (aRR)= 1.90; p=0.0002). When we restricted the analysis to biopsy-confirmed cases, the aRR for this marker increased to 2.01; p=0.00007. Among the eight other markers that demonstrated suggestive ancestry associations with sarcoidosis were rs1462906 on chromosome 8p12 which had the most significant association with European ancestry (aRR=0.65; p=0.002), and markers on chromosomes 5p13 (aRR=1.46; p=0.005) and 5q31 (aRR=0.67; p=0.005), which correspond to regions we previously identified through sib pair linkage analyses. Overall, the most significant ancestry association for Scadding stage IV cases was to marker rs7919137 on chromosome 10p11.22 (aRR=0.27; p=2×10−5), a region not associated with disease susceptibility. In summary, through admixture mapping of sarcoidosis we have confirmed previous genetic linkages and identified several novel putative candidate loci for sarcoidosis. PMID:21179114

  1. Entropy measure of credit risk in highly correlated markets

    NASA Astrophysics Data System (ADS)

    Gottschalk, Sylvia

    2017-07-01

    We compare the single and multi-factor structural models of corporate default by calculating the Jeffreys-Kullback-Leibler divergence between their predicted default probabilities when asset correlations are either high or low. Single-factor structural models assume that the stochastic process driving the value of a firm is independent of that of other companies. A multi-factor structural model, on the contrary, is built on the assumption that a single firm's value follows a stochastic process correlated with that of other companies. Our main results show that the divergence between the two models increases in highly correlated, volatile, and large markets, but that it is closer to zero in small markets, when asset correlations are low and firms are highly leveraged. These findings suggest that during periods of financial instability, when asset volatility and correlations increase, one of the models misreports actual default risk.

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

    PubMed

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

    2017-04-01

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

  3. Impact of Genetic Ancestry and Socio-Demographic Status on the Clinical Expression of Systemic Lupus Erythematosus in Amerindian-European Populations

    PubMed Central

    Sánchez, Elena; Rasmussen, Astrid; Riba, Laura; Acevedo, Eduardo; Kelly, Jennifer A.; Langefeld, Carl D.; García-De La Torre, Ignacio; Maradiaga-Ceceña, Marco A.; Cardiel, Mario H.; Esquivel-Valerio, Jorge A.; Rodriguez-Amado, Jacqueline; Moctezuma, José Francisco; Miranda, Pedro; Perandones, Carlos; Castel, Cecilia; Laborde, Hugo A.; Alba, Paula; Musuruana, Jorge; Goecke, Annelise; Anaya, Juan-Manuel; Kaufman, Kenneth M.; Adler, Adam; Brown, Elizabeth E.; Alarcón, Graciela S.; Kimberly, Robert P.; Edberg, Jeffrey C.; Criswell, Lindsey A.; Gilkeson, Gary S.; Niewold, Timothy B.; Martin, Javier; Vyse, Timothy J.; Ramsey-Goldman, Rosalind; Petri, Michelle; Merrill, Joan T.; Reveille, John D.; Tsao, Betty P.; Orozco, Lorena; Baca, Vicente; James, Judith A.; Harley, John B.; Tusié-Luna, Teresa; Pons-Estel, Bernardo A.; Jacob, Chaim O.; Alarcón-Riquelme, Marta E.

    2012-01-01

    Objective Amerindian-Europeans, Asians and African-Americans have an excess morbidity from SLE and higher prevalence of lupus nephritis than Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and socio-demographic characteristics and clinical features in a large cohort of Amerindian-European SLE patients. Methods A total of 2116 SLE patients of Amerindian-European origin and 4001 SLE patients of European descent with clinical data were used in the study. Genotyping of 253 continental ancestry informative markers was performed on the Illumina platform. The STRUCTURE and ADMIXTURE software were used to determine genetic ancestry of each individual. Correlation between ancestry and socio-demographic and clinical data were analyzed using logistic regression. Results The average Amerindian genetic ancestry of 2116 SLE patients was 40.7%. There was an increased risk of having renal involvement (P<0.0001, OR= 3.50 95%CI 2.63-4.63) and an early age of onset with the presence of Amerindian genetic ancestry (P<0.0001). Amerindian ancestry protected against photosensitivity (P<0.0001, OR= 0.58 95%CI 0.44-0.76), oral ulcers (P<0.0001, OR= 0.55 95%CI 0.42-0.72), and serositis (P<0.0001, OR= 0.56 95%CI 0.41-0.75) after adjustment by age, gender and age of onset. However, gender and age of onset had stronger effects on malar rash, discoid rash, arthritis and neurological involvement than genetic ancestry. Conclusion In general, genetic Amerindian ancestry correlates with lower socio-demographic status and increases the risk for developing renal involvement and SLE at an earlier age of onset. PMID:22886787

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

    PubMed

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

    2016-05-01

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

  5. Strong association of socioeconomic status with genetic ancestry in Latinos: implications for admixture studies of type 2 diabetes

    PubMed Central

    Florez, J. C.; Price, A. L.; Campbell, D.; Riba, L.; Parra, M. V.; Yu, F.; Duque, C.; Saxena, R.; Gallego, N.; Tello-Ruiz, M.; Franco, L.; Rodríguez-Torres, M.; Villegas, A.; Bedoya, G.; Aguilar-Salinas, C. A.; Tusié-Luna, M. T.; Ruiz-Linares, A.; Reich, D.

    2011-01-01

    Aims/hypothesis Type 2 diabetes is more prevalent in US American minority populations of African or Native American descent than it is in European Americans. However, the proportion of this epidemiological difference that can be ascribed to genetic or environmental factors is unknown. To determine whether genetic ancestry is correlated with diabetes risk in Latinos, we estimated the proportion of European ancestry in case-control samples from Mexico and Colombia in whom socioeconomic status had been carefully ascertained. Methods We genotyped 67 ancestry-informative markers in 499 participants with type 2 diabetes and 197 controls from Medellín (Colombia), as well as in 163 participants with type 2 diabetes and 72 controls from central Mexico. Each participant was assigned a socioeconomic status scale via various measures. Results Although European ancestry was associated with lower diabetes risk in Mexicans (OR [95% CI] 0.06 [0.02–0.21], p=2.0 × 10−5) and Colombians (OR 0.26 [0.08–0.78], p=0.02), adjustment for socioeconomic status eliminated the association in the Colombian sample (OR 0.64 [0.19–2.12], p=0.46) and significantly attenuated it in the Mexican sample (OR 0.17 [0.04–0.71], p=0.02). Adjustment for BMI did not change the results. Conclusions/interpretation The proportion of non-European ancestry is associated with both type 2 diabetes and lower socioeconomic status in admixed Latino populations from North and South America. We conclude that ancestry-directed search for genetic markers associated with type 2 diabetes in Latinos may benefit from information involving social factors, as these factors have a quantitatively important effect on type 2 diabetes risk relative to ancestry effects. PMID:19526211

  6. Strong association of socioeconomic status with genetic ancestry in Latinos: implications for admixture studies of type 2 diabetes.

    PubMed

    Florez, J C; Price, A L; Campbell, D; Riba, L; Parra, M V; Yu, F; Duque, C; Saxena, R; Gallego, N; Tello-Ruiz, M; Franco, L; Rodríguez-Torres, M; Villegas, A; Bedoya, G; Aguilar-Salinas, C A; Tusié-Luna, M T; Ruiz-Linares, A; Reich, D

    2009-08-01

    Type 2 diabetes is more prevalent in US American minority populations of African or Native American descent than it is in European Americans. However, the proportion of this epidemiological difference that can be ascribed to genetic or environmental factors is unknown. To determine whether genetic ancestry is correlated with diabetes risk in Latinos, we estimated the proportion of European ancestry in case-control samples from Mexico and Colombia in whom socioeconomic status had been carefully ascertained. We genotyped 67 ancestry-informative markers in 499 participants with type 2 diabetes and 197 controls from Medellín (Colombia), as well as in 163 participants with type 2 diabetes and 72 controls from central Mexico. Each participant was assigned a socioeconomic status scale via various measures. Although European ancestry was associated with lower diabetes risk in Mexicans (OR [95% CI] 0.06 [0.02-0.21], p = 2.0 x 10(-5)) and Colombians (OR 0.26 [0.08-0.78], p = 0.02), adjustment for socioeconomic status eliminated the association in the Colombian sample (OR 0.64 [0.19-2.12], p = 0.46) and significantly attenuated it in the Mexican sample (OR 0.17 [0.04-0.71], p = 0.02). Adjustment for BMI did not change the results. The proportion of non-European ancestry is associated with both type 2 diabetes and lower socioeconomic status in admixed Latino populations from North and South America. We conclude that ancestry-directed search for genetic markers associated with type 2 diabetes in Latinos may benefit from information involving social factors, as these factors have a quantitatively important effect on type 2 diabetes risk relative to ancestry effects.

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

    PubMed Central

    2016-01-01

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

  8. Genome measures used for quality control are dependent on gene function and ancestry

    PubMed Central

    Wang, Jing; Raskin, Leon; Samuels, David C.; Shyr, Yu; Guo, Yan

    2015-01-01

    Motivation: The transition/transversion (Ti/Tv) ratio and heterozygous/nonreference-homozygous (het/nonref-hom) ratio have been commonly computed in genetic studies as a quality control (QC) measurement. Additionally, these two ratios are helpful in our understanding of the patterns of DNA sequence evolution. Results: To thoroughly understand these two genomic measures, we performed a study using 1000 Genomes Project (1000G) released genotype data (N = 1092). An additional two datasets (N = 581 and N = 6) were used to validate our findings from the 1000G dataset. We compared the two ratios among continental ancestry, genome regions and gene functionality. We found that the Ti/Tv ratio can be used as a quality indicator for single nucleotide polymorphisms inferred from high-throughput sequencing data. The Ti/Tv ratio varies greatly by genome region and functionality, but not by ancestry. The het/nonref-hom ratio varies greatly by ancestry, but not by genome regions and functionality. Furthermore, extreme guanine + cytosine content (either high or low) is negatively associated with the Ti/Tv ratio magnitude. Thus, when performing QC assessment using these two measures, care must be taken to apply the correct thresholds based on ancestry and genome region. Failure to take these considerations into account at the QC stage will bias any following analysis. Contact: yan.guo@vanderbilt.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25297068

  9. Genome measures used for quality control are dependent on gene function and ancestry.

    PubMed

    Wang, Jing; Raskin, Leon; Samuels, David C; Shyr, Yu; Guo, Yan

    2015-02-01

    The transition/transversion (Ti/Tv) ratio and heterozygous/nonreference-homozygous (het/nonref-hom) ratio have been commonly computed in genetic studies as a quality control (QC) measurement. Additionally, these two ratios are helpful in our understanding of the patterns of DNA sequence evolution. To thoroughly understand these two genomic measures, we performed a study using 1000 Genomes Project (1000G) released genotype data (N=1092). An additional two datasets (N=581 and N=6) were used to validate our findings from the 1000G dataset. We compared the two ratios among continental ancestry, genome regions and gene functionality. We found that the Ti/Tv ratio can be used as a quality indicator for single nucleotide polymorphisms inferred from high-throughput sequencing data. The Ti/Tv ratio varies greatly by genome region and functionality, but not by ancestry. The het/nonref-hom ratio varies greatly by ancestry, but not by genome regions and functionality. Furthermore, extreme guanine + cytosine content (either high or low) is negatively associated with the Ti/Tv ratio magnitude. Thus, when performing QC assessment using these two measures, care must be taken to apply the correct thresholds based on ancestry and genome region. Failure to take these considerations into account at the QC stage will bias any following analysis. yan.guo@vanderbilt.edu Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Socioeconomic and Nutritional Factors Account for the Association of Gastric Cancer with Amerindian Ancestry in a Latin American Admixed Population

    PubMed Central

    Pereira, Latife; Zamudio, Roxana; Soares-Souza, Giordano; Herrera, Phabiola; Cabrera, Lilia; Hooper, Catherine C.; Cok, Jaime; Combe, Juan M.; Vargas, Gloria; Prado, William A.; Schneider, Silvana; Kehdy, Fernanda; Rodrigues, Maira R.; Chanock, Stephen J.; Berg, Douglas E.; Gilman, Robert H.; Tarazona-Santos, Eduardo

    2012-01-01

    Gastric cancer is one of the most lethal types of cancer and its incidence varies worldwide, with the Andean region of South America showing high incidence rates. We evaluated the genetic structure of the population from Lima (Peru) and performed a case-control genetic association study to test the contribution of African, European, or Native American ancestry to risk for gastric cancer, controlling for the effect of non-genetic factors. A wide set of socioeconomic, dietary, and clinic information was collected for each participant in the study and ancestry was estimated based on 103 ancestry informative markers. Although the urban population from Lima is usually considered as mestizo (i.e., admixed from Africans, Europeans, and Native Americans), we observed a high fraction of Native American ancestry (78.4% for the cases and 74.6% for the controls) and a very low African ancestry (<5%). We determined that higher Native American individual ancestry is associated with gastric cancer, but socioeconomic factors associated both with gastric cancer and Native American ethnicity account for this association. Therefore, the high incidence of gastric cancer in Peru does not seem to be related to susceptibility alleles common in this population. Instead, our result suggests a predominant role for ethnic-associated socioeconomic factors and disparities in access to health services. Since Native Americans are a neglected group in genomic studies, we suggest that the population from Lima and other large cities from Western South America with high Native American ancestry background may be convenient targets for epidemiological studies focused on this ethnic group. PMID:22870209

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

    PubMed

    Pereira, Latife; Zamudio, Roxana; Soares-Souza, Giordano; Herrera, Phabiola; Cabrera, Lilia; Hooper, Catherine C; Cok, Jaime; Combe, Juan M; Vargas, Gloria; Prado, William A; Schneider, Silvana; Kehdy, Fernanda; Rodrigues, Maira R; Chanock, Stephen J; Berg, Douglas E; Gilman, Robert H; Tarazona-Santos, Eduardo

    2012-01-01

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

  12. Ancestry and Severity of Disability: A National Study.

    ERIC Educational Resources Information Center

    Wheaton, Joe E.; Hertzfeld, Jennifer

    2002-01-01

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

  13. African Ancestry Is Associated with Higher Intraocular Pressure in Latinos.

    PubMed

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

    2016-01-01

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

  14. African ancestry is associated with higher intraocular pressure in Latinos

    PubMed Central

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

    2015-01-01

    Purpose Intraocular pressure (IOP) is a major risk factor, as well as the only modifiable risk factor, for glaucoma. Racial differences have been observed in IOP measurements with individuals of African descent experiencing the highest IOP when compared to other ethnic groups. The purpose of this study is to examine the relationship between genetic ancestry and IOP in Latinos. Design Population-based genetic association study. Participants A total of 3541 participants recruited from the Los Angeles Latino Eye Study (LALES). Methods Study participants were genotyped using the Illumina OmniExpress BeadChip (~730K markers). We used STRUCTURE to estimate individual genetic ancestry. Simple and multiple linear regression, as well as quantile regression, analyses were performed to investigate the relationship between genetic ancestry and IOP. Main Outcome Measures The relationship between genetic ancestry and IOP in Latinos. Results African ancestry was significantly associated with higher IOP in Latinos in our simple linear regression analysis (P = 0.002). After adjusting for age, gender, body mass index, systolic blood pressure, central corneal thickness, and type 2 diabetes, this association remained significant (P = 0.0005). The main association was modified by a significant interaction between African ancestry and hypertension (P = 0.037), with hypertensive individuals experiencing a larger increase in IOP with increasing African ancestry. Conclusions To our knowledge, we demonstrate for the first time that African ancestry and its interaction with hypertension are associated with higher IOP in Latinos. PMID:26477841

  15. High‐altitude ancestry protects against hypoxia‐associated reductions in fetal growth

    PubMed Central

    Julian, Colleen Glyde; Vargas, Enrique; Armaza, J Fernando; Wilson, Megan J; Niermeyer, Susan; Moore, Lorna G

    2007-01-01

    Objective The chronic hypoxia of high‐altitude (⩾2500 m) residence has been shown to decrease birth weight in all populations studied to date. However, multigenerational high‐altitude populations appear protected relative to newcomer groups. This study aimed to determine whether such protection exists independently of other factors known to influence fetal growth and whether admixed populations (ie, people having both high‐ and low‐altitude ancestry) show an intermediate level of protection. Design 3551 medical records from consecutive deliveries to Andean, European or Mestizo (ie, admixed) women at low, intermediate or high altitudes in Bolivia were evaluated for maternal characteristics influencing fetal growth as measured by birth weight and the frequency of small for gestational age births (SGA or ⩽10th percentile birth weight for gestational age and sex). Two‐way analysis of variance and χ2 tests were used to compare maternal and infant characteristics. The effects of ancestry or altitude on SGA and birth weight were assessed using logistic or linear regression models, respectively. Results Altitude decreased birth weight and increased SGA in all ancestry groups. Andean infants weighed more and were less often SGA than Mestizo or European infants at high altitude (13%, 16% and 33% respectively, p<0.01). After accounting for the influences of maternal hypertensive complications of pregnancy, parity, body weight, and number of prenatal visits, European relative to Andean ancestry increased the frequency of SGA at high altitude nearly fivefold. Conclusions Andean relative to European ancestry protects against altitude‐associated reductions in fetal growth. The intermediate protection seen in the admixed (Mestizo) group is consistent with the influence of genetic or other Andean‐specific protective characteristics. PMID:17329275

  16. A Highly Accurate Face Recognition System Using Filtering Correlation

    NASA Astrophysics Data System (ADS)

    Watanabe, Eriko; Ishikawa, Sayuri; Kodate, Kashiko

    2007-09-01

    The authors previously constructed a highly accurate fast face recognition optical correlator (FARCO) [E. Watanabe and K. Kodate: Opt. Rev. 12 (2005) 460], and subsequently developed an improved, super high-speed FARCO (S-FARCO), which is able to process several hundred thousand frames per second. The principal advantage of our new system is its wide applicability to any correlation scheme. Three different configurations were proposed, each depending on correlation speed. This paper describes and evaluates a software correlation filter. The face recognition function proved highly accurate, seeing that a low-resolution facial image size (64 × 64 pixels) has been successfully implemented. An operation speed of less than 10 ms was achieved using a personal computer with a central processing unit (CPU) of 3 GHz and 2 GB memory. When we applied the software correlation filter to a high-security cellular phone face recognition system, experiments on 30 female students over a period of three months yielded low error rates: 0% false acceptance rate and 2% false rejection rate. Therefore, the filtering correlation works effectively when applied to low resolution images such as web-based images or faces captured by a monitoring camera.

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

    PubMed Central

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

    2013-01-01

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

  18. Epidemiology, biology, and treatment of triple-negative breast cancer in women of African ancestry

    PubMed Central

    Brewster, Abenaa M; Chavez-MacGregor, Mariana; Brown, Powel

    2015-01-01

    Breast cancer incidence is increasing worldwide, and breast cancer-related mortality is highest in women of African ancestry, who are more likely to have basal-like or triple-negative breast cancer (TNBC) than are women of European ancestry. Identification of cultural, epidemiological, and genetic risk factors that predispose women of African ancestry to TNBC is an active area of research. Despite the aggressive behaviour of TNBC, achievement of a pathological complete response with chemotherapy is associated with good long-term survival outcomes, and sensitivity to chemotherapy does not seem to differ according to ethnic origin. Discovery of the molecular signalling molecules that define TNBC heterogeneity has led to the development of targeted agents such as inhibitors of poly (ADP-ribose) polymerase-1 and mTOR and immunomodulatory drugs that are in the early stages of clinical testing. First, we summarise the existing published work on the differences reported on the epidemiology, biology, and response to systemic treatment of TNBC between women of African ancestry and white women, and identify some gaps in knowledge. Second, we review the opportunities for development of new therapeutic agents in view of the potential high clinical relevance for patients with TNBC irrespective of race or ethnic origin. PMID:25456381

  19. Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian-European populations.

    PubMed

    Sánchez, Elena; Rasmussen, Astrid; Riba, Laura; Acevedo-Vasquez, Eduardo; Kelly, Jennifer A; Langefeld, Carl D; Williams, Adrianne H; Ziegler, Julie T; Comeau, Mary E; Marion, Miranda C; García-De La Torre, Ignacio; Maradiaga-Ceceña, Marco A; Cardiel, Mario H; Esquivel-Valerio, Jorge A; Rodriguez-Amado, Jacqueline; Moctezuma, José Francisco; Miranda, Pedro; Perandones, Carlos E; Castel, Cecilia; Laborde, Hugo A; Alba, Paula; Musuruana, Jorge L; Goecke, I Annelise; Anaya, Juan-Manuel; Kaufman, Kenneth M; Adler, Adam; Glenn, Stuart B; Brown, Elizabeth E; Alarcón, Graciela S; Kimberly, Robert P; Edberg, Jeffrey C; Vilá, Luis M; Criswell, Lindsey A; Gilkeson, Gary S; Niewold, Timothy B; Martín, Javier; Vyse, Timothy J; Boackle, Susan A; Ramsey-Goldman, Rosalind; Scofield, R Hal; Petri, Michelle; Merrill, Joan T; Reveille, John D; Tsao, Betty P; Orozco, Lorena; Baca, Vicente; Moser, Kathy L; Gaffney, Patrick M; James, Judith A; Harley, John B; Tusié-Luna, Teresa; Pons-Estel, Bernardo A; Jacob, Chaim O; Alarcón-Riquelme, Marta E

    2012-11-01

    American Indian-Europeans, Asians, and African Americans have an excess morbidity from systemic lupus erythematosus (SLE) and a higher prevalence of lupus nephritis than do Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and sociodemographic characteristics and clinical features in a large cohort of American Indian-European SLE patients. A total of 2,116 SLE patients of American Indian-European origin and 4,001 SLE patients of European descent for whom we had clinical data were included in the study. Genotyping of 253 continental ancestry-informative markers was performed on the Illumina platform. Structure and Admixture software were used to determine genetic ancestry proportions of each individual. Logistic regression was used to test the association between genetic ancestry and sociodemographic and clinical characteristics. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs). The average American Indian genetic ancestry of 2,116 SLE patients was 40.7%. American Indian genetic ancestry conferred increased risks of renal involvement (P < 0.0001, OR 3.50 [95% CI 2.63- 4.63]) and early age at onset (P < 0.0001). American Indian ancestry protected against photosensitivity (P < 0.0001, OR 0.58 [95% CI 0.44-0.76]), oral ulcers (P < 0.0001, OR 0.55 [95% CI 0.42-0.72]), and serositis (P < 0.0001, OR 0.56 [95% CI 0.41-0.75]) after adjustment for age, sex, and age at onset. However, age and sex had stronger effects than genetic ancestry on malar rash, discoid rash, arthritis, and neurologic involvement. In general, American Indian genetic ancestry correlates with lower sociodemographic status and increases the risk of developing renal involvement and SLE at an earlier age. Copyright © 2012 by the American College of Rheumatology.

  20. Time correlations of high energy muons in an underground detector

    NASA Astrophysics Data System (ADS)

    Becherini, Y.; Cecchini, S.; Chiarusi, T.; Cozzi, M.; Dekhissi, H.; Derkaoui, J.; Esposito, L. S.; Giacomelli, G.; Giorgini, M.; Giglietto, N.; Maaroufi, F.; Mandrioli, G.; Margiotta, A.; Manzoor, S.; Moussa, A.; Patrizii, L.; Popa, V.; Sioli, M.; Sirri, G.; Spurio, M.; Togo, V.

    2005-04-01

    We present the result of a search for correlations in the arrival times of high energy muons collected from 1995 till 2000 with the streamer tube system of the complete MACRO detector at the underground Gran Sasso Lab. Large samples of single muons (8.6 million), double muons (0.46 million) and multiple muons with multiplicities from 3 to 6 (0.08 million) were selected. These samples were used to search for time correlations of cosmic ray particles coming from the whole upper hemisphere or from selected space cones. The results of our analyses confirm with high statistics a random arrival time distribution of high energy cosmic rays.

  1. The ‘Stolen Generations' of Mothers and Daughters: Child Apprehension and Enhanced HIV Vulnerabilities for Sex Workers of Aboriginal Ancestry

    PubMed Central

    Duff, Putu; Bingham, Brittany; Simo, Annick; Jury, Delores; Reading, Charlotte; Shannon, Kate

    2014-01-01

    Objectives The number of children in care of the state continues to grow in BC, Canada with a historical legacy of child apprehension among criminalized and marginalized populations, particularly women of Aboriginal ancestry and sex workers. However, there is a paucity of research investigating child apprehension experiences among marginalized mothers. The objective of the current analysis is to examine the prevalence and correlates of child apprehensions among female sex workers in Vancouver, Canada. Methods Analyses were drawn from the AESHA (An Evaluation of Sex Workers Health Access, 2010-present), a prospective cohort of street and off-street SWs, through outreach and semi-annual visits to the research office. Bivariate and multivariate logistic regression were used to examine correlates of child apprehension. Results Of a total of 510 SWs, 350 women who had given birth to at least one child were included in the analyses (median age = 37 yrs: IQR: 31–44 yrs). The prevalence of child apprehension among mothers was 38.3%, with 37.4% reporting having been apprehended themselves by child welfare services. In multivariable analysis, servicing clients in outdoor public spaces (versus formal sex work establishments or informal indoor settings) (adjusted odds ratio, (aOR) = 2.73; 95%CI 1.27–5.90), history of injecting drugs (aOR = 2.53; 95%CI 1.42–4.49), Aboriginal ancestry (aOR = 1.66; 95%CI 1.01–2.74) were associated with increased odds of child apprehension. Discussion/Conclusions Child apprehension rates are high, particularly among the most marginalized sex workers, including sex workers who use drugs and sex workers of Aboriginal ancestry. Structural reforms to child protection are urgently needed, that support family-based care address the historical legacy of colonization affecting Aboriginal peoples. PMID:24927324

  2. Angular correlations in gluon production at high energy

    SciTech Connect

    Kovner, Alex; Lublinsky, Michael

    2011-02-01

    We present a general, model independent argument demonstrating that gluons produced in high energy hadronic collision are necessarily correlated in rapidity and also in the emission angle. The strength of the correlation depends on the process and on the structure/model of the colliding particles. In particular we argue that it is strongly affected (and underestimated) by factorized approximations frequently used to quantify the effect.

  3. The role of local ancestry adjustment in association studies using admixed populations.

    PubMed

    Zhang, Jianqi; Stram, Daniel O

    2014-09-01

    Association analysis using admixed populations imposes challenges and opportunities for disease mapping. By developing some explicit results for the variance of an allele of interest conditional on either local or global ancestry and by simulation of recently admixed genomes we evaluate power and false-positive rates under a variety of scenarios concerning linkage disequilibrium (LD) and the presence of unmeasured variants. Pairwise LD patterns were compared between admixed and nonadmixed populations using the HapMap phase 3 data. Based on the above, we showed that as follows: For causal variants with similar effect size in all populations, power is generally higher in a study using admixed population than using nonadmixed population, especially for highly differentiated SNPs. This gain of power is achieved with adjustment of global ancestry, which completely removes any cross-chromosome inflation of type I error rates, and addresses much of the intrachromosome inflation. If reliably estimated, adjusting for local ancestry precisely recovers the localization that could have been achieved in a stratified analysis of source populations. Improved localization is most evident for highly differentiated SNPs; however, the advantage of higher power is lost on exactly the same differentiated SNPs. In the real admixed populations such as African Americans and Latinos, the expansion of LD is not as dramatic as in our simulation. While adjustment for global ancestry is required prior to announcing a novel association seen in an admixed population, local ancestry adjustment may best be regarded as a localization tool not strictly required for discovery purposes. © 2014 WILEY PERIODICALS, INC.

  4. The Role of Local Ancestry Adjustment in Association Studies Using Admixed Populations

    PubMed Central

    Zhang, Jianqi; Stram, Daniel O.

    2016-01-01

    Association analysis using admixed populations imposes challenges and opportunities for disease mapping. By developing some explicit results for the variance of an allele of interest conditional on either local or global ancestry and by simulation of recently admixed genomes we evaluate power and false-positive rates under a variety of scenarios concerning linkage disequilibrium (LD) and the presence of unmeasured variants. Pairwise LD patterns were compared between admixed and nonadmixed populations using the HapMap phase 3 data. Based on the above, we showed that as follows: For causal variants with similar effect size in all populations, power is generally higher in a study using admixed population than using nonadmixed population, especially for highly differentiated SNPs. This gain of power is achieved with adjustment of global ancestry, which completely removes any cross-chromosome inflation of type I error rates, and addresses much of the intrachromosome inflation.If reliably estimated, adjusting for local ancestry precisely recovers the localization that could have been achieved in a stratified analysis of source populations. Improved localization is most evident for highly differentiated SNPs; however, the advantage of higher power is lost on exactly the same differentiated SNPs.In the real admixed populations such as African Americans and Latinos, the expansion of LD is not as dramatic as in our simulation.While adjustment for global ancestry is required prior to announcing a novel association seen in an admixed population, local ancestry adjustment may best be regarded as a localization tool not strictly required for discovery purposes. PMID:25043967

  5. Race, Ancestry, and Development of Food-Allergen Sensitization in Early Childhood

    PubMed Central

    Tsai, Hui-Ju; Hong, Xiumei; Liu, Xin; Wang, Guoying; Pearson, Colleen; Ortiz, Katherin; Fu, Melanie; Pongracic, Jacqueline A.; Bauchner, Howard; Wang, Xiaobin

    2011-01-01

    OBJECTIVE: We examined whether the risk of food-allergen sensitization varied according to self-identified race or genetic ancestry. METHODS: We studied 1104 children (mean age: 2.7 years) from an urban multiethnic birth cohort. Food sensitization was defined as specific immunoglobulin E (sIgE) levels of ≥0.35 kilo–units of allergen (kUA)/L for any of 8 common food allergens. Multivariate logistic regression analyses were used to evaluate the associations of self-identified race and genetic ancestry with food sensitization. Analyses also examined associations with numbers of food sensitizations (0, 1 or 2, and ≥3 foods) and with logarithmically transformed allergen sIgE levels. RESULTS: In this predominantly minority cohort (60.9% black and 22.5% Hispanic), 35.5% of subjects exhibited food sensitizations. In multivariate models, both self-reported black race (odds ratio [OR]: 2.34 [95% confidence interval [CI]: 1.24–4.44]) and African ancestry (in 10% increments; OR: 1.07 [95% CI: 1.02–1.14]) were associated with food sensitization. Self-reported black race (OR: 3.76 [95% CI: 1.09–12.97]) and African ancestry (OR: 1.19 [95% CI: 1.07–1.32]) were associated with a high number (≥3) of food sensitizations. African ancestry was associated with increased odds of peanut sIgE levels of ≥5 kUA/L (OR: 1.25 [95% CI: 1.01–1.52]). Similar ancestry associations were seen for egg sIgE levels of ≥2 kUA/L (OR: 1.13 [95% CI: 1.01–1.27]) and milk sIgE levels of ≥5 kUA/L (OR: 1.24 [95% CI: 0.94–1.63]), although findings were not significant for milk. CONCLUSIONS: Black children were more likely to be sensitized to food allergens and were sensitized to more foods. African ancestry was associated with peanut sensitization. PMID:21890831

  6. The Astrobiological Case for Our Cosmic Ancestry

    NASA Astrophysics Data System (ADS)

    Wickramasinghe, Chandra

    With steadily mounting evidence that points to a cosmic origin of terrestrial life, a cultural barrier prevails against admitting that such a connection exists. Astronomy continues to reveal the presence of organic molecules and organic dust on a huge cosmic scale, amounting to a third of interstellar carbon tied up in this form. Just as the overwhelming bulk of organics on Earth stored over geological timescales are derived from the degradation of living cells, so it seems most likely that interstellar organics in large measure also derive from biology. As we enter a new decade -- the year 2010 -- a clear pronouncement of our likely alien ancestry and of the existence of extraterrestrial life on a cosmic scale would seem to be overdue.

  7. The astrobiological case for our cosmic ancestry

    NASA Astrophysics Data System (ADS)

    Wickramasinghe, Chandra

    2010-04-01

    With steadily mounting evidence that points to a cosmic origin of terrestrial life, a cultural barrier prevails against admitting that such a connection exists. Astronomy continues to reveal the presence of organic molecules and organic dust on a huge cosmic scale, amounting to a third of interstellar carbon tied up in this form. Just as the overwhelming bulk of organics on Earth stored over geological timescales are derived from the degradation of living cells, so it seems likely that interstellar organics in large measure also derive from biology. As we enter a new decade - the year 2010 - a clear pronouncement of our likely alien ancestry and of the existence of extraterrestrial life on a cosmic scale would seem to be overdue.

  8. Genetics of stroke in a UK African ancestry case-control study

    PubMed Central

    Rutten-Jacobs, Loes; Curtis, Charles; Patel, Hamel; Breen, Gerome; Newhouse, Stephen; Lewis, Cathryn M.; Markus, Hugh S.

    2017-01-01

    Objective: Despite epidemiologic data showing an increased stroke incidence in African ancestry populations, genetic studies in this group have so far been limited, and there has been little characterization of the genetic contribution to stroke liability in this population, particularly for stroke subtypes. Methods: We evaluated the evidence that genetic factors contribute to stroke and stroke subtypes in a population of 917 African and African Caribbean stroke cases and 868 matched controls from London, United Kingdom. We (1) estimated the heritability of stroke in this population using genomic-relatedness matrix-restricted maximum likelihood approaches, (2) assessed loci associated with stroke in Europeans in our population, and (3) evaluated the influence of genetic factors underlying cardiovascular risk factors on stroke using polygenic risk scoring. Results: Our results indicate a substantial genetic contribution to stroke risk in African ancestry populations (h2 = 0.35 [SE = 0.19], p = 0.043). Polygenic risk scores indicate that cardiovascular risk scores contribute to the genetic liability (odds ratio [OR] 1.09 [95% confidence interval (CI) 1.01–1.17], p = 0.029) and point to a strong influence of type 2 diabetes in large vessel stroke (OR 1.62 [95% CI 1.19–2.22], p = 0.0024). Single nucleotide polymorphisms associated with ischemic stroke in Europeans shared direction of effect in SLESS (p = 0.031), suggesting that disease mechanisms are shared across ancestries. Conclusions: Stroke in African ancestry populations is highly heritable and influenced by genetic determinants underlying cardiovascular risk factors. In addition, stroke loci identified in Europeans share direction of effect in African populations. Future genome-wide association studies must focus on incorporating African ancestry individuals. PMID:28349126

  9. The utility of empirically assigning ancestry groups in cross-population genetic studies of addiction.

    PubMed

    Peterson, Roseann E; Edwards, Alexis C; Bacanu, Silviu-Alin; Dick, Danielle M; Kendler, Kenneth S; Webb, Bradley T

    2017-08-01

    Given moderate heritability and significant heterogeneity among addiction phenotypes, successful genome-wide association studies (GWAS) are expected to need very large samples. As sample sizes grow, so can genetic diversity leading to challenges in analyzing these data. Methods for empirically assigning individuals to genetically informed ancestry groups are needed. We describe a strategy for empirically assigning ancestry groups in ethnically diverse GWAS data including extensions of principal component analysis (PCA) and population matching through minimum Mahalanobis distance. We apply these methods to data from Spit for Science (S4S): the University Student Survey, a study following college students longitudinally that includes genetic and environmental data on substance use and mental health (n = 7,603). The genetic-based population assignments for S4S were 48.7% European, 22.5% African, 10.4% Americas, 9.2% East Asian, and 9.2% South Asian descent. Self-reported census categories "More than one race" and "Unknown"as well as "Hawaiian/Pacific Islander" and "American-Indian/Native Alaskan" were empirically assigned representing a +9% sample retention over conventional methods. Although there was high concordance between self-reported race and empirical population-match (+.924), there was reduction in variance for most ancestry PCs for genetic-based population assignments. We were able to create more genetically homogenous groups and reduce sample and marker loss through cross-ancestry meta-analysis, potentially increasing power to detect etiologically relevant variation. Our approach provides a framework for empirically assigning genetic ancestry groups which can be applied to other ethnically diverse genetic studies. Given the important public health impact and demonstrable gains in statistical power from studying diverse populations, empirically sound practices for genetic studies are needed. (Am J Addict 2017;26:494-501). © 2017 American Academy of

  10. Indigenous American ancestry is associated with arsenic methylation efficiency in an admixed population of northwest Mexico.

    PubMed

    Gomez-Rubio, Paulina; Klimentidis, Yann C; Cantu-Soto, Ernesto; Meza-Montenegro, Maria M; Billheimer, Dean; Lu, Zhenqiang; Chen, Zhao; Klimecki, Walter T

    2012-01-01

    Many studies provide evidence relating lower human arsenic (As) methylation efficiency, represented by high percent urinary monomethylarsonic acid (MMA(V)), with several As-induced diseases, possibly due to the fact that MMA(V) serves as a proxy for MMA(III), the most toxic As metabolite. Some epidemiological studies suggested that indigenous Americans (AME) methylate As more efficiently; however, data supporting this have been equivocal. The aim of this study was to characterize the association between AME ancestry and As methylation efficiency using a panel of ancestry informative genetic markers to determine individual ancestry proportions in an admixed population (composed of two or more isolated ancestral populations) of 746 individuals environmentally exposed to As in northwest Mexico. Total urinary As (TAs) mean and range were 170.4 and 2.3-1053.5 μg/L, while percent AME (%AME) mean and range were 72.4 and 23-100. Adjusted (gender, age, AS3MT 7388/M287T haplotypes, body mass index [BMI], and TAs) multiple regression model showed that higher AME ancestry is significantly associated with lower percentage of urinary As excreted as MMA(V) (%uMMA) in this population (p < .01). Data also demonstrated a significant interaction between BMI and gender, indicating negative association between BMI and %uMMA, stronger in women than men (p < .01). Moreover, age and the AS3MT variants 7388 (intronic) and M287T (nonsynonymous) were also significantly associated with As methylation efficiency (p < .01). This study highlights the importance of BMI and indigenous American ancestry in some of the observed variability in As methylation efficiency, underscoring the need to be considered in epidemiology studies, particularly those carried out in admixed populations.

  11. Locus-specific ancestry to detect recent response to selection in admixed Swiss Fleckvieh cattle.

    PubMed

    Khayatzadeh, N; Mészáros, G; Utsunomiya, Y T; Garcia, J F; Schnyder, U; Gredler, B; Curik, I; Sölkner, J

    2016-12-01

    Identification of selection signatures is one of the current endeavors of evolutionary genetics. Admixed populations may be used to infer post-admixture selection. We calculated local ancestry for Swiss Fleckvieh, a composite of Simmental (SI) and Red Holstein Friesian (RHF), to infer such signals. Illumina Bovine SNP50 BeadChip data for 300 admixed, 88 SI and 97 RHF bulls were used. The average RHF ancestry across the whole genome was 0.70. To identify regions with high deviation from average, we considered two significance thresholds, based on a permutation test and extreme deviation from normal distribution. Regions on chromosomes 13 (46.3-47.3 Mb) and 18 (18.7-25.9 Mb) passed both thresholds in the direction of increased SI. Extended haplotype homozygosity within (iHS) and between (Rsb) populations was calculated to explore additional patterns of pre- and post-admixture selection signals. The Rsb score of admixed and SI was significant in a wide region of chromosome 18 (6.6-24.6 Mb) overlapped with one area of strong local ancestry deviation. FTO, with pleiotropic effect on milk and fertility, NOD2 on dairy and NKD1 and SALL1 on fertility traits are located there. Genetic differentiation of RHF and SI (Fst ), an alternative indicator of pre-admixture selection in pure populations, was calculated. No considerable overlap of peaks of local ancestry deviations and Fst was observed. We found two regions with significant signatures of post-admixture selection in this very young composite, applying comparatively stringent significance thresholds. The signals cover relatively large genomic areas and did not allow pinpointing of the gene(s) responsible for the apparent shift in ancestry proportions. © 2016 Stichting International Foundation for Animal Genetics.

  12. Do people from the Jewish community prefer ancestry-based or pan-ethnic expanded carrier screening?

    PubMed Central

    Holtkamp, Kim C A; van Maarle, Merel C; Schouten, Maria J E; Dondorp, Wybo J; Lakeman, Phillis; Henneman, Lidewij

    2016-01-01

    Ancestry-based carrier screening in the Ashkenazi Jewish population entails screening for specific autosomal recessive founder mutations, which are rarer among the general population. As it is now technically feasible to screen for many more diseases, the question arises whether this population prefers a limited ancestry-based offer or a pan-ethnic expanded carrier screening panel that goes beyond the diseases that are frequent in their own population, and is offered regardless of ancestry. An online questionnaire was completed by 145 individuals from the Dutch Jewish community (≥18 years) between April and July 2014. In total, 64.8% were aware of the existence of ancestry-based carrier screening, and respondents were generally positive about screening. About half (53.8%) preferred pan-ethnic expanded carrier screening, whereas 42.8% preferred ancestry-based screening. Reasons for preferring pan-ethnic screening included ‘everyone has a right to be tested', ‘fear of stigmatization when offering ancestry-based panels', and ‘difficulties with identifying risk owing to mixed backgrounds'. ‘Preventing high healthcare costs' was the most important reason against pan-ethnic carrier screening among those in favor of an ancestry-based panel. In conclusion, these findings show that people from the Dutch Jewish community have a positive attitude regarding carrier screening in their community for a wide range of diseases. As costs of expanded carrier screening panels are most likely to drop in the near future, it is expected that these panels will receive more support in the future. PMID:25966636

  13. Do people from the Jewish community prefer ancestry-based or pan-ethnic expanded carrier screening?

    PubMed

    Holtkamp, Kim C A; van Maarle, Merel C; Schouten, Maria J E; Dondorp, Wybo J; Lakeman, Phillis; Henneman, Lidewij

    2016-02-01

    Ancestry-based carrier screening in the Ashkenazi Jewish population entails screening for specific autosomal recessive founder mutations, which are rarer among the general population. As it is now technically feasible to screen for many more diseases, the question arises whether this population prefers a limited ancestry-based offer or a pan-ethnic expanded carrier screening panel that goes beyond the diseases that are frequent in their own population, and is offered regardless of ancestry. An online questionnaire was completed by 145 individuals from the Dutch Jewish community (≥ 18 years) between April and July 2014. In total, 64.8% were aware of the existence of ancestry-based carrier screening, and respondents were generally positive about screening. About half (53.8%) preferred pan-ethnic expanded carrier screening, whereas 42.8% preferred ancestry-based screening. Reasons for preferring pan-ethnic screening included 'everyone has a right to be tested', 'fear of stigmatization when offering ancestry-based panels', and 'difficulties with identifying risk owing to mixed backgrounds'. 'Preventing high healthcare costs' was the most important reason against pan-ethnic carrier screening among those in favor of an ancestry-based panel. In conclusion, these findings show that people from the Dutch Jewish community have a positive attitude regarding carrier screening in their community for a wide range of diseases. As costs of expanded carrier screening panels are most likely to drop in the near future, it is expected that these panels will receive more support in the future.

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

    PubMed Central

    Santiago-Torres, Margarita; De Dieu Tapsoba, Jean; Kratz, Mario; Lampe, Johanna W.; Breymeyer, Kara L.; Levy, Lisa; Song, Xiaoling; Villaseñor, Adriana; Wang, Ching-Yun; Fejerman, Laura; Neuhouser, Marian L.; Carlson, Christopher S.

    2016-01-01

    Background Certain populations with a large proportion of Indigenous American (IA) genetic ancestry may be evolutionarily adapted to traditional diets high in legumes and complex carbohydrates, and may have a detrimental metabolic response to U.S. diets high in refined carbohydrates and added sugars. We tested whether IA ancestry modified the metabolic response to a U.S. versus traditional Mexican diet in a controlled dietary intervention. Methods First and second generation Mexican immigrant women (n=53) completed a randomized crossover feeding trial testing the effects of a U.S. versus traditional Mexican diet. The metabolic response to the diets was measured by fasting serum concentrations of glucose, insulin, IGF-1, IGFBP-3, adiponectin, CRP, IL-6, and computed HOMAIR. Blood collected at baseline was used for genotyping and estimation of African, European, and IA ancestries with the use of 214 Ancestry Informative Markers. Results The genetic ancestral background was 56% IA, 38% European, and 6% African. Women in the highest IA ancestry tertile (>62%) were shorter in height, less educated and less acculturated to the U.S. lifestyle, and tended to have higher waist-to-hip ratio compared to women in the middle and lowest IA ancestry tertiles, respectively. Compared to the U.S. diet, the traditional Mexican diet tended to reduce glucose, insulin, IGF-1, IGFBP-3, and HOMAIR among women in the middle IA ancestry group (IA ancestry ≤45–62%); while having no effect on biomarkers related to inflammation. Conclusions We observed modest interactions between IA ancestry and the metabolic response to a U.S. versus traditional Mexican diet among Mexican immigrant women. PMID:27966572

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

    PubMed Central

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

    2015-01-01

    Background Obesity and breast cancer risk is multifaceted and genes associated with energy homeostasis may modify this relationship. Methods We evaluated 10 genes that have been associated with obesity and energy homeostasis to determine their association with breast cancer risk in Hispanic/Native American (2111 cases, 2597 controls) and non-Hispanic white (1481 cases, 1585 controls) women. Results Cholecystokinin (CCK) rs747455 and proopiomelanocortin (POMC) rs6713532 and rs7565877 (for low Indigenous American (IA) ancestry); CCK rs8192472 and neuropeptide Y (NYP) rs16141 and rs14129 (intermediate IA ancestry); and leptin receptor (LEPR) rs11585329 (high IA ancestry) were strongly associated with multiple indicators of body size. There were no significant associations with breast cancer risk between genes and SNPs overall. However, LEPR was significantly associated with breast cancer risk among women with low IA ancestry (PARTP = 0.024); POMC was significantly associated with breast cancer risk among women with intermediate (PARTP = 0.015) and high (PARTP = 0.012) IA ancestry. The overall pathway was statistically significant for pre-menopausal women with low IA ancestry (PARTP = 0.05), as was cocaine and amphetamine regulated transcript protein (CARTPT) (PARTP = 0.014) and ghrelin (GHRL) (PARTP = 0.007). POMC was significantly associated with breast cancer risk among post-menopausal women with higher IA ancestry (PARTP = 0.005). Three SNPs in LEPR (rs6704167, rs17412175, and rs7626141), and adiponectin (ADIPOQ); rs822391) showed significant 4-way interactions (GxExMenopausexAncestry) for multiple indicators of body size among pre-menopausal women. Conclusions Energy homeostasis genes were associated with breast cancer risk; menopausal status, body size, and genetic ancestry influenced this relationship. PMID:26395295

  16. Adjusting head circumference for covariates in autism: clinical correlates of a highly heritable continuous trait

    PubMed Central

    Chaste, Pauline; Klei, Lambertus; Sanders, Stephan J.; Murtha, Michael T.; Hus, Vanessa; Lowe, Jennifer K.; Willsey, A. Jeremy; Moreno-De-Luca, Daniel; Yu, Timothy W.; Fombonne, Eric; Geschwind, Daniel; Grice, Dorothy E.; Ledbetter, David H.; Lord, Catherine; Mane, Shrikant M.; Martin, Christa Lese; Martin, Donna M.; Morrow, Eric M.; Walsh, Christopher A.; Sutcliffe, James S.; State, Matthew W.; Devlin, Bernie; Cook, Edwin H.; Kim, Soo-Jeong

    2013-01-01

    BACKGROUND Brain development follows a different trajectory in children with Autism Spectrum Disorders (ASD) than in typically developing children. A proxy for neurodevelopment could be head circumference (HC), but studies assessing HC and its clinical correlates in ASD have been inconsistent. This study investigates HC and clinical correlates in the Simons Simplex Collection cohort. METHODS We used a mixed linear model to estimate effects of covariates and the deviation from the expected HC given parental HC (genetic deviation). After excluding individuals with incomplete data, 7225 individuals in 1891 families remained for analysis. We examined the relationship between HC/genetic deviation of HC and clinical parameters. RESULTS Gender, age, height, weight, genetic ancestry and ASD status were significant predictors of HC (estimate of the ASD effect=0.2cm). HC was approximately normally distributed in probands and unaffected relatives, with only a few outliers. Genetic deviation of HC was also normally distributed, consistent with a random sampling of parental genes. Whereas larger HC than expected was associated with ASD symptom severity and regression, IQ decreased with the absolute value of the genetic deviation of HC. CONCLUSIONS Measured against expected values derived from covariates of ASD subjects, statistical outliers for HC were uncommon. HC is a strongly heritable trait and population norms for HC would be far more accurate if covariates including genetic ancestry, height and age were taken into account. The association of diminishing IQ with absolute deviation from predicted HC values suggests HC could reflect subtle underlying brain development and warrants further investigation. PMID:23746936

  17. Genetic ancestry as an effect modifier of naltrexone in smoking cessation among African Americans: an analysis of a randomized controlled trial.

    PubMed

    Bress, Adam; Kittles, Rick; Wing, Coady; Hooker, Stanley E; King, Andrea

    2015-06-01

    To determine whether there were differential quit rates between African Americans (AA) and European Americans with the experimental treatment naltrexone, and examine the role of genetic ancestry on these outcomes among AAs. Data from a previous randomized trial of 315 smokers to naltrexone versus placebo were reanalyzed using West African (WA) genetic ancestry to define subpopulations. Logistic regression models were used to estimate treatment effects on early and end of treatment quit rates, by race and WA ancestry. Among European Americans (n=136), naltrexone significantly increased quit rates at 4 weeks (62 vs. 43%, P=0.03) with directional, but not statistically significant effects at 12 weeks (30 vs. 18%, P=0.12). In contrast, among the AAs (n=95), quit rates did not differ between naltrexone and placebo groups at either interval (4 weeks: 43 vs. 32%, P=0.27; 12 weeks: 22 vs. 18%, P=0.60). A median split was conducted in AAs for WA ancestry. Among AAs with low WA ancestry, quit rates were significantly higher with naltrexone compared with placebo (60 vs. 27%, P=0.03). There was no advantage in quit rates with naltrexone for the high WA ancestry group. Naltrexone efficacy for smoking cessation varies across AA individuals with different levels of WA ancestry. These results suggest that genetic background may partially explain racial differences in drug response.

  18. Genetic ancestry as an effect modifier of naltrexone in smoking cessation among African Americans: an analysis of a randomized controlled trial

    PubMed Central

    Bress, Adam; Kittles, Rick; Wing, Coady; Hooker, Stanley E; King, Andrea

    2015-01-01

    Objectives To determine if there were differential quit rates between AA and European Americans (EA) with the experimental treatment naltrexone, and examine the role of genetic ancestry on these outcomes among AAs. Methods Data from a previous randomized trial of 315 smokers to naltrexone vs. placebo were reanalyzed using West African (WA) genetic ancestry to define sub-populations. Logistic regression models were used to estimate treatment effects on early and end of treatment quit rates, by race and WA ancestry. Results Among EAs (n=136), naltrexone significantly increased quit rates at four weeks (62% vs. 43%, p=0.03) with directional, but not statistically significant effects at 12 weeks (30% vs. 18%, p=0.12). In contrast, among the AAs (n=95), quit rates did not differ between naltrexone and placebo groups at either interval (four weeks: 43% vs. 32%, p=0.27; 12 weeks: 22% vs. 18%, p=0.60). A median split was conducted in AAs for WA ancestry. Among AAs with low WA ancestry, quit rates were significantly higher with naltrexone compared with placebo (60% vs. 27%, p=0.03). There was no advantage in quit rates with naltrexone for the high WA ancestry group. Conclusions Naltrexone efficacy for smoking cessation varies across AA subjects with different levels of WA ancestry. These results suggest that genetic background may partially explain racial differences in drug response. PMID:25918964

  19. Genetic ancestry influences asthma susceptibility and lung function among Latinos.

    PubMed

    Pino-Yanes, Maria; Thakur, Neeta; Gignoux, Christopher R; Galanter, Joshua M; Roth, Lindsey A; Eng, Celeste; Nishimura, Katherine K; Oh, Sam S; Vora, Hita; Huntsman, Scott; Nguyen, Elizabeth A; Hu, Donglei; Drake, Katherine A; Conti, David V; Moreno-Estrada, Andres; Sandoval, Karla; Winkler, Cheryl A; Borrell, Luisa N; Lurmann, Fred; Islam, Talat S; Davis, Adam; Farber, Harold J; Meade, Kelley; Avila, Pedro C; Serebrisky, Denise; Bibbins-Domingo, Kirsten; Lenoir, Michael A; Ford, Jean G; Brigino-Buenaventura, Emerita; Rodriguez-Cintron, William; Thyne, Shannon M; Sen, Saunak; Rodriguez-Santana, Jose R; Bustamante, Carlos D; Williams, L Keoki; Gilliland, Frank D; Gauderman, W James; Kumar, Rajesh; Torgerson, Dara G; Burchard, Esteban G

    2015-01-01

    Childhood asthma prevalence and morbidity varies among Latinos in the United States, with Puerto Ricans having the highest and Mexicans the lowest. To determine whether genetic ancestry is associated with the odds of asthma among Latinos, and secondarily whether genetic ancestry is associated with lung function among Latino children. We analyzed 5493 Latinos with and without asthma from 3 independent studies. For each participant, we estimated the proportion of African, European, and Native American ancestry using genome-wide data. We tested whether genetic ancestry was associated with the presence of asthma and lung function among subjects with and without asthma. Odds ratios (OR) and effect sizes were assessed for every 20% increase in each ancestry. Native American ancestry was associated with lower odds of asthma (OR = 0.72, 95% CI: 0.66-0.78, P = 8.0 × 10(-15)), while African ancestry was associated with higher odds of asthma (OR = 1.40, 95% CI: 1.14-1.72, P = .001). These associations were robust to adjustment for covariates related to early life exposures, air pollution, and socioeconomic status. Among children with asthma, African ancestry was associated with lower lung function, including both pre- and post-bronchodilator measures of FEV1 (-77 ± 19 mL; P = 5.8 × 10(-5) and -83 ± 19 mL; P = 1.1 x 10(-5), respectively) and forced vital capacity (-100 ± 21 mL; P = 2.7 × 10(-6) and -107 ± 22 mL; P = 1.0 x 10(-6), respectively). Differences in the proportions of genetic ancestry can partially explain disparities in asthma susceptibility and lung function among Latinos. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  20. Genetic Ancestry Influences Asthma Susceptibility and Lung Function Among Latinos

    PubMed Central

    Pino-Yanes, Maria; Thakur, Neeta; Gignoux, Christopher R.; Galanter, Joshua M.; Roth, Lindsey A.; Eng, Celeste; Nishimura, Katherine K.; Oh, Sam S.; Vora, Hita; Huntsman, Scott; Nguyen, Elizabeth A.; Hu, Donglei; Drake, Katherine A.; Conti, David V.; Moreno-Estrada, Andres; Sandoval, Karla; Winkler, Cheryl A.; Borrell, Luisa N.; Lurmann, Fred; Islam, Talat S.; Davis, Adam; Farber, Harold J.; Meade, Kelley; Avila, Pedro C.; Serebrisky, Denise; Bibbins-Domingo, Kirsten; Lenoir, Michael A.; Ford, Jean G.; Brigino-Buenaventura, Emerita; Rodriguez-Cintron, William; Thyne, Shannon M.; Sen, Saunak; Rodriguez-Santana, Jose R.; Bustamante, Carlos D.; Williams, L. Keoki; Gilliland, Frank D.; Gauderman, W. James; Kumar, Rajesh; Torgerson, Dara G.; Burchard, Esteban G.

    2014-01-01

    Background Childhood asthma prevalence and morbidity varies among Latinos in the United States, with Puerto Ricans having the highest and Mexicans the lowest. Objective To determine whether genetic ancestry is associated with the odds of asthma among Latinos, and secondarily whether genetic ancestry is associated with lung function among Latino children. Methods We analyzed 5,493 Latinos with and without asthma from three independent studies. For each participant we estimated the proportion of African, European, and Native American ancestry using genome-wide data. We tested whether genetic ancestry was associated with the presence of asthma and lung function among subjects with and without asthma. Odds ratios (OR) and effect sizes were assessed for every 20% increase in each ancestry. Results Native American ancestry was associated with lower odds of asthma (OR=0.72, 95% confidence interval [CI]: 0.66–0.78, p=8.0×10−15), while African ancestry was associated with higher odds of asthma (OR=1.40, 95%CI: 1.14–1.72, p=0.001). These associations were robust to adjustment for covariates related to early life exposures, air pollution and socioeconomic status. Among children with asthma, African ancestry was associated with lower lung function, including both pre- and post-bronchodilator measures of forced expiratory volume in the first second (−77±19 ml, p=5.8×10−5 and −83±19 ml, p=1.1×10−5, respectively) and forced vital capacity (−100±21 ml, p=2.7×10−6 and −107±22 ml, p=1.0×10−6, respectively). Conclusion Differences in the proportions of genetic ancestry can partially explain disparities in asthma susceptibility and lung function among Latinos. PMID:25301036

  1. Association of aldosterone synthase polymorphism (CYP11B2 -344T>C) and genetic ancestry with atrial fibrillation and serum aldosterone in African Americans with heart failure.

    PubMed

    Bress, Adam; Han, Jin; Patel, Shitalben R; Desai, Ankit A; Mansour, Ibrahim; Groo, Vicki; Progar, Kristin; Shah, Ebony; Stamos, Thomas D; Wing, Coady; Garcia, Joe G N; Kittles, Rick; Cavallari, Larisa H

    2013-01-01

    The objective of this study was to examine the extent to which aldosterone synthase genotype (CYP11B2) and genetic ancestry correlate with atrial fibrillation (AF) and serum aldosterone in African Americans with heart failure. Clinical data, echocardiographic measurements, and a genetic sample for determination of CYP11B2 -344T>C (rs1799998) genotype and genetic ancestry were collected from 194 self-reported African Americans with chronic, ambulatory heart failure. Genetic ancestry was determined using 105 autosomal ancestry informative markers. In a sub-set of patients (n = 126), serum was also collected for determination of circulating aldosterone. The CYP11B2 -344C allele frequency was 18% among the study population, and 19% of patients had AF. Multiple logistic regression revealed that the CYP11B2 -344CC genotype was a significant independent predictor of AF (OR 12.7, 95% CI 1.60-98.4, p = 0.0150, empirical p = 0.011) while holding multiple clinical factors, left atrial size, and percent European ancestry constant. Serum aldosterone was significantly higher among patients with AF (p = 0.036), whereas increased West African ancestry was inversely correlated with serum aldosterone (r = -0.19, p = 0.037). The CYP11B2 -344CC genotype was also overrepresented among patients with extreme aldosterone elevation (≥90th percentile, p = 0.0145). In this cohort of African Americans with chronic ambulatory heart failure, the CYP11B2 -344T>C genotype was a significant independent predictor of AF while holding clinical, echocardiographic predictors, and genetic ancestry constant. In addition, increased West African ancestry was associated with decreased serum aldosterone levels, potentially providing an explanation for the lower risk for AF observed among African Americans.

  2. Association of Aldosterone Synthase Polymorphism (CYP11B2 -344T>C) and Genetic Ancestry with Atrial Fibrillation and Serum Aldosterone in African Americans with Heart Failure

    PubMed Central

    Bress, Adam; Han, Jin; Patel, Shitalben R.; Desai, Ankit A.; Mansour, Ibrahim; Groo, Vicki; Progar, Kristin; Shah, Ebony; Stamos, Thomas D.; Wing, Coady; Garcia, Joe G. N.; Kittles, Rick; Cavallari, Larisa H.

    2013-01-01

    The objective of this study was to examine the extent to which aldosterone synthase genotype (CYP11B2) and genetic ancestry correlate with atrial fibrillation (AF) and serum aldosterone in African Americans with heart failure. Clinical data, echocardiographic measurements, and a genetic sample for determination of CYP11B2 -344T>C (rs1799998) genotype and genetic ancestry were collected from 194 self-reported African Americans with chronic, ambulatory heart failure. Genetic ancestry was determined using 105 autosomal ancestry informative markers. In a sub-set of patients (n = 126), serum was also collected for determination of circulating aldosterone. The CYP11B2 −344C allele frequency was 18% among the study population, and 19% of patients had AF. Multiple logistic regression revealed that the CYP11B2 −344CC genotype was a significant independent predictor of AF (OR 12.7, 95% CI 1.60–98.4, p = 0.0150, empirical p = 0.011) while holding multiple clinical factors, left atrial size, and percent European ancestry constant. Serum aldosterone was significantly higher among patients with AF (p = 0.036), whereas increased West African ancestry was inversely correlated with serum aldosterone (r = −0.19, p = 0.037). The CYP11B2 −344CC genotype was also overrepresented among patients with extreme aldosterone elevation (≥90th percentile, p = 0.0145). In this cohort of African Americans with chronic ambulatory heart failure, the CYP11B2 −344T>C genotype was a significant independent predictor of AF while holding clinical, echocardiographic predictors, and genetic ancestry constant. In addition, increased West African ancestry was associated with decreased serum aldosterone levels, potentially providing an explanation for the lower risk for AF observed among African Americans. PMID:23936266

  3. High Temperature, high pressure equation of state density correlations and viscosity correlations

    SciTech Connect

    Tapriyal, D.; Enick, R.; McHugh, M.; Gamwo, I.; Morreale, B.

    2012-07-31

    Global increase in oil demand and depleting reserves has derived a need to find new oil resources. To find these untapped reservoirs, oil companies are exploring various remote and harsh locations such as deep waters in Gulf of Mexico, remote arctic regions, unexplored deep deserts, etc. Further, the depth of new oil/gas wells being drilled has increased considerably to tap these new resources. With the increase in the well depth, the bottomhole temperature and pressure are also increasing to extreme values (i.e. up to 500 F and 35,000 psi). The density and viscosity of natural gas and crude oil at reservoir conditions are critical fundamental properties required for accurate assessment of the amount of recoverable petroleum within a reservoir and the modeling of the flow of these fluids within the porous media. These properties are also used to design appropriate drilling and production equipment such as blow out preventers, risers, etc. With the present state of art, there is no accurate database for these fluid properties at extreme conditions. As we have begun to expand this experimental database it has become apparent that there are neither equations of state for density or transport models for viscosity that can be used to predict these fundamental properties of multi-component hydrocarbon mixtures over a wide range of temperature and pressure. Presently, oil companies are using correlations based on lower temperature and pressure databases that exhibit an unsatisfactory predictive capability at extreme conditions (e.g. as great as {+-} 50%). From the perspective of these oil companies that are committed to safely producing these resources, accurately predicting flow rates, and assuring the integrity of the flow, the absence of an extensive experimental database at extreme conditions and models capable of predicting these properties over an extremely wide range of temperature and pressure (including extreme conditions) makes their task even more daunting.

  4. Read-only high accuracy volume holographic optical correlator

    NASA Astrophysics Data System (ADS)

    Zhao, Tian; Li, Jingming; Cao, Liangcai; He, Qingsheng; Jin, Guofan

    2011-10-01

    A read-only volume holographic correlator (VHC) is proposed. After the recording of all of the correlation database pages by angular multiplexing, a stand-alone read-only high accuracy VHC will be separated from the VHC recording facilities which include the high-power laser and the angular multiplexing system. The stand-alone VHC has its own low power readout laser and very compact and simple structure. Since there are two lasers that are employed for recording and readout, respectively, the optical alignment tolerance of the laser illumination on the SLM is very sensitive. The twodimensional angular tolerance is analyzed based on the theoretical model of the volume holographic correlator. The experimental demonstration of the proposed read-only VHC is introduced and discussed.

  5. Age at onset of multiple sclerosis may be influenced by place of residence during childhood rather than ancestry.

    PubMed

    Kennedy, J; O'Connor, P; Sadovnick, A D; Perara, M; Yee, I; Banwell, B

    2006-01-01

    Multiple sclerosis (MS) most commonly affects individuals of Northern European descent who live in countries at high latitude. The relative contributions of ancestry, country of birth and residence as determinants of MS risk have been studied in adult MS, but have not been explored in the pediatric MS population. In this study, we compare the demographics of pediatric- and adult-onset MS patients cared for in Toronto, Ontario, Canada, a multicultural region. The country of birth, residence during childhood, and ancestry were compared for 44 children and 573 adults. Our results demonstrate that although both the pediatric and adult cohorts were essentially born and raised in the same region of Ontario, Canada, children with MS were more likely to report Caribbean, Asian or Middle Eastern ancestry, and were less likely to have European heritage compared with individuals with adult-onset MS. The difference in ancestry between the pediatric and adult MS cohorts can be explained by two hypotheses: (1) individuals raised in a region of high MS prevalence, but whose ancestors originate from regions in which MS is rare, have an earlier age of MS onset, and (2) the place of residence during childhood, irrespective of ancestry, determines lifetime MS risk -- a fact that will be reflected in a change in the demographics of the adult MS cohort in our region as Canadian-raised children of recent immigrants reach the typical age of adult-onset MS.

  6. Alternative High School Students: Prevalence and Correlates of Overweight

    ERIC Educational Resources Information Center

    Kubik, Martha Y.; Davey, Cynthia; Fulkerson, Jayne A.; Sirard, John; Story, Mary; Arcan, Chrisa

    2009-01-01

    Objective: To determine prevalence and correlates of overweight among adolescents attending alternative high schools (AHS). Methods: AHS students (n=145) from 6 schools completed surveys and anthropometric measures. Cross-sectional associations were assessed using mixed model multivariate logistic regression. Results: Among students, 42% were…

  7. Alternative High School Students: Prevalence and Correlates of Overweight

    ERIC Educational Resources Information Center

    Kubik, Martha Y.; Davey, Cynthia; Fulkerson, Jayne A.; Sirard, John; Story, Mary; Arcan, Chrisa

    2009-01-01

    Objective: To determine prevalence and correlates of overweight among adolescents attending alternative high schools (AHS). Methods: AHS students (n=145) from 6 schools completed surveys and anthropometric measures. Cross-sectional associations were assessed using mixed model multivariate logistic regression. Results: Among students, 42% were…

  8. Inference for High-dimensional Differential Correlation Matrices *

    PubMed Central

    Cai, T. Tony; Zhang, Anru

    2015-01-01

    Motivated by differential co-expression analysis in genomics, we consider in this paper estimation and testing of high-dimensional differential correlation matrices. An adaptive thresholding procedure is introduced and theoretical guarantees are given. Minimax rate of convergence is established and the proposed estimator is shown to be adaptively rate-optimal over collections of paired correlation matrices with approximately sparse differences. Simulation results show that the procedure significantly outperforms two other natural methods that are based on separate estimation of the individual correlation matrices. The procedure is also illustrated through an analysis of a breast cancer dataset, which provides evidence at the gene co-expression level that several genes, of which a subset has been previously verified, are associated with the breast cancer. Hypothesis testing on the differential correlation matrices is also considered. A test, which is particularly well suited for testing against sparse alternatives, is introduced. In addition, other related problems, including estimation of a single sparse correlation matrix, estimation of the differential covariance matrices, and estimation of the differential cross-correlation matrices, are also discussed. PMID:26500380

  9. Inference for High-dimensional Differential Correlation Matrices.

    PubMed

    Cai, T Tony; Zhang, Anru

    2016-01-01

    Motivated by differential co-expression analysis in genomics, we consider in this paper estimation and testing of high-dimensional differential correlation matrices. An adaptive thresholding procedure is introduced and theoretical guarantees are given. Minimax rate of convergence is established and the proposed estimator is shown to be adaptively rate-optimal over collections of paired correlation matrices with approximately sparse differences. Simulation results show that the procedure significantly outperforms two other natural methods that are based on separate estimation of the individual correlation matrices. The procedure is also illustrated through an analysis of a breast cancer dataset, which provides evidence at the gene co-expression level that several genes, of which a subset has been previously verified, are associated with the breast cancer. Hypothesis testing on the differential correlation matrices is also considered. A test, which is particularly well suited for testing against sparse alternatives, is introduced. In addition, other related problems, including estimation of a single sparse correlation matrix, estimation of the differential covariance matrices, and estimation of the differential cross-correlation matrices, are also discussed.

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

    PubMed

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

    2012-01-01

    The Hmong Diaspora is one of the widest modern human migrations. Mainly localised in South-East Asia, the United States of America, and metropolitan France, a small community has also settled the Amazonian forest of French Guiana. We have biologically analysed 62 individuals of this unique Guianese population through three complementary genetic markers: mitochondrial DNA (HVS-I/II and coding region SNPs), Y-chromosome (SNPs and STRs), and the Gm allotypic system. All genetic systems showed a high conservation of the Asian gene pool (Asian ancestry: mtDNA=100.0%; NRY=99.1%; Gm=96.6%), without a trace of founder effect. When compared across various Asian populations, the highest correlations were observed with Hmong-Mien groups still living in South-East Asia (Fst<0.05; P-value<0.05). Despite a long history punctuated by exodus, the French Guianese Hmong have maintained their original genetic diversity. Copyright © 2012 Académie des sciences. Published by Elsevier SAS. All rights reserved.

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

    Ge, Bing; Tayo, Bamidele; Mathias, Rasika A.; Ding, Jingzhong; Nalls, Michael A.; Adeyemo, Adebowale; Adoue, Véronique; Ambrosone, Christine B.; Atwood, Larry; Bandera, Elisa V.; Becker, Lewis C.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Boerwinkle, Eric; Britton, Angela; Casey, Graham; Chanock, Stephen J.; Demerath, Ellen; Deming, Sandra L.; Diver, W. Ryan; Fox, Caroline; Harris, Tamara B.; Hernandez, Dena G.; Hu, Jennifer J.; Ingles, Sue A.; John, Esther M.; Johnson, Craig; Keating, Brendan; Kittles, Rick A.; Kolonel, Laurence N.; Kritchevsky, Stephen B.; Le Marchand, Loic; Lohman, Kurt; Liu, Jiankang; Millikan, Robert C.; Murphy, Adam; Musani, Solomon; Neslund-Dudas, Christine; North, Kari E.; Nyante, Sarah; Ogunniyi, Adesola; Ostrander, Elaine A.; Papanicolaou, George; Patel, Sanjay; Pettaway, Curtis A.; Press, Michael F.; Redline, Susan; Rodriguez-Gil, Jorge L.; Rotimi, Charles; Rybicki, Benjamin A.; Salako, Babatunde; Schreiner, Pamela J.; Signorello, Lisa B.; Singleton, Andrew B.; Stanford, Janet L.; Stram, Alex H.; Stram, Daniel O.; Strom, Sara S.; Suktitipat, Bhoom; Thun, Michael J.; Witte, John S.; Yanek, Lisa R.; Ziegler, Regina G.; Zheng, Wei; Zhu, Xiaofeng; Zmuda, Joseph M.; Zonderman, Alan B.; Evans, Michele K.; Liu, Yongmei; Becker, Diane M.; Cooper, Richard S.; Pastinen, Tomi; Henderson, Brian E.; Hirschhorn, Joel N.; Lettre, Guillaume; Haiman, Christopher A.

    2011-01-01

    Adult height is a classic polygenic trait of high heritability (h 2 ∼0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain ∼10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10−12 and 2p14-rs4315565, P = 1.2×10−8). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10−4 for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P<0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits. PMID:21998595

  13. WDR1 and CLNK gene polymorphisms correlate with serum glucose and high-density lipoprotein levels in Tibetan gout patients.

    PubMed

    Lan, Bing; Chen, Peng; Jiri, Mutu; He, Na; Feng, Tian; Liu, Kai; Jin, Tianbo; Kang, Longli

    2016-03-01

    Current evidence suggests heredity and metabolic syndrome contributes to gout progression. Specifically, the WDR1 and CLNK genes may play a role in gout progression in European ancestry populations. However, no studies have focused on Chinese populations, especially Tibetan individuals. This study aims to determine whether variations in these two genes correlate with gout-related indices in Chinese-Tibetan gout patients. Eleven single-nucleotide polymorphisms in the WDR1 and CLNK genes were detected in 319 Chinese-Tibetan gout patients and 318 controls. We used one-way analysis of variance to evaluate the polymorphisms' effects on gout based on mean serum levels of metabolism indicators, such as albumin, glucose (GLU), triglycerides, cholesterol, high-density lipoproteins (HDL-C), creatinine, and uric acid, from fasting venous blood samples. All p values were Bonferroni corrected. Polymorphisms of the WDR1 and CLNK genes affected multiple risk factors for gout development. Significant differences in serum GLU levels were detected between different genotypic groups with WDRI polymorphisms rs4604059 (p = 0.005) and rs12498927 (p = 0.005). In addition, significant differences in serum HDL-C levels were detected between different genotypic groups with the CLNK polymorphism rs2041215 (p = 0.001). Polymorphisms of CLNK also affected levels of albumin, triglycerides, and creatinine. This study is the first to investigate and identify positive correlations between WDR1 and CLNK gene polymorphisms in Chinese-Tibetan populations. Our findings provide significant evidence for the effect of genetic polymorphisms on gout-related factors in Chinese-Tibetan populations.

  14. PTPN22 association in systemic lupus erythematosus (SLE) with respect to individual ancestry and clinical sub-phenotypes.

    PubMed

    Namjou, Bahram; Kim-Howard, Xana; Sun, Celi; Adler, Adam; Chung, Sharon A; Kaufman, Kenneth M; Kelly, Jennifer A; Glenn, Stuart B; Guthridge, Joel M; Scofield, Robert H; Kimberly, Robert P; Brown, Elizabeth E; Alarcón, Graciela S; Edberg, Jeffrey C; Kim, Jae-Hoon; Choi, Jiyoung; Ramsey-Goldman, Rosalind; Petri, Michelle A; Reveille, John D; Vilá, Luis M; Boackle, Susan A; Freedman, Barry I; Tsao, Betty P; Langefeld, Carl D; Vyse, Timothy J; Jacob, Chaim O; Pons-Estel, Bernardo; Niewold, Timothy B; Moser Sivils, Kathy L; Merrill, Joan T; Anaya, Juan-Manuel; Gilkeson, Gary S; Gaffney, Patrick M; Bae, Sang-Cheol; Alarcón-Riquelme, Marta E; Harley, John B; Criswell, Lindsey A; James, Judith A; Nath, Swapan K

    2013-01-01

    Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical sub-phenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.7 × 10(-9), OR = 1.40 (95% CI = 1.25-1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67-0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG >20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.7 × 10(-5), OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with European ancestry. Additionally, rs

  15. PTPN22 Association in Systemic Lupus Erythematosus (SLE) with Respect to Individual Ancestry and Clinical Sub-Phenotypes

    PubMed Central

    Adler, Adam; Chung, Sharon A.; Kaufman, Kenneth M.; Kelly, Jennifer A.; Glenn, Stuart B.; Guthridge, Joel M.; Scofield, Robert H.; Kimberly, Robert P.; Brown, Elizabeth E.; Alarcón, Graciela S.; Edberg, Jeffrey C.; Kim, Jae-Hoon; Choi, Jiyoung; Ramsey-Goldman, Rosalind; Petri, Michelle A.; Reveille, John D.; Vilá, Luis M.; Boackle, Susan A.; Freedman, Barry I.; Tsao, Betty P.; Langefeld, Carl D.; Vyse, Timothy J.; Jacob, Chaim O.; Pons-Estel, Bernardo; Niewold, Timothy B.; Moser Sivils, Kathy L.; Merrill, Joan T.; Anaya, Juan-Manuel; Gilkeson, Gary S.; Gaffney, Patrick M.; Bae, Sang-Cheol; Alarcón-Riquelme, Marta E.; Harley, John B.; Criswell, Lindsey A.; James, Judith A.; Nath, Swapan K.

    2013-01-01

    Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical sub-phenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.7×10−9, OR = 1.40 (95% CI = 1.25–1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67–0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG >20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.7×10−5, OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with

  16. Inferring parental genomic ancestries using pooled semi-Markov processes.

    PubMed

    Zou, James Y; Halperin, Eran; Burchard, Esteban; Sankararaman, Sriram

    2015-06-15

    A basic problem of broad public and scientific interest is to use the DNA of an individual to infer the genomic ancestries of the parents. In particular, we are often interested in the fraction of each parent's genome that comes from specific ancestries (e.g. European, African, Native American, etc). This has many applications ranging from understanding the inheritance of ancestry-related risks and traits to quantifying human assortative mating patterns. We model the problem of parental genomic ancestry inference as a pooled semi-Markov process. We develop a general mathematical framework for pooled semi-Markov processes and construct efficient inference algorithms for these models. Applying our inference algorithm to genotype data from 231 Mexican trios and 258 Puerto Rican trios where we have the true genomic ancestry of each parent, we demonstrate that our method accurately infers parameters of the semi-Markov processes and parents' genomic ancestries. We additionally validated the method on simulations. Our model of pooled semi-Markov process and inference algorithms may be of independent interest in other settings in genomics and machine learning. © The Author 2015. Published by Oxford University Press.

  17. Accurate inference of local phased ancestry of modern admixed populations.

    PubMed

    Ma, Yamin; Zhao, Jian; Wong, Jian-Syuan; Ma, Li; Li, Wenzhi; Fu, Guoxing; Xu, Wei; Zhang, Kui; Kittles, Rick A; Li, Yun; Song, Qing

    2014-07-23

    Population stratification is a growing concern in genetic-association studies. Averaged ancestry at the genome level (global ancestry) is insufficient for detecting the population substructures and correcting population stratifications in association studies. Local and phase stratification are needed for human genetic studies, but current technologies cannot be applied on the entire genome data due to various technical caveats. Here we developed a novel approach (aMAP, ancestry of Modern Admixed Populations) for inferring local phased ancestry. It took about 3 seconds on a desktop computer to finish a local ancestry analysis for each human genome with 1.4-million SNPs. This method also exhibits the scalability to larger datasets with respect to the number of SNPs, the number of samples, and the size of reference panels. It can detect the lack of the proxy of reference panels. The accuracy was 99.4%. The aMAP software has a capacity for analyzing 6-way admixed individuals. As the biomedical community continues to expand its efforts to increase the representation of diverse populations, and as the number of large whole-genome sequence datasets continues to grow rapidly, there is an increasing demand on rapid and accurate local ancestry analysis in genetics, pharmacogenomics, population genetics, and clinical diagnosis.

  18. Amerindian ancestry and extended longevity in Nicoya, Costa Rica.

    PubMed

    Azofeifa, Jorge; Ruiz-Narváez, Edward A; Leal, Alejandro; Gerlovin, Hanna; Rosero-Bixby, Luis

    2017-09-08

    The aim of this study was to address the hypothesis that Amerindian ancestry is associated with extended longevity in the admixed population of Nicoya, Costa Rica. The Nicoya Peninsula of Costa Rica has been considered a "longevity island," particularly for males. We estimated Amerindian ancestry using 464 ancestral informative markers in 20 old Nicoyans aged ≥99 years, and 20 younger Nicoyans (60-65 years). We used logistic regression to estimate odds ratio (OR) and 95% confidence interval (CI) of the association of Amerindian ancestry and longevity. Older Nicoyans had higher Amerindian ancestry compared to younger Nicoyans (43.3% vs 36.0%, P = .04). Each 10% increase of Amerindian ancestry was associated with more than twice the odds of being long-lived (OR = 2.32, 95% CI = 1.03-5.25). To our knowledge, this is the first time that ancestry is implicated as a likely determinant of extended longevity. Amerindian-specific alleles may protect against early mortality. The identification of these protective alleles should be the focus of future studies. © 2017 Wiley Periodicals, Inc.

  19. Ancestry Testing and the Practice of Genetic Counseling.

    PubMed

    Kirkpatrick, Brianne E; Rashkin, Misha D

    2017-02-01

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

  20. A 50-SNP assay for biogeographic ancestry and phenotype prediction in the U.S. population.

    PubMed

    Gettings, Katherine Butler; Lai, Ronald; Johnson, Joni L; Peck, Michelle A; Hart, Jessica A; Gordish-Dressman, Heather; Schanfield, Moses S; Podini, Daniele S

    2014-01-01

    When an STR DNA profile obtained from crime scene evidence does not match identified suspects or profiles from available databases, further DNA analyses targeted at inferring the possible ancestral origin and phenotypic characteristics of the perpetrator could yield valuable information. Single Nucleotide Polymorphisms (SNPs), the most common form of genetic polymorphisms, have alleles associated with specific populations and/or correlated to physical characteristics. We have used single base primer extension (SBE) technology to develop a 50 SNP assay (composed of three multiplexes) designed to predict ancestry among the primary U.S. populations (African American, East Asian, European American, and Hispanic American/Native American), as well as pigmentation phenotype (eye, hair, and skin color) among European American. We have optimized this assay to a sensitivity level comparable to current forensic DNA analyses, and shown robust performance on forensic-type samples. In addition, we developed a prediction model for ancestry in the U.S. population, based on the random match probability and likelihood ratio formulas already used in forensic laboratories. Lastly, we evaluated the biogeographic ancestry prediction model using a test set, and we evaluated an existing model for eye color with our U.S. sample set. Using these models with recommended thresholds, the 50 SNP assay provided accurate ancestry information in 98.6% of the test set samples, and provided accurate eye color information in 61% of the European samples tested (25% were inconclusive and 14% were incorrect). This method, which uses equipment already available in forensic DNA laboratories, is recommended for use in U.S. forensic casework to provide additional information about the donor of a DNA sample when the STR profile has not been linked to an individual. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. A tale of two electrons: Correlation at high density

    NASA Astrophysics Data System (ADS)

    Loos, Pierre-François; Gill, Peter M. W.

    2010-11-01

    We review our recent progress in the determination of the high-density correlation energy E in two-electron systems. Several two-electron systems are considered, such as the well known helium-like ions (helium), and the Hooke's law atom (hookium). We also present results regarding two electrons on the surface of a sphere (spherium), and two electrons trapped in a spherical box (ballium). We also show that, in the large-dimension limit, the high-density correlation energy of two opposite-spin electrons interacting via a Coulomb potential is given by E˜-1/(8D2) for any radial external potential V(r), where D is the dimensionality of the space. This result explains the similarity of E in the previous two-electron systems for D=3.

  2. Correlations and multi-affinity in high frequency financial datasets

    NASA Astrophysics Data System (ADS)

    Baviera, Roberto; Pasquini, Michele; Serva, Maurizio; Vergni, Davide; Vulpiani, Angelo

    2001-11-01

    In this paper we perform a quantitative check of long term correlations and multi-affinity in Deutsche Mark/US Dollar exchange rates using high frequency data. We show that the use of business time, i.e., the ranking of the quotes in the sequences, eliminates most of the seasonality in financial-time series, allowing a precise estimation of some return anomalies.

  3. Genetic Ancestry, Skin Reflectance and Pigmentation Genotypes in Association with Serum Vitamin D Metabolite Balance

    PubMed Central

    Wilson, Robin Taylor; Roff, Alanna N.; Dai, P. Jenny; Fortugno, Tracey; Douds, Jonathan; Chen, Gang; Grove, Gary L.; Nikiforova, Sheila Ongeri; Barnholtz-Sloan, Jill; Frudakis, Tony; Chinchilli, Vernon M.; Hartman, Terryl J.; Demers, Laurence M.; Shriver, Mark D.; Canfield, Victor A.; Cheng, Keith C.

    2012-01-01

    Background Lower serum vitamin D (25(OH)D) among individuals with African ancestry is attributed primarily to skin pigmentation. However, the influence of genetic polymorphisms controlling for skin melanin content has not been investigated. Therefore, we investigated differences in non-summer serum vitamin D metabolites according to self-reported race, genetic ancestry, skin reflectance and key pigmentation genes (SLC45A2 and SLC24A5). Materials and Methods Healthy individuals reporting at least half African American or half European American heritage were frequency matched to one another on age (+/− 2 years) and sex. 176 autosomal ancestry informative markers were used to estimate genetic ancestry. Melanin index was measured by reflectance spectrometry. Serum vitamin D metabolites (25(OH)D3, 25(OH)D2 and 24,25(OH)2D3) were determined by high performance liquid chromatography (HPLC) tandem mass spectrometry. Percent 24,25(OH)2D3 was calculated as a percent of the parent metabolite (25(OH)D3). Stepwise and backward selection regression models were used to identify leading covariates. Results Fifty African Americans and 50 European Americans participated in the study. Compared with SLC24A5 111Thr homozygotes, individuals with the SLC24A5 111Thr/Ala and 111Ala/Ala genotypes had respectively lower levels of 25(OH)D3 (23.0 and 23.8 nmol/L lower, p-dominant=0.007), and percent 24,25(OH)2D3 (4.1 and 5.2 percent lower, p-dominant=0.003), controlling for tanning bed use, vitamin D/fish oil supplement intake, race/ethnicity, and genetic ancestry. Results were similar with melanin index adjustment, and were not confounded by glucocorticoid, oral contraceptive, or statin use. Conclusions The SLC24A5 111Ala allele was associated with lower serum vitamin 25(OH)D3 and lower percent 24,25(OH)2D3, independently from melanin index and West African genetic ancestry. PMID:23525585

  4. Genetic Ancestry, Skin Reflectance and Pigmentation Genotypes in Association with Serum Vitamin D Metabolite Balance.

    PubMed

    Wilson, Robin Taylor; Roff, Alanna N; Dai, P Jenny; Fortugno, Tracey; Douds, Jonathan; Chen, Gang; Grove, Gary L; Nikiforova, Sheila Ongeri; Barnholtz-Sloan, Jill; Frudakis, Tony; Chinchilli, Vernon M; Hartman, Terryl J; Demers, Laurence M; Shriver, Mark D; Canfield, Victor A; Cheng, Keith C

    2011-09-01

    Lower serum vitamin D (25(OH)D) among individuals with African ancestry is attributed primarily to skin pigmentation. However, the influence of genetic polymorphisms controlling for skin melanin content has not been investigated. Therefore, we investigated differences in non-summer serum vitamin D metabolites according to self-reported race, genetic ancestry, skin reflectance and key pigmentation genes (SLC45A2 and SLC24A5). Healthy individuals reporting at least half African American or half European American heritage were frequency matched to one another on age (+/- 2 years) and sex. 176 autosomal ancestry informative markers were used to estimate genetic ancestry. Melanin index was measured by reflectance spectrometry. Serum vitamin D metabolites (25(OH)D3, 25(OH)D 2 and 24,25(OH)2D3) were determined by high performance liquid chromatography (HPLC) tandem mass spectrometry. Percent 24,25(OH)2D3 was calculated as a percent of the parent metabolite (25(OH)D3). Stepwise and backward selection regression models were used to identify leading covariates. Fifty African Americans and 50 European Americans participated in the study. Compared with SLC24A5 111(Thr) homozygotes, individuals with the SLC24A5 111(Thr/Ala) and 111(Ala/Ala) genotypes had respectively lower levels of 25(OH)D3 (23.0 and 23.8 nmol/L lower, p-dominant=0.007), and percent 24,25(OH)2D3 (4.1 and 5.2 percent lower, p-dominant=0.003), controlling for tanning bed use, vitamin D/fish oil supplement intake, race/ethnicity, and genetic ancestry. Results were similar with melanin index adjustment, and were not confounded by glucocorticoid, oral contraceptive, or statin use. The SLC24A5 111(Ala) allele was associated with lower serum vitamin 25(OH)D3 and lower percent 24,25(OH)2D3, independently from melanin index and West African genetic ancestry.

  5. A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

    PubMed

    Rand, Kristin A; Song, Chi; Dean, Eric; Serie, Daniel J; Curtin, Karen; Sheng, Xin; Hu, Donglei; Huff, Carol Ann; Bernal-Mizrachi, Leon; Tomasson, Michael H; Ailawadhi, Sikander; Singhal, Seema; Pawlish, Karen; Peters, Edward S; Bock, Cathryn H; Stram, Alex; Van Den Berg, David J; Edlund, Christopher K; Conti, David V; Zimmerman, Todd; Hwang, Amie E; Huntsman, Scott; Graff, John; Nooka, Ajay; Kong, Yinfei; Pregja, Silvana L; Berndt, Sonja I; Blot, William J; Carpten, John; Casey, Graham; Chu, Lisa; Diver, W Ryan; Stevens, Victoria L; Lieber, Michael R; Goodman, Phyllis J; Hennis, Anselm J M; Hsing, Ann W; Mehta, Jayesh; Kittles, Rick A; Kolb, Suzanne; Klein, Eric A; Leske, Cristina; Murphy, Adam B; Nemesure, Barbara; Neslund-Dudas, Christine; Strom, Sara S; Vij, Ravi; Rybicki, Benjamin A; Stanford, Janet L; Signorello, Lisa B; Witte, John S; Ambrosone, Christine B; Bhatti, Parveen; John, Esther M; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah J; Bandera, Elisa V; Birmann, Brenda M; Ingles, Sue A; Press, Michael F; Atanackovic, Djordje; Glenn, Martha J; Cannon-Albright, Lisa A; Jones, Brandt; Tricot, Guido; Martin, Thomas G; Kumar, Shaji K; Wolf, Jeffrey L; Deming Halverson, Sandra L; Rothman, Nathaniel; Brooks-Wilson, Angela R; Rajkumar, S Vincent; Kolonel, Laurence N; Chanock, Stephen J; Slager, Susan L; Severson, Richard K; Janakiraman, Nalini; Terebelo, Howard R; Brown, Elizabeth E; De Roos, Anneclaire J; Mohrbacher, Ann F; Colditz, Graham A; Giles, Graham G; Spinelli, John J; Chiu, Brian C; Munshi, Nikhil C; Anderson, Kenneth C; Levy, Joan; Zonder, Jeffrey A; Orlowski, Robert Z; Lonial, Sagar; Camp, Nicola J; Vachon, Celine M; Ziv, Elad; Stram, Daniel O; Hazelett, Dennis J; Haiman, Christopher A; Cozen, Wendy

    2016-12-01

    Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P < 0.05) associated with multiple myeloma risk in persons of African ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10(-7)) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. Dynamics of Coulomb correlations in semiconductors in high magnetic fields

    SciTech Connect

    Fromer, Neil Alan

    2002-01-01

    Current theories have been successful in explaining many nonlinear optical experiments in undoped semiconductors. However, these theories require a ground state which is assumed to be uncorrelated. Strongly correlated systems of current interest, such as a two dimensional electron gas in a high magnetic field, cannot be explained in this manner because the correlations in the ground state and the low energy collective excitations cause a breakdown of the conventional techniques. We perform ultrafast time-resolved four-wave mixing on $n$-modulation doped quantum wells, which contain a quasi-two dimensional electron gas, in a large magnetic field, when only a single Landau level is excited and also when two levels are excited together. We find evidence for memory effects and as strong coupling between the Landau levels induced by the electron gas. We compare our results with simulations based on a new microscopic approach capable of treating the collective effects and correlations of the doped electrons, and find a good qualitative agreement. By looking at the individual contributions to the model, we determine that the unusual correlation effects seen in the experiments are caused by the scattering of photo-excited electron-hole pairs with the electron gas, leading to new excited states which are not present in undoped semiconductors, and also by exciton-exciton interactions mediated by the long-lived collective excitations of the electron gas, inter-Landau level magnetoplasmons.

  7. Simultaneous Correlative Scanning Electron and High-NA Fluorescence Microscopy

    PubMed Central

    Liv, Nalan; Zonnevylle, A. Christiaan; Narvaez, Angela C.; Effting, Andries P. J.; Voorneveld, Philip W.; Lucas, Miriam S.; Hardwick, James C.; Wepf, Roger A.; Kruit, Pieter; Hoogenboom, Jacob P.

    2013-01-01

    Correlative light and electron microscopy (CLEM) is a unique method for investigating biological structure-function relations. With CLEM protein distributions visualized in fluorescence can be mapped onto the cellular ultrastructure measured with electron microscopy. Widespread application of correlative microscopy is hampered by elaborate experimental procedures related foremost to retrieving regions of interest in both modalities and/or compromises in integrated approaches. We present a novel approach to correlative microscopy, in which a high numerical aperture epi-fluorescence microscope and a scanning electron microscope illuminate the same area of a sample at the same time. This removes the need for retrieval of regions of interest leading to a drastic reduction of inspection times and the possibility for quantitative investigations of large areas and datasets with correlative microscopy. We demonstrate Simultaneous CLEM (SCLEM) analyzing cell-cell connections and membrane protrusions in whole uncoated colon adenocarcinoma cell line cells stained for actin and cortactin with AlexaFluor488. SCLEM imaging of coverglass-mounted tissue sections with both electron-dense and fluorescence staining is also shown. PMID:23409024

  8. The application of high-speed digital image correlation.

    SciTech Connect

    Reu, Phillip L.; Miller, Timothy J.

    2008-02-01

    Digital image correlation (DIC) is a method of using digital images to calculate two-dimensional displacement and deformation or for stereo systems three-dimensional shape, displacement, and deformation. While almost any imaging system can be used with DIC, there are some important challenges when working with the technique in high- and ultra-high-speed applications. This article discusses three of these challenges: camera sensor technology, camera frame rate, and camera motion mitigation. Potential solutions are treated via three demonstration experiments showing the successful application of high-speed DIC for dynamic events. The application and practice of DIC at high speeds, rather than the experimental results themselves, provide the main thrust of the discussion.

  9. Application of an African Ancestry Index as a genomic control approach in a Brazilian population.

    PubMed

    Zembrzuski, V M; Callegari-Jacques, S M; Hutz, M H

    2006-11-01

    Ten ancestry informative markers were investigated in 101 coronary artery disease patients and 102 healthy controls from a Southern Brazilian population, in order to determine if stratification occurs in this population. The degree of African admixture detected in this population was estimated to be as high as 6%, but no differences between cases and controls were observed. Using an African Ancestry Index (AAI) that estimates admixture at the individual level it was possible to remove from the samples those individuals with evidence of African admixture. Therefore we have shown that it is possible to control for population stratification by choosing individuals, without the loss of statistical power that occurs with the use of other methods of genomic control.

  10. High-Harmonic Generation Enhanced by Dynamical Electron Correlation

    NASA Astrophysics Data System (ADS)

    Tikhomirov, Iliya; Sato, Takeshi; Ishikawa, Kenichi L.

    2017-05-01

    We theoretically study multielectron effects in high-harmonic generation (HHG), using all-electron first-principles simulations for a one-dimensional model atom. In addition to the usual plateau and cutoff (from a cation in the present case, since the neutral is immediately ionized), we find a prominent resonance peak far above the plateau and a second plateau extended beyond the first cutoff. These features originate from the dication response enhanced by orders of magnitude due to the action of the Coulomb force from the rescattering electron, and, hence, are a clear manifestation of electron correlation. Although the present simulations are done in 1D, the physical mechanism underlying the dramatic enhancement is expected to hold also for three-dimensional real systems. This will provide new possibilities to explore dynamical electron correlation in intense laser fields using HHG, which is usually considered to be of single-electron nature in most cases.

  11. SPIDER Progress Towards High Resolution Correlated Fission Product Data

    NASA Astrophysics Data System (ADS)

    Shields, Dan; Meierbachtol, Krista; Tovesson, Fredrik; Arnold, Charles; Blackeley, Rick; Bredeweg, Todd; Devlin, Matt; Hecht, Adam; Jandel, Marian; Jorgenson, Justin; Nelson, Ron; White, Morgan; Spider Team

    2014-09-01

    The SPIDER detector (SPectrometer for Ion DEtermination in fission Research) is under development with the goal of obtaining high-resolution, high-efficiency, correlated fission product data needed for many applications including the modeling of next generation nuclear reactors, stockpile stewardship, and the fundamental understanding of the fission process. SPIDER simultaneously measures velocity and energy of both fission products to calculate fission product yields (FPYs), neutron multiplicity (ν), and total kinetic energy (TKE). A detailed description of the prototype SPIDER detector components will be presented. Characterization measurements with alpha and spontaneous fission sources will also be discussed. LA-UR-14-24875. The SPIDER detector (SPectrometer for Ion DEtermination in fission Research) is under development with the goal of obtaining high-resolution, high-efficiency, correlated fission product data needed for many applications including the modeling of next generation nuclear reactors, stockpile stewardship, and the fundamental understanding of the fission process. SPIDER simultaneously measures velocity and energy of both fission products to calculate fission product yields (FPYs), neutron multiplicity (ν), and total kinetic energy (TKE). A detailed description of the prototype SPIDER detector components will be presented. Characterization measurements with alpha and spontaneous fission sources will also be discussed. LA-UR-14-24875. This work is in part supported by LANL Laboratory Directed Research and Development Projects 20110037DR and 20120077DR.

  12. Assessment of coyote-wolf-dog admixture using ancestry-informative diagnostic SNPs

    PubMed Central

    Monzón, J.; Kays, R.; Dykhuizen, D. E.

    2014-01-01

    The evolutionary importance of hybridization as a source of new adaptive genetic variation is rapidly gaining recognition. Hybridization between coyotes and wolves may have introduced adaptive alleles into the coyote gene pool that facilitated an expansion in their geographic range and dietary niche. Furthermore, hybridization between coyotes and domestic dogs may facilitate adaptation to human-dominated environments. We genotyped 63 ancestry-informative single nucleotide polymorphisms in 427 canids in order to examine the prevalence, spatial distribution, and ecology of admixture in eastern coyotes. Using multivariate methods and Bayesian clustering analyses, we estimated the relative contributions of western coyotes, western and eastern wolves, and domestic dogs to the admixed ancestry of Ohio and eastern coyotes. We found that eastern coyotes form an extensive hybrid swarm, with all our samples having varying levels of admixture. Ohio coyotes, previously thought to be free of admixture, are also highly admixed with wolves and dogs. Coyotes in areas of high deer density are genetically more wolf-like, suggesting that natural selection for wolf-like traits may result in local adaptation at a fine geographic scale. Our results, in light of other previously published studies of admixture in Canis, reveal a pattern of sex-biased hybridization, presumably generated by male wolves and dogs mating with female coyotes. This study is the most comprehensive genetic survey of admixture in eastern coyotes and demonstrates that the frequency and scope of hybridization can be quantified with relatively few ancestry-informative markers. PMID:24148003

  13. Assessment of coyote-wolf-dog admixture using ancestry-informative diagnostic SNPs.

    PubMed

    Monzón, J; Kays, R; Dykhuizen, D E

    2014-01-01

    The evolutionary importance of hybridization as a source of new adaptive genetic variation is rapidly gaining recognition. Hybridization between coyotes and wolves may have introduced adaptive alleles into the coyote gene pool that facilitated an expansion in their geographic range and dietary niche. Furthermore, hybridization between coyotes and domestic dogs may facilitate adaptation to human-dominated environments. We genotyped 63 ancestry-informative single-nucleotide polymorphisms in 427 canids to examine the prevalence, spatial distribution and the ecology of admixture in eastern coyotes. Using multivariate methods and Bayesian clustering analyses, we estimated the relative contributions of western coyotes, western and eastern wolves, and domestic dogs to the admixed ancestry of Ohio and eastern coyotes. We found that eastern coyotes form an extensive hybrid swarm, with all our samples having varying levels of admixture. Ohio coyotes, previously thought to be free of admixture, are also highly admixed with wolves and dogs. Coyotes in areas of high deer density are genetically more wolf-like, suggesting that natural selection for wolf-like traits may result in local adaptation at a fine geographic scale. Our results, in light of other previously published studies of admixture in Canis, revealed a pattern of sex-biased hybridization, presumably generated by male wolves and dogs mating with female coyotes. This study is the most comprehensive genetic survey of admixture in eastern coyotes and demonstrates that the frequency and scope of hybridization can be quantified with relatively few ancestry-informative markers. © 2013 John Wiley & Sons Ltd.

  14. Enhanced Methods for Local Ancestry Assignment in Sequenced Admixed Individuals

    PubMed Central

    Brown, Robert; Pasaniuc, Bogdan

    2014-01-01

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

  15. The Ancestry and Affiliations of Kennewick Man

    PubMed Central

    Rasmussen, Morten; Poznik, G. David; Zollikofer, Christoph P. E.; de León, Marcia Ponce; Allentoft, Morten E.; Moltke, Ida; Jónsson, Hákon; Valdiosera, Cristina; Malhi, Ripan S.; Orlando, Ludovic; Bustamante, Carlos D.; Stafford, Thomas W.; Meltzer, David J.; Nielsen, Rasmus; Willerslev, Eske

    2016-01-01

    Kennewick Man, referred to as the Ancient One by Native Americans, is a male human skeleton discovered in Washington state (USA) in 1996 and initially radiocarbon-dated to 8340–9200 calibrated years BP1. His population affinities have been the subject of scientific debate and legal controversy. Based on initial study of cranial morphology it was asserted that Kennewick Man was neither Native American nor closely related to the Claimant Plateau tribes of the Pacific Northwest, who claimed ancestral relationship and requested repatriation under the Native American Graves Protection and Repatriation Act (NAGPRA). The morphological analysis was important to judicial decisions that Kennewick Man was not Native American and that therefore NAGPRA did not apply. Instead of repatriation, additional studies of the remains were permitted2. Subsequent craniometric analysis affirmed Kennewick Man to be more closely related to circumpacific groups such as the Ainu and Polynesians than he is to modern Native Americans2. In order to resolve Kennewick Man’s ancestry and affiliations, we have sequenced his genome to ~1× coverage and compared it to worldwide genomic data including the Ainu and Polynesians. We find that Kennewick Man is closer to modern Native Americans than to any other population worldwide. Among the Native American groups for whom genome wide data is available for comparison, several appear to be descended from a population closely related to that of Kennewick Man, including the Confederated Tribes of the Colville Reservation (Colville), one of the five tribes claiming Kennewick Man. We revisit the cranial analyses and find that, as opposed to genomic-wide comparisons, it is not possible on that basis to affiliate Kennewick Man to specific contemporary groups. We therefore conclude based on genetic comparisons that Kennewick Man shows continuity with Native North Americans over at least the last eight millennia. PMID:26087396

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

    PubMed Central

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

    2013-01-01

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

  17. A panel of ancestry informative markers for the complex five-way admixed South African coloured population.

    PubMed

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

    2013-01-01

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

  18. Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans.

    PubMed

    Raghavan, Maanasa; Skoglund, Pontus; Graf, Kelly E; Metspalu, Mait; Albrechtsen, Anders; Moltke, Ida; Rasmussen, Simon; Stafford, Thomas W; Orlando, Ludovic; Metspalu, Ene; Karmin, Monika; Tambets, Kristiina; Rootsi, Siiri; Mägi, Reedik; Campos, Paula F; Balanovska, Elena; Balanovsky, Oleg; Khusnutdinova, Elza; Litvinov, Sergey; Osipova, Ludmila P; Fedorova, Sardana A; Voevoda, Mikhail I; DeGiorgio, Michael; Sicheritz-Ponten, Thomas; Brunak, Søren; Demeshchenko, Svetlana; Kivisild, Toomas; Villems, Richard; Nielsen, Rasmus; Jakobsson, Mattias; Willerslev, Eske

    2014-01-02

    The origins of the First Americans remain contentious. Although Native Americans seem to be genetically most closely related to east Asians, there is no consensus with regard to which specific Old World populations they are closest to. Here we sequence the draft genome of an approximately 24,000-year-old individual (MA-1), from Mal'ta in south-central Siberia, to an average depth of 1×. To our knowledge this is the oldest anatomically modern human genome reported to date. The MA-1 mitochondrial genome belongs to haplogroup U, which has also been found at high frequency among Upper Palaeolithic and Mesolithic European hunter-gatherers, and the Y chromosome of MA-1 is basal to modern-day western Eurasians and near the root of most Native American lineages. Similarly, we find autosomal evidence that MA-1 is basal to modern-day western Eurasians and genetically closely related to modern-day Native Americans, with no close affinity to east Asians. This suggests that populations related to contemporary western Eurasians had a more north-easterly distribution 24,000 years ago than commonly thought. Furthermore, we estimate that 14 to 38% of Native American ancestry may originate through gene flow from this ancient population. This is likely to have occurred after the divergence of Native American ancestors from east Asian ancestors, but before the diversification of Native American populations in the New World. Gene flow from the MA-1 lineage into Native American ancestors could explain why several crania from the First Americans have been reported as bearing morphological characteristics that do not resemble those of east Asians. Sequencing of another south-central Siberian, Afontova Gora-2 dating to approximately 17,000 years ago, revealed similar autosomal genetic signatures as MA-1, suggesting that the region was continuously occupied by humans throughout the Last Glacial Maximum. Our findings reveal that western Eurasian genetic signatures in modern-day Native

  19. Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans

    PubMed Central

    Raghavan, Maanasa; Skoglund, Pontus; Graf, Kelly E.; Metspalu, Mait; Albrechtsen, Anders; Moltke, Ida; Rasmussen, Simon; Stafford, Thomas W.; Orlando, Ludovic; Metspalu, Ene; Karmin, Monika; Tambets, Kristiina; Rootsi, Siiri; Mägi, Reedik; Campos, Paula F.; Balanovska, Elena; Balanovsky, Oleg; Khusnutdinova, Elza; Litvinov, Sergey; Osipova, Ludmila P.; Fedorova, Sardana A.; Voevoda, Mikhail I.; DeGiorgio, Michael; Sicheritz-Ponten, Thomas; Brunak, Søren; Demeshchenko, Svetlana; Kivisild, Toomas; Villems, Richard; Nielsen, Rasmus; Jakobsson, Mattias; Willerslev, Eske

    2014-01-01

    The origins of the First Americans remain contentious. Although Native Americans seem to be genetically most closely related to east Asians1–3, there is no consensus with regard to which specific Old World populations they are closest to4–8. Here we sequence the draft genome of an approximately 24,000-year-old individual (MA-1), from Mal’ta in south-central Siberia9, to an average depth of 13. To our knowledge this is the oldest anatomically modern human genome reported to date. The MA-1 mitochondrial genome belongs to haplogroup U, which has also been found at high frequency among Upper Palaeolithic and Mesolithic European hunter-gatherers10–12, and the Y chromosome of MA-1 is basal to modern-day western Eurasians and near the root of most Native American lineages5. Similarly, we find autosomal evidence that MA-1 is basal to modern-day western Eurasians and genetically closely related to modern-day Native Americans, with no close affinity to east Asians. This suggests that populations related to contemporary western Eurasians had a more north-easterly distribution 24,000 years ago than commonly thought. Furthermore, we estimate that 14 to 38% of Native American ancestry may originate through gene flow from this ancient population. This is likely to have occurred after the divergence of Native American ancestors from east Asian ancestors, but before the diversification of Native American populations in the New World. Gene flow from the MA-1 lineage into Native American ancestors could explain why several crania from the First Americans have been reported as bearing morphological characteristics that do not resemble those of east Asians2,13. Sequencing of another south-central Siberian, Afontova Gora-2 dating to approximately 17,000 years ago14, revealed similar autosomal genetic signatures as MA-1, suggesting that the region was continuously occupied by humans throughout the Last Glacial Maximum. Our findings reveal that western Eurasian genetic signatures

  20. High intensity positron beam and angular correlation experiments at Livermore

    SciTech Connect

    Howell, R.H.; Rosenberg, I.J.; Meyer, P.; Fluss, M.J.

    1985-03-01

    A positron beam apparatus that produces a variable energy positron beam with sufficient intensity to perform new positron experiments in an ultrahigh vacuum environment has been installed at the Lawrence Livermore 100 MeV electron linac. We have installed two large area position sensitive gamma-ray detectors to measure angular correlations in two dimensions and a separate highly collimated detector to measure positronium energy distributions by time-of-flight velocity determination. Data from measurements on single crystals of Cu will be described.

  1. Suicidal ideation in high school students: depression and other correlates.

    PubMed

    De Man, A F; Leduc, C P

    1995-03-01

    English-Canadian high school students (129 boys, 117 girls) participated in a study of the relationship between suicidal ideation and selected personal variables, stress, and social support. Associations were found between suicidal ideation and the variables of gender, self-esteem, locus of control, depression, drug use, stress, perception of health, family status, academic performance, social support, and anomie. Multiple regression analysis identified depression and alcohol use as best individual predictors among these variables. Semi-partial correlation analyses showed that removal of the effect of depression resulted in a loss of initially significant relationships between suicidal ideation and the other variables except for alcohol use, drug use, and health satisfaction.

  2. Minimal SNP overlap among multiple panels of ancestry informative markers argues for more international collaboration.

    PubMed

    Soundararajan, Usha; Yun, Libing; Shi, Meisen; Kidd, Kenneth K

    2016-07-01

    The century-old use of genetic markers to determine population relationships has morphed in modern forensics into use of markers to determine the ancestry of an individual from a DNA sample. Researchers have identified sets of SNPs that have frequency differences among populations and many sets of SNPs have been published for the purpose of inferring ancestry. Such inference also requires reference datasets for the particular set of SNPs selected. We have identified 21 largely independent published panels of ancestry informative SNPs (AISNPs) and examined their union of 1397 SNPs. No SNP occurs in more than 6 panels. The 1397 SNPs in 21 panels yield a largely empty matrix that is inhibiting progress on more refined ability to infer ancestry for a forensic sample. The most common set of reference populations is the HGDP set of 52 small population samples totaling a thousand individuals. Only 46 (3%) of the 1397 SNPs occur in three or more panels. We assembled a new dataset for 44 of those SNPs involving 4,559 individuals from 73 populations. Analyses of this dataset provided clear differentiation of only five biogeographic regions: sub-Saharan Africa, Europe and SW Asia, South Asia, East Asia, and the Americas. This is an inadequate level of biogeographic resolution already exceeded by other panels. We conclude that more such AISNP panels are not needed and that the forensic community must collaborate to develop a common set of highly differentiating AISNPs typed on a very large number of population samples. How that can be accomplished will be the subject of future discussion. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  3. Forensic genetic analysis of bio-geographical ancestry.

    PubMed

    Phillips, Chris

    2015-09-01

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

  4. The Role of Adipose Tissue in Insulin Resistance in Women of African Ancestry

    PubMed Central

    Goedecke, Julia H.; Levitt, Naomi S.; Evans, Juliet; Ellman, Nicole; Hume, David John; Kotze, Liske; Tootla, Mehreen; Victor, Hendriena; Keswell, Dheshnie

    2013-01-01

    Women of African ancestry, particularly those living in industrialized countries, experience a disproportionately higher prevalence of type 2 diabetes (T2D) compared to their white counterparts. Similarly, obesity and insulin resistance, which are major risk factors for T2D, are greater in black compared to white women. The exact mechanisms underlying these phenomena are not known. This paper will focus on the role of adipose tissue biology. Firstly, the characteristic body fat distribution of women of African ancestry will be discussed, followed by the depot-specific associations with insulin resistance. Factors involved in adipose tissue biology and their relation to insulin sensitivity will then be explored, including the role of sex hormones, glucocorticoid metabolism, lipolysis and adipogenesis, and their consequent effects on adipose tissue hypoxia, oxidative stress, and inflammation. Finally the role of ectopic fat deposition will be discussed. The paper proposes directions for future research, in particular highlighting the need for longitudinal and/or intervention studies to better understand the mechanisms underlying the high prevalence of insulin resistance and T2D in women of African ancestry. PMID:23401754

  5. Resolving the Etiology of Atopic Disorders by Genetic Analysis of Racial Ancestry

    PubMed Central

    Gupta, Jayanta; Johansson, Elisabet; Bernstein, Jonathan A.; Chakraborty, Ranajit; Khurana Hershey, Gurjit K.; Rothenberg, Marc E.; Mersha, Tesfaye B.

    2016-01-01

    Atopic dermatitis (AD), food allergy (FA), allergic rhinitis (AR) and asthma are common atopic disorders of complex etiology. The frequently observed “atopic march” from early AD to asthma and/or AR later in life as well as the extensive comorbidity of atopic disorders, suggests common causal mechanisms in addition to distinct ones. Indeed, both disease-specific and shared genomic regions exist for atopic disorders. Their prevalence also varies among races; for example, AD and asthma have a higher prevalence in African-Americans when compared to European-Americans. Whether this disparity stems from true genetic or race-specific environmental risk factors or both is unknown. Thus far, the majority of the genetic studies on atopic diseases have utilized populations of European ancestry, limiting their generalizability. Large cohort initiatives and new analytic methods such as admixture mapping are currently being employed to address this knowledge gap. Here we discuss the unique and shared genetic risk factors for atopic disorders in the context of ancestry variations, and the promise of high-throughput “-omics” based systems biology approach in providing greater insight to deconstruct into their genetic and non-genetic etiologies. Future research will also focus on deep phenotyping and genotyping of diverse racial ancestry, gene-environment, and gene-gene interactions. PMID:27297995

  6. Resolving the etiology of atopic disorders by using genetic analysis of racial ancestry.

    PubMed

    Gupta, Jayanta; Johansson, Elisabet; Bernstein, Jonathan A; Chakraborty, Ranajit; Khurana Hershey, Gurjit K; Rothenberg, Marc E; Mersha, Tesfaye B

    2016-09-01

    Atopic dermatitis (AD), food allergy, allergic rhinitis, and asthma are common atopic disorders of complex etiology. The frequently observed atopic march from early AD to asthma, allergic rhinitis, or both later in life and the extensive comorbidity of atopic disorders suggest common causal mechanisms in addition to distinct ones. Indeed, both disease-specific and shared genomic regions exist for atopic disorders. Their prevalence also varies among races; for example, AD and asthma have a higher prevalence in African Americans when compared with European Americans. Whether this disparity stems from true genetic or race-specific environmental risk factors or both is unknown. Thus far, the majority of the genetic studies on atopic diseases have used populations of European ancestry, limiting their generalizability. Large-cohort initiatives and new analytic methods, such as admixture mapping, are currently being used to address this knowledge gap. Here we discuss the unique and shared genetic risk factors for atopic disorders in the context of ancestry variations and the promise of high-throughput "-omics"-based systems biology approach in providing greater insight to deconstruct their genetic and nongenetic etiologies. Future research will also focus on deep phenotyping and genotyping of diverse racial ancestry, gene-environment, and gene-gene interactions. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. The role of adipose tissue in insulin resistance in women of African ancestry.

    PubMed

    Goedecke, Julia H; Levitt, Naomi S; Evans, Juliet; Ellman, Nicole; Hume, David John; Kotze, Liske; Tootla, Mehreen; Victor, Hendriena; Keswell, Dheshnie

    2013-01-01

    Women of African ancestry, particularly those living in industrialized countries, experience a disproportionately higher prevalence of type 2 diabetes (T2D) compared to their white counterparts. Similarly, obesity and insulin resistance, which are major risk factors for T2D, are greater in black compared to white women. The exact mechanisms underlying these phenomena are not known. This paper will focus on the role of adipose tissue biology. Firstly, the characteristic body fat distribution of women of African ancestry will be discussed, followed by the depot-specific associations with insulin resistance. Factors involved in adipose tissue biology and their relation to insulin sensitivity will then be explored, including the role of sex hormones, glucocorticoid metabolism, lipolysis and adipogenesis, and their consequent effects on adipose tissue hypoxia, oxidative stress, and inflammation. Finally the role of ectopic fat deposition will be discussed. The paper proposes directions for future research, in particular highlighting the need for longitudinal and/or intervention studies to better understand the mechanisms underlying the high prevalence of insulin resistance and T2D in women of African ancestry.

  8. High correlations between temperature and nitric oxide in the thermosphere.

    PubMed

    Weimer, D R; Mlynczak, M G; Hunt, L A; Tobiska, W Kent

    2015-07-01

    Obtaining accurate predictions of the neutral density in the thermosphere has been a long-standing problem. During geomagnetic storms the auroral heating in the polar ionospheres quickly raises the temperature of the thermosphere, resulting in higher neutral densities that exert a greater drag force on objects in low Earth orbit. Rapid increases and decreases in the temperature and density may occur within a couple days. A key parameter in the thermosphere is the total amount of nitric oxide (NO). The production of NO is accelerated by the auroral heating, and since NO is an efficient radiator of thermal energy, higher concentrations of this molecule accelerate the rate at which the thermosphere cools. This paper describes an improved technique that calculates changes in the global temperature of the thermosphere. Starting from an empirical model of the Poynting flux into the ionosphere, a set of differential equations derives the minimum, global value of the exospheric temperature, which can be used in a neutral density model to calculate the global values. The relative variations in NO content are used to obtain more accurate cooling rates. Comparisons with the global rate of NO emissions that are measured with the Sounding of the Atmosphere using Broadband Emission Radiometry instrument show that there is very good agreement with the predicted values. The NO emissions correlate highly with the total auroral heating that has been integrated over time. We also show that the NO emissions are highly correlated with thermospheric temperature, as well as indices of solar extreme ultraviolet radiation.

  9. Spatial Instabilities, Homogeneities and Proximity Effects: Highly Correlated Metals

    SciTech Connect

    Dynes, Robert C.

    2008-10-31

    We have developed a superconducting scanning tunneling microscope (S-STM) which is a direct and local probe of the pair wave function of superconducting materials via the Josephson effect and quasiparticle spectra via scanning tunneling spectroscopy (STS). The novel feature of this device is a superconducting tip (Pb with an Ag capping layer) in close proximity to a superconducting sample to form a superconductor-insulator-superconductor (SIS) tunnel junction. The operation of this S-STM has been verified in the observation of Josephson tunneling between the tip and different sample systems including Pb films and NbSe{sub 2}. This instrument was employed in the study of High T{sub c} superconductors and spatial inhomogeneities. The major accomplishments in the current grant period are observations of c-axis Josephson tunneling between a conventional superconductor (Pb) and variously doped BSSCO samples. These observations are reported: (1) C-axis Josephson couplings between Pb and both OP and OV-BSCCO. This is surprising if BSCCO is strictly a d-wave superconductor; (2) ICRN of the OP sample seemed to be much smaller than those of OV samples; (3) ICRN inhomogeneity is correlated with the gap inhomogeneity on the length scale of ξ in the OV samples; (4) Inverse correlation between ICRN and Δ in OV samples; (5) Degradations of the superconductivity of BSCCO by high current density.

  10. High correlations between temperature and nitric oxide in the thermosphere

    NASA Astrophysics Data System (ADS)

    Weimer, D. R.; Mlynczak, M. G.; Hunt, L. A.; Tobiska, W. Kent

    2015-07-01

    Obtaining accurate predictions of the neutral density in the thermosphere has been a long-standing problem. During geomagnetic storms the auroral heating in the polar ionospheres quickly raises the temperature of the thermosphere, resulting in higher neutral densities that exert a greater drag force on objects in low Earth orbit. Rapid increases and decreases in the temperature and density may occur within a couple days. A key parameter in the thermosphere is the total amount of nitric oxide (NO). The production of NO is accelerated by the auroral heating, and since NO is an efficient radiator of thermal energy, higher concentrations of this molecule accelerate the rate at which the thermosphere cools. This paper describes an improved technique that calculates changes in the global temperature of the thermosphere. Starting from an empirical model of the Poynting flux into the ionosphere, a set of differential equations derives the minimum, global value of the exospheric temperature, which can be used in a neutral density model to calculate the global values. The relative variations in NO content are used to obtain more accurate cooling rates. Comparisons with the global rate of NO emissions that are measured with the Sounding of the Atmosphere using Broadband Emission Radiometry instrument show that there is very good agreement with the predicted values. The NO emissions correlate highly with the total auroral heating that has been integrated over time. We also show that the NO emissions are highly correlated with thermospheric temperature, as well as indices of solar extreme ultraviolet radiation.

  11. Resolving the ancestry of Austronesian-speaking populations.

    PubMed

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

    2016-03-01

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

  12. Pregnancy, parturition and preeclampsia in women of African ancestry

    PubMed Central

    Nakimuli, Annettee; Chazara, Olympe; Byamugisha, Josaphat; Elliott, Alison M.; Kaleebu, Pontiano; Mirembe, Florence; Moffett, Ashley

    2014-01-01

    Maternal and associated neonatal mortality rates in sub-Saharan Africa remain unacceptably high. In Mulago Hospital (Kampala, Uganda), 2 major causes of maternal death are preeclampsia and obstructed labor and their complications, conditions occurring at the extremes of the birthweight spectrum, a situation encapsulated as the obstetric dilemma. We have questioned whether the prevalence of these disorders occurs more frequently in indigenous African women and those with African ancestry elsewhere in the world by reviewing available literature. We conclude that these women are at greater risk of preeclampsia than other racial groups. At least part of this susceptibility seems independent of socioeconomic status and likely is due to biological or genetic factors. Evidence for a genetic contribution to preeclampsia is discussed. We go on to propose that the obstetric dilemma in humans is responsible for this situation and discuss how parturition and birthweight are subject to stabilizing selection. Other data we present also suggest that there are particularly strong evolutionary selective pressures operating during pregnancy and delivery in Africans. There is much greater genetic diversity and less linkage disequilibrium in Africa, and the genes responsible for regulating birthweight and placentation may therefore be easier to define than in non-African cohorts. Inclusion of African women into research on preeclampsia is an essential component in tackling this major disparity of maternal health. PMID:24184340

  13. Pregnancy, parturition and preeclampsia in women of African ancestry.

    PubMed

    Nakimuli, Annettee; Chazara, Olympe; Byamugisha, Josaphat; Elliott, Alison M; Kaleebu, Pontiano; Mirembe, Florence; Moffett, Ashley

    2014-06-01

    Maternal and associated neonatal mortality rates in sub-Saharan Africa remain unacceptably high. In Mulago Hospital (Kampala, Uganda), 2 major causes of maternal death are preeclampsia and obstructed labor and their complications, conditions occurring at the extremes of the birthweight spectrum, a situation encapsulated as the obstetric dilemma. We have questioned whether the prevalence of these disorders occurs more frequently in indigenous African women and those with African ancestry elsewhere in the world by reviewing available literature. We conclude that these women are at greater risk of preeclampsia than other racial groups. At least part of this susceptibility seems independent of socioeconomic status and likely is due to biological or genetic factors. Evidence for a genetic contribution to preeclampsia is discussed. We go on to propose that the obstetric dilemma in humans is responsible for this situation and discuss how parturition and birthweight are subject to stabilizing selection. Other data we present also suggest that there are particularly strong evolutionary selective pressures operating during pregnancy and delivery in Africans. There is much greater genetic diversity and less linkage disequilibrium in Africa, and the genes responsible for regulating birthweight and placentation may therefore be easier to define than in non-African cohorts. Inclusion of African women into research on preeclampsia is an essential component in tackling this major disparity of maternal health. Copyright © 2014 Mosby, Inc. All rights reserved.

  14. Joint testing of genotype and ancestry association in admixed families

    PubMed Central

    Tang, Hua; Siegmund, David O.; Johnson, Nicholas; Romieu, Isabelle; London, Stephanie J.

    2011-01-01

    Current genome-wide association studies (GWAS) often involve populations that have experienced recent genetic admixture. Genotype data generated from these studies can be used to test for association directly, as in a non-admixed population. As an alternative, these data can be used to infer chromosomal ancestry, and thus allow for admixture mapping. We quantify the contribution of allele-based and ancestry-based association testing under a family-design, and demonstrate that the two tests can provide non-redundant information. We propose a joint testing procedure, which efficiently integrates the two sources information. The efficiencies of the allele, ancestry and combined tests are compared in the context of a GWAS. We discuss the impact of population history and provide guidelines for future design and analysis of GWAS in admixed populations. PMID:21031451

  15. High speed displacement analysis using digital speckle correlation

    NASA Astrophysics Data System (ADS)

    Siebert, T.; Splitthof, K.; Becker, T.; Krupka, R.

    2006-06-01

    Digital speckle correlation techniques have already been successfully proven for accurate displacement analysis. With the use of two cameras, three dimensional measurements of contours and displacements can be carried out. The principle of this technique is pretty easy to understood and realized, opening a nearly unlimited range of applications. Rapid new developments in the field of digital imaging and computer technology, especially for very much dynamic applications, opens further applications for these measurement method up to high speed deformation and strain analysis, e.g. in the fields of, material testing, fracture mechanics, high speed testing, advanced materials and component testing. The dynamic range is combined with the capability to measure very large strains (up to more than 100%). The resolution of the deformation in space and time opens a wide range of applications for vibration analysis of objects. Since the system determines the absolute position and displacements of the object in space it is capable of measuring high amplitudes and even objects with rigid body movements, which is a big advantage against full field ESPI systems. The absolute resolution depends on the field of view and is scalable. Calibration of the optical setup is a crucial point which will be discussed in detail. Examples of the analysis of high speed harmonic vibration and transient events out of material research and industrial applications are presented. Results of measurement performed on a vibrating membrane and a tensile test sample are show typical features of the system.

  16. Genetic ancestry affects the phenotype of normogonadotropic anovulatory (WHOII) subfertility.

    PubMed

    Valkenburg, O; Lao, O; Schipper, I; Louwers, Y; Uitterlinden, A G; Kayser, M; Laven, J S E

    2011-07-01

    Normogonadotropic (World Health Organization category II) anovulation is the most frequent cause of reduced fertility. Anovulation is associated with endocrine changes, i.e. hyperandrogenism, obesity, and insulin resistance. However, the phenotype is notoriously heterogeneous, depending on population characteristics and diagnostic criteria. Our objective was to study the phenotype of normogonadotropic anovulatory women among various ethnic subgroups that coexist in an urban community (The Netherlands). Moreover, we studied whether genetic ancestry testing can be used to identify bio-geographic ancestry and predict the phenotype of individual patients. A standardized clinical and endocrine examination was performed in 1517 normogonadotropic anovulatory women. Bio-geographic ancestry was ascertained by questionnaire and genetic testing (637 cases), using a set of 10 previously validated ancestry informative markers. Subgroups constituted individuals from northwestern European (n = 774), Mediterranean European (north of Sahara and Middle East, n = 220), African (n = 111), Southeast Asian (n = 53), and Hindustani (n = 83) origin. Phenotypic differences included fasting insulin levels, androgen levels, and the frequency of hyperandrogenism (ranging from 76% in Mediterranean-European women to 41% in northwestern European women). Genetic ancestry testing was able to identify population structure on a continental level, i.e. European, African and Southeast Asian descent. We did not observe improved informativeness when genotype data were added to the prediction model. Population differences add to the phenotype of normogonadotropic anovulation and need to be taken into account when evaluating the individual patient. Although effective on a continental level, the present set of ancestry markers was not sufficiently effective to describe all ethnic variation in the phenotype of anovulatory subfertility.

  17. Outlining the Ancestry Landscape of Colombian Admixed Populations

    PubMed Central

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

    2016-01-01

    The ancestry of the Colombian population comprises a large number of well differentiated Native communities belonging to diverse linguistic groups. In the late fifteenth century, a process of admixture was initiated with the arrival of the Europeans, and several years later, Africans also became part of the Colombian population. Therefore, the genepool of the current Colombian population results from the admixture of Native Americans, Europeans and Africans. This admixture occurred differently in each region of the country, producing a clearly stratified population. Considering the importance of population substructure in both clinical and forensic genetics, we sought to investigate and compare patterns of genetic ancestry in Colombia by studying samples from Native and non-Native populations living in its 5 continental regions: the Andes, Caribe, Amazonia, Orinoquía, and Pacific regions. For this purpose, 46 AIM-Indels were genotyped in 761 non-related individuals from current populations. Previously published genotype data from 214 Colombian Natives from five communities were used for population comparisons. Significant differences were observed between Native and non-Native populations, among non-Native populations from different regions and among Native populations from different ethnic groups. The Pacific was the region with the highest African ancestry, Amazonia harboured the highest Native ancestry and the Andean and Orinoquían regions showed the highest proportion of European ancestry. The Andean region was further sub-divided into 6 sub-regions: North East, Central West, Central East, West, South West and South East. Among these regions, the South West region showed a significantly lower European admixture than the other regions. Hardy-Weinberg equilibrium and variance values of ancestry among individuals within populations showed a potential stratification of the Pacific population. PMID:27736937

  18. Genetic ancestry of participants in the National Children's Study.

    PubMed

    Smith, Erin N; Jepsen, Kristen; Arias, Angelo D; Shepard, Peter J; Chambers, Christina D; Frazer, Kelly A

    2014-02-03

    The National Children's Study (NCS) is a prospective epidemiological study in the USA tasked with identifying a nationally representative sample of 100,000 children, and following them from their gestation until they are 21 years of age. The objective of the study is to measure environmental and genetic influences on growth, development, and health. Determination of the ancestry of these NCS participants is important for assessing the diversity of study participants and for examining the effect of ancestry on various health outcomes. We estimated the genetic ancestry of a convenience sample of 641 parents enrolled at the 7 original NCS Vanguard sites, by analyzing 30,000 markers on exome arrays, using the 1000 Genomes Project superpopulations as reference populations, and compared this with the measures of self-reported ethnicity and race. For 99% of the individuals, self-reported ethnicity and race agreed with the predicted superpopulation. NCS individuals self-reporting as Asian had genetic ancestry of either South Asian or East Asian groups, while those reporting as either Hispanic White or Hispanic Other had similar genetic ancestry. Of the 33 individuals who self-reported as Multiracial or Non-Hispanic Other, 33% matched the South Asian or East Asian groups, while these groups represented only 4.4% of the other reported categories. Our data suggest that self-reported ethnicity and race have some limitations in accurately capturing Hispanic and South Asian populations. Overall, however, our data indicate that despite the complexity of the US population, individuals know their ancestral origins, and that self-reported ethnicity and race is a reliable indicator of genetic ancestry.

  19. Genetic African Ancestry and Markers of Mineral Metabolism in CKD

    PubMed Central

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

    2016-01-01

    Background and objectives Disorders of mineral metabolism are more common in African Americans with CKD than in European Americans with CKD. Previous studies have focused on the differences in mineral metabolism by self-reported race, making it difficult to delineate the importance of environmental compared with biologic factors. Design, setting, participants, & measurements In a cross-sectional analysis of 3013 participants of the Chronic Renal Insufficiency Cohort study with complete data, we compared markers of mineral metabolism (phosphorus, calcium, alkaline phosphatase, parathyroid hormone, fibroblast growth factor 23, and urine calcium and phosphorus excretion) in European Americans versus African Americans and separately, across quartiles of genetic African ancestry in African Americans (n=1490). Results Compared with European Americans, African Americans had higher blood concentrations of phosphorus, alkaline phosphatase, fibroblast growth factor 23, and parathyroid hormone, lower 24-hour urinary excretion of calcium and phosphorus, and lower urinary fractional excretion of calcium and phosphorus at baseline (P<0.001 for all). Among African Americans, a higher percentage of African ancestry was associated with lower 24-hour urinary excretion of phosphorus (Ptrend<0.01) in unadjusted analyses. In linear regression models adjusted for socio-demographic characteristics, kidney function, serum phosphorus, and dietary phosphorus intake, higher percentage of African ancestry was significantly associated with lower 24-hour urinary phosphorus excretion (each 10% higher African ancestry was associated with 39.6 mg lower 24-hour urinary phosphorus, P<0.001) and fractional excretion of phosphorus (each 10% higher African ancestry was associated with an absolute 1.1% lower fractional excretion of phosphorus, P=0.01). Conclusions A higher percentage of African ancestry was independently associated with lower 24-hour urinary phosphorus excretion and lower fractional

  20. Relationship of pain and ancestry in African American women.

    PubMed

    Robbins, J A; Qi, L; Garcia, L; Younger, J W; Seldin, M F

    2015-05-01

    African Americans are reported to be more sensitive to pain than European Americans. Pain sensitivity has been shown to be genetically linked in animal models and is likely to be in humans. Exactly, 11,239 self-identified African American post-menopausal women enrolled in the Women's Health Initiative had percentage African ancestry determined by ancestry informative markers, "Pain Construct" measurements and covariate information. They answered five questions about specific types and location of pain, such as joint, neck, low back, headache and urinary. They also answered two questions which were used to derive a "Pain Construct", a measure of general pain scored on a scale of 1-100. Associations were tested in linear regression models adjusting for age, self-reported medical conditions, neighbourhood socio-economic status, education and depression. In the unadjusted model of the five specific types of pain measures, greater pain perception was associated with a higher proportion of African ancestry. However, some of the specific types of pain measures were no longer associated with African ancestry after adjustment for other study covariates. The Pain Construct was statistically significantly associated with African ancestry in both the unadjusted [β = -0.132, 95% confidence interval (CI) = -099 to -0.164; r = -0.075, 95% CI -0.056 to -0.093] and the adjusted models (β = -0.069 95% CI = -0.04 to -0.10). Greater African ancestry was associated with higher levels of self-reported pain, although this accounted for only a minor fraction of the overall variation in the Pain Construct. © 2015 European Pain Federation - EFIC®

  1. Relationship of Pain and Ancestry in African American Women

    PubMed Central

    Robbins, John A.; Qi, Lihong; Garcia, Lorena; Younger, Jarred W.; Seldin, Michael F.

    2015-01-01

    Background African Americans are reported to be more sensitive to pain than European Americans. Pain sensitivity has been shown to be genetically linked in animal models and is likely to be in humans. Methods 11,239 self-identified African American post menopausal women enrolled in the Women’s Health Initiative had percentage African ancestry determined by ancestry informative markers, “Pain Construct” measurements and covariate information. They answered 5 questions about specific types and location of pain, such as joint, neck, low back, headache, and urinary. They also answered 2 questions which were used to derive a “Pain Construct”, a measure of general pain scored on a scale of 1 to 100. Associations were tested in linear regression models adjusting for age, self-reported medical conditions, neighborhood socio-economic status, education, and depression. Results In the unadjusted model of the 5 specific types of pain measures, greater pain perception was associated with a higher proportion of African ancestry. However, some of the specific types of pain measures were no longer associated with African ancestry after adjustment for other study covariates. The Pain Construct was statistically significantly associated with African ancestry in both the unadjusted [Beta = −0.132, 95% confidence interval (C I) = −099 – −0.164; r = −0.075, 95% CI −0.056 – −0.093] and the adjusted models (Beta = −0.069 95% CI = −0.04 – 0.10). Conclusions Greater African ancestry was associated with higher levels of self-reported pain although this accounted for only a minor fraction of the overall variation in the Pain Construct. PMID:25752262

  2. Outlining the Ancestry Landscape of Colombian Admixed Populations.

    PubMed

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

    2016-01-01

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

  3. Genetic African Ancestry and Markers of Mineral Metabolism in CKD.

    PubMed

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

    2016-04-07

    Disorders of mineral metabolism are more common in African Americans with CKD than in European Americans with CKD. Previous studies have focused on the differences in mineral metabolism by self-reported race, making it difficult to delineate the importance of environmental compared with biologic factors. In a cross-sectional analysis of 3013 participants of the Chronic Renal Insufficiency Cohort study with complete data, we compared markers of mineral metabolism (phosphorus, calcium, alkaline phosphatase, parathyroid hormone, fibroblast growth factor 23, and urine calcium and phosphorus excretion) in European Americans versus African Americans and separately, across quartiles of genetic African ancestry in African Americans (n=1490). Compared with European Americans, African Americans had higher blood concentrations of phosphorus, alkaline phosphatase, fibroblast growth factor 23, and parathyroid hormone, lower 24-hour urinary excretion of calcium and phosphorus, and lower urinary fractional excretion of calcium and phosphorus at baseline (P<0.001 for all). Among African Americans, a higher percentage of African ancestry was associated with lower 24-hour urinary excretion of phosphorus (Ptrend<0.01) in unadjusted analyses. In linear regression models adjusted for socio-demographic characteristics, kidney function, serum phosphorus, and dietary phosphorus intake, higher percentage of African ancestry was significantly associated with lower 24-hour urinary phosphorus excretion (each 10% higher African ancestry was associated with 39.6 mg lower 24-hour urinary phosphorus, P<0.001) and fractional excretion of phosphorus (each 10% higher African ancestry was associated with an absolute 1.1% lower fractional excretion of phosphorus, P=0.01). A higher percentage of African ancestry was independently associated with lower 24-hour urinary phosphorus excretion and lower fractional excretion of phosphorus among African Americans with CKD. These findings suggest that genetic

  4. Unravelling the hidden ancestry of American admixed populations

    PubMed Central

    Montinaro, Francesco; Busby, George B.J.; Pascali, Vincenzo L.; Myers, Simon; Hellenthal, Garrett; Capelli, Cristian

    2015-01-01

    The movement of people into the Americas has brought different populations into contact, and contemporary American genomes are the product of a range of complex admixture events. Here we apply a haplotype-based ancestry identification approach to a large set of genome-wide SNP data from a variety of American, European and African populations to determine the contributions of different ancestral populations to the Americas. Our results provide a fine-scale characterization of the source populations, identify a series of novel, previously unreported contributions from Africa and Europe and highlight geohistorical structure in the ancestry of American admixed populations. PMID:25803618

  5. Unravelling the hidden ancestry of American admixed populations.

    PubMed

    Montinaro, Francesco; Busby, George B J; Pascali, Vincenzo L; Myers, Simon; Hellenthal, Garrett; Capelli, Cristian

    2015-03-24

    The movement of people into the Americas has brought different populations into contact, and contemporary American genomes are the product of a range of complex admixture events. Here we apply a haplotype-based ancestry identification approach to a large set of genome-wide SNP data from a variety of American, European and African populations to determine the contributions of different ancestral populations to the Americas. Our results provide a fine-scale characterization of the source populations, identify a series of novel, previously unreported contributions from Africa and Europe and highlight geohistorical structure in the ancestry of American admixed populations.

  6. Testing for non-random mating: evidence for ancestry-related assortative mating in the Framingham heart study.

    PubMed

    Sebro, Ronnie; Hoffman, Thomas J; Lange, Christoph; Rogus, John J; Risch, Neil J

    2010-11-01

    Population stratification leads to a predictable phenomenon-a reduction in the number of heterozygotes compared to that calculated assuming Hardy-Weinberg Equilibrium (HWE). We show that population stratification results in another phenomenon-an excess in the proportion of spouse-pairs with the same genotypes at all ancestrally informative markers, resulting in ancestrally related positive assortative mating. We use principal components analysis to show that there is evidence of population stratification within the Framingham Heart Study, and show that the first principal component correlates with a North-South European cline. We then show that the first principal component is highly correlated between spouses (r = 0.58, p = 0.0013), demonstrating that there is ancestrally related positive assortative mating among the Framingham Caucasian population. We also show that the single nucleotide polymorphisms loading most heavily on the first principal component show an excess of homozygotes within the spouses, consistent with similar ancestry-related assortative mating in the previous generation. This nonrandom mating likely affects genetic structure seen more generally in the North American population of European descent today, and decreases the rate of decay of linkage disequilibrium for ancestrally informative markers.

  7. Associations of PON1 and Genetic Ancestry with Obesity in Early Childhood

    PubMed Central

    Huen, Karen; Harley, Kim; Beckman, Kenneth; Eskenazi, Brenda; Holland, Nina

    2013-01-01

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

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

    PubMed

    Huen, Karen; Harley, Kim; Beckman, Kenneth; Eskenazi, Brenda; Holland, Nina

    2013-01-01

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

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

    PubMed

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

    2010-06-15

    Studies report that warfarin doses required to maintain therapeutic anticoagulation decrease with age; however, these studies almost exclusively enrolled patients of European ancestry. Consequently, universal application of dosing paradigms based on such evidence may be confounded because ethnicity also influences dose. Therefore, we determined if warfarin dose decreased with age in Americans of African ancestry, if older African and European ancestry patients required different doses, and if their daily dose frequency distributions differed. Our chart review examined 170 patients of African ancestry and 49 patients of European ancestry cared for in our anticoagulation clinic. We calculated the average weekly dose required for each stable, anticoagulated patient to maintain an international normalized ratio of 2.0 to 3.0, determined dose averages for groups <70, 70-79, and >80 years of age and plotted dose as a function of age. The maintenance dose in patients of African ancestry decreased with age (P<0.001). In addition, older patients of African ancestry required higher average weekly doses than patients of European ancestry: 33% higher in the 70- to 79-year-old group (38.2+/-1.9 vs. 28.8+/-1.7 mg; P=0.006) and 52% in the >80-year-old group (33.2+/-1.7 vs. 21.8+/-3.8 mg; P=0.011). Therefore, 43% of older patients of African ancestry required daily doses >5mg and hence would have been under-dosed using current starting-dose guidelines. The dose frequency distribution was wider for older patients of African ancestry compared to those of European ancestry (P<0.01). The higher doses required by older patients of African ancestry indicate that strategies for initiating warfarin therapy based on studies of patients of European ancestry could result in insufficient anticoagulation and thereby potentially increase their thromboembolism risk. Copyright 2010 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2012-07-01

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

  11. Ancient west Eurasian ancestry in southern and eastern Africa

    PubMed Central

    Pickrell, Joseph K.; Patterson, Nick; Loh, Po-Ru; Lipson, Mark; Berger, Bonnie; Stoneking, Mark; Pakendorf, Brigitte; Reich, David

    2014-01-01

    The history of southern Africa involved interactions between indigenous hunter–gatherers and a range of populations that moved into the region. Here we use genome-wide genetic data to show that there are at least two admixture events in the history of Khoisan populations (southern African hunter–gatherers and pastoralists who speak non-Bantu languages with click consonants). One involved populations related to Niger–Congo-speaking African populations, and the other introduced ancestry most closely related to west Eurasian (European or Middle Eastern) populations. We date this latter admixture event to ∼900–1,800 y ago and show that it had the largest demographic impact in Khoisan populations that speak Khoe–Kwadi languages. A similar signal of west Eurasian ancestry is present throughout eastern Africa. In particular, we also find evidence for two admixture events in the history of Kenyan, Tanzanian, and Ethiopian populations, the earlier of which involved populations related to west Eurasians and which we date to ∼2,700–3,300 y ago. We reconstruct the allele frequencies of the putative west Eurasian population in eastern Africa and show that this population is a good proxy for the west Eurasian ancestry in southern Africa. The most parsimonious explanation for these findings is that west Eurasian ancestry entered southern Africa indirectly through eastern Africa. PMID:24550290

  12. Ancient west Eurasian ancestry in southern and eastern Africa.

    PubMed

    Pickrell, Joseph K; Patterson, Nick; Loh, Po-Ru; Lipson, Mark; Berger, Bonnie; Stoneking, Mark; Pakendorf, Brigitte; Reich, David

    2014-02-18

    The history of southern Africa involved interactions between indigenous hunter-gatherers and a range of populations that moved into the region. Here we use genome-wide genetic data to show that there are at least two admixture events in the history of Khoisan populations (southern African hunter-gatherers and pastoralists who speak non-Bantu languages with click consonants). One involved populations related to Niger-Congo-speaking African populations, and the other introduced ancestry most closely related to west Eurasian (European or Middle Eastern) populations. We date this latter admixture event to ∼900-1,800 y ago and show that it had the largest demographic impact in Khoisan populations that speak Khoe-Kwadi languages. A similar signal of west Eurasian ancestry is present throughout eastern Africa. In particular, we also find evidence for two admixture events in the history of Kenyan, Tanzanian, and Ethiopian populations, the earlier of which involved populations related to west Eurasians and which we date to ∼2,700-3,300 y ago. We reconstruct the allele frequencies of the putative west Eurasian population in eastern Africa and show that this population is a good proxy for the west Eurasian ancestry in southern Africa. The most parsimonious explanation for these findings is that west Eurasian ancestry entered southern Africa indirectly through eastern Africa.

  13. African ancestry, lung function and the effect of genetics.

    PubMed

    Menezes, Ana Maria B; Wehrmeister, Fernando C; Hartwig, Fernando P; Perez-Padilla, Rogelio; Gigante, Denise P; Barros, Fernando C; Oliveira, Isabel O; Ferreira, Gustavo D; Horta, Bernardo L

    2015-06-01

    African-Americans have smaller lung function compared with European-Americans. The aim of this study was to disentangle the contribution of genetics from other variables on lung function. A cohort was followed from birth to 30 years of age in Brazil. Several variables were collected: genomic analysis based on DNA; forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) obtained by spirometry; height measured by anthropometrists; and thorax circumference evaluated by photonic scanner. Crude and adjusted linear regression models were calculated according to African ancestry. The sample comprised 2869 participants out of 3701 members of the cohort. Males with higher African ancestry by DNA analysis had a smaller FEV1 (-0.13 L, 95% CI -0.23- -0.03 L) and FVC (-0.21 L, 95% CI -0.32- -0.09 L) compared with those with less African ancestry, having accounted for height, sitting to standing height ratio and other confounders. Similar effects were seen in females. After adjustment, ancestry remained significantly associated with lung function, but the large effect of adjustment for confounding among males (but not females) does not allow us to exclude the possibility that residual confounding may still account for these findings. Copyright ©ERS 2015.

  14. Assessing Patterns of Admixture and Ancestry in Canadian Honey Bees

    USDA-ARS?s Scientific Manuscript database

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

  15. Recent Admixture in an Indian Population of African Ancestry

    PubMed Central

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

    2011-01-01

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

  16. African ancestry, lung function and the effect of genetics

    PubMed Central

    Wehrmeister, Fernando C.; Hartwig, Fernando P.; Perez-Padilla, Rogelio; Gigante, Denise P.; Barros, Fernando C.; Oliveira, Isabel O.; Ferreira, Gustavo D.; Horta, Bernardo L.

    2015-01-01

    African-Americans have smaller lung function compared with European-Americans. The aim of this study was to disentangle the contribution of genetics from other variables on lung function. A cohort was followed from birth to 30 years of age in Brazil. Several variables were collected: genomic analysis based on DNA; forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) obtained by spirometry; height measured by anthropometrists; and thorax circumference evaluated by photonic scanner. Crude and adjusted linear regression models were calculated according to African ancestry. The sample comprised 2869 participants out of 3701 members of the cohort. Males with higher African ancestry by DNA analysis had a smaller FEV1 (−0.13 L, 95% CI −0.23– −0.03 L) and FVC (−0.21 L, 95% CI −0.32– −0.09 L) compared with those with less African ancestry, having accounted for height, sitting to standing height ratio and other confounders. Similar effects were seen in females. After adjustment, ancestry remained significantly associated with lung function, but the large effect of adjustment for confounding among males (but not females) does not allow us to exclude the possibility that residual confounding may still account for these findings. PMID:25700383

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

    PubMed Central

    Goodman, Morris; Sterner, Kirstin N.

    2010-01-01

    In Charles Darwin’s tree model for life’s evolution, natural selection adaptively modifies newly arisen species as they branch apart from their common ancestor. In accord with this Darwinian concept, the phylogenomic approach to elucidating adaptive evolution in genes and genomes in the ancestry of modern humans requires a well supported and well sampled phylogeny that accurately places humans and other primates and mammals with respect to one another. For more than a century, first from the comparative immunological work of Nuttall on blood sera and now from comparative genomic studies, molecular findings have demonstrated the close kinship of humans to chimpanzees. The close genetic correspondence of chimpanzees to humans and the relative shortness of our evolutionary separation suggest that most distinctive features of the modern human phenotype had already evolved during our ancestry with chimpanzees. Thus, a phylogenomic assessment of being human should examine earlier stages of human ancestry as well as later stages. In addition, with the availability of a number of mammalian genomes, similarities in phenotype between distantly related taxa should be explored for evidence of convergent or parallel adaptive evolution. As an example, recent phylogenomic evidence has shown that adaptive evolution of aerobic energy metabolism genes may have helped shape such distinctive modern human features as long life spans and enlarged brains in the ancestries of both humans and elephants. PMID:20445097

  18. Differences in vaginal microbiome in African American women versus women of European ancestry.

    PubMed

    Fettweis, Jennifer M; Brooks, J Paul; Serrano, Myrna G; Sheth, Nihar U; Girerd, Philippe H; Edwards, David J; Strauss, Jerome F; Jefferson, Kimberly K; Buck, Gregory A

    2014-10-01

    Women of European ancestry are more likely to harbour a Lactobacillus-dominated microbiome, whereas African American women are more likely to exhibit a diverse microbial profile. African American women are also twice as likely to be diagnosed with bacterial vaginosis and are twice as likely to experience preterm birth. The objective of this study was to further characterize and contrast the vaginal microbial profiles in African American versus European ancestry women. Through the Vaginal Human Microbiome Project at Virginia Commonwealth University, 16S rRNA gene sequence analysis was used to compare the microbiomes of vaginal samples from 1268 African American women and 416 women of European ancestry. The results confirmed significant differences in the vaginal microbiomes of the two groups and identified several taxa relevant to these differences. Major community types were dominated by Gardnerella vaginalis and the uncultivated bacterial vaginosis-associated bacterium-1 (BVAB1) that were common among African Americans. Moreover, the prevalence of multiple bacterial taxa that are associated with microbial invasion of the amniotic cavity and preterm birth, including Mycoplasma, Gardnerella, Prevotella and Sneathia, differed between the two ethnic groups. We investigated the contributions of intrinsic and extrinsic factors, including pregnancy, body mass index, diet, smoking and alcohol use, number of sexual partners, and household income, to vaginal community composition. Ethnicity, pregnancy and alcohol use correlated significantly with the relative abundance of bacterial vaginosis-associated species. Trends between microbial profiles and smoking and number of sexual partners were observed; however, these associations were not statistically significant. These results support and extend previous findings that there are significant differences in the vaginal microbiome related to ethnicity and demonstrate that these differences are pronounced even in healthy women

  19. Differences in vaginal microbiome in African American women versus women of European ancestry

    PubMed Central

    Fettweis, Jennifer M.; Brooks, J. Paul; Serrano, Myrna G.; Sheth, Nihar U.; Girerd, Philippe H.; Edwards, David J.; Strauss, Jerome F.; Jefferson, Kimberly K.

    2014-01-01

    Women of European ancestry are more likely to harbour a Lactobacillus-dominated microbiome, whereas African American women are more likely to exhibit a diverse microbial profile. African American women are also twice as likely to be diagnosed with bacterial vaginosis and are twice as likely to experience preterm birth. The objective of this study was to further characterize and contrast the vaginal microbial profiles in African American versus European ancestry women. Through the Vaginal Human Microbiome Project at Virginia Commonwealth University, 16S rRNA gene sequence analysis was used to compare the microbiomes of vaginal samples from 1268 African American women and 416 women of European ancestry. The results confirmed significant differences in the vaginal microbiomes of the two groups and identified several taxa relevant to these differences. Major community types were dominated by Gardnerella vaginalis and the uncultivated bacterial vaginosis-associated bacterium-1 (BVAB1) that were common among African Americans. Moreover, the prevalence of multiple bacterial taxa that are associated with microbial invasion of the amniotic cavity and preterm birth, including Mycoplasma, Gardnerella, Prevotella and Sneathia, differed between the two ethnic groups. We investigated the contributions of intrinsic and extrinsic factors, including pregnancy, body mass index, diet, smoking and alcohol use, number of sexual partners, and household income, to vaginal community composition. Ethnicity, pregnancy and alcohol use correlated significantly with the relative abundance of bacterial vaginosis-associated species. Trends between microbial profiles and smoking and number of sexual partners were observed; however, these associations were not statistically significant. These results support and extend previous findings that there are significant differences in the vaginal microbiome related to ethnicity and demonstrate that these differences are pronounced even in healthy women

  20. A methodology for high resolution digital image correlation in high temperature experiments

    NASA Astrophysics Data System (ADS)

    Blaber, Justin; Adair, Benjamin S.; Antoniou, Antonia

    2015-03-01

    We propose a methodology for performing high resolution Digital Image Correlation (DIC) analysis during high-temperature mechanical tests. Specifically, we describe a technique for producing a stable, high-quality pattern on metal surfaces along with a simple optical system that uses a visible-range camera and a long-range microscope. The results are analyzed with a high-quality open-source DIC software developed by us. Using the proposed technique, we successfully acquired high-resolution strain maps of the crack tip field in a nickel superalloy sample at 1000 °C.

  1. Improved ancestry inference using weights from external reference panels

    PubMed Central

    Chen, Chia-Yen; Pollack, Samuela; Hunter, David J.; Hirschhorn, Joel N.; Kraft, Peter; Price, Alkes L.

    2013-01-01

    Motivation: Inference of ancestry using genetic data is motivated by applications in genetic association studies, population genetics and personal genomics. Here, we provide methods and software for improved ancestry inference using genome-wide single nucleotide polymorphism (SNP) weights from external reference panels. This approach makes it possible to leverage the rich ancestry information that is available from large external reference panels, without the administrative and computational complexities of re-analyzing the raw genotype data from the reference panel in subsequent studies. Results: We extensively validate our approach in multiple African American, Latino American and European American datasets, making use of genome-wide SNP weights derived from large reference panels, including HapMap 3 populations and 6546 European Americans from the Framingham Heart Study. We show empirically that our approach provides much greater accuracy than either the prevailing ancestry-informative marker (AIM) approach or the analysis of genome-wide target genotypes without a reference panel. For example, in an independent set of 1636 European American genome-wide association study samples, we attained prediction accuracy (R2) of 1.000 and 0.994 for the first two principal components using our method, compared with 0.418 and 0.407 using 150 published AIMs or 0.955 and 0.003 by applying principal component analysis directly to the target samples. We finally show that the higher accuracy in inferring ancestry using our method leads to more effective correction for population stratification in association studies. Availability: The SNPweights software is available online at http://www.hsph.harvard.edu/faculty/alkes-price/software/. Contact: aprice@hsph.harvard.edu or cychen@mail.harvard.edu. Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23539302

  2. Maternal maya ancestry and birth weight in Yucatan, Mexico.

    PubMed

    Azcorra, Hugo; Vázquez-Vázquez, Adriana; Mendez, Nina; Carlos Salazar, Juan; Datta-Banik, Sudip

    2016-05-01

    The purpose of this study was to analyze the association between maternal Maya ancestry and the birth weight of infants born in Yucatan, Mexico, during 2013. A total of 30,435 singletons born at term (≥37 weeks) in Yucatan during 2013 were analyzed. Birth weights, gestational ages, and maternal socioeconomic data were provided by the Ministry of Health of Yucatan. Maternal Maya ancestry was defined by the presence of Maya surnames in: (1) non-Maya surnames (NM-NM), (2) one Maya surname (NM-M), and (3) two Maya surnames (M-M). Biological and socioeconomic parameters were compared between the categories of ancestry through one-way analysis of variance (ANOVA) and a multiple regression model was used to analyze the association between ancestry and infants' birth weight controlling for influence of covariates. Mean birth weight was 3,114 g (SD = 406) (NM-NM: 3,150 g [SD = 404], NM-M: 3,106 g [SD = 402], M-M: 3,088 g [SD = 408]). With the biological and socioeconomic variables statistically adjusted for, the presence of one and two maternal Maya surnames was associated with decreases in birth weight of 42 g and 63 g, respectively. None of the interactions between ancestry and other predictors was statistically significant. The lower mean birth weights of Maya infants are consistent with studies reporting poor growth and nutritional status of Maya children from Yucatan. Historically adverse socioeconomic conditions experienced by the Maya population are probably linked to the relatively lower birth weights of their infants. Am. J. Hum. Biol. 28:436-439, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  3. Covariance fitting of highly-correlated data in lattice QCD

    NASA Astrophysics Data System (ADS)

    Yoon, Boram; Jang, Yong-Chull; Jung, Chulwoo; Lee, Weonjong

    2013-07-01

    We address a frequently-asked question on the covariance fitting of highly-correlated data such as our B K data based on the SU(2) staggered chiral perturbation theory. Basically, the essence of the problem is that we do not have a fitting function accurate enough to fit extremely precise data. When eigenvalues of the covariance matrix are small, even a tiny error in the fitting function yields a large chi-square value and spoils the fitting procedure. We have applied a number of prescriptions available in the market, such as the cut-off method, modified covariance matrix method, and Bayesian method. We also propose a brand new method, the eigenmode shift (ES) method, which allows a full covariance fitting without modifying the covariance matrix at all. We provide a pedagogical example of data analysis in which the cut-off method manifestly fails in fitting, but the rest work well. In our case of the B K fitting, the diagonal approximation, the cut-off method, the ES method, and the Bayesian method work reasonably well in an engineering sense. However, interpreting the meaning of χ 2 is easier in the case of the ES method and the Bayesian method in a theoretical sense aesthetically. Hence, the ES method can be a useful alternative optional tool to check the systematic error caused by the covariance fitting procedure.

  4. Absorption and loss of iron in toddlers are highly correlated.

    PubMed

    Fomon, Samuel J; Nelson, Steven E; Serfass, Robert E; Ziegler, Ekhard E

    2005-04-01

    For estimating the requirements for dietary iron, it is important to know the amount of iron that is lost from the body. Inevitable losses of iron have been determined in adult humans but not in infants or children. We administered (58)Fe, the least abundant stable isotope of iron, to free-living infants at 168 d of age (5.6 mo) and followed them to age 26 mo. There was no dietary restriction after isotope administration. Blood was obtained at regular intervals for determination of isotopic enrichment and indices of iron status. We estimated the quantity of circulating iron, noncirculating active iron, and storage iron at each age. The administered isotope equilibrated with total body iron by 13 mo of age. From 13 to 26 mo of age, we estimated inevitable loss and absorption of iron from the change in tracer abundance in circulating iron. The rate of decrease of tracer abundance was proportional to addition of tracee, i.e., absorption of iron. Conversely, the rate of decrease in quantity of tracer was proportional to removal of tracee, i.e., loss of iron. From 13 to 26 mo of age, iron absorption was (mean +/- SD) 0.49 +/- 0.13 mg/d and inevitable iron loss was 0.25 +/- 0.12 mg/d. Intersubject variability of iron loss and iron absorption was high, and iron loss and absorption were highly correlated (r = 0.789, P < 0.001). Iron stores were low throughout the study and decreased significantly from 13 to 26 mo of age, suggesting that iron absorption from the diet was inadequate to maintain or increase iron nutritional status. The data suggest that, in this cohort, which may be representative, the intake of bioavailable iron from 13 to 26 mo of age was insufficient to maintain iron nutritional status.

  5. OSBPL10, RXRA and lipid metabolism confer African-ancestry protection against dengue haemorrhagic fever in admixed Cubans

    PubMed Central

    Soares, Pedro; Garcia, Gissel; Perez, Ana B.; Aguirre, Eglys; Cavadas, Bruno; Regnault, Béatrice; Alvarez, Mayling; Ruiz, Didye; Guzman, Maria G.

    2017-01-01

    Ethnic groups can display differential genetic susceptibility to infectious diseases. The arthropod-born viral dengue disease is one such disease, with empirical and limited genetic evidence showing that African ancestry may be protective against the haemorrhagic phenotype. Global ancestry analysis based on high-throughput genotyping in admixed populations can be used to test this hypothesis, while admixture mapping can map candidate protective genes. A Cuban dengue fever cohort was genotyped using a 2.5 million SNP chip. Global ancestry was ascertained through ADMIXTURE and used in a fine-matched corrected association study, while local ancestry was inferred by the RFMix algorithm. The expression of candidate genes was evaluated by RT-PCR in a Cuban dengue patient cohort and gene set enrichment analysis was performed in a Thai dengue transcriptome. OSBPL10 and RXRA candidate genes were identified, with most significant SNPs placed in inferred weak enhancers, promoters and lncRNAs. OSBPL10 had significantly lower expression in Africans than Europeans, while for RXRA several SNPs may differentially regulate its transcription between Africans and Europeans. Their expression was confirmed to change through dengue disease progression in Cuban patients and to vary with disease severity in a Thai transcriptome dataset. These genes interact in the LXR/RXR activation pathway that integrates lipid metabolism and immune functions, being a key player in dengue virus entrance into cells, its replication therein and in cytokine production. Knockdown of OSBPL10 expression in THP-1 cells by two shRNAs followed by DENV2 infection tests led to a significant reduction in DENV replication, being a direct functional proof that the lower OSBPL10 expression profile in Africans protects this ancestry against dengue disease. PMID:28241052

  6. OSBPL10, RXRA and lipid metabolism confer African-ancestry protection against dengue haemorrhagic fever in admixed Cubans.

    PubMed

    Sierra, Beatriz; Triska, Petr; Soares, Pedro; Garcia, Gissel; Perez, Ana B; Aguirre, Eglys; Oliveira, Marisa; Cavadas, Bruno; Regnault, Béatrice; Alvarez, Mayling; Ruiz, Didye; Samuels, David C; Sakuntabhai, Anavaj; Pereira, Luisa; Guzman, Maria G

    2017-02-01

    Ethnic groups can display differential genetic susceptibility to infectious diseases. The arthropod-born viral dengue disease is one such disease, with empirical and limited genetic evidence showing that African ancestry may be protective against the haemorrhagic phenotype. Global ancestry analysis based on high-throughput genotyping in admixed populations can be used to test this hypothesis, while admixture mapping can map candidate protective genes. A Cuban dengue fever cohort was genotyped using a 2.5 million SNP chip. Global ancestry was ascertained through ADMIXTURE and used in a fine-matched corrected association study, while local ancestry was inferred by the RFMix algorithm. The expression of candidate genes was evaluated by RT-PCR in a Cuban dengue patient cohort and gene set enrichment analysis was performed in a Thai dengue transcriptome. OSBPL10 and RXRA candidate genes were identified, with most significant SNPs placed in inferred weak enhancers, promoters and lncRNAs. OSBPL10 had significantly lower expression in Africans than Europeans, while for RXRA several SNPs may differentially regulate its transcription between Africans and Europeans. Their expression was confirmed to change through dengue disease progression in Cuban patients and to vary with disease severity in a Thai transcriptome dataset. These genes interact in the LXR/RXR activation pathway that integrates lipid metabolism and immune functions, being a key player in dengue virus entrance into cells, its replication therein and in cytokine production. Knockdown of OSBPL10 expression in THP-1 cells by two shRNAs followed by DENV2 infection tests led to a significant reduction in DENV replication, being a direct functional proof that the lower OSBPL10 expression profile in Africans protects this ancestry against dengue disease.

  7. Exploring the Y Chromosomal Ancestry of Modern Panamanians

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-10-01

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

  9. Examining population stratification via individual ancestry estimates versus self-reported race.

    PubMed

    Barnholtz-Sloan, Jill S; Chakraborty, Ranajit; Sellers, Thomas A; Schwartz, Ann G

    2005-06-01

    Population stratification has the potential to affect the results of genetic marker studies. Estimating individual ancestry provides a continuous measure to assess population structure in case-control studies of complex disease, instead of using self-reported racial groups. We estimate individual ancestry using the Federal Bureau of Investigation CODIS Core short tandem repeat set of 13 loci using two different analysis methods in a case-control study of early-onset lung cancer. Individual ancestry proportions were estimated for "European" and "West African" groups using published allele frequencies. The majority of Caucasian, non-Hispanics had >50% European ancestry, whereas the majority of African Americans had <20% European ancestry, regardless of ancestry estimation method, although significant overlap by self-reported race and ancestry also existed. When we further investigated the effect of ancestry and self-reported race on the frequency of a lung cancer risk genotype, we found that the frequency of the GSTM1 null genotype varies by individual European ancestry and case-control status within self-reported race (particularly for African Americans). Genetic risk models showed that adjusting for individual European ancestry provided a better fit to the data compared with the model with no group adjustment or adjustment for self-reported race. This study suggests that significant population substructure differences exist that self-reported race alone does not capture and that individual ancestry may be confounded with disease status and/or a candidate gene risk genotype.

  10. Genomic Variation of Inbreeding and Ancestry in the Remaining Two Isle Royale Wolves.

    PubMed

    Hedrick, Philip W; Kardos, Marty; Peterson, Rolf O; Vucetich, John A

    2017-03-01

    Inbreeding, relatedness, and ancestry have traditionally been estimated with pedigree information, however, molecular genomic data can provide more detailed examination of these properties. For example, pedigree information provides estimation of the expected value of these measures but molecular genomic data can estimate the realized values of these measures in individuals. Here, we generate the theoretical distribution of inbreeding, relatedness, and ancestry for the individuals in the pedigree of the Isle Royale wolves, the first examination of such variation in a wild population with a known pedigree. We use the 38 autosomes of the dog genome and their estimated map lengths in our genomic analysis. Although it is known that the remaining wolves are highly inbred, closely related, and descend from only 3 ancestors, our analyses suggest that there is significant variation in the realized inbreeding and relatedness around pedigree expectations. For example, the expected inbreeding in a hypothetical offspring from the 2 remaining wolves is 0.438 but the realized 95% genomic confidence interval is from 0.311 to 0.565. For individual chromosomes, a substantial proportion of the whole chromosomes are completely identical by descent. This examination provides a background to use when analyzing molecular genomic data for individual levels of inbreeding, relatedness, and ancestry. The level of variation in these measures is a function of the time to the common ancestor(s), the number of chromosomes, and the rate of recombination. In the Isle Royale wolf population, the few generations to a common ancestor results in the high variance in genomic inbreeding. © The American Genetic Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Estimating ancestry and heterozygosity of hybrids using molecular markers

    PubMed Central

    2012-01-01

    Background Hybridization, genetic mixture of distinct populations, gives rise to myriad recombinant genotypes. Characterizing the genomic composition of hybrids is critical for studies of hybrid zone dynamics, inheritance of traits, and consequences of hybridization for evolution and conservation. Hybrid genomes are often summarized either by an estimate of the proportion of alleles coming from each ancestral population or classification into discrete categories like F1, F2, backcross, or merely “hybrid” vs. “pure”. In most cases, it is not realistic to classify individuals into the restricted set of classes produced in the first two generations of admixture. However, the continuous ancestry index misses an important dimension of the genotype. Joint consideration of ancestry together with interclass heterozygosity (proportion of loci with alleles from both ancestral populations) captures all of the information in the discrete classification without the unrealistic assumption that only two generations of admixture have transpired. Methods I describe a maximum likelihood method for joint estimation of ancestry and interclass heterozygosity. I present two worked examples illustrating the value of the approach for describing variation among hybrid populations and evaluating the validity of the assumption underlying discrete classification. Results Naively classifying natural hybrids into the standard six line cross categories can be misleading, and false classification can be a serious problem for datasets with few molecular markers. My analysis underscores previous work showing that many (50 or more) ancestry informative markers are needed to avoid erroneous classification. Conclusion Although classification of hybrids might often be misleading, valuable inferences can be obtained by focusing directly on distributions of ancestry and heterozygosity. Estimating and visualizing the joint distribution of ancestry and interclass heterozygosity is an effective way

  12. mtDNA and the Islands of the North Atlantic: Estimating the Proportions of Norse and Gaelic Ancestry

    PubMed Central

    Helgason, Agnar; Hickey, Eileen; Goodacre, Sara; Bosnes, Vidar; Stefánsson, Kári; Ward, Ryk; Sykes, Bryan

    2001-01-01

    A total of 1,664 new mtDNA control-region sequences were analyzed in order to estimate Gaelic and Scandinavian matrilineal ancestry in the populations of Iceland, Orkney, the Western Isles, and the Isle of Skye and to investigate other aspects of their genetic history. A relative excess of private lineages in the Icelanders is indicative of isolation, whereas the scarcity of private lineages in Scottish island populations may be explained by recent gene flow and population decline. Differences in the frequencies of lineage clusters are observed between the Scandinavian and the Gaelic source mtDNA pools, and, on a continent-wide basis, such differences between populations seem to be associated with geography. A multidimensional scaling analysis of genetic distances, based on mtDNA lineage-cluster frequencies, groups the North Atlantic islanders with the Gaelic and the Scandinavian populations, whereas populations from the central, southern, and Baltic regions of Europe are arranged in clusters in broad agreement with their geographic locations. This pattern is highly significant, according to a Mantel correlation between genetic and geographic distances (r=.716). Admixture analyses indicate that the ancestral contributions of mtDNA lineages from Scandinavia to the populations of Iceland, Orkney, the Western Isles, and the Isle of Skye are 37.5%, 35.5%, 11.5%, and 12.5%, respectively. PMID:11179019

  13. Assessment of genetic ancestry and population substructure in Costa Rica by analysis of individuals with a familial history of mental disorder

    PubMed Central

    Segura-Wang, Maia; Raventós, Henriette; Escamilla, Michael; Barrantes, Ramiro

    2010-01-01

    The population of Costa Rica has been considered valuable for locating susceptibility genes of complex disorders because of historical events and a gradual admixture process. We present an assessment of 426 unrelated individuals with a familial history of mental disorder and with ancestors born in the Central Valley, genotyped at 730 microsatellites to evaluate genetic diversity, ancestry and substructure at the general and regional population levels using quantitative methods. Low population substructure was found. Estimated mean ancestry proportions were 54%, 32% and 13% for European, Amerindian and African components respectively, with some regional variation. The Fst values obtained confirm the largest genetic similarity to Europeans. Subdivision of the Amerindians into individual populations revealed strong similarity to Chibchan groups. Analysis of the African ancestry showed high similarity to West and Central African populations. Gene ancestries from other African areas were also detected, probably resulting from ancestral admixture within Africa prior to colonial times. Our analyses show, in an ethnohistorical-genetic context, that gene flow and admixture are important components of Costa Rican population history. The results confirm the need to consider the particular regional genetic structure, the effects of genetic drift and the ancestry when designing and interpreting investigations of genetic traits in this population. PMID:20946256

  14. West African and Amerindian ancestry and risk of myocardial infarction and metabolic syndrome in the Central Valley population of Costa Rica.

    PubMed

    Ruiz-Narváez, Edward A; Bare, Lance; Arellano, Andre; Catanese, Joseph; Campos, Hannia

    2010-06-01

    Genetic ancestry and environmental factors may contribute to the ethnic differences in risk of coronary heart disease (CHD), metabolic syndrome (MS) or its individual components. The population of the Central Valley of Costa Rica offers a unique opportunity to assess the role of genetic ancestry in these chronic diseases because it derived from the admixture of a relatively small number of founders of Southern European, Amerindian, and West African origin. We aimed to determine whether genetic ancestry is associated with risk of myocardial infarction (MI), MS and its individual components in the Central Valley of Costa Rica. We genotyped 39 ancestral informative markers in cases (n = 1,998) with a first non-fatal acute MI and population-based controls (n = 1,998) matched for age, sex, and area of residence, to estimate individual ancestry proportions. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated using conditional (MI) and unconditional (MS and its components) logistic regression adjusting for relevant confounders. Mean individual ancestry proportions in cases and controls were 57.5 versus 57.8% for the Southern European, 38.4 versus 38.3% for the Amerindian and 4.1 versus 3.8% for the West African ancestry. Compared with Southern European ancestry, each 10% increase in West African ancestry was associated with a 29% increase in MI, OR (95% CI) = 1.29 (1.07, 1.56), and with a 30% increase on the risk of hypertension, OR (95% CI) = 1.30 (1.00, 1.70). Each 10% increase in Amerindian ancestry was associated with a 14% increase on the risk of MS, OR (95% CI) = 1.14 (1.00, 1.30), and 20% increase on the risk of impaired fasting glucose, OR (95% CI) = 1.20 (1.01, 1.42). These results show that the high variability of admixture proportions in the Central Valley population offers a unique opportunity to uncover the genetic basis of ethnic differences on the risk of disease.

  15. Genetics of ancestry-specific risk for relapse in acute lymphoblastic leukemia

    PubMed Central

    Karol, Seth E.; Larsen, Eric; Cheng, Cheng; Cao, Xueyuan; Yang, Wenjian; Ramsey, Laura B.; Fernandez, Christian A.; McCorkle, Joseph R.; Paugh, Steven W.; Autry, Robert J.; Lopez-Lopez, Elixabet; Diouf, Barthelemy; Jeha, Sima; Pui, Ching-Hon; Raetz, Elizabeth A.; Winick, Naomi J.; Carroll, William L.; Hunger, Stephen P.; Loh, Mignon L.; Devidas, Meenakshi; Evans, William E.; Yang, Jun J.; Relling, Mary V.

    2017-01-01

    The causes of individual relapses in children with acute lymphoblastic leukemia (ALL) remain incompletely understood. We evaluated the contribution of germline genetic factors to relapse in 2,225 children treated on Children’s Oncology Group trial AALL0232. We identified 302 germline single nucleotide polymorphisms (SNPs) associated with relapse after adjusting for treatment and ancestry and 715 additional SNPs associated with relapse in an ancestry-specific manner. We tested for replication of these relapse-associated SNPs in external data sets of antileukemic drug pharmacokinetics and pharmacodynamics and an independent clinical cohort. 224 SNPs were associated with rapid drug clearance or drug resistance, and 32 were replicated in the independent cohort. The adverse risk associated with black and Hispanic ancestries was attenuated by addition of the 4 SNPs most strongly associated with relapse in these populations [for blacks: model without SNPs hazard ratio (HR) =2.32, P=2.27×10−4, model with SNPs HR=1.07, P=0.79; for Hispanics: model without SNPs HR=1.7, P=8.23×10−5, model with SNPs HR=1.31, P=0.065]. Relapse SNPs associated with asparaginase resistance or allergy were overrepresented among SNPs associated with relapse in the more asparaginase intensive treatment arm (20/54 in Capizzi-methorexate arm vs. 8/54 in high-dose methotrexate arm, P=0.015). Inherited genetic variation contributes to race-specific and treatment-specific relapse risk. PMID:28096535

  16. Vortex dynamics and correlated disorder in high-{Tc} superconductors

    SciTech Connect

    Vinokur, V.M.

    1993-08-01

    We develop a theory for the vortex motion in the presence of correlated disorder in the form of the twin boundaries and columnar defects. Mapping vortex trajectories onto boson world lines enables us to establish the duality of the vortex transport in the systems with correlated disorder and hopping conductivity of charged particles in 2D systems. A glassy-like dynamics of the vortex lines with zero linear-resistivity and strongly nonlinear current-voltage behavior as V {proportional_to} exp[{minus} const/J{sup {mu}}] in a Bose glass state is predicted.

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

    PubMed

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

    2017-06-01

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

  18. Fast model-based estimation of ancestry in unrelated individuals

    PubMed Central

    Alexander, David H.; Novembre, John; Lange, Kenneth

    2009-01-01

    Population stratification has long been recognized as a confounding factor in genetic association studies. Estimated ancestries, derived from multi-locus genotype data, can be used to perform a statistical correction for population stratification. One popular technique for estimation of ancestry is the model-based approach embodied by the widely applied program structure. Another approach, implemented in the program EIGENSTRAT, relies on Principal Component Analysis rather than model-based estimation and does not directly deliver admixture fractions. EIGENSTRAT has gained in popularity in part owing to its remarkable speed in comparison to structure. We present a new algorithm and a program, ADMIXTURE, for model-based estimation of ancestry in unrelated individuals. ADMIXTURE adopts the likelihood model embedded in structure. However, ADMIXTURE runs considerably faster, solving problems in minutes that take structure hours. In many of our experiments, we have found that ADMIXTURE is almost as fast as EIGENSTRAT. The runtime improvements of ADMIXTURE rely on a fast block relaxation scheme using sequential quadratic programming for block updates, coupled with a novel quasi-Newton acceleration of convergence. Our algorithm also runs faster and with greater accuracy than the implementation of an Expectation-Maximization (EM) algorithm incorporated in the program FRAPPE. Our simulations show that ADMIXTURE's maximum likelihood estimates of the underlying admixture coefficients and ancestral allele frequencies are as accurate as structure's Bayesian estimates. On real-world data sets, ADMIXTURE's estimates are directly comparable to those from structure and EIGENSTRAT. Taken together, our results show that ADMIXTURE's computational speed opens up the possibility of using a much larger set of markers in model-based ancestry estimation and that its estimates are suitable for use in correcting for population stratification in association studies. PMID:19648217

  19. Fast model-based estimation of ancestry in unrelated individuals.

    PubMed

    Alexander, David H; Novembre, John; Lange, Kenneth

    2009-09-01

    Population stratification has long been recognized as a confounding factor in genetic association studies. Estimated ancestries, derived from multi-locus genotype data, can be used to perform a statistical correction for population stratification. One popular technique for estimation of ancestry is the model-based approach embodied by the widely applied program structure. Another approach, implemented in the program EIGENSTRAT, relies on Principal Component Analysis rather than model-based estimation and does not directly deliver admixture fractions. EIGENSTRAT has gained in popularity in part owing to its remarkable speed in comparison to structure. We present a new algorithm and a program, ADMIXTURE, for model-based estimation of ancestry in unrelated individuals. ADMIXTURE adopts the likelihood model embedded in structure. However, ADMIXTURE runs considerably faster, solving problems in minutes that take structure hours. In many of our experiments, we have found that ADMIXTURE is almost as fast as EIGENSTRAT. The runtime improvements of ADMIXTURE rely on a fast block relaxation scheme using sequential quadratic programming for block updates, coupled with a novel quasi-Newton acceleration of convergence. Our algorithm also runs faster and with greater accuracy than the implementation of an Expectation-Maximization (EM) algorithm incorporated in the program FRAPPE. Our simulations show that ADMIXTURE's maximum likelihood estimates of the underlying admixture coefficients and ancestral allele frequencies are as accurate as structure's Bayesian estimates. On real-world data sets, ADMIXTURE's estimates are directly comparable to those from structure and EIGENSTRAT. Taken together, our results show that ADMIXTURE's computational speed opens up the possibility of using a much larger set of markers in model-based ancestry estimation and that its estimates are suitable for use in correcting for population stratification in association studies.

  20. High-Stakes & Assessment Innovation: A Negative Correlation? Research Report.

    ERIC Educational Resources Information Center

    Ananda, Sri; Rabinowitz, Stanley

    This paper makes the case that, as implemented so far, there has been an inverse correlation between innovation and accountability in statewide assessment systems. The higher the stakes attached to the assessment results, the more conservative the assessment methodology ultimately used. Case studies of two state assessment programs were carried…

  1. Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia.

    PubMed

    Yang, Jun J; Cheng, Cheng; Devidas, Meenakshi; Cao, Xueyuan; Fan, Yiping; Campana, Dario; Yang, Wenjian; Neale, Geoff; Cox, Nancy J; Scheet, Paul; Borowitz, Michael J; Winick, Naomi J; Martin, Paul L; Willman, Cheryl L; Bowman, W Paul; Camitta, Bruce M; Carroll, Andrew; Reaman, Gregory H; Carroll, William L; Loh, Mignon; Hunger, Stephen P; Pui, Ching-Hon; Evans, William E; Relling, Mary V

    2011-03-01

    Although five-year survival rates for childhood acute lymphoblastic leukemia (ALL) are now over 80% in most industrialized countries, not all children have benefited equally from this progress. Ethnic differences in survival after childhood ALL have been reported in many clinical studies, with poorer survival observed among African Americans or those with Hispanic ethnicity when compared with European Americans or Asians. The causes of ethnic differences remain uncertain, although both genetic and non-genetic factors are likely important. Interrogating genome-wide germline SNP genotypes in an unselected large cohort of children with ALL, we observed that the component of genomic variation that co-segregated with Native American ancestry was associated with risk of relapse (P = 0.0029) even after adjusting for known prognostic factors (P = 0.017). Ancestry-related differences in relapse risk were abrogated by the addition of a single extra phase of chemotherapy, indicating that modifications to therapy can mitigate the ancestry-related risk of relapse.

  2. Meiotic genes are enriched in regions of reduced archaic ancestry.

    PubMed

    Jégou, B; Sankararaman, S; Rolland, A D; Reich, D; Chalmel, F

    2017-04-21

    About 1-6% of the genetic ancestry of modern humans today originates from admixture with archaic humans. It has recently been shown that autosomal genomic regions with a reduced proportion of Neanderthal and Denisovan ancestries are significantly enriched in genes that are more expressed in testis than in other tissues. To determine whether a cellular segregation pattern would exist, we combined maps of archaic introgression with a cross-analysis of three transcriptomic datasets deciphering the transcriptional landscape of human gonadal cell types. We reveal that the regions deficient in both Neanderthal and Denisovan ancestries contain a significant enrichment of genes transcribed in meiotic germ cells. The interbreeding of anatomically modern humans with archaic humans may have introduced archaic-derived alleles that contributed to genetic incompatibilities affecting meiosis that were subsequently purged by natural selection. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Ancestry informative markers and admixture proportions in northeastern Mexico.

    PubMed

    Martinez-Fierro, Margarita L; Beuten, Joke; Leach, Robin J; Parra, Esteban J; Cruz-Lopez, Miguel; Rangel-Villalobos, Hector; Riego-Ruiz, Lina R; Ortiz-Lopez, Rocio; Martinez-Rodriguez, Herminia G; Rojas-Martinez, Augusto

    2009-09-01

    To investigate the ancestral admixture in the Mestizo population in northeastern Mexico, we genotyped 74 ancestral informative markers (AIMs) and 15 Y-single-nucleotide polymorphisms (Y-SNPs) in 100 individuals. The Native American contribution is 56% (range: 27.4-81.2%), the European contribution is 38% (range: 16.7-70.5%) and the West African contribution is 6%. The results show a higher European contribution than was reported in other similar studies in the country, albeit with a predominant Native American ancestry. No remarkable differences in the ancestry proportions were observed using subgroups of 74, 54, 34 and 24 AIMs. The paternal lineage calculated by genotyping of 15 Y-SNPs, shows a major component of European and Eurasian ancestry markers ( approximately 78%), compared with Amerindian ( approximately 12%) and African markers (10%). This information will set a reference for future determinations of admixture proportions in the Mestizo population from Mexico and for population-based association studies of complex diseases.

  4. A formal test of the theory of universal common ancestry.

    PubMed

    Theobald, Douglas L

    2010-05-13

    Universal common ancestry (UCA) is a central pillar of modern evolutionary theory. As first suggested by Darwin, the theory of UCA posits that all extant terrestrial organisms share a common genetic heritage, each being the genealogical descendant of a single species from the distant past. The classic evidence for UCA, although massive, is largely restricted to 'local' common ancestry-for example, of specific phyla rather than the entirety of life-and has yet to fully integrate the recent advances from modern phylogenetics and probability theory. Although UCA is widely assumed, it has rarely been subjected to formal quantitative testing, and this has led to critical commentary emphasizing the intrinsic technical difficulties in empirically evaluating a theory of such broad scope. Furthermore, several researchers have proposed that early life was characterized by rampant horizontal gene transfer, leading some to question the monophyly of life. Here I provide the first, to my knowledge, formal, fundamental test of UCA, without assuming that sequence similarity implies genetic kinship. I test UCA by applying model selection theory to molecular phylogenies, focusing on a set of ubiquitously conserved proteins that are proposed to be orthologous. Among a wide range of biological models involving the independent ancestry of major taxonomic groups, the model selection tests are found to overwhelmingly support UCA irrespective of the presence of horizontal gene transfer and symbiotic fusion events. These results provide powerful statistical evidence corroborating the monophyly of all known life.

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

    PubMed

    Hedrick, Philip W

    2017-07-01

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

  6. HIGH PERPENDICULAR CHARGED PARTICLES AZIMUTHAL CORRELATION IN PHENIX.

    SciTech Connect

    RAK,J. FOR THE PHENIX COLLABORATION

    2002-01-13

    A two-particle azimuthal correlation analysis of the PHENIX data taken at {radical}s{sub NN} = 130 GeV/c is discussed. A comparison of the magnitude of v{sub 2}(p{perpendicular}) extracted from the correlation analysis with those obtained from a reaction plane analysis by the STAR collaboration, indicate surprisingly small non-flow contributions. A similar comparison obtained from the CERES experiment at {radical}s{sub NN} = 17 GeV/c shows stronger non-flow contributions for a similar p{perpendicular}-range which can be attributed to the presence of mini-jets. It is argued that for the p{perpendicular}-range below 2-3 GeV/c the RHIC results may be indicative of a novel particle production mechanism related to low-x gluon saturation.

  7. Breed-specific ancestry studies and genome-wide association analysis highlight an association between the MYH9 gene and heat tolerance in Alaskan sprint racing sled dogs.

    PubMed

    Huson, Heather J; vonHoldt, Bridgett M; Rimbault, Maud; Byers, Alexandra M; Runstadler, Jonathan A; Parker, Heidi G; Ostrander, Elaine A

    2012-02-01

    Alaskan sled dogs are a genetically distinct population shaped by generations of selective interbreeding with purebred dogs to create a group of high-performance athletes. As a result of selective breeding strategies, sled dogs present a unique opportunity to employ admixture-mapping techniques to investigate how breed composition and trait selection impact genomic structure. We used admixture mapping to investigate genetic ancestry across the genomes of two classes of sled dogs, sprint and long-distance racers, and combined that with genome-wide association studies (GWAS) to identify regions that correlate with performance-enhancing traits. The sled dog genome is enhanced by differential contributions from four non-admixed breeds (Alaskan Malamute, Siberian Husky, German Shorthaired Pointer, and Borzoi). A principal components analysis (PCA) of 115,000 genome-wide SNPs clearly resolved the sprint and distance populations as distinct genetic groups, with longer blocks of linkage disequilibrium (LD) observed in the distance versus sprint dogs (7.5-10 and 2.5-3.75 kb, respectively). Furthermore, we identified eight regions with the genomic signal from either a selective sweep or an association analysis, corroborated by an excess of ancestry when comparing sprint and distance dogs. A comparison of elite and poor-performing sled dogs identified a single region significantly associated with heat tolerance. Within the region we identified seven SNPs within the myosin heavy chain 9 gene (MYH9) that were significantly associated with heat tolerance in sprint dogs, two of which correspond to conserved promoter and enhancer regions in the human ortholog.

  8. Breed-Specific Ancestry Studies and Genome-Wide Association Analysis Highlight an Association Between the MYH9 Gene and Heat Tolerance in Alaskan Sprint Racing Sled Dogs

    PubMed Central

    Huson, Heather J.; vonHoldt, Bridgett M.; Rimbault, Maud; Byers, Alexandra M.; Runstadler, Jonathan A.; Parker, Heidi G.; Ostrander, Elaine A.

    2012-01-01

    Alaskan sled dogs are a genetically distinct population shaped by generations of selective interbreeding with purebred dogs to create a group of high performance athletes. As a result of selective breeding strategies, sled dogs present a unique opportunity to employ admixture-mapping techniques to investigate how breed composition and trait selection impact genomic structure. We used admixture mapping to investigate genetic ancestry across the genomes of two classes of sled dogs, sprint and long distance racers, and combined that with genome wide association studies (GWAS) to identify regions correlating with performance enhancing traits. The sled dog genome is enhanced by differential contributions from four non-admixed breeds (Alaskan Malamute, Siberian Husky, German Shorthaired Pointer, and Borzoi). A principle components analysis (PCA) of 115,000 genome-wide SNPs clearly resolved the sprint and distance populations as distinct genetic groups, with longer blocks of linkage disequilibrium (LD) observed in the distance versus sprint dogs (7.5–10 and 2.5–3.75 kb, respectively). Further, we identified eight regions with the genomic signal either from a selective sweep or an association analysis, corroborated by an excess of ancestry when comparing sprint and distance dogs. A comparison of elite and poor performing sled dogs identified a single region significantly association with heat tolerance. Within the region we identified seven SNPs within the myosin heavy chain 9 gene (MYH9) that were significantly associated with heat tolerance in sprint dogs, two of which correspond to conserved promoter and enhancer regions in the human ortholog. PMID:22105876

  9. Ancestry informative markers for distinguishing between Thai populations based on genome-wide association datasets.

    PubMed

    Vongpaisarnsin, Kornkiat; Listman, Jennifer Beth; Malison, Robert T; Gelernter, Joel

    2015-07-01

    The main purpose of this work was to identify a set of AIMs that stratify the genetic structure and diversity of the Thai population from a high-throughput autosomal genome-wide association study. In this study, more than one million SNPs from the international HapMap database and the Thai depression genome-wide association study have been examined to identify ancestry informative markers (AIMs) that distinguish between Thai populations. An efficient strategy is proposed to identify and characterize such SNPs and to test high-resolution SNP data from international HapMap populations. The best AIMs are identified to stratify the population and to infer genetic ancestry structure. A total of 124 AIMs were clearly clustered geographically across the continent, whereas only 89 AIMs stratified the Thai population from East Asian populations. Finally, a set of 273 AIMs was able to distinguish northern from southern Thai subpopulations. These markers will be of particular value in identifying the ethnic origins in regions where matching by self-reports is unavailable or unreliable, which usually occurs in real forensic cases.

  10. Ancestry informative markers for distinguishing between Thai populations based on genome-wide association datasets

    PubMed Central

    Vongpaisarnsin, Kornkiat; Listman, Jennifer Beth; Malison, Robert T; Gelernter, Joel

    2015-01-01

    The main purpose of this work was to identify a set of AIMs that stratify the genetic structure and diversity of the Thai population from a high-throughput autosomal genome-wide association study. In this study, more than one million SNPs from the International HapMap database and the Thai depression genome-wide association study have been examined to identify ancestry informative markers (AIMs) that distinguish between Thai populations. An efficient strategy is proposed to identify and characterize such SNPs and to test high-resolution SNP data from international HapMap populations. The best AIMs are identified to stratify the population and to infer genetic ancestry structure. A total of 124 AIMs were clearly clustered geographically across the continent, whereas only 89 AIMs stratified the Thai population from East Asian populations. Finally, a set of 273 AIMs was able to distinguish northern from southern Thai subpopulations. These markers will be of particular value in identifying the ethnic origins in regions where matching by self-reports is unavailable or unreliable, which usually occurs in real forensic cases. PMID:25759192

  11. High extracellular potassium and its correlates after severe head injury: relationship to high intracranial pressure.

    PubMed

    Reinert, M; Khaldi, A; Zauner, A; Doppenberg, E; Choi, S; Bullock, R

    2000-01-01

    Disturbed ionic and neurotransmitter homeostasis are now recognized to be probably the most important mechanisms contributing to the development of secondary brain swelling after traumatic brian injury (TBI). Evidence obtained from animal models indicates that posttraumatic neuronal excitation via excitatory amino acids leads to an increase in extracellular potassium, probably due to ion channel activation. The purpose of this study was therefore to measure dialysate potassium in severely head injured patients and to correlate these results with intracranial pressure (ICP), outcome, and also with the levels of dialysate glutamate, lactate, and cerebral blood flow (CBF) so as to determine the role of ischemia in this posttraumatic ionic dysfunction. Eighty-five patients with severe TBI (Glasgow Coma Scale score < 8) were treated according to an intensive ICP management-focused protocol. All patients underwent intracerebral microdialyis. Dialysate potassium levels were analyzed by flame photometry, as were dialysate glutamate and dialysate lactate levels, which were measured using high-performance liquid chromatography and an enzyme-linked amperometric method in 72 and 84 patients respectively. Cerebral blood flow studies (stable Xenon--computerized tomography scanning) were performed in 59 patients. In approximately 20% of the patients, potassium values were increased (dialysate potassium > 1.8 mmol). Mean dialysate potassium (> 2 mmol) was associated with ICP above 30 mm Hg and fatal outcome. Dialysate potassium correlated positively with dialysate glutamate (p < 0.0001) and lactate levels (p < 0.0001). Dialysate potassium was significantly inversely correlated with reduced CBF (p = 0.019). Dialysate potassium was increased after TBI in 20% of measurements. High levels of dialysate potassium were associated with increased ICP and poor outcome. The simultaneous increase of potassium, together with dialysate glutamate and lactate, supports the hypothesis that

  12. Biogeographic Ancestry in the African Descent and Glaucoma Evaluation Study (ADAGES): Association With Corneal and Optic Nerve Structure.

    PubMed

    Girkin, Christopher A; Nievergelt, Caroline M; Kuo, Jane Z; Maihofer, Adam X; Huisingh, Carrie; Liebmann, Jeffrey M; Ayyagari, Radha; Weinreb, Robert N; Ritch, Robert; Zangwill, Linda M

    2015-03-05

    We determined if quantitative measurements of biogeographic ancestry (BGA) correlate with variations in optic disc area, corneal thickness (CCT), and retinal nerve fiber layer (RNFL) thickness. Data were obtained from 656 participants in the African Descent and Glaucoma Evaluation Study (ADAGES) cohort who consented to BGA testing. Data for CCT, optic disc area, and RNFL thickness were obtained from subjects in the ADAGES study who also had participated in the current substudy. A total of 31 ancestry informative markers (AIMs) with large allele frequencies differences between populations was used to calculate admixture proportion (implemented in STRUCTURE). Correlations with BGA adjusted for diagnosis, age, and sex for CCT and optic disc area using the whole group and RNFL thickness adjusted for age and sex for the normal study participants were determined. The mean percentage of African admixture was 79.6% in the self-described African Descent (AD) group and 3.5% in the European Descent (ED) group. Percent African ancestry was significantly correlated with CCT (ρ = -0.27, P < 0.0001) and disc area (ρ = 0.15, P < 0.0001), but only marginally associated with RNFL thickness (ρ = 0.20, P = 0.092) in adjusted models. The BGA correlates with variation in ocular features that significantly differ across racial groups and that have been associated with the development of glaucoma. While BGA can provide an objective measurement of the biologic component of self-described race for ocular research, for most nongenetic epidemiologic studies, self-described race may adequately describe the associations with these ocular characteristics. (ClinicalTrials.gov number, NCT00221923.). Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  13. Biogeographic Ancestry in the African Descent and Glaucoma Evaluation Study (ADAGES): Association With Corneal and Optic Nerve Structure

    PubMed Central

    Girkin, Christopher A.; Nievergelt, Caroline M.; Kuo, Jane Z.; Maihofer, Adam X.; Huisingh, Carrie; Liebmann, Jeffrey M.; Ayyagari, Radha; Weinreb, Robert N.; Ritch, Robert; Zangwill, Linda M.

    2015-01-01

    Purpose. We determined if quantitative measurements of biogeographic ancestry (BGA) correlate with variations in optic disc area, corneal thickness (CCT), and retinal nerve fiber layer (RNFL) thickness. Methods. Data were obtained from 656 participants in the African Descent and Glaucoma Evaluation Study (ADAGES) cohort who consented to BGA testing. Data for CCT, optic disc area, and RNFL thickness were obtained from subjects in the ADAGES study who also had participated in the current substudy. A total of 31 ancestry informative markers (AIMs) with large allele frequencies differences between populations was used to calculate admixture proportion (implemented in STRUCTURE). Correlations with BGA adjusted for diagnosis, age, and sex for CCT and optic disc area using the whole group and RNFL thickness adjusted for age and sex for the normal study participants were determined. Results. The mean percentage of African admixture was 79.6% in the self-described African Descent (AD) group and 3.5% in the European Descent (ED) group. Percent African ancestry was significantly correlated with CCT (ρ = −0.27, P < 0.0001) and disc area (ρ = 0.15, P < 0.0001), but only marginally associated with RNFL thickness (ρ = 0.20, P = 0.092) in adjusted models. Conclusions. The BGA correlates with variation in ocular features that significantly differ across racial groups and that have been associated with the development of glaucoma. While BGA can provide an objective measurement of the biologic component of self-described race for ocular research, for most nongenetic epidemiologic studies, self-described race may adequately describe the associations with these ocular characteristics. (ClinicalTrials.gov number, NCT00221923.) PMID:25744975

  14. Analysis of exome sequencing data sets reveals structural variation in the coding region of ABO in individuals of African ancestry.

    PubMed

    Fox, Keolu; Johnsen, Jill M; Coe, Bradley P; Frazar, Chris D; Reiner, Alexander P; Eichler, Evan E; Nickerson, Deborah A

    2016-11-01

    ABO is a blood group system of high clinical significance due to the prevalence of ABO variation that can cause major, potentially life-threatening, transfusion reactions. Using multiple large-scale next-generation sequence data sets, we demonstrate the application of read-depth approaches to discover previously unsuspected structural variation (SV) in the ABO gene in individuals of African ancestry. Our analysis of SV in the ABO gene across 6432 exomes reveals a partial deletion in the ABO gene in 32 individuals of African ancestry that predicts a novel O allele. Our study demonstrates the power that analyses of large-scale sequencing data, particularly data sets containing underrepresented populations, can provide in identifying novel SVs. © 2016 AABB.

  15. [Physical growth in stature of school children of Japanese ancestry in the city of São Paulo, Brazil

    PubMed

    Kac; Santos

    1996-04-01

    This paper reports the results of a cross-sectional survey describing the growth in stature of a sample of school children of Japanese ancestry (three or four grandparents born in Japan) and of high socio-economic status living in São Paulo, Brazil. The sample comprises 124 individuals 7-10 years of age, of both sexes. The results show that the children present mean values of stature below the median values of the NCHS curves ("National Center for Health Statistics", U.S.A.). The values are similar to the medians of a sample of Japanese children and below those of well-to-do Brazilian children of non-Japanese ancestry studied by the PNSN ("Pesquisa Nacional sobre Saúde e Nutrição", Brazil). The findings do not support the hypothesis of uniformity of growth potential in stature, casting doubts on the utilization of a single anthropometric reference in the assessment of nutritional status.

  16. Genomics assisted ancestry deconvolution in grape

    USDA-ARS?s Scientific Manuscript database

    The genus Vitis (the grapevine) is a group of highly diverse, diploid woody perennial vines consisting of approximately 60 species from across the northern hemisphere. It is the world’s most valuable horticultural crop with ~8 million hectares planted, most of which is processed into wine. To gain i...

  17. Phase-image-correlation-based high sensitive optical nanoscope

    NASA Astrophysics Data System (ADS)

    Kim, Daesuk; Baek, Byung Joon; Zvyagin, Andrei V.; Lee, Hyungchul; Cho, Yong Jai

    2010-12-01

    We describe a novel real time optical 3D nanoscope scheme that can be applied for both metrology and inspection in various semiconductor fields. Since the proposed off-axis scheme based on a matched filter correlation method basically measure the phase information of a nano object, the proposed scheme has some benefits in terms of sensitivity in both 3D geometry measurement and defect inspection capability. In this study, the feasibility of the proposed scheme has been evaluated by combining the conical diffraction and wave propagation simulation codes.

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

    PubMed

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

    2017-01-30

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

  19. Characterizing highly correlated video traffic in high-speed asynchronous transfer mode networks

    NASA Astrophysics Data System (ADS)

    Shroff, Ness; Schwartz, Mischa

    1996-04-01

    The enormous bandwidth potential of optical fiber has resulted in a worldwide effort to develop high-speed ATM networks, also called broadband integrated services digital networks (B-ISDN). Many of the applications that ATM networks will support will have a strong video component to them. Hence, it is important to understand the behavior of video traffic as it travels through these networks. To that end, we develop the generalized histogram model (GHM) to characterize 'highly correlated' traffic, such as motion JPEG or 'smoothed' MPEG traffic over ATM networks end-to- end. Using our GHM model we show how to determine the loss rate at any node in an ATM network. We find that, for highly correlated video sources, increasing the buffer size beyond a certain region called the 'cell region' only marginally decreases the probability of loss. This implies that large buffers cannot be used to control the loss for such sources. The analytical model provided in this paper can be used for admission control, and network dimensioning and design in ATM networks. We have validated our results using simulations of real traces of video sources.

  20. Developmental validation of mitochondrial DNA genotyping assays for adept matrilineal inference of biogeographic ancestry at a continental level.

    PubMed

    Chaitanya, Lakshmi; van Oven, Mannis; Weiler, Natalie; Harteveld, Joyce; Wirken, Laura; Sijen, Titia; de Knijff, Peter; Kayser, Manfred

    2014-07-01

    Mitochondrial DNA (mtDNA) can be used for matrilineal biogeographic ancestry prediction and can thus provide investigative leads towards identifying unknown suspects, when conventional autosomal short tandem repeat (STR) profiling fails to provide a match. Recently, six multiplex genotyping assays targeting 62 ancestry-informative mitochondrial single nucleotide polymorphisms (mt-SNPs) were developed. This hierarchical system of assays allows detection of the major haplogroups present in Africa, America, Western Eurasia, Eastern Eurasia, Australia and Oceania, thus revealing the broad geographic region of matrilineal origin of a DNA donor. Here, we provide a forensic developmental validation study of five multiplex assays targeting all the 62 ancestry-informative mt-SNPs following the Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines. We demonstrate that the assays are highly sensitive; being able to produce full profiles at input DNA amounts of as little as 1pg. The assays were shown to be highly robust and efficient in providing information from degraded samples and from simulated casework samples of different substrates such as blood, semen, hair, saliva and trace DNA samples. Reproducible results were successfully achieved from concordance testing across three independent laboratories depicting the ease and reliability of these assays. Overall, our results demonstrate the suitability of these five mt-SNP assays for application to forensic casework and other purposes aiming to establish an individual's matrilineal genetic ancestry. With this validated tool, it is now possible to determine the matrilineal biogeographic origin of unknown individuals on the level of continental resolution from forensic DNA samples to provide investigative leads in criminal and missing person cases where autosomal STR profiling is uninformative.

  1. Ancestry and pathology in King Tutankhamun's family.

    PubMed

    Hawass, Zahi; Gad, Yehia Z; Ismail, Somaia; Khairat, Rabab; Fathalla, Dina; Hasan, Naglaa; Ahmed, Amal; Elleithy, Hisham; Ball, Markus; Gaballah, Fawzi; Wasef, Sally; Fateen, Mohamed; Amer, Hany; Gostner, Paul; Selim, Ashraf; Zink, Albert; Pusch, Carsten M

    2010-02-17

    The New Kingdom in ancient Egypt, comprising the 18th, 19th, and 20th dynasties, spanned the mid-16th to the early 11th centuries bc. The late 18th dynasty, which included the reigns of pharaohs Akhenaten and Tutankhamun, was an extraordinary time. The identification of a number of royal mummies from this era, the exact relationships between some members of the royal family, and possible illnesses and causes of death have been matters of debate. To introduce a new approach to molecular and medical Egyptology, to determine familial relationships among 11 royal mummies of the New Kingdom, and to search for pathological features attributable to possible murder, consanguinity, inherited disorders, and infectious diseases. From September 2007 to October 2009, royal mummies underwent detailed anthropological, radiological, and genetic studies as part of the King Tutankhamun Family Project. Mummies distinct from Tutankhamun's immediate lineage served as the genetic and morphological reference. To authenticate DNA results, analytical steps were repeated and independently replicated in a second ancient DNA laboratory staffed by a separate group of personnel. Eleven royal mummies dating from circa 1410-1324 bc and suspected of being kindred of Tutankhamun and 5 royal mummies dating to an earlier period, circa 1550-1479 bc, were examined. Microsatellite-based haplotypes in the mummies, generational segregation of alleles within possible pedigree variants, and correlation of identified diseases with individual age, archeological evidence, and the written historical record. Genetic fingerprinting allowed the construction of a 5-generation pedigree of Tutankhamun's immediate lineage. The KV55 mummy and KV35YL were identified as the parents of Tutankhamun. No signs of gynecomastia and craniosynostoses (eg, Antley-Bixler syndrome) or Marfan syndrome were found, but an accumulation of malformations in Tutankhamun's family was evident. Several pathologies including Köhler disease

  2. Why do hypertensive patients of African ancestry respond better to calcium blockers and diuretics than to ACE inhibitors and β-adrenergic blockers? A systematic review

    PubMed Central

    2013-01-01

    Background Clinicians are encouraged to take an individualized approach when treating hypertension in patients of African ancestry, but little is known about why the individual patient may respond well to calcium blockers and diuretics, but generally has an attenuated response to drugs inhibiting the renin-angiotensin system and to β-adrenergic blockers. Therefore, we systematically reviewed the factors associated with the differential drug response of patients of African ancestry to antihypertensive drug therapy. Methods Using the methodology of the systematic reviews narrative synthesis approach, we sought for published or unpublished studies that could explain the differential clinical efficacy of antihypertensive drugs in patients of African ancestry. PUBMED, EMBASE, LILACS, African Index Medicus and the Food and Drug Administration and European Medicines Agency databases were searched without language restriction from their inception through June 2012. Results We retrieved 3,763 papers, and included 72 reports that mainly considered the 4 major classes of antihypertensive drugs, calcium blockers, diuretics, drugs that interfere with the renin-angiotensin system and β-adrenergic blockers. Pharmacokinetics, plasma renin and genetic polymorphisms did not well predict the response of patients of African ancestry to antihypertensive drugs. An emerging view that low nitric oxide and high creatine kinase may explain individual responses to antihypertensive drugs unites previous observations, but currently clinical data are very limited. Conclusion Available data are inconclusive regarding why patients of African ancestry display the typical response to antihypertensive drugs. In lieu of biochemical or pharmacogenomic parameters, self-defined African ancestry seems the best available predictor of individual responses to antihypertensive drugs. PMID:23721258

  3. Why do hypertensive patients of African ancestry respond better to calcium blockers and diuretics than to ACE inhibitors and β-adrenergic blockers? A systematic review.

    PubMed

    Brewster, Lizzy M; Seedat, Yackoob K

    2013-05-30

    Clinicians are encouraged to take an individualized approach when treating hypertension in patients of African ancestry, but little is known about why the individual patient may respond well to calcium blockers and diuretics, but generally has an attenuated response to drugs inhibiting the renin-angiotensin system and to β-adrenergic blockers. Therefore, we systematically reviewed the factors associated with the differential drug response of patients of African ancestry to antihypertensive drug therapy. Using the methodology of the systematic reviews narrative synthesis approach, we sought for published or unpublished studies that could explain the differential clinical efficacy of antihypertensive drugs in patients of African ancestry. PUBMED, EMBASE, LILACS, African Index Medicus and the Food and Drug Administration and European Medicines Agency databases were searched without language restriction from their inception through June 2012. We retrieved 3,763 papers, and included 72 reports that mainly considered the 4 major classes of antihypertensive drugs, calcium blockers, diuretics, drugs that interfere with the renin-angiotensin system and β-adrenergic blockers. Pharmacokinetics, plasma renin and genetic polymorphisms did not well predict the response of patients of African ancestry to antihypertensive drugs. An emerging view that low nitric oxide and high creatine kinase may explain individual responses to antihypertensive drugs unites previous observations, but currently clinical data are very limited. Available data are inconclusive regarding why patients of African ancestry display the typical response to antihypertensive drugs. In lieu of biochemical or pharmacogenomic parameters, self-defined African ancestry seems the best available predictor of individual responses to antihypertensive drugs.

  4. Correlation spectrometer having high resolution and multiplexing capability

    NASA Technical Reports Server (NTRS)

    Margolis, J. S.; Martonchik, J. V. (Inventor)

    1984-01-01

    A correlation spectrometer permanently incorporates a reference cell and an electro-optical phase modulator (EOPM) in the light path between a sample cell and a detector. The effect of the EOPM is such that its frequency modulates all of the monochromatic component of the incoherent radiation passing through it. The EOPM is adjusted so that when it is ON all of the energy in the monochromatic components is thrown into sidebands differing from the original frequencies by integral multiples of the modulation frequency with the total amount of energy absorbed from the original radiation remaining constant. When there is no coincidence between the constituents in the two cells, the detector's output is the same when the EOPM is ON and when it is OFF. However, when there is coincidence the detector's output changes when the EOPM is switched between its two states. The change in the detector's output is related to the quantity of the constituents in the sample cell.

  5. Performance correlations for high temperature potassium heat pipes

    SciTech Connect

    Merrigan, M.A.; Keddy, E.S.; Sena, J.T.

    1987-01-01

    Potassium heat pipes designed for operation at a nominal temperature of 775K have been developed for use in a heat pipe cooled reactor design. The heat pipes operate in a gravity assist mode with a maximum required power throughput of approximately 16 kW per heat pipe. Based on a series of sub-scale experiments with 2.12 and 3.2 cm diameter heat pipes the prototypic heat pipe diameter was set at 5.7 cm with a simple knurled wall wick used in the interests of mechanical simplicity. The performance levels required for this design had been demonstrated in prior work with gutter assisted wicks and emphasis in the present work was on the attainment of similar performance with a simplified wick structure. The wick structure used in the experiment consisted of a pattern of knurled grooves in the internal wall of the heat pipe. The knurl depth required for the planned heat pipe performance was determined by scaling of wick characteristic data from the sub-scale tests. These tests indicated that the maximum performance limits of the test heat pipes did not follow normal entrainment limit predictions for textured wall gravity assist heat pipes. Test data was therefore scaled to the prototype design based on the assumption that the performance was controlled by an entrainment parameter based on the liquid flow depth in the groove structure. This correlation provided a reasonable fit to the sub-scale test data and was used in scale up of the design from the 8.0 cm/sup 2/ cross section of the largest sub-scale heat pipe to the 25.5 cm/sup 2/ cross section prototype. Correlation of the model predictions with test data from the prototype is discussed.

  6. Ancestry Matters: Patrilineage Growth and Extinction

    PubMed Central

    Song, Xi; Campbell, Cameron D.; Lee, James Z.

    2016-01-01

    Patrilineality, the organization of kinship, inheritance, and other key social processes based on patrilineal male descent, has been a salient feature of social organization in China and many other societies for centuries. Because continuity or growth of the patrilineage was the central focus of reproductive strategies in such societies, we introduce the number of patrilineal male descendants generations later as a stratification outcome. By reconstructing and analyzing 20,000 patrilineages in two prospective, multi-generational population databases from 18th and 19th century China, we show that patrilineages founded by high status males had higher growth rates for the next 150 years. The elevated growth rate of these patrilineages was due more to their having a lower probability of extinction at each point in time than to surviving patrilineal male descendants having larger numbers of sons on average. As a result, patrilineal male descendants of high status males account for a disproportionately large share of the male population in later generations. In China and elsewhere, patrilineal kin network characteristics influence individuals’ life chances; thus effects of a male founder’s characteristics on patrilineage size many generations later represent an indirect channel of status transmission that has not been considered previously. PMID:27041745

  7. Quasiparticles of strongly correlated Fermi liquids at high temperatures and in high magnetic fields

    NASA Astrophysics Data System (ADS)

    Shaginyan, V. R.

    2011-08-01

    Strongly correlated Fermi systems are among the most intriguing, best experimentally studied and fundamental systems in physics. There is, however, lack of theoretical understanding in this field of physics. The ideas based on the concepts like Kondo lattice and involving quantum and thermal fluctuations at a quantum critical point have been used to explain the unusual physics. Alas, being suggested to describe one property, these approaches fail to explain the others. This means a real crisis in theory suggesting that there is a hidden fundamental law of nature. It turns out that the hidden fundamental law is well forgotten old one directly related to the Landau-Migdal quasiparticles, while the basic properties and the scaling behavior of the strongly correlated systems can be described within the framework of the fermion condensation quantum phase transition (FCQPT). The phase transition comprises the extended quasiparticle paradigm that allows us to explain the non-Fermi liquid (NFL) behavior observed in these systems. In contrast to the Landau paradigm stating that the quasiparticle effective mass is a constant, the effective mass of new quasiparticles strongly depends on temperature, magnetic field, pressure, and other parameters. Our observations are in good agreement with experimental facts and show that FCQPT is responsible for the observed NFL behavior and quasiparticles survive both high temperatures and high magnetic fields.

  8. Quasiparticles of strongly correlated Fermi liquids at high temperatures and in high magnetic fields

    SciTech Connect

    Shaginyan, V. R.

    2011-08-15

    Strongly correlated Fermi systems are among the most intriguing, best experimentally studied and fundamental systems in physics. There is, however, lack of theoretical understanding in this field of physics. The ideas based on the concepts like Kondo lattice and involving quantum and thermal fluctuations at a quantum critical point have been used to explain the unusual physics. Alas, being suggested to describe one property, these approaches fail to explain the others. This means a real crisis in theory suggesting that there is a hidden fundamental law of nature. It turns out that the hidden fundamental law is well forgotten old one directly related to the Landau-Migdal quasiparticles, while the basic properties and the scaling behavior of the strongly correlated systems can be described within the framework of the fermion condensation quantum phase transition (FCQPT). The phase transition comprises the extended quasiparticle paradigm that allows us to explain the non-Fermi liquid (NFL) behavior observed in these systems. In contrast to the Landau paradigm stating that the quasiparticle effective mass is a constant, the effective mass of new quasiparticles strongly depends on temperature, magnetic field, pressure, and other parameters. Our observations are in good agreement with experimental facts and show that FCQPT is responsible for the observed NFL behavior and quasiparticles survive both high temperatures and high magnetic fields.

  9. Ancestry, Socioeconomic Status, and Age-Related Cataract in Asians: The Singapore Epidemiology of Eye Diseases Study.

    PubMed

    Chua, Jacqueline; Koh, Jia Yu; Tan, Ava Grace; Zhao, Wanting; Lamoureux, Ecosse; Mitchell, Paul; Wang, Jie Jin; Wong, Tien Yin; Cheng, Ching-Yu

    2015-11-01

    To determine the prevalence of age-related cataract and its ancestral and socioeconomic risk factors in a multi-ethnic Asian population. Population-based, cross-sectional study. A total of 10 033 adults (3353 Chinese, 3280 Malays, and 3400 Indians) aged >40 years in the Singapore Epidemiology of Eye Diseases Study. Study participants were invited for a structured interview and received a standardized comprehensive eye examination. Digital lens photographs were taken from eyes of each participant and graded for nuclear, cortical, and posterior subcapsular (PSC) cataract, following the Wisconsin Cataract Grading System. Prevalence data were compared with the Blue Mountains Eye Study (BMES) in Australia. Information on medical and lifestyle factors was collected using questionnaires and blood samples. To increase the precision of racial definition, genetic ancestry was derived from genome-wide single nucleotide polymorphism markers using principal component analysis. Regression models were used to investigate the association of cataract with socioeconomic factors (education and income) and genetic ancestry. Age-related cataract. A total of 8750 participants (94.0%) had gradable lens photographs. The age-standardized prevalence of cataract surgery in Chinese (16.0%), Malays (10.6%), and Indians (20.2%) was higher than in white subjects (4.1%). We found the age-standardized cataract prevalence in Chinese (30.4%), Malays (37.8%), and Indians (33.1%) was higher than in whites (18.5%). Cataract was 1.5 to 2 times more common in Asians and began 10 years earlier than in white subjects. Malays had significantly higher age-standardized prevalence of nuclear, cortical, and PSC cataract than Chinese (P<0.001). The severity of nuclear, cortical, and PSC cataract was significantly correlated with genetic ancestry in our South East Asian population. Less education and lower income were associated with cataract for Chinese and Indians but not Malays. The presence of visual

  10. Genetically determined ancestry is more informative than self-reported race in HIV-infected and -exposed children

    PubMed Central

    Spector, Stephen A.; Brummel, Sean S.; Nievergelt, Caroline M.; Maihofer, Adam X.; Singh, Kumud K.; Purswani, Murli U.; Williams, Paige L.; Hazra, Rohan; Van Dyke, Russell; Seage, George R.

    2016-01-01

    Abstract The Pediatric HIV/AIDS Cohort Study (PHACS), the largest ongoing longitudinal study of perinatal HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) children in the United States, comprises the Surveillance Monitoring of Antiretroviral Therapy [ART] Toxicities (SMARTT) Study in PHEU children and the Adolescent Master Protocol (AMP) that includes PHIV and PHEU children ≥7 years. Although race/ethnicity is often used to assess health outcomes, this approach remains controversial and may fail to accurately reflect the backgrounds of ancestry-diverse populations as represented in the PHACS participants. In this study, we compared genetically determined ancestry (GDA) and self-reported race/ethnicity (SRR) in the PHACS cohort. GDA was estimated using a highly discriminative panel of 41 single nucleotide polymorphisms and compared to SRR. Because SRR was similar between the PHIV and PHEU, and between the AMP and SMARTT cohorts, data for all unique 1958 participants were combined. According to SRR, 63% of study participants identified as Black/African-American, 27% White, and 34% Hispanic. Using the highest percentage of ancestry/ethnicity to identify GDA, 9.5% of subjects were placed in the incorrect superpopulation based on SRR. When ≥50% or ≥75% GDA of a given superpopulation was required, 12% and 25%, respectively, of subjects were placed in the incorrect superpopulation based on SRR, and the percent of subjects classified as multiracial increased. Of 126 participants with unidentified SRR, 71% were genetically identified as Eurasian. GDA provides a more robust assessment of race/ethnicity when compared to self-report, and study participants with unidentified SRR could be assigned GDA using genetic markers. In addition, identification of continental ancestry removes the taxonomic identification of race as a variable when identifying risk for clinical outcomes. PMID:27603370

  11. Genetically determined ancestry is more informative than self-reported race in HIV-infected and -exposed children.

    PubMed

    Spector, Stephen A; Brummel, Sean S; Nievergelt, Caroline M; Maihofer, Adam X; Singh, Kumud K; Purswani, Murli U; Williams, Paige L; Hazra, Rohan; Van Dyke, Russell; Seage, George R

    2016-09-01

    The Pediatric HIV/AIDS Cohort Study (PHACS), the largest ongoing longitudinal study of perinatal HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) children in the United States, comprises the Surveillance Monitoring of Antiretroviral Therapy [ART] Toxicities (SMARTT) Study in PHEU children and the Adolescent Master Protocol (AMP) that includes PHIV and PHEU children ≥7 years. Although race/ethnicity is often used to assess health outcomes, this approach remains controversial and may fail to accurately reflect the backgrounds of ancestry-diverse populations as represented in the PHACS participants.In this study, we compared genetically determined ancestry (GDA) and self-reported race/ethnicity (SRR) in the PHACS cohort. GDA was estimated using a highly discriminative panel of 41 single nucleotide polymorphisms and compared to SRR. Because SRR was similar between the PHIV and PHEU, and between the AMP and SMARTT cohorts, data for all unique 1958 participants were combined.According to SRR, 63% of study participants identified as Black/African-American, 27% White, and 34% Hispanic. Using the highest percentage of ancestry/ethnicity to identify GDA, 9.5% of subjects were placed in the incorrect superpopulation based on SRR. When ≥50% or ≥75% GDA of a given superpopulation was required, 12% and 25%, respectively, of subjects were placed in the incorrect superpopulation based on SRR, and the percent of subjects classified as multiracial increased. Of 126 participants with unidentified SRR, 71% were genetically identified as Eurasian.GDA provides a more robust assessment of race/ethnicity when compared to self-report, and study participants with unidentified SRR could be assigned GDA using genetic markers. In addition, identification of continental ancestry removes the taxonomic identification of race as a variable when identifying risk for clinical outcomes.

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

    PubMed Central

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

    2016-01-01

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

  13. IL1B-CGTC haplotype is associated with colorectal cancer in admixed individuals with increased African ancestry

    PubMed Central

    Sanabria-Salas, María Carolina; Hernández-Suárez, Gustavo; Umaña-Pérez, Adriana; Rawlik, Konrad; Tenesa, Albert; Serrano-López, Martha Lucía; Sánchez de Gómez, Myriam; Rojas, Martha Patricia; Bravo, Luis Eduardo; Albis, Rosario; Plata, José Luis; Green, Heather; Borgovan, Theodor; Li, Li; Majumdar, Sumana; Garai, Jone; Lee, Edward; Ashktorab, Hassan; Brim, Hassan; Li, Li; Margolin, David; Fejerman, Laura; Zabaleta, Jovanny

    2017-01-01

    Single-nucleotide polymorphisms (SNPs) in cytokine genes can affect gene expression and thereby modulate inflammation and carcinogenesis. However, the data on the association between SNPs in the interleukin 1 beta gene (IL1B) and colorectal cancer (CRC) are conflicting. We found an association between a 4-SNP haplotype block of the IL1B (-3737C/-1464G/-511T/-31C) and CRC risk, and this association was exclusively observed in individuals with a higher proportion of African ancestry, such as individuals from the Coastal Colombian region (odds ratio, OR 2.06; 95% CI 1.31–3.25; p < 0.01). Moreover, a significant interaction between this CRC risk haplotype and local African ancestry dosage was identified in locus 2q14 (p = 0.03). We conclude that Colombian individuals with high African ancestry proportions at locus 2q14 harbour more IL1B-CGTC copies and are consequently at an increased risk of CRC. This haplotype has been previously found to increase the IL1B promoter activity and is the most frequent haplotype in African Americans. Despite of limitations in the number of samples and the lack of functional analysis to examine the effect of these haplotypes on CRC cell lines, our results suggest that inflammation and ethnicity play a major role in the modulation of CRC risk. PMID:28157220

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

    PubMed

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

    2016-01-01

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

  15. Admixture dynamics in Hispanics: a shift in the nuclear genetic ancestry of a South American population isolate.

    PubMed

    Bedoya, Gabriel; Montoya, Patricia; García, Jenny; Soto, Ivan; Bourgeois, Stephane; Carvajal, Luis; Labuda, Damian; Alvarez, Victor; Ospina, Jorge; Hedrick, Philip W; Ruiz-Linares, Andrés

    2006-05-09

    Although it is well established that Hispanics generally have a mixed Native American, African, and European ancestry, the dynamics of admixture at the foundation of Hispanic populations is heterogeneous and poorly documented. Genetic analyses are potentially very informative for probing the early demographic history of these populations. Here we evaluate the genetic structure and admixture dynamics of a province in northwest Colombia (Antioquia), which prior analyses indicate was founded mostly by Spanish men and native women. We examined surname, Y chromosome, and mtDNA diversity in a geographically structured sample of the region and obtained admixture estimates with highly informative autosomal and X chromosome markers. We found evidence of reduced surname diversity and support for the introduction of several common surnames by single founders, consistent with the isolation of Antioquia after the colonial period. Y chromosome and mtDNA data indicate little population substructure among founder Antioquian municipalities. Interestingly, despite a nearly complete Native American mtDNA background, Antioquia has a markedly predominant European ancestry at the autosomal and X chromosome level, which suggests that, after foundation, continuing admixture with Spanish men (but not with native women) increased the European nuclear ancestry of Antioquia. This scenario is consistent with historical information and with results from population genetics theory.

  16. Admixture dynamics in Hispanics: A shift in the nuclear genetic ancestry of a South American population isolate

    PubMed Central

    Bedoya, Gabriel; Montoya, Patricia; García, Jenny; Soto, Ivan; Bourgeois, Stephane; Carvajal, Luis; Labuda, Damian; Alvarez, Victor; Ospina, Jorge; Hedrick, Philip W.; Ruiz-Linares, Andrés

    2006-01-01

    Although it is well established that Hispanics generally have a mixed Native American, African, and European ancestry, the dynamics of admixture at the foundation of Hispanic populations is heterogeneous and poorly documented. Genetic analyses are potentially very informative for probing the early demographic history of these populations. Here we evaluate the genetic structure and admixture dynamics of a province in northwest Colombia (Antioquia), which prior analyses indicate was founded mostly by Spanish men and native women. We examined surname, Y chromosome, and mtDNA diversity in a geographically structured sample of the region and obtained admixture estimates with highly informative autosomal and X chromosome markers. We found evidence of reduced surname diversity and support for the introduction of several common surnames by single founders, consistent with the isolation of Antioquia after the colonial period. Y chromosome and mtDNA data indicate little population substructure among founder Antioquian municipalities. Interestingly, despite a nearly complete Native American mtDNA background, Antioquia has a markedly predominant European ancestry at the autosomal and X chromosome level, which suggests that, after foundation, continuing admixture with Spanish men (but not with native women) increased the European nuclear ancestry of Antioquia. This scenario is consistent with historical information and with results from population genetics theory. PMID:16648268

  17. Validation of an Arab names algorithm in the determination of Arab ancestry for use in health research

    PubMed Central

    El-Sayed, Abdulrahman M.; Lauderdale, Diane S.; Galea, Sandro

    2010-01-01

    Objective Data about Arab-Americans, a growing ethnic minority, is not routinely collected in vital statistics, registry, or administrative data in the US. The difficulty in identifying Arab-Americans using publicly available data sources is a barrier to health research about this group. Here, we validate an empirically-based, probabilistic Arab name algorithm (ANA) for identifying Arab-Americans in health research. Design We used data from all Michigan birth certificates between 2000-2005. Fathers’ surnames and mothers’ maiden names were coded as Arab or non-Arab according to the ANA. We calculated sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of Arab ethnicity inferred using the ANA as compared to self-reported Arab ancestry. Results State-wide, the ANA had a specificity of 98.9%, a sensitivity of 50.3%, a PPV of 57.0%, and a NPV of 98.6%. Both the false positive and false negative rates were higher among men than among women. As the concentration of Arab-Americans in a study locality increased, the ANA false positive rate increased and false-negative rate decreased. Conclusion The ANA is highly specific but only moderately sensitive as a means of detecting Arab ancestry. Future research should compare health characteristics among Arab-American populations defined by Arab ancestry and those defined by the ANA. PMID:20845117

  18. Genetic ancestry modifies pharmacogenetic gene–gene interaction for asthma

    PubMed Central

    Corvol, Harriet; De Giacomo, Anthony; Eng, Celeste; Seibold, Max; Ziv, Elad; Chapela, Rocio; Rodriguez-Santana, Jose R.; Rodriguez-Cintron, William; Thyne, Shannon; Watson, H. Geoffrey; Meade, Kelley; LeNoir, Michael; Avila, Pedro C.; Choudhry, Shweta; Burchard, Esteban Gonz!lez

    2009-01-01

    Objective A recent admixture mapping analysis identified interleukin 6 (IL6) and IL6 receptor (IL6R) as candidate genes for inflammatory diseases. In the airways during allergic inflammation, IL6 signaling controls the production of proinflammatory and anti-inflammatory factors. In addition, albuterol, a commonly prescribed asthma therapy, has been shown to influence IL6 gene expression. Therefore, we reasoned that interactions between the IL6 and IL6R genes might be associated with bronchodilator drug responsiveness to albuterol in asthmatic patients. Methods Four functional IL6 single nucleotide polymorphisms (SNPs) and a nonsynonymous IL6R SNP were genotyped in 700 Mexican and Puerto Rican asthma families and in 443 African-American asthma cases and controls. Both family-based association tests and linear regression models were used to assess the association between individual SNPs and haplotypes with bronchodilator response. Gene–gene interactions were tested by using multiple linear regression analyses. Results No single SNP was consistently associated with drug response in all the three populations. However, on the gene level, we found a consistent IL6 and IL6R pharmacogenetic interaction in the three populations. This pharmacogenetic gene–gene interaction was contextual and dependent upon ancestry (racial background). This interaction resulted in higher drug response to albuterol in Latinos, but lower drug response in African-Americans. Herein, we show that there is an effect modification by ancestry on bronchodilator responsiveness to albuterol. Conclusion Genetic variants in the IL6 and IL6R genes act synergistically to modify the bronchodilator drug responsiveness in asthma and this pharmacogenetic interaction is modified by the genetic ancestry. PMID:19503017

  19. Genetic ancestry modifies pharmacogenetic gene-gene interaction for asthma.

    PubMed

    Corvol, Harriet; De Giacomo, Anthony; Eng, Celeste; Seibold, Max; Ziv, Elad; Chapela, Rocio; Rodriguez-Santana, Jose R; Rodriguez-Cintron, William; Thyne, Shannon; Watson, H Geoffrey; Meade, Kelley; LeNoir, Michael; Avila, Pedro C; Choudhry, Shweta; Burchard, Esteban González

    2009-07-01

    A recent admixture mapping analysis identified interleukin 6 (IL6) and IL6 receptor (IL6R) as candidate genes for inflammatory diseases. In the airways during allergic inflammation, IL6 signaling controls the production of proinflammatory and anti-inflammatory factors. In addition, albuterol, a commonly prescribed asthma therapy, has been shown to influence IL6 gene expression. Therefore, we reasoned that interactions between the IL6 and IL6R genes might be associated with bronchodilator drug responsiveness to albuterol in asthmatic patients. Four functional IL6 single nucleotide polymorphisms (SNPs) and a nonsynonymous IL6R SNP were genotyped in 700 Mexican and Puerto Rican asthma families and in 443 African-American asthma cases and controls. Both family-based association tests and linear regression models were used to assess the association between individual SNPs and haplotypes with bronchodilator response. Gene-gene interactions were tested by using multiple linear regression analyses. No single SNP was consistently associated with drug response in all the three populations. However, on the gene level, we found a consistent IL6 and IL6R pharmacogenetic interaction in the three populations. This pharmacogenetic gene-gene interaction was contextual and dependent upon ancestry (racial background). This interaction resulted in higher drug response to albuterol in Latinos, but lower drug response in African-Americans. Herein, we show that there is an effect modification by ancestry on bronchodilator responsiveness to albuterol. Genetic variants in the IL6 and IL6R genes act synergistically to modify the bronchodilator drug responsiveness in asthma and this pharmacogenetic interaction is modified by the genetic ancestry.

  20. Neural Correlates of High Performance in Foreign Language Vocabulary Learning

    ERIC Educational Resources Information Center

    Macedonia, Manuela; Muller, Karsten; Friederici, Angela D.

    2010-01-01

    Learning vocabulary in a foreign language is a laborious task which people perform with varying levels of success. Here, we investigated the neural underpinning of high performance on this task. In a within-subjects paradigm, participants learned 92 vocabulary items under two multimodal conditions: one condition paired novel words with iconic…

  1. Charge and spin correlations in high temperature superconductors

    NASA Astrophysics Data System (ADS)

    Hayden, Stephen

    2013-03-01

    The cuprate high temperatures superconductors are characterised by numerous competing, and in some cases, co-existing broken symmetries. A important question is to what extent such additional ordered states exist for compositions with high superconducting transition temperatures. I will discuss high-energy X-ray diffraction measurements which show that a charge density wave state (CDW) develops at zero field in the normal state of superconducting YBa2Cu3O6.67 (Tc = 67 K). This material has a hole doping of 0.12 per copper and a well-ordered oxygen chain superstructure. Below Tc, the application of a magnetic field suppresses superconductivity and enhances the CDW. We find that the CDW and superconductivity are competing orders with similar energy scales, and the high-Tc superconductivity forms from a pre-existing CDW environment. Our results provide a mechanism for the formation of small Fermi surface pockets which can explain the negative Hall and Seebeck effects and the Tc plateau in this material. Work performed in collaboration with J. Chang, E. Blackburn, A. T. Holmes, N. B. Christensen, J. Larsen, J. Mesot, Ruixing Liang, D. A. Bonn, W. N. Hardy, A. Watenphul, M. v. Zimmermann and E. M. Forgan.

  2. Some Correlates of High School Foreign Language Achievement.

    ERIC Educational Resources Information Center

    Beanblossom, Gary F.

    This paper investigates the influences of traditional kinds of verbal and quantitative achievement and aptitude variables on high school foreign language achievement, as measured by Modern Language Association and University of Washington tests of language skills administered to entering college students. The report focuses on: (1) the sample and…

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

    PubMed

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

    2016-02-01

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

  4. Disparities in breast cancer and african ancestry: a global perspective.

    PubMed

    Newman, Lisa A

    2015-01-01

    Recognition of breast cancer disparities between African-American and White American women has generated exciting research opportunities investigating the biologic and hereditary factors that contribute to the observed outcome differences, leading to international studies of breast cancer in Africa. The study of breast cancer in women with African ancestry has opened the door to unique investigations regarding breast cancer subtypes and the genetics of this disease. International research efforts can advance our understanding of race/ethnicity-associated breast cancer disparities within the USA; the pathogenesis of triple negative breast cancer; and hereditary susceptibility for breast cancer.

  5. Effect of Genetic African Ancestry on eGFR and Kidney Disease

    PubMed Central

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

    2015-01-01

    Self-reported ancestry, genetically determined ancestry, and APOL1 polymorphisms are associated with variation in kidney function and related disease risk, but the relative importance of these factors remains unclear. We estimated the global proportion of African ancestry for 9048 individuals at Mount Sinai Medical Center in Manhattan (3189 African Americans, 1721 European Americans, and 4138 Hispanic/Latino Americans by self-report) using genome-wide genotype data. CKD-EPI eGFR and genotypes of three APOL1 coding variants were available. In admixed African Americans and Hispanic/Latino Americans, serum creatinine values increased as African ancestry increased (per 10% increase in African ancestry, creatinine values increased 1% in African Americans and 0.9% in Hispanic/Latino Americans; P≤1x10−7). eGFR was likewise significantly associated with African genetic ancestry in both populations. In contrast, APOL1 risk haplotypes were significantly associated with CKD, eGFR<45 ml/min per 1.73 m2, and ESRD, with effects increasing with worsening disease states and the contribution of genetic African ancestry decreasing in parallel. Using genetic ancestry in the eGFR equation to reclassify patients as black on the basis of ≥50% African ancestry resulted in higher eGFR for 14.7% of Hispanic/Latino Americans and lower eGFR for 4.1% of African Americans, affecting CKD staging in 4.3% and 1% of participants, respectively. Reclassified individuals had electrolyte values consistent with their newly assigned CKD stage. In summary, proportion of African ancestry was significantly associated with normal-range creatinine and eGFR, whereas APOL1 risk haplotypes drove the associations with CKD. Recalculation of eGFR on the basis of genetic ancestry affected CKD staging and warrants additional investigation. PMID:25349204

  6. Effect of Genetic African Ancestry on eGFR and Kidney Disease.

    PubMed

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

    2015-07-01

    Self-reported ancestry, genetically determined ancestry, and APOL1 polymorphisms are associated with variation in kidney function and related disease risk, but the relative importance of these factors remains unclear. We estimated the global proportion of African ancestry for 9048 individuals at Mount Sinai Medical Center in Manhattan (3189 African Americans, 1721 European Americans, and 4138 Hispanic/Latino Americans by self-report) using genome-wide genotype data. CKD-EPI eGFR and genotypes of three APOL1 coding variants were available. In admixed African Americans and Hispanic/Latino Americans, serum creatinine values increased as African ancestry increased (per 10% increase in African ancestry, creatinine values increased 1% in African Americans and 0.9% in Hispanic/Latino Americans; P≤1x10(-7)). eGFR was likewise significantly associated with African genetic ancestry in both populations. In contrast, APOL1 risk haplotypes were significantly associated with CKD, eGFR<45 ml/min per 1.73 m(2), and ESRD, with effects increasing with worsening disease states and the contribution of genetic African ancestry decreasing in parallel. Using genetic ancestry in the eGFR equation to reclassify patients as black on the basis of ≥50% African ancestry resulted in higher eGFR for 14.7% of Hispanic/Latino Americans and lower eGFR for 4.1% of African Americans, affecting CKD staging in 4.3% and 1% of participants, respectively. Reclassified individuals had electrolyte values consistent with their newly assigned CKD stage. In summary, proportion of African ancestry was significantly associated with normal-range creatinine and eGFR, whereas APOL1 risk haplotypes drove the associations with CKD. Recalculation of eGFR on the basis of genetic ancestry affected CKD staging and warrants additional investigation. Copyright © 2015 by the American Society of Nephrology.

  7. Correlation of theory and experiment for high-pressure hydrogen

    NASA Technical Reports Server (NTRS)

    Hoover, W. G.; Ross, M.; Bender, C. F.; Rogers, F. J.; Olness, R. J.

    1972-01-01

    Recent quantum calculations and high-pressure experiments both agree on the magnitude of the forces with which hydrogen molecules interact. The calculated forces have to be determined in two steps: the repulsion is determined by Hartree-Fock calculations while the attraction is deduced semiempirically. The experimental forces are inferred from recent data on hydrogen shockcompressed to 214 kbar. The agreement indicates the usefulness of a pair-potential description of dense hydrogen and suggests, using potentials consistent with both theory and experiment, that pressures of at least 1.7 Mbar will be required to make metallic hydrogen. The expected lifetime of the metal at atmospheric pressure is very short.

  8. Stealing among High School Students: Prevalence and Clinical Correlates

    PubMed Central

    Grant, Jon E.; Potenza, Marc N.; Krishnan-Sarin, Suchitra; Cavallo, Dana A.; Desai, Rani A.

    2013-01-01

    Although stealing among adolescents appears to be fairly common, an assessment of adolescent stealing and its relationship to other behaviors and health issues is incompletely understood. A large sample of high school students (n=3999) was examined using a self-report survey with 153 questions concerning demographic characteristics, stealing behaviors, other health behaviors including substance use, and functioning variables such as grades and violent behavior. The overall prevalence of stealing was 15.2% (95%CI: 14.8–17.0). Twenty-nine (0.72%) students endorsed symptoms consistent with a diagnosis of DSM-IV kleptomania. Poor grades, alcohol and drug use, regular smoking, sadness and hopelessness, and other antisocial behaviors were all significantly (p<.05) associated with any stealing behavior. Stealing appears fairly common among high school students and is associated with a range of potentially addictive and antisocial behaviors. Significant distress and loss of control over this behavior suggests that stealing often has significant associated morbidity. PMID:21389165

  9. Exchange-correlation asymptotics and high harmonic spectra

    NASA Astrophysics Data System (ADS)

    Mack, Michael R.; Whitenack, Daniel; Wasserman, Adam

    2013-02-01

    High harmonic spectra of N2 are calculated using time-dependent density functional theory. The adiabatic local density approximation (A-LDA) and the adiabatic van Leeuwen-Baerends (A-LB94) approximations are used to study effects of differing spatial asymptotics. The LB94 potential corrects the LDA potential to the exact -1/r decay, but does not satisfy the zero-force condition. The A-LB94 makes a significant change in ionization probabilities but not in the relevant orbital contributions to ionization. This leads to qualitatively similar spectra, the exception being harmonic intensities. We also discuss why spurious dipoles induced by the A-LB94 do not affect significantly the structure of the N2 harmonic spectrum.

  10. Individual differences and correlates of highly superior autobiographical memory.

    PubMed

    Patihis, Lawrence

    2016-08-01

    Highly superior autobiographical memory (HSAM) is a recently identified ability that has been difficult to explain with existing memory science. The present study measured HSAM participants' and age/gender-matched controls' on a number of behavioural measures to test three main hypotheses: imaginative absorption, emotional arousal, and sleep. HSAM participants were significantly higher than controls on the dispositions absorption and fantasy proneness. These two dispositions also were associated with a measure of HSAM ability within the hyperthymesia participants. The emotional-arousal hypothesis yielded only weak support. The sleep hypothesis was not supported in terms of quantity, but sleep quality may be a small factor worthy of further research. Other individual differences are also documented using a predominantly exploratory analysis. Speculative pathways describing how the tendencies to absorb and fantasise could lead to enhanced autobiographical memory are discussed.

  11. Electrophysiological correlates of high-level perception during spatial navigation

    PubMed Central

    Weidemann, Christoph T.; Mollison, Matthew V.; Kahana, Michael J.

    2009-01-01

    We studied the electrophysiological basis o object recognition by recording scalp EEG while participants played a virtual reality taxi driver game. Participants searched for passengers and stores during virtual navigation in simulated towns. We compared oscillatory brain activity for store views that were targets or non-targets (during store search) or neutral (during passenger search). Even though store category was solely defined by task context (rather than sensory cues), frontal electrophysiological activity in low frequency bands (primarily in the theta [4–8 Hz] band) reliably distinguished between target, non-target, and neutral store views. These results implicate low frequency oscillatory brain activity in frontal regions as an important variable in the study of cognitive processes involved in object recognition, categorization, and other forms of high-level perception. PMID:19293100

  12. Correlates of gambling on high-school grounds

    PubMed Central

    Foster, Dawn W.; Hoff, Rani A.; Pilver, Corey E.; Yau, Yvonne H. C.; Steinberg, Marvin A.; Wampler, Jeremy; Krishnan-Sarin, Suchitra; Potenza, Marc N.

    2015-01-01

    Objective This study examined adolescent gambling on school grounds (GS+) and how such behavior was associated with gambling-related attitudes. Further, we examined whether GS+ moderated associations between at-risk problem-gambling (ARPG) and gambling behaviors related to gambling partners. Method Participants were 1988 high-school students who completed survey materials. Demographic, perceptions, attitudes, and gambling variables were stratified by problem-gambling severity (ARPG versus recreational gambling) and GS+ status. Chi-square and adjusted logistic regression models were used to examine relationships among study variables. Results Nearly 40% (39.58%) of students reported past-year GS+, with 12.91% of GS+ students, relative to 2.63% of those who did not report gambling on school grounds (GS), meeting DSM-IV criteria for pathological gambling (p<0.0001). In comparison to GS- students, GS+ students were more likely to report poorer academic achievement and more permissive attitudes towards gambling behaviors. Weaker links in GS+ students, in comparison with GS-, students, were observed between problem-gambling severity and gambling with family members (interaction odds ratio (IOR)=0.60; 95%CI=0.39–0.92) and gambling with friends (IOR=0.21; 95%CI=0.11–0.39). Conclusions GS+ is common and associated with pathological gambling and more permissive attitudes towards gambling. The finding that GS+ (relative to GS-) youth show differences in how problem-gambling is related to gambling partners (friends and family) warrants further investigation regarding whether and how peer and familial interactions might be improved to diminish youth problem-gambling severity. The high frequency of GS+ and its relationship with ARPG highlight a need for school administrators and personnel to consider interventions that target school-based gambling. PMID:26232102

  13. Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort

    PubMed Central

    Banda, Yambazi; Kvale, Mark N.; Hoffmann, Thomas J.; Hesselson, Stephanie E.; Ranatunga, Dilrini; Tang, Hua; Sabatti, Chiara; Croen, Lisa A.; Dispensa, Brad P.; Henderson, Mary; Iribarren, Carlos; Jorgenson, Eric; Kushi, Lawrence H.; Ludwig, Dana; Olberg, Diane; Quesenberry, Charles P.; Rowell, Sarah; Sadler, Marianne; Sakoda, Lori C.; Sciortino, Stanley; Shen, Ling; Smethurst, David; Somkin, Carol P.; Van Den Eeden, Stephen K.; Walter, Lawrence; Whitmer, Rachel A.; Kwok, Pui-Yan; Schaefer, Catherine; Risch, Neil

    2015-01-01

    Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality categories, which were collapsed into seven major race/ethnicity groups. By self-report the cohort is 80.8% white and 19.2% minority; 93.8% endorsed a single race/ethnicity group, while 6.2% endorsed two or more. Principal component (PC) and admixture analyses were generally consistent with prior studies. Approximately 17% of subjects had genetic ancestry from more than one continent, and 12% were genetically admixed, considering only nonadjacent geographical origins. Self-reported whites were spread on a continuum along the first two PCs, indicating extensive mixing among European nationalities. Self-identified East Asian nationalities correlated with genetic clustering, consistent with extensive endogamy. Individuals of mixed East Asian–European genetic ancestry were easily identified; we also observed a modest amount of European genetic ancestry in individuals self-identified as Filipinos. Self-reported African Americans and Latinos showed extensive European and African genetic ancestry, and Native American genetic ancestry for the latter. Among 3741 genetically identified parent–child pairs, 93% were concordant for self-reported race/ethnicity; among 2018 genetically identified full-sib pairs, 96% were concordant; the lower rate for parent–child pairs was largely due to intermarriage. The parent–child pairs revealed a trend toward increasing exogamy over time; the presence in the cohort of individuals endorsing multiple race/ethnicity categories creates interesting challenges and future opportunities for genetic epidemiologic studies. PMID:26092716

  14. Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort.

    PubMed

    Banda, Yambazi; Kvale, Mark N; Hoffmann, Thomas J; Hesselson, Stephanie E; Ranatunga, Dilrini; Tang, Hua; Sabatti, Chiara; Croen, Lisa A; Dispensa, Brad P; Henderson, Mary; Iribarren, Carlos; Jorgenson, Eric; Kushi, Lawrence H; Ludwig, Dana; Olberg, Diane; Quesenberry, Charles P; Rowell, Sarah; Sadler, Marianne; Sakoda, Lori C; Sciortino, Stanley; Shen, Ling; Smethurst, David; Somkin, Carol P; Van Den Eeden, Stephen K; Walter, Lawrence; Whitmer, Rachel A; Kwok, Pui-Yan; Schaefer, Catherine; Risch, Neil

    2015-08-01

    Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality categories, which were collapsed into seven major race/ethnicity groups. By self-report the cohort is 80.8% white and 19.2% minority; 93.8% endorsed a single race/ethnicity group, while 6.2% endorsed two or more. Principal component (PC) and admixture analyses were generally consistent with prior studies. Approximately 17% of subjects had genetic ancestry from more than one continent, and 12% were genetically admixed, considering only nonadjacent geographical origins. Self-reported whites were spread on a continuum along the first two PCs, indicating extensive mixing among European nationalities. Self-identified East Asian nationalities correlated with genetic clustering, consistent with extensive endogamy. Individuals of mixed East Asian-European genetic ancestry were easily identified; we also observed a modest amount of European genetic ancestry in individuals self-identified as Filipinos. Self-reported African Americans and Latinos showed extensive European and African genetic ancestry, and Native American genetic ancestry for the latter. Among 3741 genetically identified parent-child pairs, 93% were concordant for self-reported race/ethnicity; among 2018 genetically identified full-sib pairs, 96% were concordant; the lower rate for parent-child pairs was largely due to intermarriage. The parent-child pairs revealed a trend toward increasing exogamy over time; the presence in the cohort of individuals endorsing multiple race/ethnicity categories creates interesting challenges and future opportunities for genetic epidemiologic studies. Copyright © 2015 by the Genetics Society of America.

  15. Phylogenomic analyses reveal convergent patterns of adaptive evolution in elephant and human ancestries.

    PubMed

    Goodman, Morris; Sterner, Kirstin N; Islam, Munirul; Uddin, Monica; Sherwood, Chet C; Hof, Patrick R; Hou, Zhuo-Cheng; Lipovich, Leonard; Jia, Hui; Grossman, Lawrence I; Wildman, Derek E

    2009-12-08

    Specific sets of brain-expressed genes, such as aerobic energy metabolism genes, evolved adaptively in the ancestry of humans and may have evolved adaptively in the ancestry of other large-brained mammals. The recent addition of genomes from two afrotherians (elephant and tenrec) to the expanding set of publically available sequenced mammalian genomes provided an opportunity to test this hypothesis. Elephants resemble humans by having large brains and long life spans; tenrecs, in contrast, have small brains and short life spans. Thus, we investigated whether the phylogenomic patterns of adaptive evolution are more similar between elephant and human than between either elephant and tenrec lineages or human and mouse lineages, and whether aerobic energy metabolism genes are especially well represented in the elephant and human patterns. Our analyses encompassed approximately 6,000 genes in each of these lineages with each gene yielding extensive coding sequence matches in interordinal comparisons. Each gene's nonsynonymous and synonymous nucleotide substitution rates and dN/dS ratios were determined. Then, from gene ontology information on genes with the higher dN/dS ratios, we identified the more prevalent sets of genes that belong to specific functional categories and that evolved adaptively. Elephant and human lineages showed much slower nucleotide substitution rates than tenrec and mouse lineages but more adaptively evolved genes. In correlation with absolute brain size and brain oxygen consumption being largest in elephants and next largest in humans, adaptively evolved aerobic energy metabolism genes were most evident in the elephant lineage and next most evident in the human lineage.

  16. Phylogenomic analyses reveal convergent patterns of adaptive evolution in elephant and human ancestries

    PubMed Central

    Goodman, Morris; Sterner, Kirstin N.; Islam, Munirul; Uddin, Monica; Sherwood, Chet C.; Hof, Patrick R.; Hou, Zhuo-Cheng; Lipovich, Leonard; Jia, Hui; Grossman, Lawrence I.; Wildman, Derek E.

    2009-01-01

    Specific sets of brain-expressed genes, such as aerobic energy metabolism genes, evolved adaptively in the ancestry of humans and may have evolved adaptively in the ancestry of other large-brained mammals. The recent addition of genomes from two afrotherians (elephant and tenrec) to the expanding set of publically available sequenced mammalian genomes provided an opportunity to test this hypothesis. Elephants resemble humans by having large brains and long life spans; tenrecs, in contrast, have small brains and short life spans. Thus, we investigated whether the phylogenomic patterns of adaptive evolution are more similar between elephant and human than between either elephant and tenrec lineages or human and mouse lineages, and whether aerobic energy metabolism genes are especially well represented in the elephant and human patterns. Our analyses encompassed ≈6,000 genes in each of these lineages with each gene yielding extensive coding sequence matches in interordinal comparisons. Each gene's nonsynonymous and synonymous nucleotide substitution rates and dN/dS ratios were determined. Then, from gene ontology information on genes with the higher dN/dS ratios, we identified the more prevalent sets of genes that belong to specific functional categories and that evolved adaptively. Elephant and human lineages showed much slower nucleotide substitution rates than tenrec and mouse lineages but more adaptively evolved genes. In correlation with absolute brain size and brain oxygen consumption being largest in elephants and next largest in humans, adaptively evolved aerobic energy metabolism genes were most evident in the elephant lineage and next most evident in the human lineage. PMID:19926857

  17. Future directions for probing two and three nucleon short-range correlations at high energies

    SciTech Connect

    Frankfurt, Leonid; Sargsian, Misak; Strikman, Mark

    2008-10-13

    We summarize recent progress in the studies of the short-rang correlations (SRC) in nuclei in high energy electron and hadron nucleus scattering and suggest directions for the future high energy studies aimed at establishing detailed structure of two-nucleon SRCs, revealing structure of three nucleon SRC correlations and discovering non-nucleonic degrees of freedom in nuclei.

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

    PubMed

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

    2017-06-01

    The Sjögren's International Collaborative Clinical Alliance (SICCA) is an international data registry and biorepository derived from a multisite observational study of participants in whom genotyping was performed on the Omni2.5M platform and who had undergone deep phenotyping using common protocol-directed methods. The aim of this study was to examine the genetic etiology of Sjögren's syndrome (SS) across ancestry and disease subsets. We performed genome-wide association study analyses using SICCA subjects and external controls obtained from dbGaP data sets, one using all participants (1,405 cases, 1,622 SICCA controls, and 3,125 external controls), one using European participants (585, 966, and 580, respectively), and one using Asian participants (460, 224, and 901, respectively) with ancestry adjustments via principal components analyses. We also investigated whether subphenotype distributions differ by ethnicity, and whether this contributes to the heterogeneity of genetic associations. We observed significant associations in established regions of the major histocompatibility complex (MHC), IRF5, and STAT4 (P = 3 × 10(-42) , P = 3 × 10(-14) , and P = 9 × 10(-10) , respectively), and several novel suggestive regions (those with 2 or more associations at P < 1 × 10(-5) ). Two regions have been previously implicated in autoimmune disease: KLRG1 (P = 6 × 10(-7) [Asian cluster]) and SH2D2A (P = 2 × 10(-6) [all participants]). We observed striking differences between the associations in Europeans and Asians, with high heterogeneity especially in the MHC; representative single-nucleotide polymorphisms from established and suggestive regions had highly significant differences in the allele frequencies in the study populations. We showed that SSA/SSB autoantibody production and the labial salivary gland focus score criteria were associated with the first worldwide principal component, indicative of higher non-European ancestry (P = 4

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

    PubMed

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

    2013-04-09

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

  20. Captive Ancestry Upwardly Biases Estimates of Relative Reproductive Success.

    PubMed

    Willoughby, Janna R; Christie, Mark R

    2017-07-01

    Supplementation programs, which release captive-born individuals into the wild, are commonly used to demographically bolster declining populations. In order to evaluate the effectiveness of these programs, the reproductive success of captive-born individuals released into the wild is often compared to the reproductive success of wild-born individuals in the recipient population (relative reproductive success, RRS). However, if there are heritable reductions in fitness associated with captive breeding, gene flow from captive-born individuals into the wild population can reduce the fitness of the wild population. Here, we show that when captive ancestry in the wild population reduces mean population fitness, estimates of RRS are upwardly biased, meaning that the relative fitness of captive-born individuals is over-estimated. Furthermore, the magnitude of this bias increases with the length of time that a supplementation program has been releasing captive-born individuals. This phenomenon has long-term conservation impacts since management decisions regarding the design of a supplementation program and the number of individuals to release can be based, at least in part, on RRS estimates. Therefore, we urge caution in the interpretation of relative fitness measures when the captive ancestry of the wild population cannot be precisely measured. © The American Genetic Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Stroke genomics in people of African ancestry: charting new paths.

    PubMed

    Akinyemi, R O; Ovbiagele, B; Akpalu, A; Jenkins, C; Sagoe, K; Owolabi, L; Sarfo, F; Obiako, R; Gebreziabher, M; Melikam, E; Warth, S; Arulogun, O; Lackland, D; Ogunniyi, A; Tiwari, H; Kalaria, R N; Arnett, D; Owolabi, M O

    2015-01-01

    One in six people worldwide will experience a stroke in his/her lifetime. While people in Africa carry a disproportionately higher burden of poor stroke outcomes, compared to the rest of the world, the exact contribution of genomic factors to this disparity is unknown. Despite noteworthy research into stroke genomics, studies exploring the genetic contribution to stroke among populations of African ancestry in the United States are few. Furthermore, genomics data in populations living in Africa are lacking. The wide genomic variation of African populations offers a unique opportunity to identify genomic variants with causal relationships to stroke across different ethnic groups. The Stroke Investigative Research and Educational Network (SIREN), a component of the Human Health and Heredity in Africa (H3Africa) Consortium, aims to explore genomic and environmental risk factors for stroke in populations of African ancestry in West Africa and the United States. In this article, we review the literature on the genomics of stroke with particular emphasis on populations of African origin.

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

    PubMed Central

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

    2013-01-01

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

  3. Statistical evidence for common ancestry: Application to primates.

    PubMed

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

    2016-06-01

    Since Darwin, biologists have come to recognize that the theory of descent from common ancestry (CA) is very well supported by diverse lines of evidence. However, while the qualitative evidence is overwhelming, we also need formal methods for quantifying the evidential support for CA over the alternative hypothesis of separate ancestry (SA). In this article, we explore a diversity of statistical methods using data from the primates. We focus on two alternatives to CA, species SA (the separate origin of each named species) and family SA (the separate origin of each family). We implemented statist