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Sample records for african ancestry proportions

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

    PubMed

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

    2015-11-01

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

  2. 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

  3. 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.

  4. 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

  5. Charting the Ancestry of African Americans

    PubMed Central

    Salas, Antonio; Carracedo, Ángel; Richards, Martin; Macaulay, Vincent

    2005-01-01

    The Atlantic slave trade promoted by West European empires (15th–19th centuries) forcibly moved at least 11 million people from Africa, including about one-third from west-central Africa, to European and American destinations. The mitochondrial DNA (mtDNA) genome has retained an imprint of this process, but previous analyses lacked west-central African data. Here, we make use of an African database of 4,860 mtDNAs, which include 948 mtDNA sequences from west-central Africa and a further 154 from the southwest, and compare these for the first time with a publicly available database of 1,148 African Americans from the United States that contains 1,053 mtDNAs of sub-Saharan ancestry. We show that >55% of the U.S. lineages have a West African ancestry, with <41% coming from west-central or southwestern Africa. These results are remarkably similar to the most up-to-date analyses of the historical record. PMID:16175514

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  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. 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.

  18. Biogeographic Ancestry Is Associated with Higher Total Body Adiposity among African-American Females: The Boston Area Community Health Survey

    PubMed Central

    Goonesekera, Sunali D.; Fang, Shona C.; Piccolo, Rebecca S.; Florez, Jose C.; McKinlay, John B.

    2015-01-01

    Objectives The prevalence of obesity is disproportionately higher among African-Americans and Hispanics as compared to whites. We investigated the role of biogeographic ancestry (BGA) on adiposity and changes in adiposity in the Boston Area Community Health Survey. Methods We evaluated associations between BGA, assessed via Ancestry Informative Markers, and adiposity (body mass index (BMI), percent body fat (PBF), and waist-to-hip ratio (WHR)) and changes in adiposity over 7 years for BMI and WHR and 2.5 years for PBF, per 10% greater proportion of BGA using multivariable linear regression. We also examined effect-modification by demographic and socio-behavioral variables. Results We observed positive associations between West-African ancestry and cross-sectional BMI (percent difference=0.62%; 95% CI: 0.04%, 1.20%), and PBF (β=0.35; 95% CI: 0.11, 0.58). We also observed significant effect-modification of the association between West-African ancestry and BMI by gender (p-interaction: <0.002) with a substantially greater association in women. We observed no main associations between Native-American ancestry and adiposity but observed significant effect-modification of the association with BMI by diet (p-interaction: <0.003) with inverse associations among participants with higher Healthy Eating Scores. No associations were observed between BGA and changes in adiposity over time. Conclusion Findings support that West-African ancestry may contribute to high prevalence of total body adiposity among African-Americans, particularly African-American women. PMID:25875902

  19. Ancestry Informative Marker Sets for Determining Continental Origin and Admixture Proportions in Common Populations in America

    PubMed Central

    Kosoy, Roman; Nassir, Rami; Tian, Chao; White, Phoebe A; Butler, Lesley M.; Silva, Gabriel; Kittles, Rick; Alarcon-Riquelme, Marta E.; Gregersen, Peter K.; Belmont, John W.; De La Vega, Francisco M.; Seldin, Michael F.

    2011-01-01

    To provide a resource for assessing continental ancestry in a wide variety of genetic studies we identified, validated and characterized a set of 128 ancestry informative markers (AIMs). The markers were chosen for informativeness, genome-wide distribution, and genotype reproducibility on two platforms (TaqMan® assays and Illumina arrays). We analyzed genotyping data from 825 subjects with diverse ancestry, including European, East Asian, Amerindian, African, South Asian, Mexican, and Puerto Rican. A comprehensive set of 128 AIMs and subsets as small as 24 AIMs are shown to be useful tools for ascertaining the origin of subjects from particular continents, and to correct for population stratification in admixed population sample sets. Our findings provide general guidelines for the application of specific AIM subsets as a resource for wide application. We conclude that investigators can use TaqMan assays for the selected AIMs as a simple and cost efficient tool to control for differences in continental ancestry when conducting association studies in ethnically diverse populations. PMID:18683858

  20. Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America.

    PubMed

    Kosoy, Roman; Nassir, Rami; Tian, Chao; White, Phoebe A; Butler, Lesley M; Silva, Gabriel; Kittles, Rick; Alarcon-Riquelme, Marta E; Gregersen, Peter K; Belmont, John W; De La Vega, Francisco M; Seldin, Michael F

    2009-01-01

    To provide a resource for assessing continental ancestry in a wide variety of genetic studies, we identified, validated, and characterized a set of 128 ancestry informative markers (AIMs). The markers were chosen for informativeness, genome-wide distribution, and genotype reproducibility on two platforms (TaqMan assays and Illumina arrays). We analyzed genotyping data from 825 subjects with diverse ancestry, including European, East Asian, Amerindian, African, South Asian, Mexican, and Puerto Rican. A comprehensive set of 128 AIMs and subsets as small as 24 AIMs are shown to be useful tools for ascertaining the origin of subjects from particular continents, and to correct for population stratification in admixed population sample sets. Our findings provide general guidelines for the application of specific AIM subsets as a resource for wide application. We conclude that investigators can use TaqMan assays for the selected AIMs as a simple and cost efficient tool to control for differences in continental ancestry when conducting association studies in ethnically diverse populations.

  1. African Genetic Ancestry is Associated with Sleep Depth in Older African Americans

    PubMed Central

    Halder, Indrani; Matthews, Karen A.; Buysse, Daniel J.; Strollo, Patrick J.; Causer, Victoria; Reis, Steven E.; Hall, Martica H.

    2015-01-01

    Study Objectives: The mechanisms that underlie differences in sleep characteristics between European Americans (EA) and African Americans (AA) are not fully known. Although social and psychological processes that differ by race are possible mediators, the substantial heritability of sleep characteristics also suggests genetic underpinnings of race differences. We hypothesized that racial differences in sleep phenotypes would show an association with objectively measured individual genetic ancestry in AAs. Design: Cross sectional. Setting: Community-based study. Participants: Seventy AA adults (mean age 59.5 ± 6.7 y; 62% female) and 101 EAs (mean age 60.5 ± 7 y, 39% female). Measurements and Results: Multivariate tests were used to compare the Pittsburgh Sleep Quality Index (PSQI) and in-home polysomnographic measures of sleep duration, sleep efficiency, apnea-hypopnea index (AHI), and indices of sleep depth including percent visually scored slow wave sleep (SWS) and delta EEG power of EAs and AAs. Sleep duration, efficiency, and sleep depth differed significantly by race. Individual % African ancestry (%AF) was measured in AA subjects using a panel of 1698 ancestry informative genetic markers and ranged from 10% to 88% (mean 67%). Hierarchical linear regression showed that higher %AF was associated with lower percent SWS in AAs (β (standard error) = −4.6 (1.5); P = 0.002), and explained 11% of the variation in SWS after covariate adjustment. A similar association was observed for delta power. No association was observed for sleep duration and efficiency. Conclusion: African genetic ancestry is associated with indices of sleep depth in African Americans. Such an association suggests that part of the racial differences in slow-wave sleep may have genetic underpinnings. Citation: Halder I, Matthews KA, Buysse DJ, Strollo PJ, Causer V, Reis SE, Hall MH. African genetic ancestry is associated with sleep depth in older African Americans. SLEEP 2015;38(8):1185–1193

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

    PubMed Central

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

    2015-01-01

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

  3. Age at breast cancer diagnosis in populations of african and European ancestry.

    PubMed

    Kadhel, Philippe; Multigner, Luc

    2014-01-01

    Based on US national cancer registry data, age differences at breast cancer diagnosis have been reported between African-American women and European-American women. Such differences between populations of African and European ancestry have not been studied in other countries at a nationwide level. Here, we report and compare descriptive nationwide epidemiological indicators of invasive breast cancer for the populations of European ancestry living in the US and in mainland France and for women of African ancestry living in the US and in the French West Indies (Martinique and Guadeloupe). Based on the available data, we determined age frequency distributions, world age-standardized incidence, and the distribution of expected cases of breast cancer in a standard population of women by age. The age frequency distributions revealed that women of African ancestry were younger at diagnosis than women of European ancestry. By contrast, compared with the US regardless of ancestry and mainland France, the standardized incidences appeared lower, and the largest numbers of expected cases younger, in the French West Indies. The populations with African ancestry were not homogeneous in terms of epidemiologic indicators of age-related breast cancer. These descriptive findings suggest that populations of African ancestry cannot be considered uniform when determining whether it would be appropriate to decrease the age of entry into screening programs for breast cancer.

  4. 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.

  5. 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.

  6. 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

  7. Replication and fine mapping of asthma-associated loci in individuals of African ancestry.

    PubMed

    Kantor, David B; Palmer, Cameron D; Young, Taylor R; Meng, Yan; Gajdos, Zofia K; Lyon, Helen; Price, Alkes L; Pollack, Samuela; London, Stephanie J; Loehr, Laura R; Smith, Lewis J; Kumar, Rajesh; Jacobs, David R; Petrini, Marcy F; O'Connor, George T; White, Wendy B; Papanicolaou, George; Burkart, Kristin M; Heckbert, Susan R; Barr, R Graham; Hirschhorn, Joel N

    2013-09-01

    Asthma originates from genetic and environmental factors with about half the risk of disease attributable to heritable causes. Genome-wide association studies, mostly in populations of European ancestry, have identified numerous asthma-associated single nucleotide polymorphisms (SNPs). Studies in populations with diverse ancestries allow both for identification of robust associations that replicate across ethnic groups and for improved resolution of associated loci due to different patterns of linkage disequilibrium between ethnic groups. Here we report on an analysis of 745 African-American subjects with asthma and 3,238 African-American control subjects from the Candidate Gene Association Resource (CARe) Consortium, including analysis of SNPs imputed using 1,000 Genomes reference panels and adjustment for local ancestry. We show strong evidence that variation near RAD50/IL13, implicated in studies of European ancestry individuals, replicates in individuals largely of African ancestry. Fine mapping in African ancestry populations also refined the variants of interest for this association. We also provide strong or nominal evidence of replication at loci near ORMDL3/GSDMB, IL1RL1/IL18R1, and 10p14, all previously associated with asthma in European or Japanese populations, but not at the PYHIN1 locus previously reported in studies of African-American samples. These results improve the understanding of asthma genetics and further demonstrate the utility of genetic studies in populations other than those of largely European ancestry.

  8. 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. PMID:26395555

  9. 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.

  10. 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.

  11. Associations of adiponectin with individual European ancestry in African Americans: the Jackson Heart Study

    PubMed Central

    Bidulescu, Aurelian; Choudhry, Shweta; Musani, Solomon K.; Buxbaum, Sarah G.; Liu, Jiankang; Rotimi, Charles N.; Wilson, James G.; Taylor, Herman A.; Gibbons, Gary H.

    2014-01-01

    Background: Compared with European Americans, African Americans (AAs) exhibit lower levels of the cardio-metabolically protective adiponectin even after accounting for adiposity measures. Because few studies have examined in AA the association between adiponectin and genetic admixture, a dense panel of ancestry informative markers (AIMs) was used to estimate the individual proportions of European ancestry (PEA) for the AAs enrolled in a large community-based cohort, the Jackson Heart Study (JHS). We tested the hypothesis that plasma adiponectin and PEA are directly associated and assessed the interaction with a series of cardio-metabolic risk factors. Methods: Plasma specimens from 1439 JHS participants were analyzed by ELISA for adiponectin levels. Using pseudo-ancestral population genotype data from the HapMap Consortium, PEA was estimated with a panel of up to 1447 genome-wide preselected AIMs by a maximum likelihood approach. Interaction assessment, stepwise linear and cubic multivariable-adjusted regression models were used to analyze the cross-sectional association between adiponectin and PEA. Results: Among the study participants (62% women; mean age 48 ± 12 years), the median (interquartile range) of PEA was 15.8 (9.3)%. Body mass index (BMI) (p = 0.04) and insulin resistance (p = 0.0001) modified the association between adiponectin and PEA. Adiponectin was directly and linearly associated with PEA (β = 0.62 ± 0.28, p = 0.03) among non-obese (n = 673) and insulin sensitive participants (n = 1141; β = 0.74 ± 0.23, p = 0.001), but not among those obese or with insulin resistance. No threshold point effect was detected for non-obese participants. Conclusions: In a large AA population, the individual proportion of European ancestry was linearly and directly associated with plasma adiponectin among non-obese and non insulin-resistant participants, pointing to the interaction of genetic and metabolic factors influencing adiponectin levels. PMID:24575123

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

    PubMed

    Seedat, Yackoob K; Brewster, Lizzy M

    2014-02-01

    This article is a summary of the response of the four commonly used antihypertensive agents in African ancestry patients. They are thiazide like diuretics or indapamide, calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers, and β-adrenergic blockers (ARB). Response was superior in African ancestry patients on a thiazide like diuretic or indapamide and CCB, while the response to β-adrenergic blockers and ACEI are attenuated. Available data are very limited but self-defined ancestry seems to be the best predictor of individual responses to antihypertensive drugs. Knowledge of the factors like economic and social consideration affect the lower rate of detection, treatment and control of hypertension in the African ancestry population of the USA. For regions in which health care resources are particularly scarce, investment in population-based primary prevention strategies may yield the largest benefit. PMID:24215578

  13. 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.

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

    PubMed Central

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

    2015-01-01

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

  15. The genetic ancestry of African Americans, Latinos, and European Americans across the United States.

    PubMed

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

    2015-01-01

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

  16. The genetic ancestry of African Americans, Latinos, and European Americans across the United States.

    PubMed

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

    2015-01-01

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

  17. Extensive Copy Number Variations in Admixed Indian Population of African Ancestry: Potential Involvement in Adaptation

    PubMed Central

    Dash, Debasis; Mukerji, Mitali

    2014-01-01

    Admixture mapping has been enormously resourceful in identifying genetic variations linked to phenotypes, adaptation, and diseases. In this study through analysis of copy number variable regions (CNVRs), we report extensive restructuring in the genomes of the recently admixed African-Indian population (OG-W-IP) that inhabits a highly saline environment in Western India. The study included subjects from OG-W-IP (OG), five different Indian and three HapMap populations that were genotyped using Affymetrix version 6.0 arrays. Copy number variations (CNVs) detected using Birdsuite were used to define CNVRs. Population structure with respect to CNVRs was delineated using random forest approach. OG genomes have a surprising excess of CNVs in comparison to other studied populations. Individual ancestry proportions computed using STRUCTURE also reveals a unique genetic component in OGs. Population structure analysis with CNV genotypes indicates OG to be distant from both the African and Indian ancestral populations. Interestingly, it shows genetic proximity with respect to CNVs to only one Indian population IE-W-LP4, which also happens to reside in the same geographical region. We also observe a significant enrichment of molecular processes related to ion binding and receptor activity in genes encompassing OG-specific CNVRs. Our results suggest that retention of CNVRs from ancestral natives and de novo acquisition of CNVRs could accelerate the process of adaptation especially in an extreme environment. Additionally, this population would be enormously useful for dissecting genes and delineating the involvement of CNVs in salt adaptation. PMID:25398783

  18. 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

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

    PubMed

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

    2014-04-14

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

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

    PubMed

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

    2014-04-14

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

  1. Teaching through the Prism of Difference: A Dialogue among Four Bilingual, African-Ancestry Teachers.

    ERIC Educational Resources Information Center

    Casimir, Myriam; Mattox, Norman; Hays, John; Vasquez, Carla Llewelyn

    2000-01-01

    Four bilingual educators of African ancestry discuss issues that affect them as teachers and that affect their students as ethnolinguistic minorities. The paper discusses views of culture and language; teachers' identity construction; students' identity construction; and a twofold educational response to students' academic and social needs as…

  2. African genetic ancestry is associated with a protective effect on Dengue severity in colombian populations.

    PubMed

    Chacón-Duque, Juan Camilo; Adhikari, Kaustubh; Avendaño, Efren; Campo, Omer; Ramirez, Ruth; Rojas, Winston; Ruiz-Linares, Andrés; Restrepo, Berta Nelly; Bedoya, Gabriel

    2014-10-01

    The wide variation in severity displayed during Dengue Virus (DENV) infection may be influenced by host susceptibility. In several epidemiological approaches, differences in disease outcomes have been found between some ethnic groups, suggesting that human genetic background has an important role in disease severity. In the Caribbean, It has been reported that populations of African descent present considerable less frequency of severe forms compared with Mestizo and White self-reported groups. Admixed populations offer advantages for genetic epidemiology studies due to variation and distribution of alleles, such as those involved in disease susceptibility, as well to provide explanations of individual variability in clinical outcomes. The current study analysed three Colombian populations, which like most of Latin American populations, are made up of the product of complex admixture processes between European, Native American and African ancestors; having as a main goal to assess the effect of genetic ancestry, estimated with 30 Ancestry Informative Markers (AIMs), on DENV infection severity. We found that African ancestry has a protective effect against severe outcomes under several systems of clinical classification: Severe Dengue (OR: 0.963 for every 1% increase in African ancestry, 95% confidence interval (0.934-0.993), p-value: 0.016), Dengue Haemorrhagic Fever (OR: 0.969, 95% CI (0.947-0.991), p-value: 0.006), and occurrence of haemorrhages (OR: 0.971, 95% CI (0.952-0.989), p-value: 0.002). Conversely, decrease from 100% to 0% African ancestry significantly increases the chance of severe outcomes: OR is 44-fold for Severe Dengue, 24-fold for Dengue Haemorrhagic Fever, and 20-fold for occurrence of haemorrhages. Furthermore, several warning signs also showed statistically significant association given more evidences in specific stages of DENV infection. These results provide consistent evidence in order to infer statistical models providing a framework for

  3. Ancestry informative marker panels for African Americans based on subsets of commercially available SNP arrays.

    PubMed

    Tandon, Arti; Patterson, Nick; Reich, David

    2011-01-01

    Admixture mapping is a widely used method for localizing disease genes in African Americans. Most current methods for inferring ancestry at each locus in the genome use a few thousand single nucleotide polymorphisms (SNPs) that are very different in frequency between West Africans and European Americans, and that are required to not be in linkage disequilibrium in the ancestral populations. Modern SNP arrays provide data on hundreds of thousands of SNPs per sample, and to use these to infer ancestry, using many of the standard methods, it is necessary to choose subsets of the SNPs for analysis. Here we present panels of about 4,300 ancestry informative markers (AIMs) that are subsets respectively of SNPs on the Illumina 1 M, Illumina 650, Illumina 610, Affymetrix 6.0 and Affymetrix 5.0 arrays. To validate the usefulness of these panels, we applied them to samples that are different from the ones used to select the SNPs. The panels provide about 80% of the maximum information about African or European ancestry, even with up to 10% missing data.

  4. 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

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

    PubMed Central

    Chen, Fang; Chen, Gary K.; Stram, Daniel O.; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Palmer, Julie R.; Hu, Jennifer J.; Rebbeck, Tim R.; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue A.; Press, Michael F.; Ruiz-Narvaez, Edward A.; Deming, Sandra L.; Rodriguez-Gil, Jorge L.; DeMichele, Angela; Chanock, Stephen J.; Blot, William; Signorello, Lisa; Cai, Qiuyin; Li, Guoliang; Long, Jirong; Huo, Dezheng; Zheng, Yonglan; Cox, Nancy J.; Olopade, Olufunmilayo I.; Ogundiran, Temidayo O.; Adebamowo, Clement; Nathanson, Katherine L.; Domchek, Susan M.; Simon, Michael S.; Hennis, Anselm; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina; Ambs, Stefan; Hutter, Carolyn M.; Young, Alicia; Kooperberg, Charles; Peters, Ulrike; Rhie, Suhn K.; Wan, Peggy; Sheng, Xin; Pooler, Loreall C.; Van Den Berg, David J.; Le Marchand, Loic; Kolonel, Laurence N.; Henderson, Brian E.; Haiman, Christopher A.

    2013-01-01

    Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of > 1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p < 0.05) in stage 2, which reached statistical significance levels of 10−6 and 10−5 in the stage 1 and 2 combined analysis (rs4322600 at chromosome 14q31: OR = 1.18, p = 4.3×10−6; rs10510333 at chromosome 3p26: OR = 1.15, p = 1.5×10−5). These suggestive risk loci have not been identified in previous GWAS in other populations and will need to be examined in additional samples. Identification of novel risk variants for breast cancer in women of African ancestry will demand testing of a substantially larger set of markers from stage 1 in a larger replication sample. PMID:22923054

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

    PubMed

    Chen, Fang; Chen, Gary K; Stram, Daniel O; Millikan, Robert C; Ambrosone, Christine B; John, Esther M; Bernstein, Leslie; Zheng, Wei; Palmer, Julie R; Hu, Jennifer J; Rebbeck, Tim R; Ziegler, Regina G; Nyante, Sarah; Bandera, Elisa V; Ingles, Sue A; Press, Michael F; Ruiz-Narvaez, Edward A; Deming, Sandra L; Rodriguez-Gil, Jorge L; Demichele, Angela; Chanock, Stephen J; Blot, William; Signorello, Lisa; Cai, Qiuyin; Li, Guoliang; Long, Jirong; Huo, Dezheng; Zheng, Yonglan; Cox, Nancy J; Olopade, Olufunmilayo I; Ogundiran, Temidayo O; Adebamowo, Clement; Nathanson, Katherine L; Domchek, Susan M; Simon, Michael S; Hennis, Anselm; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M Cristina; Ambs, Stefan; Hutter, Carolyn M; Young, Alicia; Kooperberg, Charles; Peters, Ulrike; Rhie, Suhn K; Wan, Peggy; Sheng, Xin; Pooler, Loreall C; Van Den Berg, David J; Le Marchand, Loic; Kolonel, Laurence N; Henderson, Brian E; Haiman, Christopher A

    2013-01-01

    Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of >1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p < 0.05) in stage 2, which reached statistical significance levels of 10(-6) and 10(-5) in the stage 1 and 2 combined analysis (rs4322600 at chromosome 14q31: OR = 1.18, p = 4.3 × 10(-6); rs10510333 at chromosome 3p26: OR = 1.15, p = 1.5 × 10(-5)). These suggestive risk loci have not been identified in previous GWAS in other populations and will need to be examined in additional samples. Identification of novel risk variants for breast cancer in women of African ancestry will demand testing of a substantially larger set of markers from stage 1 in a larger replication sample.

  7. An African ancestry-specific allele of CTLA4 confers protection against rheumatoid arthritis in African Americans.

    PubMed

    Kelley, James M; Hughes, Laura B; Faggard, Jeffrey D; Danila, Maria I; Crawford, Monica H; Edberg, Yuanqing; Padilla, Miguel A; Tiwari, Hemant K; Westfall, Andrew O; Alarcón, Graciela S; Conn, Doyt L; Jonas, Beth L; Callahan, Leigh F; Smith, Edwin A; Brasington, Richard D; Allison, David B; Kimberly, Robert P; Moreland, Larry W; Edberg, Jeffrey C; Bridges, S Louis

    2009-03-01

    Cytotoxic T-lymphocyte associated protein 4 (CTLA4) is a negative regulator of T-cell proliferation. Polymorphisms in CTLA4 have been inconsistently associated with susceptibility to rheumatoid arthritis (RA) in populations of European ancestry but have not been examined in African Americans. The prevalence of RA in most populations of European and Asian ancestry is approximately 1.0%; RA is purportedly less common in black Africans, with little known about its prevalence in African Americans. We sought to determine if CTLA4 polymorphisms are associated with RA in African Americans. We performed a 2-stage analysis of 12 haplotype tagging single nucleotide polymorphisms (SNPs) across CTLA4 in a total of 505 African American RA patients and 712 African American controls using Illumina and TaqMan platforms. The minor allele (G) of the rs231778 SNP was 0.054 in RA patients, compared to 0.209 in controls (4.462 x 10(-26), Fisher's exact). The presence of the G allele was associated with a substantially reduced odds ratio (OR) of having RA (AG+GG genotypes vs. AA genotype, OR 0.19, 95% CI: 0.13-0.26, p = 2.4 x 10(-28), Fisher's exact), suggesting a protective effect. This SNP is polymorphic in the African population (minor allele frequency [MAF] 0.09 in the Yoruba population), but is very rare in other groups (MAF = 0.002 in 530 Caucasians genotyped for this study). Markers associated with RA in populations of European ancestry (rs3087243 [+60C/T] and rs231775 [+49A/G]) were not replicated in African Americans. We found no confounding of association for rs231778 after stratifying for the HLA-DRB1 shared epitope, presence of anti-cyclic citrullinated peptide antibody, or degree of admixture from the European population. An African ancestry-specific genetic variant of CTLA4 appears to be associated with protection from RA in African Americans. This finding may explain, in part, the relatively low prevalence of RA in black African populations.

  8. Socioeconomic Position, But Not African Genomic Ancestry, Is Associated With Blood Pressure in the Bambui-Epigen (Brazil) Cohort Study of Aging.

    PubMed

    Lima-Costa, M Fernanda; Mambrini, Juliana Vaz de Mello; Leite, Maria Lea Corrêa; Peixoto, Sérgio Viana; Firmo, Josélia Oliveira Araújo; Loyola Filho, Antônio Ignácio de; Gouveia, Mateus H; Leal, Thiago P; Pereira, Alexandre Costa; Macinko, James; Tarazona-Santos, Eduardo

    2016-02-01

    The study objective is to examine the role of African genome origin on baseline and 11-year blood pressure trajectories in community-based ethnoracially admixed older adults in Brazil. Data come from 1272 participants (aged ≥60 years) of the Bambui cohort study of aging during 11 years of follow-up. Outcome measures were systolic blood pressure, diastolic blood pressure, and hypertension control. Potential confounding variables were demographic characteristics, socioeconomic position (schooling and household income), and health indicators (smoking, sedentary lifestyle, high-density lipoprotein cholesterol, waist circumference, diabetes mellitus, and cardiovascular diseases), including antihypertensive drug use. We used 370 539 single-nucleotide polymorphisms to estimate each individual's African, European, and Native American trihybrid ancestry proportions. Median African, European, and Native American ancestry were 9.6%, 84.0%, and 5.3%, respectively. Among those with African ancestry, 59.4% came from East and 40.6% from West Africa. Baseline systolic and diastolic blood pressure, controlled hypertension, and their respective trajectories, were not significantly (P>0.05) associated with level (in quintiles) of African genomic ancestry. Similar results were found for West and East African subcontinental origins. Lower schooling level (<4 years versus higher) showed a significant and positive association with systolic blood pressure (Adjusted β=2.92; 95% confidence interval, 0.85-4.99). Lower monthly household income per capita (

  9. 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.

  10. Importance of mitochondrial haplotypes and maternal lineage in sprint performance among individuals of West African ancestry.

    PubMed

    Deason, M; Scott, R; Irwin, L; Macaulay, V; Fuku, N; Tanaka, M; Irving, R; Charlton, V; Morrison, E; Austin, K; Pitsiladis, Y P

    2012-04-01

    Mitochondrial DNA (mtDNA) is inherited solely along the matriline, giving insight into both ancestry and prehistory. Individuals of sub-Saharan ancestry are overrepresented in sprint athletics, suggesting a genetic advantage. The purpose of this study was to compare the mtDNA haplogroup data of elite groups of Jamaican and African-American sprinters against respective controls to assess any differences in maternal lineage. The first hypervariable region of mtDNA was haplogrouped in elite Jamaican athletes (N=107) and Jamaican controls (N=293), and elite African-American athletes (N=119) and African-American controls (N=1148). Exact tests of total population differentiation were performed on total haplogroup frequencies. The frequency of non-sub-Saharan haplogroups in Jamaican athletes and Jamaican controls was similar (1.87% and 1.71%, respectively) and lower than that of African-American athletes and African-American controls (21.01% and 8.19%, respectively). There was no significant difference in total haplogroup frequencies between Jamaican athletes and Jamaican controls (P=0.551 ± 0.005); however, there was a highly significant difference between African-American athletes and African-American controls (P<0.001). The finding of statistically similar mtDNA haplogroup distributions in Jamaican athletes and Jamaican controls suggests that elite Jamaican sprinters are derived from the same source population and there is neither population stratification nor isolation for sprint performance. The significant difference between African-American sprinters and African-American controls suggests that the maternal admixture may play a role in sprint performance.

  11. 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

  12. 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

  13. 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.

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

    PubMed Central

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

    2016-01-01

    Background Large genome-wide association (GWA) studies of European ancestry individuals have identified multiple genetic variants influencing iron status. Studies on the generalizability of these associations to African ancestry populations have been limited. These studies are important given interethnic differences in iron status and the disproportionate burden of iron deficiency among African ancestry populations. Methods We tested the associations of 20 previously identified iron status-associated single nucleotide polymorphisms (SNPs) in 628 Kenyans, 609 Tanzanians, 608 South Africans and 228 African Americans. In each study, we examined the associations present between 20 SNPs with ferritin and haemoglobin, adjusting for age, sex and CRP levels. Results In the meta analysis including all 4 African ancestry cohorts, we replicated previously reported associations with lowered haemoglobin concentrations for rs2413450 (β = -0.19, P = 0.02) and rs4820268 (β = -0.16, P = 0.04) in TMPRSS6. An association with increased ferritin concentrations was also confirmed for rs1867504 in TF (β = 1.04, P = <0.0001) in the meta analysis including the African cohorts only. Conclusions In all meta analyses, we only replicated 4 of the 20 single nucleotide polymorphisms reported to be associated with iron status in large GWA studies of European ancestry individuals. While there is now evidence for the associations of a number of genetic variants with iron status in both European and African ancestry populations, the considerable lack of concordance highlights the importance of continued ancestry-specific studies to elucidate the genetic underpinnings of iron status in ethnically diverse populations. PMID:27332551

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

    PubMed Central

    Huo, Dezheng

    2013-01-01

    Numerous single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified by genome-wide association studies (GWAS). However, these SNPs were primarily discovered and validated in women of European and Asian ancestry. Because linkage disequilibrium is ancestry-dependent and heterogeneous among racial/ethnic populations, we evaluated common genetic variants at 22 GWAS-identified breast cancer susceptibility loci in a pooled sample of 1502 breast cancer cases and 1378 controls of African ancestry. None of the 22 GWAS index SNPs could be validated, challenging the direct generalizability of breast cancer risk variants identified in Caucasians or Asians to other populations. Novel breast cancer risk variants for women of African ancestry were identified in regions including 5p12 (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.11–1.76; P = 0.004), 5q11.2 (OR = 1.22, 95% CI = 1.09–1.36; P = 0.00053) and 10p15.1 (OR = 1.22, 95% CI = 1.08–1.38; P = 0.0015). We also found positive association signals in three regions (6q25.1, 10q26.13 and 16q12.1–q12.2) previously confirmed by fine mapping in women of African ancestry. In addition, polygenic model indicated that eight best markers in this study, compared with 22 GWAS-identified SNPs, could better predict breast cancer risk in women of African ancestry (per-allele OR = 1.21, 95% CI = 1.16–1.27; P = 9.7 × 10–16). Our results demonstrate that fine mapping is a powerful approach to better characterize the breast cancer risk alleles in diverse populations. Future studies and new GWAS in women of African ancestry hold promise to discover additional variants for breast cancer susceptibility with clinical implications throughout the African diaspora. PMID:23475944

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

    PubMed

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

    2013-07-01

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

  17. The Genetic Contribution of West-African Ancestry to Protection against Central Obesity in African-American Men but Not Women: Results from the ARIC and MESA Studies

    PubMed Central

    Klimentidis, Yann C.; Arora, Amit; Zhou, Jin; Kittles, Rick; Allison, David B.

    2016-01-01

    Over 80% of African-American (AA) women are overweight or obese. A large racial disparity between AA and European-Americans (EA) in obesity rates exists among women, but curiously not among men. Although socio-economic and/or cultural factors may partly account for this race-by-sex interaction, the potential involvement of genetic factors has not yet been investigated. Among 2814 self-identified AA in the Atherosclerosis Risk in Communities study, we estimated each individual's degree of West-African genetic ancestry using 3437 ancestry informative markers. We then tested whether sex modifies the association between West-African genetic ancestry and body mass index (BMI), waist-circumference (WC), and waist-to-hip ratio (WHR), adjusting for income and education levels, and examined associations of ancestry with the phenotypes separately in males and females. We replicated our findings in the Multi-Ethnic Study of Atherosclerosis (n = 1611 AA). In both studies, we find that West-African ancestry is negatively associated with obesity, especially central obesity, among AA men, but not among AA women (pinteraction = 4.14 × 10−5 in pooled analysis of WHR). In conclusion, our results suggest that the combination of male gender and West-African genetic ancestry is associated with protection against central adiposity, and suggest that the large racial disparity that exists among women, but not men, may be at least partly attributed to genetic factors. PMID:27313598

  18. 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 (h2 ∼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

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

    PubMed

    N'Diaye, Amidou; Chen, Gary K; Palmer, Cameron D; 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

    2011-10-01

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

  20. Prostate Cancer Susceptibility in Men of African Ancestry at 8q24.

    PubMed

    Han, Ying; Rand, Kristin A; Hazelett, Dennis J; Ingles, Sue A; Kittles, Rick A; Strom, Sara S; Rybicki, Benjamin A; Nemesure, Barbara; Isaacs, William B; Stanford, Janet L; Zheng, Wei; Schumacher, Fredrick R; Berndt, Sonja I; Wang, Zhaoming; Xu, Jianfeng; Rohland, Nadin; Reich, David; Tandon, Arti; Pasaniuc, Bogdan; Allen, Alex; Quinque, Dominique; Mallick, Swapan; Notani, Dimple; Rosenfeld, Michael G; Jayani, Ranveer Singh; Kolb, Suzanne; Gapstur, Susan M; Stevens, Victoria L; Pettaway, Curtis A; Yeboah, Edward D; Tettey, Yao; Biritwum, Richard B; Adjei, Andrew A; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Chokkalingam, Anand P; John, Esther M; Murphy, Adam B; Signorello, Lisa B; Carpten, John; Leske, M Cristina; Wu, Suh-Yuh; Hennis, Anslem J M; Neslund-Dudas, Christine; Hsing, Ann W; Chu, Lisa; Goodman, Phyllis J; Klein, Eric A; Zheng, S Lilly; Witte, John S; Casey, Graham; Lubwama, Alex; Pooler, Loreall C; Sheng, Xin; Coetzee, Gerhard A; Cook, Michael B; Chanock, Stephen J; Stram, Daniel O; Watya, Stephen; Blot, William J; Conti, David V; Henderson, Brian E; Haiman, Christopher A

    2016-07-01

    The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.

  1. 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.

  2. Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk.

    PubMed

    Rand, Kristin A; Rohland, Nadin; Tandon, Arti; Stram, Alex; Sheng, Xin; Do, Ron; Pasaniuc, Bogdan; Allen, Alex; Quinque, Dominique; Mallick, Swapan; Le Marchand, Loic; Kaggwa, Sam; Lubwama, Alex; Stram, Daniel O; Watya, Stephen; Henderson, Brian E; Conti, David V; Reich, David; Haiman, Christopher A

    2016-01-15

    Prostate cancer is the most common non-skin cancer in males, with a ∼1.5-2-fold higher incidence in African American men when compared with whites. Epidemiologic evidence supports a large heritable contribution to prostate cancer, with over 100 susceptibility loci identified to date that can explain ∼33% of the familial risk. To explore the contribution of both rare and common variation in coding regions to prostate cancer risk, we sequenced the exomes of 2165 prostate cancer cases and 2034 controls of African ancestry at a mean coverage of 10.1×. We identified 395 220 coding variants down to 0.05% frequency [57% non-synonymous (NS), 42% synonymous and 1% gain or loss of stop codon or splice site variant] in 16 751 genes with the strongest associations observed in SPARCL1 on 4q22.1 (rs13051, Ala49Asp, OR = 0.78, P = 1.8 × 10(-6)) and PTPRR on 12q15 (rs73341069, Val239Ile, OR = 1.62, P = 2.5 × 10(-5)). In gene-level testing, the two most significant genes were C1orf100 (P = 2.2 × 10(-4)) and GORAB (P = 2.3 × 10(-4)). We did not observe exome-wide significant associations (after correcting for multiple hypothesis testing) in single variant or gene-level testing in the overall case-control or case-case analyses of disease aggressiveness. In this first whole-exome sequencing study of prostate cancer, our findings do not provide strong support for the hypothesis that NS coding variants down to 0.5-1.0% frequency have large effects on prostate cancer risk in men of African ancestry. Higher-coverage sequencing efforts in larger samples will be needed to study rarer variants with smaller effect sizes associated with prostate cancer risk.

  3. Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk.

    PubMed

    Rand, Kristin A; Rohland, Nadin; Tandon, Arti; Stram, Alex; Sheng, Xin; Do, Ron; Pasaniuc, Bogdan; Allen, Alex; Quinque, Dominique; Mallick, Swapan; Le Marchand, Loic; Kaggwa, Sam; Lubwama, Alex; Stram, Daniel O; Watya, Stephen; Henderson, Brian E; Conti, David V; Reich, David; Haiman, Christopher A

    2016-01-15

    Prostate cancer is the most common non-skin cancer in males, with a ∼1.5-2-fold higher incidence in African American men when compared with whites. Epidemiologic evidence supports a large heritable contribution to prostate cancer, with over 100 susceptibility loci identified to date that can explain ∼33% of the familial risk. To explore the contribution of both rare and common variation in coding regions to prostate cancer risk, we sequenced the exomes of 2165 prostate cancer cases and 2034 controls of African ancestry at a mean coverage of 10.1×. We identified 395 220 coding variants down to 0.05% frequency [57% non-synonymous (NS), 42% synonymous and 1% gain or loss of stop codon or splice site variant] in 16 751 genes with the strongest associations observed in SPARCL1 on 4q22.1 (rs13051, Ala49Asp, OR = 0.78, P = 1.8 × 10(-6)) and PTPRR on 12q15 (rs73341069, Val239Ile, OR = 1.62, P = 2.5 × 10(-5)). In gene-level testing, the two most significant genes were C1orf100 (P = 2.2 × 10(-4)) and GORAB (P = 2.3 × 10(-4)). We did not observe exome-wide significant associations (after correcting for multiple hypothesis testing) in single variant or gene-level testing in the overall case-control or case-case analyses of disease aggressiveness. In this first whole-exome sequencing study of prostate cancer, our findings do not provide strong support for the hypothesis that NS coding variants down to 0.5-1.0% frequency have large effects on prostate cancer risk in men of African ancestry. Higher-coverage sequencing efforts in larger samples will be needed to study rarer variants with smaller effect sizes associated with prostate cancer risk. PMID:26604137

  4. African Ancestry, Social Factors, and Hypertension Among Non-Hispanic Blacks in the Health and Retirement Study.

    PubMed

    Marden, Jessica R; Walter, Stefan; Kaufman, Jay S; Glymour, M Maria

    2016-01-01

    The biomedical literature contains much speculation about possible genetic explanations for the large and persistent black-white disparities in hypertension, but profound social inequalities are also hypothesized to contribute to this outcome. Our goal is to evaluate whether socioeconomic status (SES) differences provide a plausible mechanism for associations between African ancestry and hypertension in a U.S. cohort of older non-Hispanic blacks. We included only non-Hispanic black participants (N = 998) from the Health and Retirement Study who provided genetic data. We estimated percent African ancestry based on 84,075 independent single nucleotide polymorphisms using ADMIXTURE V1.23, imposing K = 4 ancestral populations, and categorized into quartiles. Hypertension status was self-reported in the year 2000. We used linear probability models (adjusted for age, sex, and southern birth) to predict prevalent hypertension with African ancestry quartile, before and after accounting for a small set of SES measures. Respondents with the highest quartile of African ancestry had 8 percentage points' (RD = 0.081; 95% CI: -0.001, 0.164) higher prevalence of hypertension compared to the lowest quartile. Adjustment for childhood disadvantage, education, income, and wealth explained over one-third (RD = 0.050; 95% CI: -0.034, 0.135) of the disparity. Explanations for the residual disparity remain unspecified and may include other indicators of SES or diet, lifestyle, and psychosocial mechanisms. PMID:27050031

  5. Single-nucleotide polymorphisms in LPA explain most of the ancestry-specific variation in Lp(a) levels in African Americans.

    PubMed

    Deo, Rahul C; Wilson, James G; Xing, Chao; Lawson, Kim; Kao, W H Linda; Reich, David; Tandon, Arti; Akylbekova, Ermeg; Patterson, Nick; Mosley, Thomas H; Boerwinkle, Eric; Taylor, Herman A

    2011-01-24

    Lipoprotein(a) (Lp(a)) is an important causal cardiovascular risk factor, with serum Lp(a) levels predicting atherosclerotic heart disease and genetic determinants of Lp(a) levels showing association with myocardial infarction. Lp(a) levels vary widely between populations, with African-derived populations having nearly 2-fold higher Lp(a) levels than European Americans. We investigated the genetic basis of this difference in 4464 African Americans from the Jackson Heart Study (JHS) using a panel of up to 1447 ancestry informative markers, allowing us to accurately estimate the African ancestry proportion of each individual at each position in the genome. In an unbiased genome-wide admixture scan for frequency-differentiated genetic determinants of Lp(a) level, we found a convincing peak (LOD = 13.6) at 6q25.3, which spans the LPA locus. Dense fine-mapping of the LPA locus identified a number of strongly associated, common biallelic SNPs, a subset of which can account for up to 7% of the variation in Lp(a) level, as well as >70% of the African-European population differences in Lp(a) level. We replicated the association of the most strongly associated SNP, rs9457951 (p = 6 × 10(-22), 27% change in Lp(a) per allele, ∼5% of Lp(a) variance explained in JHS), in 1,726 African Americans from the Dallas Heart Study and found an even stronger association after adjustment for the kringle(IV) repeat copy number. Despite the strong association with Lp(a) levels, we find no association of any LPA SNP with incident coronary heart disease in 3,225 African Americans from the Atherosclerosis Risk in Communities Study.

  6. Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.

    PubMed

    Franceschini, Nora; Fox, Ervin; Zhang, Zhaogong; Edwards, Todd L; Nalls, Michael A; Sung, Yun Ju; Tayo, Bamidele O; Sun, Yan V; Gottesman, Omri; Adeyemo, Adebawole; Johnson, Andrew D; Young, J Hunter; Rice, Ken; Duan, Qing; Chen, Fang; Li, Yun; Tang, Hua; Fornage, Myriam; Keene, Keith L; Andrews, Jeanette S; Smith, Jennifer A; Faul, Jessica D; Guangfa, Zhang; Guo, Wei; Liu, Yu; Murray, Sarah S; Musani, Solomon K; Srinivasan, Sathanur; Velez Edwards, Digna R; Wang, Heming; Becker, Lewis C; Bovet, Pascal; Bochud, Murielle; Broeckel, Ulrich; Burnier, Michel; Carty, Cara; Chasman, Daniel I; Ehret, Georg; Chen, Wei-Min; Chen, Guanjie; Chen, Wei; Ding, Jingzhong; Dreisbach, Albert W; Evans, Michele K; Guo, Xiuqing; Garcia, Melissa E; Jensen, Rich; Keller, Margaux F; Lettre, Guillaume; Lotay, Vaneet; Martin, Lisa W; Moore, Jason H; Morrison, Alanna C; Mosley, Thomas H; Ogunniyi, Adesola; Palmas, Walter; Papanicolaou, George; Penman, Alan; Polak, Joseph F; Ridker, Paul M; Salako, Babatunde; Singleton, Andrew B; Shriner, Daniel; Taylor, Kent D; Vasan, Ramachandran; Wiggins, Kerri; Williams, Scott M; Yanek, Lisa R; Zhao, Wei; Zonderman, Alan B; Becker, Diane M; Berenson, Gerald; Boerwinkle, Eric; Bottinger, Erwin; Cushman, Mary; Eaton, Charles; Nyberg, Fredrik; Heiss, Gerardo; Hirschhron, Joel N; Howard, Virginia J; Karczewsk, Konrad J; Lanktree, Matthew B; Liu, Kiang; Liu, Yongmei; Loos, Ruth; Margolis, Karen; Snyder, Michael; Psaty, Bruce M; Schork, Nicholas J; Weir, David R; Rotimi, Charles N; Sale, Michele M; Harris, Tamara; Kardia, Sharon L R; Hunt, Steven C; Arnett, Donna; Redline, Susan; Cooper, Richard S; Risch, Neil J; Rao, D C; Rotter, Jerome I; Chakravarti, Aravinda; Reiner, Alex P; Levy, Daniel; Keating, Brendan J; Zhu, Xiaofeng

    2013-09-01

    High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.

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

    PubMed Central

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

    2013-01-01

    Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry, and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one novel locus at 5q33 (GALNT10, rs7708584, p=3.4×10−11) and another at 7p15 when combined with data from the Giant consortium (MIR148A/NFE2L3, rs10261878, p=1.2×10−10). We also found suggestive evidence of an association at a third locus at 6q16 in the African ancestry sample (KLHL32, rs974417, p=6.9×10−8). Thirty-two of the 36 previously established BMI variants displayed directionally consistent effect estimates in our GWAS (binomial p=9.7×10−7), of which five reached genome-wide significance. These findings provide strong support for shared BMI loci across populations as well as for the utility of studying ancestrally diverse populations. PMID:23583978

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

    PubMed

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

    2013-06-01

    Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.

  9. Genome-wide association study identifies African-ancestry specific variants for metabolic syndrome.

    PubMed

    Tekola-Ayele, Fasil; Doumatey, Ayo P; Shriner, Daniel; Bentley, Amy R; Chen, Guanjie; Zhou, Jie; Fasanmade, Olufemi; Johnson, Thomas; Oli, Johnnie; Okafor, Godfrey; Eghan, Benjami A; Agyenim-Boateng, Kofi; Adebamowo, Clement; Amoah, Albert; Acheampong, Joseph; Adeyemo, Adebowale; Rotimi, Charles N

    2015-12-01

    The metabolic syndrome (MetS) is a constellation of metabolic disorders that increase the risk of developing several diseases including type 2 diabetes and cardiovascular diseases. Although genome-wide association studies (GWAS) have successfully identified variants associated with individual traits comprising MetS, the genetic basis and pathophysiological mechanisms underlying the clustering of these traits remain unclear. We conducted GWAS of MetS in 1427 Africans from Ghana and Nigeria followed by replication testing and meta-analysis in another continental African sample from Kenya. Further replication testing was performed in an African American sample from the Atherosclerosis Risk in Communities (ARIC) study. We found two African-ancestry specific variants that were significantly associated with MetS: SNP rs73989312[A] near CA10 that conferred increased risk (P=3.86 × 10(-8), OR=6.80) and SNP rs77244975[C] in CTNNA3 that conferred protection against MetS (P=1.63 × 10(-8), OR=0.15). Given the exclusive expression of CA10 in the brain, our CA10 finding strengthens previously reported link between brain function and MetS. We also identified two variants that are not African specific: rs76822696[A] near RALYL associated with increased MetS risk (P=7.37 × 10(-9), OR=1.59) and rs7964157[T] near KSR2 associated with reduced MetS risk (P=4.52 × 10(-8), Pmeta=7.82 × 10(-9), OR=0.53). The KSR2 locus displayed pleiotropic associations with triglyceride and measures of blood pressure. Rare KSR2 mutations have been reported to be associated with early onset obesity and insulin resistance. Finally, we replicated the LPL and CETP loci previously found to be associated with MetS in Europeans. These findings provide novel insights into the genetics of MetS in Africans and demonstrate the utility of conducting trans-ethnic disease gene mapping studies for testing the cosmopolitan significance of GWAS signals of cardio-metabolic traits.

  10. 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

  11. The birth prevalence of PKU in populations of European, South Asian and sub-Saharan African ancestry living in South East England.

    PubMed

    Hardelid, P; Cortina-Borja, M; Munro, A; Jones, H; Cleary, M; Champion, M P; Foo, Y; Scriver, C R; Dezateux, C

    2008-01-01

    Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism (OMIM 261600). Treatment with a low-phenylalanine diet following early ascertainment by newborn screening prevents impaired cognitive development, the major disease phenotype in PKU. The overall birth prevalence of PKU in European, Chinese and Korean populations is approximately 1/10,000. Since the human PAH locus contains PKU-causing alleles and polymorphic core haplotypes that describe and corroborate an out-of-Africa range expansion in modern human populations, it is of interest to know the prevalence of PKU in different ethnic groups with diverse geographical origin. We estimated PKU prevalence in South East England, where a sizeable proportion of the population are of Sub-Saharan African or South Asian ancestry. Over the period 1994 to 2004 167 children were diagnosed with PKU. Using birth registration and census data to derive denominators, PKU birth prevalence per 10,000 live births (95% Bayesian credible intervals) was estimated to be 1.14 (0.96-1.33) among white, 0.11 (0.02-0.37) among black, and 0.29 (0.10-0.63) among Asian ethnic groups. This suggests that PKU is up to an order of magnitude less prevalent in populations with Sub-Saharan African and South Asian ancestry that have migrated to the UK.

  12. Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype.

    PubMed

    Krause, Amanda; Mitchell, Claire; Essop, Fahmida; Tager, Susan; Temlett, James; Stevanin, Giovanni; Ross, Christopher; Rudnicki, Dobrila; Margolis, Russell

    2015-10-01

    Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations.

  13. East African pigs have a complex Indian, Far Eastern and Western ancestry.

    PubMed

    Noce, A; Amills, M; Manunza, A; Muwanika, V; Muhangi, D; Aliro, T; Mayega, J; Ademun, R; Sànchez, A; Egbhalsaied, S; Mercadé, A; Masembe, C

    2015-08-01

    In this study, we have characterized the mitochondrial diversity of 81 swine from Uganda. Median-joining network analysis of D-loop sequences from these individuals and others characterized in previous studies allowed us to determine that Ugandan pigs cluster with populations from the West (Europe/North Africa), Far East and India. In addition, partial sequencing of the Y-chromosome UTY locus in 18 Ugandan domestic pigs revealed the segregation of a single HY1 lineage that has a cosmopolitan distribution. A Western and Far Eastern ancestry for East African pigs had been already reported, but this is the first study demonstrating an additional contribution from the Indian porcine gene pool. This result is consistent with the high frequency of zebuine alleles in cattle from East Africa. The geographic coordinates of East Africa, at the crossroads of many trading routes that, through the ages, linked Europe, Africa and Asia, might explain the rich and complex genetic heritage of livestock native to this area. PMID:26011180

  14. Archaic African and Asian lineages in the genetic ancestry of modern humans.

    PubMed Central

    Harding, R M; Fullerton, S M; Griffiths, R C; Bond, J; Cox, M J; Schneider, J A; Moulin, D S; Clegg, J B

    1997-01-01

    A 3-kb region encompassing the beta-globin gene has been analyzed for allelic sequence polymorphism in nine populations from Africa, Asia, and Europe. A unique gene tree was constructed from 326 sequences of 349 in the total sample. New maximum-likelihood methods for analyzing gene trees on the basis of coalescence theory have been used. The most recent common ancestor of the beta-globin gene tree is a sequence found only in Africa and estimated to have arisen approximately 800,000 years ago. There is no evidence for an exponential expansion out of a bottlenecked founding population, and an effective population size of approximately 10,000 has been maintained. Modest differences in levels of beta-globin diversity between Africa and Asia are better explained by greater African effective population size than by greater time depth. There may have been a reduction of Asian effective population size in recent evolutionary history. Characteristically Asian ancestry is estimated to be older than 200,000 years, suggesting that the ancestral hominid population at this time was widely dispersed across Africa and Asia. Patterns of beta-globin diversity suggest extensive worldwide late Pleistocene gene flow and are not easily reconciled with a unidirectional migration out of Africa 100,000 years ago and total replacement of archaic populations in Asia. PMID:9106523

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

    PubMed Central

    Lange, Leslie; Demerath, Ellen W.; Palmas, Walter; Wojczynski, Mary K.; Ellis, Jaclyn C.; Vitolins, Mara Z.; Liu, Simin; Papanicolaou, George J.; Irvin, Marguerite R.; Xue, Luting; Griffin, Paula J.; Nalls, Michael A.; Adeyemo, Adebowale; Liu, Jiankang; Li, Guo; Ruiz-Narvaez, Edward A.; Chen, Wei-Min; Chen, Fang; Henderson, Brian E.; Millikan, Robert C.; Ambrosone, Christine B.; Strom, Sara S.; Guo, Xiuqing; Andrews, Jeanette S.; Sun, Yan V.; Mosley, Thomas H.; Yanek, Lisa R.; Shriner, Daniel; Haritunians, Talin; Rotter, Jerome I.; Speliotes, Elizabeth K.; Smith, Megan; Rosenberg, Lynn; Mychaleckyj, Josyf; Nayak, Uma; Spruill, Ida; Garvey, W. Timothy; Pettaway, Curtis; Nyante, Sarah; Bandera, Elisa V.; Britton, Angela F.; Zonderman, Alan B.; Rasmussen-Torvik, Laura J.; Chen, Yii-Der Ida; Ding, Jingzhong; Lohman, Kurt; Kritchevsky, Stephen B.; Zhao, Wei; Peyser, Patricia A.; Kardia, Sharon L. R.; Kabagambe, Edmond; Broeckel, Ulrich; Chen, Guanjie; Zhou, Jie; Wassertheil-Smoller, Sylvia; Neuhouser, Marian L.; Rampersaud, Evadnie; Psaty, Bruce; Kooperberg, Charles; Manson, JoAnn E.; Kuller, Lewis H.; Ochs-Balcom, Heather M.; Johnson, Karen C.; Sucheston, Lara; Ordovas, Jose M.; Palmer, Julie R.; Haiman, Christopher A.; McKnight, Barbara; Howard, Barbara V.; Becker, Diane M.; Bielak, Lawrence F.; Liu, Yongmei; Allison, Matthew A.; Grant, Struan F. A.; Burke, Gregory L.; Patel, Sanjay R.; Schreiner, Pamela J.; Borecki, Ingrid B.; Evans, Michele K.; Taylor, Herman; Sale, Michele M.; Howard, Virginia; Carlson, Christopher S.; Rotimi, Charles N.; Cushman, Mary; Harris, Tamara B.; Reiner, Alexander P.; Cupples, L. Adrienne; North, Kari E.; Fox, Caroline S.

    2013-01-01

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

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

    PubMed

    Liu, Ching-Ti; Monda, Keri L; Taylor, Kira C; Lange, Leslie; Demerath, Ellen W; Palmas, Walter; Wojczynski, Mary K; Ellis, Jaclyn C; Vitolins, Mara Z; Liu, Simin; Papanicolaou, George J; Irvin, Marguerite R; Xue, Luting; Griffin, Paula J; Nalls, Michael A; Adeyemo, Adebowale; Liu, Jiankang; Li, Guo; Ruiz-Narvaez, Edward A; Chen, Wei-Min; Chen, Fang; Henderson, Brian E; Millikan, Robert C; Ambrosone, Christine B; Strom, Sara S; Guo, Xiuqing; Andrews, Jeanette S; Sun, Yan V; Mosley, Thomas H; Yanek, Lisa R; Shriner, Daniel; Haritunians, Talin; Rotter, Jerome I; Speliotes, Elizabeth K; Smith, Megan; Rosenberg, Lynn; Mychaleckyj, Josyf; Nayak, Uma; Spruill, Ida; Garvey, W Timothy; Pettaway, Curtis; Nyante, Sarah; Bandera, Elisa V; Britton, Angela F; Zonderman, Alan B; Rasmussen-Torvik, Laura J; Chen, Yii-Der Ida; Ding, Jingzhong; Lohman, Kurt; Kritchevsky, Stephen B; Zhao, Wei; Peyser, Patricia A; Kardia, Sharon L R; Kabagambe, Edmond; Broeckel, Ulrich; Chen, Guanjie; Zhou, Jie; Wassertheil-Smoller, Sylvia; Neuhouser, Marian L; Rampersaud, Evadnie; Psaty, Bruce; Kooperberg, Charles; Manson, Joann E; Kuller, Lewis H; Ochs-Balcom, Heather M; Johnson, Karen C; Sucheston, Lara; Ordovas, Jose M; Palmer, Julie R; Haiman, Christopher A; McKnight, Barbara; Howard, Barbara V; Becker, Diane M; Bielak, Lawrence F; Liu, Yongmei; Allison, Matthew A; Grant, Struan F A; Burke, Gregory L; Patel, Sanjay R; Schreiner, Pamela J; Borecki, Ingrid B; Evans, Michele K; Taylor, Herman; Sale, Michele M; Howard, Virginia; Carlson, Christopher S; Rotimi, Charles N; Cushman, Mary; Harris, Tamara B; Reiner, Alexander P; Cupples, L Adrienne; North, Kari E; Fox, Caroline S

    2013-01-01

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

  17. 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.

  18. Genome-wide association study of ancestry-specific TB risk in the South African Coloured population.

    PubMed

    Chimusa, Emile R; Zaitlen, Noah; Daya, Michelle; Möller, Marlo; van Helden, Paul D; Mulder, Nicola J; Price, Alkes L; Hoal, Eileen G

    2014-02-01

    The worldwide burden of tuberculosis (TB) remains an enormous problem, and is particularly severe in the admixed South African Coloured (SAC) population residing in the Western Cape. Despite evidence from twin studies suggesting a strong genetic component to TB resistance, only a few loci have been identified to date. In this work, we conduct a genome-wide association study (GWAS), meta-analysis and trans-ethnic fine mapping to attempt the replication of previously identified TB susceptibility loci. Our GWAS results confirm the WT1 chr11 susceptibility locus (rs2057178: odds ratio = 0.62, P = 2.71e(-06)) previously identified by Thye et al., but fail to replicate previously identified polymorphisms in the TLR8 gene and locus 18q11.2. Our study demonstrates that the genetic contribution to TB risk varies between continental populations, and illustrates the value of including admixed populations in studies of TB risk and other complex phenotypes. Our evaluation of local ancestry based on the real and simulated data demonstrates that case-only admixture mapping is currently impractical in multi-way admixed populations, such as the SAC, due to spurious deviations in average local ancestry generated by current local ancestry inference methods. This study provides insights into identifying disease genes and ancestry-specific disease risk in multi-way admixed populations.

  19. Genome-wide association study of ancestry-specific TB risk in the South African Coloured population

    PubMed Central

    Chimusa, Emile R.; Zaitlen, Noah; Daya, Michelle; Möller, Marlo; van Helden, Paul D.; Mulder, Nicola J.; Price, Alkes L.; Hoal, Eileen G.

    2014-01-01

    The worldwide burden of tuberculosis (TB) remains an enormous problem, and is particularly severe in the admixed South African Coloured (SAC) population residing in the Western Cape. Despite evidence from twin studies suggesting a strong genetic component to TB resistance, only a few loci have been identified to date. In this work, we conduct a genome-wide association study (GWAS), meta-analysis and trans-ethnic fine mapping to attempt the replication of previously identified TB susceptibility loci. Our GWAS results confirm the WT1 chr11 susceptibility locus (rs2057178: odds ratio = 0.62, P = 2.71e−06) previously identified by Thye et al., but fail to replicate previously identified polymorphisms in the TLR8 gene and locus 18q11.2. Our study demonstrates that the genetic contribution to TB risk varies between continental populations, and illustrates the value of including admixed populations in studies of TB risk and other complex phenotypes. Our evaluation of local ancestry based on the real and simulated data demonstrates that case-only admixture mapping is currently impractical in multi-way admixed populations, such as the SAC, due to spurious deviations in average local ancestry generated by current local ancestry inference methods. This study provides insights into identifying disease genes and ancestry-specific disease risk in multi-way admixed populations. PMID:24057671

  20. 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.

  1. Association between Plasma 25-Hydroxyvitamin D, Ancestry and Aggressive Prostate Cancer among African Americans and European Americans in PCaP

    PubMed Central

    Steck, Susan E.; Arab, Lenore; Zhang, Hongmei; Bensen, Jeannette T.; Fontham, Elizabeth T. H.; Johnson, Candace S.; Mohler, James L.; Smith, Gary J.; Su, Joseph L.; Trump, Donald L.; Woloszynska-Read, Anna

    2015-01-01

    Background African Americans (AAs) have lower circulating 25-hydroxyvitamin D3 [25(OH)D3] concentrations and higher prostate cancer (CaP) aggressiveness than other racial/ethnic groups. The purpose of the current study was to examine the relationship between plasma 25(OH)D3, African ancestry and CaP aggressiveness among AAs and European Americans (EAs). Methods Plasma 25(OH)D3 was measured using LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in 537 AA and 663 EA newly-diagnosed CaP patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP) classified as having either ‘high’ or ‘low’ aggressive disease based on clinical stage, Gleason grade and prostate specific antigen at diagnosis. Mean plasma 25(OH)D3 concentrations were compared by proportion of African ancestry. Logistic regression was used to calculate multivariable adjusted odds ratios (OR) and 95% confidence intervals (95%CI) for high aggressive CaP by tertile of plasma 25(OH)D3. Results AAs with highest percent African ancestry (>95%) had the lowest mean plasma 25(OH)D3 concentrations. Overall, plasma 25(OH)D3 was associated positively with aggressiveness among AA men, an association that was modified by calcium intake (ORT3vs.T1: 2.23, 95%CI: 1.26–3.95 among men with low calcium intake, and ORT3vs.T1: 0.19, 95%CI: 0.05–0.70 among men with high calcium intake). Among EAs, the point estimates of the ORs were <1.0 for the upper tertiles with CIs that included the null. Conclusions Among AAs, plasma 25(OH)D3 was associated positively with CaP aggressiveness among men with low calcium intake and inversely among men with high calcium intake. The clinical significance of circulating concentrations of 25(OH)D3 and interactions with calcium intake in the AA population warrants further study. PMID:25919866

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

    PubMed

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

    2016-05-01

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

  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 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

  4. Ancestral proportions and admixture dynamics in geographically defined African Americans living in South Carolina.

    PubMed

    Parra, E J; Kittles, R A; Argyropoulos, G; Pfaff, C L; Hiester, K; Bonilla, C; Sylvester, N; Parrish-Gause, D; Garvey, W T; Jin, L; McKeigue, P M; Kamboh, M I; Ferrell, R E; Pollitzer, W S; Shriver, M D

    2001-01-01

    We analyzed admixture in samples of six different African-American populations from South Carolina: Gullah-speaking Sea Islanders in coastal South Carolina, residents of four counties in the "Low Country" (Berkeley, Charleston, Colleton, and Dorchester), and persons living in the city of Columbia, located in central South Carolina. We used a battery of highly informative autosomal, mtDNA, and Y-chromosome markers. Two of the autosomal markers (FY and AT3) are linked and lie 22 cM apart on chromosome 1. The results of this study indicate, in accordance with previous historical, cultural, and anthropological evidence, a very low level of European admixture in the Gullah Sea Islanders (m = 3.5 +/- 0.9%). The proportion of European admixture is higher in the Low Country (m ranging between 9. 9 +/- 1.8% and 14.0 +/- 1.9%), and is highest in Columbia (m = 17.7 +/- 3.1%). A sex-biased European gene flow and a small Native American contribution to the African-American gene pool are also evident in these data. We studied the pattern of pairwise allelic associations between the FY locus and the nine other autosomal markers in our samples. In the combined sample from the Low Country (N = 548), a high level of linkage disequilibrium was observed between the linked markers, FY and AT3. Additionally, significant associations were also detected between FY and 4 of the 8 unlinked markers, suggesting the existence of significant genetic structure in this population. A continuous gene flow model of admixture could explain the observed pattern of genetic structure. A test conditioning on the overall admixture of each individual showed association of ancestry between the two linked markers (FY and AT3), but not between any of the unlinked markers, as theory predicts. Thus, even in the presence of genetic structure due to continuous gene flow or some other factor, it is possible to differentiate associations due to linkage from spurious associations due to genetic structure.

  5. 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.

  6. 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

  7. African ancestry allelic variation at the MYH9 gene contributes to increased susceptibility to non-diabetic end-stage kidney disease in Hispanic Americans

    PubMed Central

    Behar, Doron M.; Rosset, Saharon; Tzur, Shay; Selig, Sara; Yudkovsky, Guennady; Bercovici, Sivan; Kopp, Jeffrey B.; Winkler, Cheryl A.; Nelson, George W.; Wasser, Walter G.; Skorecki, Karl

    2010-01-01

    Recent studies identified MYH9 as a major susceptibility gene for common forms of non-diabetic end-stage kidney disease (ESKD). A set of African ancestry DNA sequence variants comprising the E-1 haplotype, was significantly associated with ESKD. In order to determine whether African ancestry variants are also associated with disease susceptibility in admixed populations with differing genomic backgrounds, we genotyped a total of 1425 African and Hispanic American subjects comprising dialysis patients with diabetic and non-diabetic ESKD and controls, using 42 single nucleotide polymorphisms (SNPs) within the MYH9 gene and 40 genome-wide and 38 chromosome 22 ancestry informative markers. Following ancestry correction, logistic regression demonstrated that three of the E-1 SNPs are also associated with non-diabetic ESKD in the new sample sets of both African and Hispanic Americans, with a stronger association in Hispanic Americans. We also identified MYH9 SNPs that are even more powerfully associated with the disease phenotype than the E-1 SNPs. These newly associated SNPs, could be divided into those comprising a haplotype termed S-1 whose association was significant under a recessive or additive inheritance mode (rs5750248, OR 4.21, P < 0.01, Hispanic Americans, recessive), and those comprising a haplotype termed F-1 whose association was significant under a dominant or additive inheritance mode (rs11912763, OR 4.59, P < 0.01, Hispanic Americans, dominant). These findings strengthen the contention that a sequence variant of MYH9, common in populations with varying degrees of African ancestry admixture, and in strong linkage disequilibrium with the associated SNPs and haplotypes reported herein, strongly predisposes to non-diabetic ESKD. PMID:20144966

  8. African ancestry allelic variation at the MYH9 gene contributes to increased susceptibility to non-diabetic end-stage kidney disease in Hispanic Americans.

    PubMed

    Behar, Doron M; Rosset, Saharon; Tzur, Shay; Selig, Sara; Yudkovsky, Guennady; Bercovici, Sivan; Kopp, Jeffrey B; Winkler, Cheryl A; Nelson, George W; Wasser, Walter G; Skorecki, Karl

    2010-05-01

    Recent studies identified MYH9 as a major susceptibility gene for common forms of non-diabetic end-stage kidney disease (ESKD). A set of African ancestry DNA sequence variants comprising the E-1 haplotype, was significantly associated with ESKD. In order to determine whether African ancestry variants are also associated with disease susceptibility in admixed populations with differing genomic backgrounds, we genotyped a total of 1425 African and Hispanic American subjects comprising dialysis patients with diabetic and non-diabetic ESKD and controls, using 42 single nucleotide polymorphisms (SNPs) within the MYH9 gene and 40 genome-wide and 38 chromosome 22 ancestry informative markers. Following ancestry correction, logistic regression demonstrated that three of the E-1 SNPs are also associated with non-diabetic ESKD in the new sample sets of both African and Hispanic Americans, with a stronger association in Hispanic Americans. We also identified MYH9 SNPs that are even more powerfully associated with the disease phenotype than the E-1 SNPs. These newly associated SNPs, could be divided into those comprising a haplotype termed S-1 whose association was significant under a recessive or additive inheritance mode (rs5750248, OR 4.21, P < 0.01, Hispanic Americans, recessive), and those comprising a haplotype termed F-1 whose association was significant under a dominant or additive inheritance mode (rs11912763, OR 4.59, P < 0.01, Hispanic Americans, dominant). These findings strengthen the contention that a sequence variant of MYH9, common in populations with varying degrees of African ancestry admixture, and in strong linkage disequilibrium with the associated SNPs and haplotypes reported herein, strongly predisposes to non-diabetic ESKD.

  9. Determining the effects and challenges of incorporating genetic testing into primary care management of hypertensive patients with African ancestry.

    PubMed

    Horowitz, C R; Abul-Husn, N S; Ellis, S; Ramos, M A; Negron, R; Suprun, M; Zinberg, R E; Sabin, T; Hauser, D; Calman, N; Bagiella, E; Bottinger, E P

    2016-03-01

    People of African ancestry (Blacks) have increased risk of kidney failure due to numerous socioeconomic, environmental, and clinical factors. Two variants in the APOL1 gene are now thought to account for much of the racial disparity associated with hypertensive kidney failure in Blacks. However, this knowledge has not been translated into clinical care to help improve patient outcomes and address disparities. GUARDD is a randomized trial to evaluate the effects and challenges of incorporating genetic risk information into primary care. Hypertensive, non-diabetic, adults with self-reported African ancestry, without kidney dysfunction, are recruited from diverse clinical settings and randomized to undergo APOL1 genetic testing at baseline (intervention) or at one year (waitlist control). Providers are educated about genomics and APOL1. Guided by a genetic counselor, trained staff return APOL1 results to patients and provide low-literacy educational materials. Real-time clinical decision support tools alert clinicians of their patients' APOL1 results and associated risk status at the point of care. Our academic-community-clinical partnership designed a study to generate information about the impact of genetic risk information on patient care (blood pressure and renal surveillance) and on patient and provider knowledge, attitudes, beliefs, and behaviors. GUARDD will help establish the effective implementation of APOL1 risk-informed management of hypertensive patients at high risk of CKD, and will provide a robust framework for future endeavors to implement genomic medicine in diverse clinical practices. It will also add to the important dialog about factors that contribute to and may help eliminate racial disparities in kidney disease. PMID:26747051

  10. 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

    2012-10-01

    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.

  11. 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

  12. Is HIV-1 infection associated with endothelial dysfunction in a population of African ancestry in South Africa?

    PubMed

    Fourie, C; van Rooyen, J; Pieters, M; Conradie, K; Hoekstra, T; Schutte, A

    2011-01-01

    The chronic infection status suffered by HIV-infected individuals promotes chronic arterial inflammation and injury, which leads to dysfunction of the endothelium, atherosclerosis and thrombosis. Although HIV-1 subtype C is prevalent in South Africa and accounts for almost a third of the infections worldwide, this subtype differs genetically from HIV-1 subtype B on which the majority of studies have been done. The objective of this study was to assess whether newly identified, never-treated, HIV-1-infected South African participants showed signs of endothelial dysfunction, accelerated atherosclerosis and increased blood coagulation. We compared 300 newly diagnosed (never antiretroviraltreated) HIV-infected participants to 300 age-, gender-, body mass index- and locality-matched uninfected controls. Levels of high-density lipoprotein cholesterol (HDL-C), triglycerides, interleukin-6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), fibrinogen and plasminogen activator inhibitor-1 (PAI-1), and carotid radialis pulse wave velocity (cr-PWV) were determined. The HIV-infected participants showed lower HDL-C and higher IL-6, CRP, ICAM-1 and VCAM-1 levels compared to the uninfected controls. No differences in fibrinogen and PAI-1 levels were detected. A continuous positive trend of increasing age with cr-PWV was detected in the HIV-infected group. Our findings suggest inflammatory injury of the endothelium, pointing to endothelial dysfunction of never-treated HIV-1-infected South Africans of African ancestry. Although no indication of a prothrombotic state could be detected, there was an indication of accelerated vascular aging and probable early atherosclerosis in the older HIV-infected participants. PMID:21713302

  13. Genome-wide ancestry of 17th-century enslaved Africans from the Caribbean.

    PubMed

    Schroeder, Hannes; Ávila-Arcos, María C; Malaspinas, Anna-Sapfo; Poznik, G David; Sandoval-Velasco, Marcela; Carpenter, Meredith L; Moreno-Mayar, José Víctor; Sikora, Martin; Johnson, Philip L F; Allentoft, Morten Erik; Samaniego, José Alfredo; Haviser, Jay B; Dee, Michael W; Stafford, Thomas W; Salas, Antonio; Orlando, Ludovic; Willerslev, Eske; Bustamante, Carlos D; Gilbert, M Thomas P

    2015-03-24

    Between 1500 and 1850, more than 12 million enslaved Africans were transported to the New World. The vast majority were shipped from West and West-Central Africa, but their precise origins are largely unknown. We used genome-wide ancient DNA analyses to investigate the genetic origins of three enslaved Africans whose remains were recovered on the Caribbean island of Saint Martin. We trace their origins to distinct subcontinental source populations within Africa, including Bantu-speaking groups from northern Cameroon and non-Bantu speakers living in present-day Nigeria and Ghana. To our knowledge, these findings provide the first direct evidence for the ethnic origins of enslaved Africans, at a time for which historical records are scarce, and demonstrate that genomic data provide another type of record that can shed new light on long-standing historical questions.

  14. Genome-wide ancestry of 17th-century enslaved Africans from the Caribbean

    PubMed Central

    Schroeder, Hannes; Ávila-Arcos, María C.; Malaspinas, Anna-Sapfo; Sandoval-Velasco, Marcela; Carpenter, Meredith L.; Moreno-Mayar, José Víctor; Sikora, Martin; Johnson, Philip L. F.; Allentoft, Morten Erik; Samaniego, José Alfredo; Haviser, Jay B.; Dee, Michael W.; Stafford, Thomas W.; Salas, Antonio; Orlando, Ludovic; Willerslev, Eske; Bustamante, Carlos D.; Gilbert, M. Thomas P.

    2015-01-01

    Between 1500 and 1850, more than 12 million enslaved Africans were transported to the New World. The vast majority were shipped from West and West-Central Africa, but their precise origins are largely unknown. We used genome-wide ancient DNA analyses to investigate the genetic origins of three enslaved Africans whose remains were recovered on the Caribbean island of Saint Martin. We trace their origins to distinct subcontinental source populations within Africa, including Bantu-speaking groups from northern Cameroon and non-Bantu speakers living in present-day Nigeria and Ghana. To our knowledge, these findings provide the first direct evidence for the ethnic origins of enslaved Africans, at a time for which historical records are scarce, and demonstrate that genomic data provide another type of record that can shed new light on long-standing historical questions. PMID:25755263

  15. Genome-wide ancestry of 17th-century enslaved Africans from the Caribbean.

    PubMed

    Schroeder, Hannes; Ávila-Arcos, María C; Malaspinas, Anna-Sapfo; Poznik, G David; Sandoval-Velasco, Marcela; Carpenter, Meredith L; Moreno-Mayar, José Víctor; Sikora, Martin; Johnson, Philip L F; Allentoft, Morten Erik; Samaniego, José Alfredo; Haviser, Jay B; Dee, Michael W; Stafford, Thomas W; Salas, Antonio; Orlando, Ludovic; Willerslev, Eske; Bustamante, Carlos D; Gilbert, M Thomas P

    2015-03-24

    Between 1500 and 1850, more than 12 million enslaved Africans were transported to the New World. The vast majority were shipped from West and West-Central Africa, but their precise origins are largely unknown. We used genome-wide ancient DNA analyses to investigate the genetic origins of three enslaved Africans whose remains were recovered on the Caribbean island of Saint Martin. We trace their origins to distinct subcontinental source populations within Africa, including Bantu-speaking groups from northern Cameroon and non-Bantu speakers living in present-day Nigeria and Ghana. To our knowledge, these findings provide the first direct evidence for the ethnic origins of enslaved Africans, at a time for which historical records are scarce, and demonstrate that genomic data provide another type of record that can shed new light on long-standing historical questions. PMID:25755263

  16. Europeans have a higher proportion of high‑frequency deleterious variants than Africans.

    PubMed

    Subramanian, Sankar

    2016-01-01

    Recent studies have shown that a high proportion of rare variants in European and African populations are deleterious in nature. However, the deleterious fraction of high-frequency variants is unclear. Using more than 6500 exomes we show a much higher fraction (11 %) of relatively high-frequency nonsynonymous (amino acid altering) variants (DAF 0.1–10 %) in European Americans (EA) compared to those from African Americans (AA). In contrast, this difference was only marginal (<2 %) for low-frequency nonsynonymous variants (DAF <0.1 %). Our results also revealed that the proportion of high-frequency deleterious nonsynonymous variants in EA was much higher (24 %) than that in AA and this difference was very small (4 %) for the low-frequency deleterious amino acid altering variants. We also show that EA have significantly more number of high-frequency deleterious nonsynonymous variants per genome than AA. The high proportion of high-frequency deleterious variants in EA could be the result of the well-known bottleneck experienced by European populations in which harmful mutations may have drifted to high frequencies. The estimated ages of deleterious variants support this prediction. Our results suggest that high-frequency variants could be relatively more likely to be associated with diseases in Europeans than in Africans and hence emphasize the need for population-specific strategies in genomic medicine studies.

  17. Epidermal gene expression and ethnic pigmentation variations among individuals of Asian, European and African ancestry.

    PubMed

    Yin, Lanlan; Coelho, Sergio G; Ebsen, Dominik; Smuda, Christoph; Mahns, Andre; Miller, Sharon A; Beer, Janusz Z; Kolbe, Ludger; Hearing, Vincent J

    2014-10-01

    Differences in visible skin pigmentation give rise to the wide variation of skin colours seen in racial/ethnic populations. Skin pigmentation is important not only from cosmetic and psychological points of view, but more importantly because of its implications for the risk of all types of skin cancers, on photoaging, etc. Despite differences in those parameters in Caucasian and Asian skin types, they are remarkably similar in their production and distribution of melanins, and the mechanism(s) underlying their different characteristics have remained obscure. In this study, we used microarray analysis of skin suction blisters to investigate molecular differences underlying the determination of pigmentation in various skin types, and we used immunohistochemistry to validate the expression patterns of several interesting targets that were identified. Intriguingly, Caucasian and Asian skins had highly similar gene expression patterns that differed significantly from the pattern of African skin. The results of this study suggest the dynamic interactions of different types of cells in human skin that regulate its pigmentation, reveal that the known pigmentation genes have a limited contribution and uncover a new array of genes, including NINL and S100A4, that might be involved in that regulation.

  18. Smoking and genetic risk variation across populations of European, Asian, and African American ancestry--a meta-analysis of chromosome 15q25.

    PubMed

    Chen, Li-Shiun; Saccone, Nancy L; Culverhouse, Robert C; Bracci, Paige M; Chen, Chien-Hsiun; Dueker, Nicole; Han, Younghun; Huang, Hongyan; Jin, Guangfu; Kohno, Takashi; Ma, Jennie Z; Przybeck, Thomas R; Sanders, Alan R; Smith, Jennifer A; Sung, Yun Ju; Wenzlaff, Angie S; Wu, Chen; Yoon, Dankyu; Chen, Ying-Ting; Cheng, Yu-Ching; Cho, Yoon Shin; David, Sean P; Duan, Jubao; Eaton, Charles B; Furberg, Helena; Goate, Alison M; Gu, Dongfeng; Hansen, Helen M; Hartz, Sarah; Hu, Zhibin; Kim, Young Jin; Kittner, Steven J; Levinson, Douglas F; Mosley, Thomas H; Payne, Thomas J; Rao, D C; Rice, John P; Rice, Treva K; Schwantes-An, Tae-Hwi; Shete, Sanjay S; Shi, Jianxin; Spitz, Margaret R; Sun, Yan V; Tsai, Fuu-Jen; Wang, Jen C; Wrensch, Margaret R; Xian, Hong; Gejman, Pablo V; He, Jiang; Hunt, Steven C; Kardia, Sharon L; Li, Ming D; Lin, Dongxin; Mitchell, Braxton D; Park, Taesung; Schwartz, Ann G; Shen, Hongbing; Wiencke, John K; Wu, Jer-Yuarn; Yokota, Jun; Amos, Christopher I; Bierut, Laura J

    2012-05-01

    Recent meta-analyses of European ancestry subjects show strong evidence for association between smoking quantity and multiple genetic variants on chromosome 15q25. This meta-analysis extends the examination of association between distinct genes in the CHRNA5-CHRNA3-CHRNB4 region and smoking quantity to Asian and African American populations to confirm and refine specific reported associations. Association results for a dichotomized cigarettes smoked per day phenotype in 27 datasets (European ancestry (N = 14,786), Asian (N = 6,889), and African American (N = 10,912) for a total of 32,587 smokers) were meta-analyzed by population and results were compared across all three populations. We demonstrate association between smoking quantity and markers in the chromosome 15q25 region across all three populations, and narrow the region of association. Of the variants tested, only rs16969968 is associated with smoking (P < 0.01) in each of these three populations (odds ratio [OR] = 1.33, 95% CI = 1.25-1.42, P = 1.1 × 10(-17) in meta-analysis across all population samples). Additional variants displayed a consistent signal in both European ancestry and Asian datasets, but not in African Americans. The observed consistent association of rs16969968 with heavy smoking across multiple populations, combined with its known biological significance, suggests rs16969968 is most likely a functional variant that alters risk for heavy smoking. We interpret additional association results that differ across populations as providing evidence for additional functional variants, but we are unable to further localize the source of this association. Using the cross-population study paradigm provides valuable insights to narrow regions of interest and inform future biological experiments.

  19. 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.

  20. 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

  1. Cytokine and cytokine receptor genes of the adaptive immune response are differentially associated with breast cancer risk in American women of African and European ancestry.

    PubMed

    Quan, Lei; Gong, Zhihong; Yao, Song; Bandera, Elisa V; Zirpoli, Gary; Hwang, Helena; Roberts, Michelle; Ciupak, Gregory; Davis, Warren; Sucheston, Lara; Pawlish, Karen; Bovbjerg, Dana H; Jandorf, Lina; Cabasag, Citadel; Coignet, Jean-Gabriel; Ambrosone, Christine B; Hong, Chi-Chen

    2014-03-15

    Disparities in breast cancer biology are evident between American women of African ancestry (AA) and European ancestry (EA) and may be due, in part, to differences in immune function. To assess the potential role of constitutional host immunity on breast carcinogenesis, we tested associations between breast cancer risk and 47 single nucleotide polymorphisms (SNPs) in 26 cytokine-related genes of the adaptive immune system using 650 EA (n = 335 cases) and 864 AA (n = 458 cases) women from the Women's Circle of Health Study (WCHS). With additional participant accrual to the WCHS, promising SNPs from the initial analysis were evaluated in a larger sample size (1,307 EAs and 1,365 AAs). Multivariate logistic regression found SNPs in genes important for T helper type 1 (Th1) immunity (IFNGR2 rs1059293, IL15RA rs2296135, LTA rs1041981), Th2 immunity (IL4R rs1801275), and T regulatory cell-mediated immunosuppression (TGFB1 rs1800469) associated with breast cancer risk, mainly among AAs. The combined effect of these five SNPs was highly significant among AAs (P-trend = 0.0005). When stratified by estrogen receptor (ER) status, LTA rs1041981 was associated with ER-positive breast cancers among EAs and marginally among AAs. Only among AA women, IL15 rs10833 and IL15RA rs2296135 were associated with ER-positive tumors, and IL12RB1 rs375947, IL15 rs10833 and TGFB1 rs1800469 were associated with ER-negative tumors. Our study systematically identified genetic variants in the adaptive immune response pathway associated with breast cancer risk, which appears to differ by ancestry groups, menopausal status and ER status.

  2. 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

  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. 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. PMID:25254375

  5. 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

  6. Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry.

    PubMed

    Qian, Frank; Feng, Ye; Zheng, Yonglan; Ogundiran, Temidayo O; Ojengbede, Oladosu; Zheng, Wei; Blot, William; Ambrosone, Christine B; John, Esther M; Bernstein, Leslie; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah; Bandera, Elisa V; Ingles, Sue A; Press, Michael F; Nathanson, Katherine L; Hennis, Anselm; Nemesure, Barbara; Ambs, Stefan; Kolonel, Laurence N; Olopade, Olufunmilayo I; Haiman, Christopher A; Huo, Dezheng

    2016-10-01

    MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55-0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82-0.95, P = 3.99 × 10(-4)), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11-1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63-0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology.

  7. Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry.

    PubMed

    Qian, Frank; Feng, Ye; Zheng, Yonglan; Ogundiran, Temidayo O; Ojengbede, Oladosu; Zheng, Wei; Blot, William; Ambrosone, Christine B; John, Esther M; Bernstein, Leslie; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah; Bandera, Elisa V; Ingles, Sue A; Press, Michael F; Nathanson, Katherine L; Hennis, Anselm; Nemesure, Barbara; Ambs, Stefan; Kolonel, Laurence N; Olopade, Olufunmilayo I; Haiman, Christopher A; Huo, Dezheng

    2016-10-01

    MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55-0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82-0.95, P = 3.99 × 10(-4)), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11-1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63-0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology. PMID:27380242

  8. Association of polymorphisms at the ADIPOR1 regulatory region with type 2 diabetes and body mass index in a Brazilian population with European or African ancestry.

    PubMed

    Yeh, E; Kimura, L; Errera, F I V; Angeli, C B; Mingroni-Netto, R C; Silva, M E R; Canani, L H S; Passos-Bueno, M R

    2008-06-01

    Association studies between ADIPOR1 genetic variants and predisposition to type 2 diabetes (DM2) have provided contradictory results. We determined if two single nucleotide polymorphisms (SNP c.-8503G>A and SNP c.10225C>G) in regulatory regions of ADIPOR1 in 567 Brazilian individuals of European (EA; N = 443) or African (AfA; N = 124) ancestry from rural (quilombo remnants; N = 439) and urban (N = 567) areas. We detected a significant effect of ethnicity on the distribution of the allelic frequencies of both SNPs in these populations (EA: -8503A = 0.27; AfA: -8503A = 0.16; P = 0.001 and EA: 10225G = 0.35; AfA: 10225G = 0.51; P < 0.001). Neither of the polymorphisms were associated with DM2 in the case-control study in EA (SNP c.-8503G>A: DM2 group -8503A = 0.26; control group -8503A = 0.30; P = 0.14/SNP 10225C>G: DM2 group 10225G = 0.37; control group 10225G = 0.32; P = 0.40) and AfA populations (SNP c.-8503G>A: DM2 group -8503A = 0.16; control group -8503A = 0.15; P = 0.34/SNP 10225C>G: DM2 group 10225G = 0.51; control group 10225G = 0.52; P = 0.50). Similarly, none of the polymorphisms were associated with metabolic/anthropometric risk factors for DM2 in any of the three populations, except for HDL cholesterol, which was significantly higher in AfA heterozygotes (GC = 53.75 +/- 17.26 mg/dL) than in homozygotes. We conclude that ADIPOR1 polymorphisms are unlikely to be major risk factors for DM2 or for metabolic/anthropometric measurements that represent risk factors for DM2 in populations of European and African ancestries.

  9. Y chromosome STR haplotypes and the genetic structure of U.S. populations of African, European, and Hispanic ancestry.

    PubMed

    Kayser, Manfred; Brauer, Silke; Schädlich, Hiltrud; Prinz, Mechthild; Batzer, Mark A; Zimmerman, Peter A; Boatin, B A; Stoneking, Mark

    2003-04-01

    To investigate geographic structure within U.S. ethnic populations, we analyzed 1705 haplotypes on the basis of 9 short tandem repeat (STR) loci on the Y-chromosome from 9-11 groups each of African-Americans, European-Americans, and Hispanics. There were no significant differences in the distribution of Y-STR haplotypes among African-American groups, whereas European-American and Hispanic groups did exhibit significant geographic heterogeneity. However, the significant heterogeneity resulted from one sample; removal of that sample in each case eliminated the significant heterogeneity. Multidimensional scaling analysis of R(ST) values indicated that African-American groups formed a distinct cluster, whereas there was some intermingling of European-American and Hispanic groups. MtDNA data exist for many of these same groups; estimates of the European-American genetic contribution to the African-American gene pool were 27.5%-33.6% for the Y-STR haplotypes and 9%-15.4% for the mtDNA types. The lack of significant geographic heterogeneity among Y-STR and mtDNA haplotypes in U.S ethnic groups means that forensic DNA databases do not need to be constructed for separate geographic regions of the U.S. Moreover, absence of significant geographic heterogeneity for these two loci means that regional variation in disease susceptibility within ethnic groups is more likely to reflect cultural/environmental factors, rather than any underlying genetic heterogeneity.

  10. Genome-wide Comparison of African-Ancestry Populations from CARe and Other Cohorts Reveals Signals of Natural Selection

    PubMed Central

    Bhatia, Gaurav; Patterson, Nick; Pasaniuc, Bogdan; Zaitlen, Noah; Genovese, Giulio; Pollack, Samuela; Mallick, Swapan; Myers, Simon; Tandon, Arti; Spencer, Chris; Palmer, Cameron D.; Adeyemo, Adebowale A.; Akylbekova, Ermeg L.; Cupples, L. Adrienne; Divers, Jasmin; Fornage, Myriam; Kao, W.H. Linda; Lange, Leslie; Li, Mingyao; Musani, Solomon; Mychaleckyj, Josyf C.; Ogunniyi, Adesola; Papanicolaou, George; Rotimi, Charles N.; Rotter, Jerome I.; Ruczinski, Ingo; Salako, Babatunde; Siscovick, David S.; Tayo, Bamidele O.; Yang, Qiong; McCarroll, Steve; Sabeti, Pardis; Lettre, Guillaume; De Jager, Phil; Hirschhorn, Joel; Zhu, Xiaofeng; Cooper, Richard; Reich, David; Wilson, James G.; Price, Alkes L.

    2011-01-01

    The study of recent natural selection in human populations has important applications to human history and medicine. Positive natural selection drives the increase in beneficial alleles and plays a role in explaining diversity across human populations. By discovering traits subject to positive selection, we can better understand the population level response to environmental pressures including infectious disease. Our study examines unusual population differentiation between three large data sets to detect natural selection. The populations examined, African Americans, Nigerians, and Gambians, are genetically close to one another (FST < 0.01 for all pairs), allowing us to detect selection even with moderate changes in allele frequency. We also develop a tree-based method to pinpoint the population in which selection occurred, incorporating information across populations. Our genome-wide significant results corroborate loci previously reported to be under selection in Africans including HBB and CD36. At the HLA locus on chromosome 6, results suggest the existence of multiple, independent targets of population-specific selective pressure. In addition, we report a genome-wide significant (p = 1.36 × 10−11) signal of selection in the prostate stem cell antigen (PSCA) gene. The most significantly differentiated marker in our analysis, rs2920283, is highly differentiated in both Africa and East Asia and has prior genome-wide significant associations to bladder and gastric cancers. PMID:21907010

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

    PubMed Central

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

    2014-01-01

    Although substantial variation exists in individual responses to omega-3 (ω-3) (n–3) fatty acid supplementation, the causes for differences in response are largely unknown. Here we investigated the associations between the efficacy of ω-3 fatty acid supplementation and a broad range of nutritional and clinical factors collected during a double-blind, placebo-controlled trial in participants of African ancestry, randomly assigned to receive either 2 g eicosapentaenoic acid (EPA) + 1 g docosahexaenoic acid (n = 41) or corn/soybean oil placebo (n = 42) supplements for 6 wk. Food-frequency questionnaires were administered, and changes in erythrocyte lipids, lipoproteins, and monocyte 5-lipoxygenase–dependent metabolism were measured before and after supplementation. Mixed-mode linear regression modeling identified high (n = 28) and low (n = 13) ω-3 fatty acid response groups on the basis of changes in erythrocyte EPA abundance (P < 0.001). Compliance was equivalent (∼88%), whereas decreases in plasma triglycerides and VLDL particle sizes and reductions in stimulated monocyte leukotriene B4 production were larger in the high-response group. Although total diet quality scores were similar, the low-response group showed lower estimated 2005 Healthy Eating Index subscores for dark-green and orange vegetables and legumes (P = 0.01) and a lower intake of vegetables (P = 0.02), particularly dark-green vegetables (P = 0.002). Because the findings reported here are associative in nature, prospective studies are needed to determine if dietary dark-green vegetables or nutrients contained in these foods can enhance the efficacy of ω-3 fatty acid supplements. This trial was registered at clinicaltrials.gov as NCT00536185. PMID:24259553

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

    PubMed

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

    2014-02-01

    Although substantial variation exists in individual responses to omega-3 (ω-3) (n-3) fatty acid supplementation, the causes for differences in response are largely unknown. Here we investigated the associations between the efficacy of ω-3 fatty acid supplementation and a broad range of nutritional and clinical factors collected during a double-blind, placebo-controlled trial in participants of African ancestry, randomly assigned to receive either 2 g eicosapentaenoic acid (EPA) + 1 g docosahexaenoic acid (n = 41) or corn/soybean oil placebo (n = 42) supplements for 6 wk. Food-frequency questionnaires were administered, and changes in erythrocyte lipids, lipoproteins, and monocyte 5-lipoxygenase-dependent metabolism were measured before and after supplementation. Mixed-mode linear regression modeling identified high (n = 28) and low (n = 13) ω-3 fatty acid response groups on the basis of changes in erythrocyte EPA abundance (P < 0.001). Compliance was equivalent (∼88%), whereas decreases in plasma triglycerides and VLDL particle sizes and reductions in stimulated monocyte leukotriene B4 production were larger in the high-response group. Although total diet quality scores were similar, the low-response group showed lower estimated 2005 Healthy Eating Index subscores for dark-green and orange vegetables and legumes (P = 0.01) and a lower intake of vegetables (P = 0.02), particularly dark-green vegetables (P = 0.002). Because the findings reported here are associative in nature, prospective studies are needed to determine if dietary dark-green vegetables or nutrients contained in these foods can enhance the efficacy of ω-3 fatty acid supplements. This trial was registered at clinicaltrials.gov as NCT00536185.

  13. Reconstructing population history using JC virus: Amerinds, Spanish, and Africans in the ancestry of modern Puerto Ricans.

    PubMed

    Fernandez-Cobo, M; Jobes, D V; Yanagihara, R; Nerurkar, V R; Yamamura, Y; Ryschkewitsch, C F; Stoner, G L

    2001-06-01

    The roots of the Hispanic populations of the Caribbean Islands and Central and South America go back to three continents of the Old World. In Puerto Rico major genetic contributions have come from (1) Asians in the form of the aboriginal Taino population, an Arawak tribe, present when Columbus arrived on the Island, (2) Europeans, largely Spanish explorers, settlers, government administrators, and soldiers, and (3) Africans who came as part of the slave trade. Since JC virus (JCV) genotypes characteristic of Asia, Europe, and Africa have been identified, and excretion of JCV in urine has been proposed as a marker for human migrations, we sought to characterize the JCV strains present in a Caribbean Hispanic population. We found that the strains of JCV present today in Puerto Rico are those derived from the Old World populations represented there: Types 1B and 4 from Spain, Types 3A, 3B, and 6 from Africa, and Type 2A from Asia. The Type 2A genotype represents the indigenous Taino people. This JCV genotype was represented much more frequently (61%) than would be predicted by the trihybrid model of genetic admixture. This might be attributable to characteristics of JCV Type 2A itself, as well as to the nature of the early relationships between Spanish men and native women. These findings indicate that the JCV strains carried by the Taino Indians can be found in today's Puerto Rican population despite the apparent demise of these people more than two centuries ago. Therefore, molecular characterization of JCV provides a tool to supplement genetic techniques for reconstructing population histories including admixed populations.

  14. 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

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

    PubMed

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

    2014-01-01

    Inferring the ancestral origin of DNA samples can be helpful in correcting population stratification in disease association studies or guiding crime investigations. Populations throughout the world vary in appearance features and biological characteristics. Based on this idea, we performed a genome-wide scan for SNPs within genes that are related to physical and biological traits. Using the HapMap database, we screened 52 genes and their flanking regions. Thirty-five SNPs that displayed highly contrasting allele frequencies (F(st)>0.3, linkage disequilibrium r(2)<0.2, and Hardy-Weinberg equilibrium P>0.001) among Africans, Europeans, and East Asians were selected and validated. A multiplexed assay was developed to genotype these 35 SNPs in 357 individuals from 10 populations worldwide. This panel provided accurate estimates of individual ancestry proportions with balanced discriminatory power among the three continental ancestries: Africans, Europeans, and East Asians. It also proved very effective in evaluating admixed populations living in joint regions of continents (e.g., Uyghurs and Indians) and discriminating some subpopulations within each of the three continents. Structure analysis was performed to establish and evaluate the panel of ancestry-informative markers, and the components of each population were also described to indicate the structural composition. The 21 population structures in our study are consistent with geographic patterns, and individuals were properly assigned to their original ancestral populations with proportion analyses and random match probability calculations. Thus, the panel and its population information will be useful resources to minimize the effects of population stratification in association analyses and to assign the most likely origin of an unknown DNA contributor in forensic investigations.

  16. Results from a prostate cancer admixture mapping study in African-American men.

    PubMed

    Bock, Cathryn Hufford; Schwartz, Ann G; Ruterbusch, Julie J; Levin, Albert M; Neslund-Dudas, Christine; Land, Susan J; Wenzlaff, Angela S; Reich, David; McKeigue, Paul; Chen, Wei; Heath, Elisabeth I; Powell, Isaac J; Kittles, Rick A; Rybicki, Benjamin A

    2009-11-01

    There are considerable racial disparities in prostate cancer risk, with a 60% higher incidence rate among African-American (AA) men compared with European-American (EA) men, and a 2.4-fold higher mortality rate in AA men than in EA men. Recently, studies have implicated several African-ancestry associated prostate cancer susceptibility loci on chromosome 8q24. In the current study, we performed admixture mapping in AA men from two independent case-control studies of prostate cancer to confirm the 8q24 ancestry association and also identify other genomic regions that may harbor prostate cancer susceptibility genes. A total of 482 cases and 261 controls were genotyped for 1,509 ancestry informative markers across the genome. The mean estimated individual admixture proportions were 20% European and 80% African. The most significant observed increase in European ancestry occurred at rs2141360 on chromosome 7q31 in both the case-only (P = 0.0000035) and case-control analyses. The most significant observed increase in African ancestry across the genome occurred at a locus on chromosome 5q35 identified by SNPs rs7729084 (case-only analysis P = 0.002), and rs12474977 (case-control analysis P = 0.004), which are separated by 646 kb and were adjacent to one another on the panel. On chromosome 8, rs4367565 was associated with the greatest excess African ancestry in both the case-only and case-control analyses (case-only and case-control P = 0.02), confirming previously reported African-ancestry associations with chromosome 8q24. In conclusion, we confirmed ancestry associations on 8q24, and identified additional ancestry-associated regions potentially harboring prostate cancer susceptibility loci.

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

    PubMed

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

    2016-08-01

    Breast cancer-related lymphedema (BCRL) is a serious chronic condition after breast cancer (BC) surgery and treatment. It is unclear if BCRL risk varies by race/ethnicity. In a multiethnic prospective cohort study of 2953 BC patients, we examined the association of self-reported BCRL status with self-reported race/ethnicity and estimated genetic ancestry. Hazard ratios (HR) and 95 % confidence intervals (CI) were calculated by multivariable Cox proportional hazards models, with follow-up starting 6 months post-BC diagnosis. Estimates were further stratified by body mass index (BMI). By 48 months of follow-up, 342 (11.6 %) women reported having BCRL. Younger age at BC diagnosis, higher BMI at baseline, and lower physical activity were associated with greater BCRL risk. African American (AA) women had a 2-fold increased risk of BCRL compared with White women (HR = 2.04; 95 % CI 1.35-3.08). African genetic ancestry was also associated with an increased risk (HR = 2.50; 95 % CI 1.43, 4.36). Both risks were attenuated but remained elevated after adjusting for known risk factors and became more pronounced when restricted to the nonobese women (adjusted HR = 2.31 for AA and HR = 3.70 for African ancestry, both p < 0.05). There was also evidence of increased BCRL risk with Hispanic ethnicity in the nonobese women. Nonobese AA women had a higher risk of BCRL than White women, which cannot be fully explained by known risk factors. This is the first large-scale, prospective study demonstrating differences in BCRL risk according to race/ethnicity as assessed by both self-report and genetic ancestry data, with a potential ancestry-obesity interaction. PMID:27449493

  18. Gene-based sequencing identifies lipid-influencing variants with ethnicity-specific effects in African Americans.

    PubMed

    Bentley, Amy R; Chen, Guanjie; Shriner, Daniel; Doumatey, Ayo P; Zhou, Jie; Huang, Hanxia; Mullikin, James C; Blakesley, Robert W; Hansen, Nancy F; Bouffard, Gerard G; Cherukuri, Praveen F; Maskeri, Baishali; Young, Alice C; Adeyemo, Adebowale; Rotimi, Charles N

    2014-03-01

    Although a considerable proportion of serum lipids loci identified in European ancestry individuals (EA) replicate in African Americans (AA), interethnic differences in the distribution of serum lipids suggest that some genetic determinants differ by ethnicity. We conducted a comprehensive evaluation of five lipid candidate genes to identify variants with ethnicity-specific effects. We sequenced ABCA1, LCAT, LPL, PON1, and SERPINE1 in 48 AA individuals with extreme serum lipid concentrations (high HDLC/low TG or low HDLC/high TG). Identified variants were genotyped in the full population-based sample of AA (n = 1694) and tested for an association with serum lipids. rs328 (LPL) and correlated variants were associated with higher HDLC and lower TG. Interestingly, a stronger effect was observed on a "European" vs. "African" genetic background at this locus. To investigate this effect, we evaluated the region among West Africans (WA). For TG, the effect size among WA was the same in AA with only African local ancestry (2-3% lower TG), while the larger association among AA with local European ancestry matched previous reports in EA (10%). For HDLC, there was no association with rs328 in AA with only African local ancestry or in WA, while the association among AA with European local ancestry was much greater than what has been observed for EA (15 vs. ∼ 5 mg/dl), suggesting an interaction with an environmental or genetic factor that differs by ethnicity. Beyond this ancestry effect, the importance of African ancestry-focused, sequence-based work was also highlighted by serum lipid associations of variants that were in higher frequency (or present only) among those of African ancestry. By beginning our study with the sequence variation present in AA individuals, investigating local ancestry effects, and seeking replication in WA, we were able to comprehensively evaluate the role of a set of candidate genes in serum lipids in AA. PMID:24603370

  19. Gene-based sequencing identifies lipid-influencing variants with ethnicity-specific effects in African Americans.

    PubMed

    Bentley, Amy R; Chen, Guanjie; Shriner, Daniel; Doumatey, Ayo P; Zhou, Jie; Huang, Hanxia; Mullikin, James C; Blakesley, Robert W; Hansen, Nancy F; Bouffard, Gerard G; Cherukuri, Praveen F; Maskeri, Baishali; Young, Alice C; Adeyemo, Adebowale; Rotimi, Charles N

    2014-03-01

    Although a considerable proportion of serum lipids loci identified in European ancestry individuals (EA) replicate in African Americans (AA), interethnic differences in the distribution of serum lipids suggest that some genetic determinants differ by ethnicity. We conducted a comprehensive evaluation of five lipid candidate genes to identify variants with ethnicity-specific effects. We sequenced ABCA1, LCAT, LPL, PON1, and SERPINE1 in 48 AA individuals with extreme serum lipid concentrations (high HDLC/low TG or low HDLC/high TG). Identified variants were genotyped in the full population-based sample of AA (n = 1694) and tested for an association with serum lipids. rs328 (LPL) and correlated variants were associated with higher HDLC and lower TG. Interestingly, a stronger effect was observed on a "European" vs. "African" genetic background at this locus. To investigate this effect, we evaluated the region among West Africans (WA). For TG, the effect size among WA was the same in AA with only African local ancestry (2-3% lower TG), while the larger association among AA with local European ancestry matched previous reports in EA (10%). For HDLC, there was no association with rs328 in AA with only African local ancestry or in WA, while the association among AA with European local ancestry was much greater than what has been observed for EA (15 vs. ∼ 5 mg/dl), suggesting an interaction with an environmental or genetic factor that differs by ethnicity. Beyond this ancestry effect, the importance of African ancestry-focused, sequence-based work was also highlighted by serum lipid associations of variants that were in higher frequency (or present only) among those of African ancestry. By beginning our study with the sequence variation present in AA individuals, investigating local ancestry effects, and seeking replication in WA, we were able to comprehensively evaluate the role of a set of candidate genes in serum lipids in AA.

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

    PubMed

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

    2010-12-01

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

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

    PubMed

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

    2009-08-11

    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 achieved

  2. 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

  3. Gene-Based Sequencing Identifies Lipid-Influencing Variants with Ethnicity-Specific Effects in African Americans

    PubMed Central

    Bentley, Amy R.; Chen, Guanjie; Shriner, Daniel; Doumatey, Ayo P.; Zhou, Jie; Huang, Hanxia; Mullikin, James C.; Blakesley, Robert W.; Hansen, Nancy F.; Bouffard, Gerard G.; Cherukuri, Praveen F.; Maskeri, Baishali; Young, Alice C.; Adeyemo, Adebowale; Rotimi, Charles N.

    2014-01-01

    Although a considerable proportion of serum lipids loci identified in European ancestry individuals (EA) replicate in African Americans (AA), interethnic differences in the distribution of serum lipids suggest that some genetic determinants differ by ethnicity. We conducted a comprehensive evaluation of five lipid candidate genes to identify variants with ethnicity-specific effects. We sequenced ABCA1, LCAT, LPL, PON1, and SERPINE1 in 48 AA individuals with extreme serum lipid concentrations (high HDLC/low TG or low HDLC/high TG). Identified variants were genotyped in the full population-based sample of AA (n = 1694) and tested for an association with serum lipids. rs328 (LPL) and correlated variants were associated with higher HDLC and lower TG. Interestingly, a stronger effect was observed on a “European” vs. “African” genetic background at this locus. To investigate this effect, we evaluated the region among West Africans (WA). For TG, the effect size among WA was the same in AA with only African local ancestry (2–3% lower TG), while the larger association among AA with local European ancestry matched previous reports in EA (10%). For HDLC, there was no association with rs328 in AA with only African local ancestry or in WA, while the association among AA with European local ancestry was much greater than what has been observed for EA (15 vs. ∼5 mg/dl), suggesting an interaction with an environmental or genetic factor that differs by ethnicity. Beyond this ancestry effect, the importance of African ancestry-focused, sequence-based work was also highlighted by serum lipid associations of variants that were in higher frequency (or present only) among those of African ancestry. By beginning our study with the sequence variation present in AA individuals, investigating local ancestry effects, and seeking replication in WA, we were able to comprehensively evaluate the role of a set of candidate genes in serum lipids in AA. PMID:24603370

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

    PubMed

    Pool, John E

    2015-12-01

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

  5. 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

  6. Frequencies of immune hypersensitivity reaction-associated HLA class I alleles in healthy South African Indian and mixed ancestry populations determined by a novel real-time PCR assay.

    PubMed

    Loubser, S; Paximadis, M; Gentle, N; Puren, A; Gray, C M; Tiemessen, C T

    2014-10-01

    We have determined the frequencies of human leucocyte antigen (HLA)-B*57:01, HLA-B*35:05, HLA-C*04 and HLA-C*08 in healthy individuals of South African Indian (SAI) ethnicity (n = 50) and South African mixed (SAM) ancestry (n = 50) using real-time allele-specific polymerase chain reaction (AS-PCR) assay. HLA-B*57:01 associates with immune hypersensitivity reaction (IHR) in individuals exposed to abacavir (ABC), while nevirapine (NVP) IHR associates with HLA-B*35:05, HLA-C*04 and HLA-C*08. Real-time AS-PCR assays typically use less DNA, are more cost-effective and rapid compared with conventional genotyping methods, such as sequence-based typing (SBT). The assay was developed using samples of known HLA class I genotype and subsequently applied to the SAI and SAM samples. HLA-B*57:01 was detected in SAM and SAI populations at frequencies of 8.0% and 12.0%, respectively, while HLA-B*35:05 was not found in SAI individuals, but was present in 6.0% of SAM individuals. HLA-C*04 was detected in 22.0% and 24.0% of SAM and SAI individuals, respectively, while 10.0% and 8.0% of SAM and SAI individuals, respectively, were HLA-C*08 positive. This study reports the development of a novel real-time AS-PCR assay to identify HLA class I alleles associated with ABC and NVP IHR and has established the frequencies of these alleles present in healthy SAI and SAM populations. Using South African demographic data, our hypothetical analysis suggests that a substantial number of individuals would benefit from the assay.

  7. Linkage disequilibrium analysis reveals an albuminuria risk haplotype containing three missense mutations in the cubilin gene with striking differences among European and African ancestry populations

    PubMed Central

    2012-01-01

    Background A recent meta-analysis described a variant (p.Ile2984Val) in the cubilin gene (CUBN) that is associated with levels of albuminuria in the general population and in diabetics. Methods We implemented a Linkage Disequilibrium (LD) search with data from the 1000 Genomes Project, on African and European population genomic sequences. Results We found that the p.Ile2984Val variation is part of a larger haplotype in European populations and it is almost absent in west Africans. This haplotype contains 19 single nucleotide polymorphisms (SNPs) in very high LD, three of which are missense mutations (p.Leu2153Phe, p.Ile2984Val, p.Glu3002Gly), and two have not been previously reported. Notably, this European haplotype is absent in west African populations, and the frequency of each individual polymorphism differs significantly in Africans. Conclusions Genotyping of these variants in existing African origin sample sets coupled to measurements of urine albumin excretion levels should reveal which is the most likely functional candidate for albuminuria risk. The unique haplotypic structure of CUBN in different populations may leverage the effort to identify the functional variant and to shed light on evolution of the CUBN gene locus. PMID:23114252

  8. Associations Between Genetic Ancestries and Nicotine Metabolism Biomarkers in the Multiethnic Cohort Study.

    PubMed

    Wang, Hansong; Park, Sungshim L; Stram, Daniel O; Haiman, Christopher A; Wilkens, Lynne R; Hecht, Stephen S; Kolonel, Laurence N; Murphy, Sharon E; Le Marchand, Loïc

    2015-12-01

    Differences in internal dose of nicotine and tobacco-derived carcinogens among ethnic/racial groups have been observed. In this study, we explicitly examined the relationships between genetic ancestries (genome-wide average) and 19 tobacco-derived biomarkers in smokers from 3 admixed groups in the Multiethnic Cohort Study (1993-present), namely, African ancestry in African Americans (n = 362), Amerindian ancestry in Latinos (n = 437), and Asian and Native Hawaiian ancestries in Native Hawaiians (n = 300). After multiple comparison adjustment, both African and Asian ancestries were significantly related to a greater level of free cotinine; African ancestry was also significantly related to lower cotinine glucuronidation (P's < 0.00156). The predicted decrease in cotinine glucuronidation was 8.6% (P = 4.5 × 10(-6)) per a 20% increase in African ancestry. Follow-up admixture mapping revealed that African ancestry in a 12-Mb region on chromosome 4q was related to lower cotinine glucuronidation (P's < 2.7 × 10(-7), smallest P = 1.5 × 10(-9)), although this is the same region reported in our previous genome-wide association study. Our results implicate a genetic ancestral component in the observed ethnic/racial variation in nicotine metabolism. Further studies are needed to identify the underlying genetic variation that could potentially be ethnic/racial specific. PMID:26568573

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

    PubMed Central

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

    2012-01-01

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

  10. Male ancestry structure and interethnic admixture in African-descent communities from the Amazon as revealed by Y-chromosome Strs.

    PubMed

    Palha, Teresinha de Jesus Brabo Ferreira; Ribeiro-Rodrigues, Elzemar Martins; Ribeiro-dos-Santos, Andrea; Guerreiro, João Farias; de Moura, Luciene Soraya Souza; Santos, Sidney

    2011-03-01

    Some genetic markers on both the Y chromosome and mtDNA are highly polymorphic and population-specific in humans, representing useful tools for reconstructing the past history of populations with poor historical records. Such lack of information is usually true in the case of recent African-descent populations of the New World founded by fugitive slaves throughout the slavery period in the Americas, particularly in Brazil, where those communities are known as quilombos. Aiming to recover male-derived ethnic structure of nine quilombos from the Brazilian Amazon, a total of 300 individuals, belonging to Mazagão Velho (N = 24), Curiaú (N = 48), Mazagão (N = 36), Trombetas (N = 20), Itacoã (N = 22), Saracura (N = 46), Marajó (N = 58), Pitimandeua (N = 26), and Pontal (N = 20), were investigated for nine Y-STRs (DYS393, DYS19, DYS390, DYS389 I, DYS389 II, DYS392, DYS391, DYS385 I/II). From the 169 distinct haplotypes obtained, 120 were singletons. The results suggest the West African coast as the main origin of slaves brought to Brazil (54% of male contribution); the European contribution was high (41%), while the Amerindian's was low (5%). Those results contrast with previous mtDNA data that showed high Amerindian female contribution (46.6%) in African-descent populations. AMOVA suggests that the genetic differentiation among the quilombos is mainly influenced by admixture with European. However, when restricting AMOVA to African-specific haplotypes, low differentiation was detected, suggesting great genetic homogeneity of the African founding populations and/or a later homogenization by intense slave trade inside Brazil. PMID:21302273

  11. 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

  12. Genomic Ancestry, Self-Rated Health and Its Association with Mortality in an Admixed Population: 10 Year Follow-Up of the Bambui-Epigen (Brazil) Cohort Study of Ageing

    PubMed Central

    Lima-Costa, M. Fernanda; Macinko, James; Mambrini, Juliana Vaz de Melo; Cesar, Cibele C.; Peixoto, Sérgio V.; Magalhães, Wagner C. S.; Horta, Bernardo L.; Barreto, Mauricio; Castro-Costa, Erico; Firmo, Josélia O. A.; Proietti, Fernando A.; Leal, Thiago Peixoto; Rodrigues, Maira R.; Pereira, Alexandre; Tarazona-Santos, Eduardo

    2015-01-01

    Background Self-rated health (SRH) has strong predictive value for mortality in different contexts and cultures, but there is inconsistent evidence on ethnoracial disparities in SRH in Latin America, possibly due to the complexity surrounding ethnoracial self-classification. Materials/Methods We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual genomic proportions of African, European and Native American ancestry, and ethnoracial self-classification, with baseline and 10-year SRH trajectories in 1,311 community dwelling older Brazilians. We also examined whether genomic ancestry and ethnoracial self-classification affect the predictive value of SRH for subsequent mortality. Results European ancestry predominated among participants, followed by African and Native American (median = 84.0%, 9.6% and 5.3%, respectively); the prevalence of Non-White (Mixed and Black) was 39.8%. Persons at higher levels of African and Native American genomic ancestry, and those self-identified as Non-White, were more likely to report poor health than other groups, even after controlling for socioeconomic conditions and an array of self-reported and objective physical health measures. Increased risks for mortality associated with worse SRH trajectories were strong and remarkably similar (hazard ratio ~3) across all genomic ancestry and ethno-racial groups. Conclusions Our results demonstrated for the first time that higher levels of African and Native American genomic ancestry—and the inverse for European ancestry—were strongly correlated with worse SRH in a Latin American admixed population. Both genomic ancestry and ethnoracial self-classification did not modify the strong association between baseline SRH or SRH trajectory, and subsequent mortality. PMID:26680774

  13. The Global AIMs Nano set: A 31-plex SNaPshot assay of ancestry-informative SNPs.

    PubMed

    de la Puente, M; Santos, C; Fondevila, M; Manzo, L; Carracedo, Á; Lareu, M V; Phillips, C

    2016-05-01

    A 31-plex SNaPshot assay, named 'Global AIMs Nano', has been developed by reassembling the most differentiated markers of the EUROFORGEN Global AIM-SNP set. The SNPs include three tri-allelic loci and were selected with the goal of maintaining a balanced differentiation of: Africans, Europeans, East Asians, Oceanians and Native Americans. The Global AIMs Nano SNP set provides higher divergence between each of the five continental population groups than previous small-scale AIM sets developed for forensic ancestry analysis with SNaPshot. Both of these characteristics minimise potential bias when estimating co-ancestry proportions in individuals with admixed ancestry; more likely to be observed when using markers disproportionately informative for only certain population group comparisons. The optimised multiplex is designed to be easily implemented using standard capillary electrophoresis regimes and has been used to successfully genotype challenging forensic samples from highly degraded material with low level DNA. The ancestry predictive performance of the Global AIMs Nano set has been evaluated by the analysis of samples previously characterised with larger AIM sets. PMID:26881328

  14. 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. PMID:26501420

  15. 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.

  16. 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

  17. Mapping human genetic ancestry.

    PubMed

    Ebersberger, Ingo; Galgoczy, Petra; Taudien, Stefan; Taenzer, Simone; Platzer, Matthias; von Haeseler, Arndt

    2007-10-01

    The human genome is a mosaic with respect to its evolutionary history. Based on a phylogenetic analysis of 23,210 DNA sequence alignments from human, chimpanzee, gorilla, orangutan, and rhesus, we present a map of human genetic ancestry. For about 23% of our genome, we share no immediate genetic ancestry with our closest living relative, the chimpanzee. This encompasses genes and exons to the same extent as intergenic regions. We conclude that about 1/3 of our genes started to evolve as human-specific lineages before the differentiation of human, chimps, and gorillas took place. This explains recurrent findings of very old human-specific morphological traits in the fossils record, which predate the recent emergence of the human species about 5-6 MYA. Furthermore, the sorting of such ancestral phenotypic polymorphisms in subsequent speciation events provides a parsimonious explanation why evolutionary derived characteristics are shared among species that are not each other's closest relatives.

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

    PubMed

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

    2015-05-01

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

  19. Association of Self-Reported Race/Ethnicity and Genetic Ancestry with Arterial Elasticity: The Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Wassel, Christina L.; Jacobs, David R; Duprez, Daniel A.; Bluemke, David A.; Sibley, Christopher T.; Criqui, Michael H.; Peralta, Carmen A.

    2011-01-01

    Background African-Americans have a disproportionate burden of hypertension compared to Caucasians, while data on Hispanics is less well-defined. Mechanisms underlying these differences are unclear, but could be due in part to ancestral background and vascular function. Methods and Results 660 African-Americans and 635 Hispanics from the Multi-Ethnic Study of Atherosclerosis (MESA) with complete data on genetic ancestry, pulse pressure (PP), and large and small arterial elasticity (LAE, SAE) were studied. LAE and SAE were obtained using the HDI PulseWave CR-2000 Research CardioVascular Profiling Instrument. Among African-Americans higher European ancestry was marginally associated with higher LAE (p=0.05) and lower PP (p=0.05) among African-Americans; results for LAE were attenuated after adjustment for potential mediators (p=0.30). Ancestry was not associated with SAE in African-Americans. Among Hispanics, higher Native American ancestry was associated with higher SAE (p=0.0006); higher African ancestry was marginally associated with lower SAE (p=0.07). Ancestry was not significantly associated with LAE or PP in Hispanics. Conclusions Among African-Americans, higher European ancestry may be associated with less large artery damage as measured by LAE and PP, although these associations warrant further study. Among Hispanics, ancestry is strongly associated with SAE. Future studies should consider information on genetic ancestry when studying hypertension burden in race/ethnic minorities, particularly among Hispanics. PMID:21890448

  20. 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.

  1. 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.

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

    PubMed

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

    2016-07-01

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

  3. Ancestry variation and footprints of natural selection along the genome in Latin American populations.

    PubMed

    Deng, Lian; Ruiz-Linares, Andrés; Xu, Shuhua; Wang, Sijia

    2016-01-01

    Latin American populations stem from the admixture of Europeans, Africans and Native Americans, which started over 400 years ago and had lasted for several centuries. Extreme deviation over the genome-wide average in ancestry estimations at certain genomic locations could reflect recent natural selection. We evaluated the distribution of ancestry estimations using 678 genome-wide microsatellite markers in 249 individuals from 13 admixed populations across Latin America. We found significant deviations in ancestry estimations including three locations with more than 3.5 times standard deviations from the genome-wide average: an excess of European ancestry at 1p36 and 14q32, and an excess of African ancestry at 6p22. Using simulations, we could show that at least the deviation at 6p22 was unlikely to result from genetic drift alone. By applying different linguistic groups as well as the most likely ancestral Native American populations as the ancestry, we showed that the choice of Native American ancestry could affect the local ancestry estimation. However, the signal at 6p22 consistently appeared in most of the analyses using various ancestral groups. This study provided important insights for recent natural selection in the context of the unique history of the New World and implications for disease mapping. PMID:26887503

  4. The Genetic Structure and History of Africans and African Americans

    PubMed Central

    Tishkoff, Sarah A.; Reed, Floyd A.; Friedlaender, Françoise R.; Ehret, Christopher; Ranciaro, Alessia; Froment, Alain; Hirbo, Jibril B.; Awomoyi, Agnes A.; Bodo, Jean-Marie; Doumbo, Ogobara; Ibrahim, Muntaser; Juma, Abdalla T.; Kotze, Maritha J.; Lema, Godfrey; Moore, Jason H.; Mortensen, Holly; Nyambo, Thomas B.; Omar, Sabah A.; Powell, Kweli; Pretorius, Gideon S.; Smith, Michael W.; Thera, Mahamadou A.; Wambebe, Charles; Weber, James L.; Williams, Scott M.

    2010-01-01

    Africa is the source of all modern humans, but characterization of genetic variation and of relationships among populations across the continent has been enigmatic. We studied 121 African populations, four African American populations, and 60 non-African populations for patterns of variation at 1327 nuclear microsatellite and insertion/deletion markers. We identified 14 ancestral population clusters in Africa that correlate with self-described ethnicity and shared cultural and/or linguistic properties. We observed high levels of mixed ancestry in most populations, reflecting historical migration events across the continent. Our data also provide evidence for shared ancestry among geographically diverse hunter-gatherer populations (Khoesan speakers and Pygmies). The ancestry of African Americans is predominantly from Niger-Kordofanian (~71%), European (~13%), and other African (~8%) populations, although admixture levels varied considerably among individuals. This study helps tease apart the complex evolutionary history of Africans and African Americans, aiding both anthropological and genetic epidemiologic studies. PMID:19407144

  5. Comparison of Statistical Methods for Estimating Genetic Admixture in a Lung Cancer Study of African Americans and Latinos

    PubMed Central

    Selvin, Steve; Hansen, Helen M.; Barcellos, Lisa F.; Wrensch, Margaret R.; Sison, Jennette D.; Quesenberry, Charles P.; Kittles, Rick A.; Silva, Gabriel; Buffler, Patricia A.; Seldin, Michael F.; Wiencke, John K.

    2008-01-01

    A variety of methods are available for estimating genetic admixture proportions in populations; however, few investigators have conducted detailed comparisons using empirical data. The authors characterized admixture proportions among self-identified African Americans (n = 535) and Latinos (n = 412) living in the San Francisco Bay Area who participated in a lung cancer case-control study (1998–2003). Individual estimates of genetic ancestry based on 184 informative markers were obtained from a Bayesian approach and 2 maximum likelihood approaches and were compared using descriptive statistics, Pearson correlation coefficients, and Bland-Altman plots. Case-control differences in individual admixture proportions were assessed using 2-sample t tests and logistic regression analysis. Results indicated that Bayesian and frequentist approaches to estimating admixture provide similar estimates and inferences. No difference was observed in admixture proportions between African-American cases and controls, but Latino cases and controls significantly differed according to Amerindian and European genetic ancestry. Differences in admixture proportions between Latino cases and controls were not unexpected, since cases were more likely to have been born in the United States. Genetic admixture proportions provide a quantitative measure of ancestry differences among Latinos that can be used in analyses of genetic risk factors. PMID:18791191

  6. The common ancestry of life

    PubMed Central

    2010-01-01

    Background It is common belief that all cellular life forms on earth have a common origin. This view is supported by the universality of the genetic code and the universal conservation of multiple genes, particularly those that encode key components of the translation system. A remarkable recent study claims to provide a formal, homology independent test of the Universal Common Ancestry hypothesis by comparing the ability of a common-ancestry model and a multiple-ancestry model to predict sequences of universally conserved proteins. Results We devised a computational experiment on a concatenated alignment of universally conserved proteins which shows that the purported demonstration of the universal common ancestry is a trivial consequence of significant sequence similarity between the analyzed proteins. The nature and origin of this similarity are irrelevant for the prediction of "common ancestry" of by the model-comparison approach. Thus, homology (common origin) of the compared proteins remains an inference from sequence similarity rather than an independent property demonstrated by the likelihood analysis. Conclusion A formal demonstration of the Universal Common Ancestry hypothesis has not been achieved and is unlikely to be feasible in principle. Nevertheless, the evidence in support of this hypothesis provided by comparative genomics is overwhelming. Reviewers this article was reviewed by William Martin, Ivan Iossifov (nominated by Andrey Rzhetsky) and Arcady Mushegian. For the complete reviews, see the Reviewers' Report section. PMID:21087490

  7. 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

  8. 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

  9. Ancestry dependent DNA methylation and influence of maternal nutrition.

    PubMed

    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

  10. Ancestry reported by white adults with cutaneous melanoma and control subjects in central Alabama

    PubMed Central

    Acton, Ronald T; Barton, Ellen H; Hollowell, William W; Dreibelbis, Amy L; Go, Rodney CP; Barton, James C

    2004-01-01

    Background We sought to evaluate the hypothesis that the high incidence of cutaneous melanoma in white persons in central Alabama is associated with a predominance of Irish and Scots descent. Methods Frequencies of country of ancestry reports were tabulated. The reports were also converted to scores that reflect proportional countries of ancestry in individuals. Using the scores, we computed aggregate country of ancestry indices as estimates of group ancestry composition. HLA-DRB1*04 allele frequencies and relationships to countries of ancestry were compared in probands and controls. Results were compared to those of European populations with HLA-DRB1*04 frequencies. Results Ninety evaluable adult white cutaneous melanoma probands and 324 adult white controls reported countries of ancestry of their grandparents. The respective frequencies of Ireland, and Scotland and "British Isles" reported countries of ancestry were significantly greater in probands than in controls. The respective frequencies of Wales, France, Italy and Poland were significantly greater in controls. 16.7% of melanoma probands and 23.8% of controls reported "Native American" ancestry; the corresponding "Native American" country of ancestry index was not significantly different in probands and controls. The frequency of HLA-DRB1*04 was significantly greater in probands, but was not significantly associated with individual or aggregate countries of ancestry. The frequency of DRB1*04 observed in Alabama was compared to DRB1*04 frequencies reported from England, Wales, Ireland, Orkney Island, France, Germany, and Australia. Conclusion White adults with cutaneous melanoma in central Alabama have a predominance of Irish, Scots, and "British Isles" ancestry and HLA-DRB1*04 that likely contributes to their high incidence of cutaneous melanoma. PMID:15310399

  11. Men of African Descent and Carcinoma of the Prostate Consortium

    Cancer.gov

    The Men of African Descent and Carcinoma of the Prostate Consortium collaborates on epidemiologic studies to address the high burden of prostate cancer and to understand the causes of etiology and outcomes among men of African ancestry.

  12. Estimating ancestral proportions in a multi-ethnic US sample: implications for studies of admixed populations.

    PubMed

    Levran, Orna; Awolesi, Olaoluwakitan; Shen, Pei-Hong; Adelson, Miriam; Kreek, Mary Jeanne

    2012-07-05

    This study was designed to determine the ancestral composition of a multi-ethnic sample collected for studies of drug addictions in New York City and Las Vegas, and to examine the reliability of self-identified ethnicity and three-generation family history data. Ancestry biographical scores for seven clusters corresponding to world major geographical regions were obtained using STRUCTURE, based on genotypes of 168 ancestry informative markers (AIMs), for a sample of 1,291 African Americans (AA), European Americans (EA), and Hispanic Americans (HA) along with data from 1,051 HGDP-CEPH 'diversity panel' as a reference. Self-identified ethnicity and family history data, obtained in an interview, were accurate in identifying the individual major ancestry in the AA and the EA samples (approximately 99% and 95%, respectively) but were not useful for the HA sample and could not predict the extent of admixture in any group. The mean proportions of the combined clusters corresponding to European and Middle Eastern populations in the AA sample, revealed by AIMs analysis, were 0.13. The HA subjects, predominantly Puerto Ricans, showed a highly variable hybrid contribution pattern of clusters corresponding to Europe (0.27), Middle East (0.27), Africa (0.20), and Central Asia (0.14). The effect of admixture on allele frequencies is demonstrated for two single-nucleotide polymorphisms (118A > G, 17 C > T) of the mu opioid receptor gene (OPRM1). This study reiterates the importance of AIMs in defining ancestry, especially in admixed populations.

  13. 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

  14. 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.

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

    PubMed Central

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

    2014-01-01

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

  16. Genetic ancestry is associated with colorectal adenomas and adenocarcinomas in Latino populations.

    PubMed

    Hernandez-Suarez, Gustavo; Sanabria, Maria Carolina; Serrano, Marta; Herran, Oscar F; Perez, Jesus; Plata, Jose L; Zabaleta, Jovanny; Tenesa, Albert

    2014-10-01

    Colorectal cancer rates in Latin American countries are less than half of those observed in the United States. Latin Americans are the resultant of generations of an admixture of Native American, European, and African individuals. The potential role of genetic admixture in colorectal carcinogenesis has not been examined. We evaluate the association of genetic ancestry with colorectal neoplasms in 190 adenocarcinomas, 113 sporadic adenomas and 243 age- and sex-matched controls enrolled in a multicentric case-control study in Colombia. Individual ancestral genetic fractions were estimated using the STRUCTURE software, based on allele frequencies and assuming three distinct population origins. We used the Illumina Cancer Panel to genotype 1,421 sparse single-nucleotide polymorphisms (SNPs), and Northern and Western European ancestry, LWJ and Han Chinese in Beijing, China populations from the HapMap project as references. A total of 678 autosomal SNPs overlapped with the HapMap data set SNPs and were used for ancestry estimations. African mean ancestry fraction was higher in adenomas (0.13, 95% confidence interval (95% CI)=0.11-0.15) and cancer cases (0.14, 95% CI=0.12-0.16) compared with controls (0.11, 95% CI=0.10-0.12). Conditional logistic regression analysis, controlling for known risk factors, showed a positive association of African ancestry per 10% increase with both colorectal adenoma (odds ratio (OR)=1.12, 95% CI=0.97-1.30) and adenocarcinoma (OR=1.19, 95% CI=1.05-1.35). In conclusion, increased African ancestry (or variants linked to it) contributes to the increased susceptibility of colorectal cancer in admixed Latin American population. PMID:24518838

  17. 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

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

    PubMed

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

    2012-07-01

    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.

  19. Adjustment for local ancestry in genetic association analysis of admixed populations

    PubMed Central

    Wang, Xuexia; Zhu, Xiaofeng; Qin, Huaizhen; Cooper, Richard S.; Ewens, Warren J.; Li, Chun; Li, Mingyao

    2011-01-01

    Motivation: Admixed populations offer a unique opportunity for mapping diseases that have large disease allele frequency differences between ancestral populations. However, association analysis in such populations is challenging because population stratification may lead to association with loci unlinked to the disease locus. Methods and results: We show that local ancestry at a test single nucleotide polymorphism (SNP) may confound with the association signal and ignoring it can lead to spurious association. We demonstrate theoretically that adjustment for local ancestry at the test SNP is sufficient to remove the spurious association regardless of the mechanism of population stratification, whether due to local or global ancestry differences among study subjects; however, global ancestry adjustment procedures may not be effective. We further develop two novel association tests that adjust for local ancestry. Our first test is based on a conditional likelihood framework which models the distribution of the test SNP given disease status and flanking marker genotypes. A key advantage of this test lies in its ability to incorporate different directions of association in the ancestral populations. Our second test, which is computationally simpler, is based on logistic regression, with adjustment for local ancestry proportion. We conducted extensive simulations and found that the Type I error rates of our tests are under control; however, the global adjustment procedures yielded inflated Type I error rates when stratification is due to local ancestry difference. Contact: mingyao@upenn.edu; chun.li@vanderbilt.edu. Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21169375

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

    PubMed

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

    2012-07-15

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

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

    PubMed Central

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

    2015-01-01

    Breast cancer (BC) is the most common newly diagnosed cancer among women in Trinidad and Tobago (TT) and BC mortality rates are among the highest in the world. Globally, racial/ethnic trends in BC incidence, mortality and survival have been reported. However, such investigations have not been conducted in TT, which has been noted for its rich diversity. In this study, we investigated associations among ancestry, geography and BC incidence, mortality and survival in TT. Data on 3767 incident BC cases, reported to the National Cancer Registry of TT, from 1995 to 2007, were analyzed in this study. Women of African ancestry had significantly higher BC incidence and mortality rates (Incidence: 66.96; Mortality: 30.82 per 100,000) compared to women of East Indian (Incidence: 41.04, Mortality: 14.19 per 100,000) or mixed ancestry (Incidence: 36.72, Mortality: 13.80 per 100,000). Geographically, women residing in the North West Regional Health Authority (RHA) catchment area followed by the North Central RHA exhibited the highest incidence and mortality rates. Notable ancestral differences in survival were also observed. Women of East Indian and mixed ancestry experienced significantly longer survival than those of African ancestry. Differences in survival by geography were not observed. In TT, ancestry and geographical residence seem to be strong predictors of BC incidence and mortality rates. Additionally, disparities in survival by ancestry were found. These data should be considered in the design and implementation of strategies to reduce BC incidence and mortality rates in TT. PMID:26338451

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

    PubMed

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

    2012-09-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Lao, Oscar; Vallone, Peter M; Coble, Michael D; Diegoli, Toni M; van Oven, Mannis; van der Gaag, Kristiaan J; Pijpe, Jeroen; de Knijff, Peter; Kayser, Manfred

    2010-12-01

    The current U.S. population represents an amalgam of individuals originating mainly from four continental regions (Africa, Europe, Asia and America). To study the genetic ancestry and compare with self-declared ancestry we have analyzed paternally, maternally and bi-parentally inherited DNA markers sensitive for indicating continental genetic ancestry in all four major U.S. American groups. We found that self-declared U.S. Hispanics and U.S. African Americans tend to show variable degrees of continental genetic admixture among the three genetic systems, with evidence for a marked sex-biased admixture history. Moreover, for these two groups we observed significant regional variation across the country in genetic admixture. In contrast, self-declared U.S. European and U.S. Asian Americans were genetically more homogeneous at the continental ancestry level. Two autosomal ancestry-sensitive markers located in skin pigmentation candidate genes showed significant differences in self-declared U.S. African Americans or U.S. European Americans, relative to their assumed parental populations from Africa or Europe. This provides genetic support for the importance of skin color in the complex process of ancestry identification.

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

    PubMed Central

    2010-01-01

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

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

    PubMed

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

    2016-05-01

    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.

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

    PubMed

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

    2016-05-01

    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. PMID:27032491

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

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

  11. Eurasiaplex: a forensic SNP assay for differentiating European and South Asian ancestries.

    PubMed

    Phillips, C; Freire Aradas, A; Kriegel, A K; Fondevila, M; Bulbul, O; Santos, C; Serrulla Rech, F; Perez Carceles, M D; Carracedo, Á; Schneider, P M; Lareu, M V

    2013-05-01

    We have selected a set of single nucleotide polymorphisms (SNPs) with the specific aim of differentiating European and South Asian ancestries. The SNPs were combined into a 23-plex SNaPshot primer extension assay: Eurasiaplex, designed to complement an existing 34-plex forensic ancestry test with both marker sets occupying well-spaced genomic positions, enabling their combination as single profile submissions to the Bayesian Snipper forensic ancestry inference system. We analyzed the ability of Eurasiaplex plus 34plex SNPs to assign ancestry to a total 1648 profiles from 16 European, 7 Middle East, 13 Central-South Asian and 21 East Asian populations. Ancestry assignment likelihoods were estimated from Snipper using training sets of five-group data (three Eurasian groups, East Asian and African genotypes) and four-group data (Middle East genotypes removed). Five-group differentiations gave assignment success of 91% for NW European populations, 72% for Middle East populations and 39% for Central-South Asian populations, indicating Middle East individuals are not reliably differentiated from either Europeans or Central-South Asians. Four-group differentiations provided markedly improved assignment success rates of 97% for most continental Europeans tested (excluding Turkish and Adygei at the far eastern edge of Europe) and 95% for Central-South Asians, despite applying a probability threshold for the highest likelihood ratio above '100 times more likely'. As part of the assessment of the sensitivity of Eurasiaplex to analyze challenging forensic material we detail Eurasiaplex and 34-plex SNP typing to infer ancestry of a cranium recovered from the sea, achieving 82% SNP genotype completeness. Therefore, Eurasiaplex provides an informative and forensically robust approach to the differentiation of European and South Asian ancestries amongst Eurasian populations.

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

    PubMed

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

    2015-12-01

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

  13. 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.

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

    PubMed

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

    2016-01-01

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

  15. 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

  16. 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

  17. Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults.

    PubMed

    Chen, Fang; He, Jing; Zhang, Jianqi; Chen, Gary K; Thomas, Venetta; Ambrosone, Christine B; Bandera, Elisa V; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Cai, Qiuyin; Carpten, John; Casey, Graham; Chanock, Stephen J; Cheng, Iona; Chu, Lisa; Deming, Sandra L; Driver, W Ryan; Goodman, Phyllis; Hayes, Richard B; Hennis, Anselm J M; Hsing, Ann W; Hu, Jennifer J; Ingles, Sue A; John, Esther M; Kittles, Rick A; Kolb, Suzanne; Leske, M Cristina; Millikan, Robert C; Monroe, Kristine R; Murphy, Adam; Nemesure, Barbara; Neslund-Dudas, Christine; Nyante, Sarah; Ostrander, Elaine A; Press, Michael F; Rodriguez-Gil, Jorge L; Rybicki, Ben A; Schumacher, Fredrick; Stanford, Janet L; Signorello, Lisa B; Strom, Sara S; Stevens, Victoria; Van Den Berg, David; Wang, Zhaoming; Witte, John S; Wu, Suh-Yuh; Yamamura, Yuko; Zheng, Wei; Ziegler, Regina G; Stram, Alexander H; Kolonel, Laurence N; Le Marchand, Loïc; Henderson, Brian E; Haiman, Christopher A; Stram, Daniel O

    2015-01-01

    Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability

  18. Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults

    PubMed Central

    Chen, Fang; He, Jing; Zhang, Jianqi; Chen, Gary K.; Thomas, Venetta; Ambrosone, Christine B.; Bandera, Elisa V.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Cai, Qiuyin; Carpten, John; Casey, Graham; Chanock, Stephen J.; Cheng, Iona; Chu, Lisa; Deming, Sandra L.; Driver, W. Ryan; Goodman, Phyllis; Hayes, Richard B.; Hennis, Anselm J. M.; Hsing, Ann W.; Hu, Jennifer J.; Ingles, Sue A.; John, Esther M.; Kittles, Rick A.; Kolb, Suzanne; Leske, M. Cristina; Monroe, Kristine R.; Murphy, Adam; Nemesure, Barbara; Neslund-Dudas, Christine; Nyante, Sarah; Ostrander, Elaine A; Press, Michael F.; Rodriguez-Gil, Jorge L.; Rybicki, Ben A.; Schumacher, Fredrick; Stanford, Janet L.; Signorello, Lisa B.; Strom, Sara S.; Stevens, Victoria; Van Den Berg, David; Wang, Zhaoming; Witte, John S.; Wu, Suh-Yuh; Yamamura, Yuko; Zheng, Wei; Ziegler, Regina G.; Stram, Alexander H.; Kolonel, Laurence N.; Marchand, Loïc Le; Henderson, Brian E.; Haiman, Christopher A.; Stram, Daniel O.

    2015-01-01

    Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability

  19. 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

  20. 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

    2013-04-01

    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

  1. 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.

  2. 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. PMID:26104010

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

    PubMed

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

    2015-12-29

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

    2012-01-01

    Background Populations of the Americas were founded by early migrants from Asia, and some have experienced recent genetic admixture. To better characterize the native and non-native ancestry components in populations from the Americas, we analyzed 815,377 autosomal SNPs, mitochondrial hypervariable segments I and II, and 36 Y-chromosome STRs from 24 Mesoamerican Totonacs and 23 South American Bolivians. Results and Conclusions We analyzed common genomic regions from native Bolivian and Totonac populations to identify 324 highly predictive Native American ancestry informative markers (AIMs). As few as 40–50 of these AIMs perform nearly as well as large panels of random genome-wide SNPs for predicting and estimating Native American ancestry and admixture levels. These AIMs have greater New World vs. Old World specificity than previous AIMs sets. We identify highly-divergent New World SNPs that coincide with high-frequency haplotypes found at similar frequencies in all populations examined, including the HGDP Pima, Maya, Colombian, Karitiana, and Surui American populations. Some of these regions are potential candidates for positive selection. European admixture in the Bolivian sample is approximately 12%, though individual estimates range from 0–48%. We estimate that the admixture occurred ~360–384 years ago. Little evidence of European or African admixture was found in Totonac individuals. Bolivians with pre-Columbian mtDNA and Y-chromosome haplogroups had 5–30% autosomal European ancestry, demonstrating the limitations of Y-chromosome and mtDNA haplogroups and the need for autosomal ancestry informative markers for assessing ancestry in admixed populations. PMID:22606979

  8. A genome-wide admixture scan identifies MYH9 as a candidate locus associated with non-diabetic end stage renal disease in African Americans

    PubMed Central

    Linda Kao, WH; Klag, Michael J; Meoni, Lucy A; Reich, David; Berthier-Schaad, Yvette; Li, Man; Coresh, Josef; Patterson, Nick; Tandon, Arti; Powe, Neil R; Fink, Nancy E; Sadler, John H; Weir, Matthew R; Abboud, Hanna E; Adler, Sharon; Divers, Jasmin; Iyengar, Sudha K; Freedman, Barry I; Kimmel, Paul L; Knowler, William C; Kohn, Orly F; Kramp, Kristopher; Leehey, David J; Nicholas, Susanne; Pahl, Madeleine; Schelling, Jeffrey R; Sedor, John R; Thornley-Brown, Denyse; Winkler, Cheryl A; Smith, Michael W.; Parekh, Rulan S.

    2008-01-01

    End stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans. This led to the hypothesis that susceptibility alleles for ESRD have a higher frequency in West African than European gene pool. We performed a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and demonstrated a highly significant association between excess African ancestry and non-diabetic ESRD (LOD 5.70) but not diabetic ESRD (LOD 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% credible interval 0.39 – 0.63) compared to African ancestry. Multiple common SNPs (allele frequency ranging from 0.2 to 0.6) in the gene that encodes non-muscle myosin heavy chain type II isoform A (MYH9) were associated with 2-4 times greater risk of non-diabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans. PMID:18794854

  9. Selection and reduced population size cannot explain higher amounts of Neandertal ancestry in East Asian than in European human populations.

    PubMed

    Kim, Bernard Y; Lohmueller, Kirk E

    2015-03-01

    It has been hypothesized that the greater proportion of Neandertal ancestry in East Asians than in Europeans is due to the fact that purifying selection is less effective at removing weakly deleterious Neandertal alleles from East Asian populations. Using simulations of a broad range of models of selection and demography, we have shown that this hypothesis cannot account for the higher proportion of Neandertal ancestry in East Asians than in Europeans. Instead, more complex demographic scenarios, most likely involving multiple pulses of Neandertal admixture, are required to explain the data.

  10. Selection and Reduced Population Size Cannot Explain Higher Amounts of Neandertal Ancestry in East Asian than in European Human Populations

    PubMed Central

    Kim, Bernard Y.; Lohmueller, Kirk E.

    2015-01-01

    It has been hypothesized that the greater proportion of Neandertal ancestry in East Asians than in Europeans is due to the fact that purifying selection is less effective at removing weakly deleterious Neandertal alleles from East Asian populations. Using simulations of a broad range of models of selection and demography, we have shown that this hypothesis cannot account for the higher proportion of Neandertal ancestry in East Asians than in Europeans. Instead, more complex demographic scenarios, most likely involving multiple pulses of Neandertal admixture, are required to explain the data. PMID:25683122

  11. 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. PMID:25047253

  12. 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

  13. 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…

  14. Genetic architecture of skin and eye color in an African-European admixed population.

    PubMed

    Beleza, Sandra; Johnson, Nicholas A; Candille, Sophie I; Absher, Devin M; Coram, Marc A; Lopes, Jailson; Campos, Joana; Araújo, Isabel Inês; Anderson, Tovi M; Vilhjálmsson, Bjarni J; Nordborg, Magnus; Correia E Silva, António; Shriver, Mark D; Rocha, Jorge; Barsh, Gregory S; Tang, Hua

    2013-03-01

    Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3 × 10(-62), SLC24A5 P = 9.6 × 10(-9)) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4 × 10(-27), TYR P = 1.1 × 10(-9), APBA2[OCA2] P = 1.5 × 10(-8), SLC45A2 P = 6 × 10(-9)) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (~44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ~70% of the estimated heritability.

  15. Application of FORDISC 3.0 to explore differences among crania of North American and South African blacks and whites.

    PubMed

    L'Abbé, Ericka N; Kenyhercz, Michael; Stull, Kyra E; Keough, Natalie; Nawrocki, Stephen

    2013-11-01

    Using discriminant function analysis, classification accuracies for ancestry and sex in white and black South Africans were compared using North American (FDB), African groups in Howells (HDB), and South African (SADB) databases in FORDISC 3.0. (FD3). Twenty-four standard linear measures were collected from a total of 86 black and 101 white crania obtained from the Pretoria Bone Collection. White and black South Africans classified 73% correctly in FDB, 55% correctly in HDB, and 71% correctly in SADB. The percentage of atypical cases was higher with FDB than SADB. In all three databases, misclassification occurred more with sex than ancestry revealing differences in sexual dimorphism between population groups. Broad ancestral differences may explain low misclassification rates for ancestry. FD3, with a modern South African reference sample, can assist South African anthropologists to standardize methodology and to justify procedures for estimating ancestry.

  16. Genetic ancestry of a Moroccan population as inferred from autosomal STRs

    PubMed Central

    Bentayebi, K.; Abada, F.; Ihzmad, H.; Amzazi, S.

    2014-01-01

    Detecting population substructure and ancestry is a critical issue for both association studies of health behaviors and forensic genetics. Determining aspects of a population's genetic history as potential sources of substructure can aid in design of future genetic studies. Within this context, fifteen autosomal short tandem repeat (STR), were used to examine population genetic structure and hypotheses of the origin of the modern Moroccan population from individuals belonging to three different ethnical groups from Morocco (Arab, Berber and Sahrawi), by comparing their autosomal STR variation with that of neighboring and non-neighboring populations in North Africa, Europe and Middle East as well as proposed ancestral populations in Morocco (Berber). We report on the results that the gradient of North African ancestry accounts for previous observations of low levels of sharing with Near East and a substantially increased gene flow especially from Morocco and Spain. PMID:25606427

  17. 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.

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

    PubMed Central

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

    2014-01-01

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

  19. 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

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

    PubMed

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

    2014-01-01

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

  1. 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

  2. Exploring the Y Chromosomal Ancestry of Modern Panamanians.

    PubMed

    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

  3. Genome-wide genotype and sequence-based reconstruction of the 140,000 year history of modern human ancestry.

    PubMed

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

    2014-01-01

    We investigated ancestry of 3,528 modern humans from 163 samples. We identified 19 ancestral components, with 94.4% of individuals showing mixed ancestry. After using whole genome sequences to correct for ascertainment biases in genome-wide genotype data, we dated the oldest divergence event to 140,000 years ago. We detected an Out-of-Africa migration 100,000-87,000 years ago, leading to peoples of the Americas, east and north Asia, and Oceania, followed by another migration 61,000-44,000 years ago, leading to peoples of the Caucasus, Europe, the Middle East, and south Asia. We dated eight divergence events to 33,000-20,000 years ago, coincident with the Last Glacial Maximum. We refined understanding of the ancestry of several ethno-linguistic groups, including African Americans, Ethiopians, the Kalash, Latin Americans, Mozabites, Pygmies, and Uygurs, as well as the CEU sample. Ubiquity of mixed ancestry emphasizes the importance of accounting for ancestry in history, forensics, and health. PMID:25116736

  4. Genome-wide genotype and sequence-based reconstruction of the 140,000 year history of modern human ancestry

    PubMed Central

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

    2014-01-01

    We investigated ancestry of 3,528 modern humans from 163 samples. We identified 19 ancestral components, with 94.4% of individuals showing mixed ancestry. After using whole genome sequences to correct for ascertainment biases in genome-wide genotype data, we dated the oldest divergence event to 140,000 years ago. We detected an Out-of-Africa migration 100,000–87,000 years ago, leading to peoples of the Americas, east and north Asia, and Oceania, followed by another migration 61,000–44,000 years ago, leading to peoples of the Caucasus, Europe, the Middle East, and south Asia. We dated eight divergence events to 33,000–20,000 years ago, coincident with the Last Glacial Maximum. We refined understanding of the ancestry of several ethno-linguistic groups, including African Americans, Ethiopians, the Kalash, Latin Americans, Mozabites, Pygmies, and Uygurs, as well as the CEU sample. Ubiquity of mixed ancestry emphasizes the importance of accounting for ancestry in history, forensics, and health. PMID:25116736

  5. The Great Migration and African-American Genomic Diversity

    PubMed Central

    Barakatt, Maxime; Gignoux, Christopher R.; Errington, Jacob; Blot, William J.; Bustamante, Carlos D.; Kenny, Eimear E.; Williams, Scott M.; Aldrich, Melinda C.; Gravel, Simon

    2016-01-01

    We present a comprehensive assessment of genomic diversity in the African-American population by studying three genotyped cohorts comprising 3,726 African-Americans from across the United States that provide a representative description of the population across all US states and socioeconomic status. An estimated 82.1% of ancestors to African-Americans lived in Africa prior to the advent of transatlantic travel, 16.7% in Europe, and 1.2% in the Americas, with increased African ancestry in the southern United States compared to the North and West. Combining demographic models of ancestry and those of relatedness suggests that admixture occurred predominantly in the South prior to the Civil War and that ancestry-biased migration is responsible for regional differences in ancestry. We find that recent migrations also caused a strong increase in genetic relatedness among geographically distant African-Americans. Long-range relatedness among African-Americans and between African-Americans and European-Americans thus track north- and west-bound migration routes followed during the Great Migration of the twentieth century. By contrast, short-range relatedness patterns suggest comparable mobility of ∼15–16km per generation for African-Americans and European-Americans, as estimated using a novel analytical model of isolation-by-distance. PMID:27232753

  6. The Great Migration and African-American Genomic Diversity.

    PubMed

    Baharian, Soheil; Barakatt, Maxime; Gignoux, Christopher R; Shringarpure, Suyash; Errington, Jacob; Blot, William J; Bustamante, Carlos D; Kenny, Eimear E; Williams, Scott M; Aldrich, Melinda C; Gravel, Simon

    2016-05-01

    We present a comprehensive assessment of genomic diversity in the African-American population by studying three genotyped cohorts comprising 3,726 African-Americans from across the United States that provide a representative description of the population across all US states and socioeconomic status. An estimated 82.1% of ancestors to African-Americans lived in Africa prior to the advent of transatlantic travel, 16.7% in Europe, and 1.2% in the Americas, with increased African ancestry in the southern United States compared to the North and West. Combining demographic models of ancestry and those of relatedness suggests that admixture occurred predominantly in the South prior to the Civil War and that ancestry-biased migration is responsible for regional differences in ancestry. We find that recent migrations also caused a strong increase in genetic relatedness among geographically distant African-Americans. Long-range relatedness among African-Americans and between African-Americans and European-Americans thus track north- and west-bound migration routes followed during the Great Migration of the twentieth century. By contrast, short-range relatedness patterns suggest comparable mobility of ∼15-16km per generation for African-Americans and European-Americans, as estimated using a novel analytical model of isolation-by-distance. PMID:27232753

  7. The Great Migration and African-American Genomic Diversity.

    PubMed

    Baharian, Soheil; Barakatt, Maxime; Gignoux, Christopher R; Shringarpure, Suyash; Errington, Jacob; Blot, William J; Bustamante, Carlos D; Kenny, Eimear E; Williams, Scott M; Aldrich, Melinda C; Gravel, Simon

    2016-05-01

    We present a comprehensive assessment of genomic diversity in the African-American population by studying three genotyped cohorts comprising 3,726 African-Americans from across the United States that provide a representative description of the population across all US states and socioeconomic status. An estimated 82.1% of ancestors to African-Americans lived in Africa prior to the advent of transatlantic travel, 16.7% in Europe, and 1.2% in the Americas, with increased African ancestry in the southern United States compared to the North and West. Combining demographic models of ancestry and those of relatedness suggests that admixture occurred predominantly in the South prior to the Civil War and that ancestry-biased migration is responsible for regional differences in ancestry. We find that recent migrations also caused a strong increase in genetic relatedness among geographically distant African-Americans. Long-range relatedness among African-Americans and between African-Americans and European-Americans thus track north- and west-bound migration routes followed during the Great Migration of the twentieth century. By contrast, short-range relatedness patterns suggest comparable mobility of ∼15-16km per generation for African-Americans and European-Americans, as estimated using a novel analytical model of isolation-by-distance.

  8. Strip Diagrams: Illuminating Proportions

    ERIC Educational Resources Information Center

    Cohen, Jessica S.

    2013-01-01

    Proportional reasoning is both complex and layered, making it challenging to define. Lamon (1999) identified characteristics of proportional thinkers, such as being able to understand covariance of quantities; distinguish between proportional and nonproportional relationships; use a variety of strategies flexibly, most of which are nonalgorithmic,…

  9. Ancestry assessment using random forest modeling.

    PubMed

    Hefner, Joseph T; Spradley, M Kate; Anderson, Bruce

    2014-05-01

    A skeletal assessment of ancestry relies on morphoscopic traits and skeletal measurements. Using a sample of American Black (n = 38), American White (n = 39), and Southwest Hispanics (n = 72), the present study investigates whether these data provide similar biological information and combines both data types into a single classification using a random forest model (RFM). Our results indicate that both data types provide similar information concerning the relationships among population groups. Also, by combining both in an RFM, the correct allocation of ancestry for an unknown cranium increases. The distribution of cross-validated grouped cases correctly classified using discriminant analyses and RFMs ranges between 75.4% (discriminant function analysis, morphoscopic data only) and 89.6% (RFM). Unlike the traditional, experience-based approach using morphoscopic traits, the inclusion of both data types in a single analysis is a quantifiable approach accounting for more variation within and between groups, reducing misclassification rates, and capturing aspects of cranial shape, size, and morphology.

  10. Russia's Literary Genius Alexander Pushkin: The Great-Grandson of an African Slave.

    ERIC Educational Resources Information Center

    Lounsbery, Anne

    2000-01-01

    Alexander Pushkin, Russia's most celebrated literary figure, descended from an African slave. On both parents' sides, he was related to Avram Petrovich Gannibal, who was born to an African prince and abducted to become a slave to a Russian diplomat. Pushkin chose to pride himself on both his aristocratic life and his African ancestry. (SM)

  11. 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

  12. 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.

  13. Completion of a worldwide reference panel of samples for an ancestry informative Indel assay.

    PubMed

    Santos, Carla; Phillips, Christopher; Oldoni, Fabio; Amigo, Jorge; Fondevila, Manuel; Pereira, Rui; Carracedo, Ángel; Lareu, Maria Victoria

    2015-07-01

    The use of ancestry informative markers (AIMs) in forensic analysis is of considerable utility since ancestry inference can progress an investigation when no identification has been made of DNA from the crime-scene. Short-amplicon markers, including insertion deletion polymorphisms, are particularly useful in forensic analysis due to their mutational stability, capacity to amplify degraded samples and straightforward amplification technique. In this study we report the completion of H952 HGDP-CEPH panel genotyping with a set of 46 AIM-Indels. The study adds Central South Asian and Middle Eastern population data, allowing a comparison of patterns of variation in Eurasia for these markers, in order to enhance their use in forensic analyses, particularly when combined with sets of ancestry informative SNPs. Ancestry analysis using principal component analysis and Bayesian methods indicates that a proportion of classification error occurs with European-Middle East population comparisons, but the 46 AIM-Indels have the capability to differentiate six major population groups when European-Central South Asian comparisons are made. These findings have relevance for forensic ancestry analyses in countries where South Asians form much of the demographic profile, including the UK, USA and South Africa. A novel third allele detected in MID-548 was characterized - despite a low frequency in the HGDP-CEPH panel samples, it appears confined to Central South Asian populations, increasing the ability to differentiate this population group. The H952 data set was implemented in a new open access SPSmart frequency browser - forInDel: Forensic Indel browser. PMID:25840342

  14. 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. PMID:27297995

  15. Managed European-Derived Honey Bee, Apis mellifera sspp, Colonies Reduce African-Matriline Honey Bee, A. m. scutellata, Drones at Regional Mating Congregations.

    PubMed

    Mortensen, Ashley N; Ellis, James D

    2016-01-01

    African honey bees (Apis mellifera scutellata) dramatically changed the South American beekeeping industry as they rapidly spread through the Americas following their introduction into Brazil. In the present study, we aimed to determine if the management of European-derived honey bees (A. mellifera sspp.) could reduce the relative abundance of African-matriline drones at regional mating sites known as drone congregation areas (DCAs). We collected 2,400 drones at six DCAs either 0.25 km or >2.8 km from managed European-derived honey bee apiaries. The maternal ancestry of each drone was determined by Bgl II enzyme digestion of an amplified portion of the mitochondrial Cytochrome b gene. Furthermore, sibship reconstruction via nuclear microsatellites was conducted for a subset of 1,200 drones to estimate the number of colonies contributing drones to each DCA. Results indicate that DCAs distant to managed European apiaries (>2.8 km) had significantly more African-matriline drones (34.33% of the collected drones had African mitochondrial DNA) than did DCAs close (0.25 km) to managed European apiaries (1.83% of the collected drones had African mitochondrial DNA). Furthermore, nuclear sibship reconstruction demonstrated that the reduction in the proportion of African matriline drones at DCAs near apiaries was not simply an increase in the number of European matriline drones at the DCAs but also the result of fewer African matriline colonies contributing drones to the DCAs. Our data demonstrate that the management of European honey bee colonies can dramatically influence the proportion of drones with African matrilines at nearby drone congregation areas, and would likely decreasing the probability that virgin European queens will mate with African drones at those drone congregation areas.

  16. Managed European-Derived Honey Bee, Apis mellifera sspp, Colonies Reduce African-Matriline Honey Bee, A. m. scutellata, Drones at Regional Mating Congregations.

    PubMed

    Mortensen, Ashley N; Ellis, James D

    2016-01-01

    African honey bees (Apis mellifera scutellata) dramatically changed the South American beekeeping industry as they rapidly spread through the Americas following their introduction into Brazil. In the present study, we aimed to determine if the management of European-derived honey bees (A. mellifera sspp.) could reduce the relative abundance of African-matriline drones at regional mating sites known as drone congregation areas (DCAs). We collected 2,400 drones at six DCAs either 0.25 km or >2.8 km from managed European-derived honey bee apiaries. The maternal ancestry of each drone was determined by Bgl II enzyme digestion of an amplified portion of the mitochondrial Cytochrome b gene. Furthermore, sibship reconstruction via nuclear microsatellites was conducted for a subset of 1,200 drones to estimate the number of colonies contributing drones to each DCA. Results indicate that DCAs distant to managed European apiaries (>2.8 km) had significantly more African-matriline drones (34.33% of the collected drones had African mitochondrial DNA) than did DCAs close (0.25 km) to managed European apiaries (1.83% of the collected drones had African mitochondrial DNA). Furthermore, nuclear sibship reconstruction demonstrated that the reduction in the proportion of African matriline drones at DCAs near apiaries was not simply an increase in the number of European matriline drones at the DCAs but also the result of fewer African matriline colonies contributing drones to the DCAs. Our data demonstrate that the management of European honey bee colonies can dramatically influence the proportion of drones with African matrilines at nearby drone congregation areas, and would likely decreasing the probability that virgin European queens will mate with African drones at those drone congregation areas. PMID:27518068

  17. Coincidence Proportional Counter

    DOEpatents

    Manley, J H

    1950-11-21

    A coincidence proportional counter having a plurality of collecting electrodes so disposed as to measure the range or energy spectrum of an ionizing particle-emitting source such as an alpha source, is disclosed.

  18. Genetic structure and differentiation analysis of a Eurasian Uyghur population by use of 27 continental ancestry-informative SNPs.

    PubMed

    Wei, Yi-Liang; Sun, Qi-Fan; Li, Qing; Yi, Jun-Ling; Zhao, Lei; Ou, Yuan; Jiang, Li; Zhang, Tao; Liu, Hai-Bo; Chen, Jian-Gang; Zhu, Bo-Feng; Ye, Jian; Hu, Lan; Li, Cai-Xia

    2016-07-01

    Previously, we developed and validated a multiplex assay of 27 ancestry-informative markers (AIMs) for analyzing African (AFR), European (EUR), and East Asian (EAS) ancestry components. In this study, we typed and collectively analyzed a large Uyghur sample of 979 individuals to estimate the genetic coefficients of the 27 AIMs and investigate differentiation parameters between Uyghur and Han. The Uyghur allele frequencies ranged from 0.243 to 0.952, and heterozygosities ranged from 0.091 to 0.500. Values of F st 3 and I n 3 for EUR, Uyghur, and EAS ranged from 0.028 to 0.550 and 0.0002 to 0.345, respectively. The Uyghur population displays a substantial ancestry contribution of 50.3:49.7 (EUR:EAS) and was efficiently discriminated from Han Chinese with an accuracy of 99.285 %. All populations were clustered into AFR, EUR, EAS, and admixture groups of these three ancestries. Central Asian was obviously stratified from the other admixture populations of South Asians, North Asians, and the Americans. The 27 SNPs yield a circle with an average distance of 0.936 from the center (0, 0) in PCA analysis. Using this set, Chinese Uyghur and Han populations achieved accurate differentiation, and our updated genotype database (by citing 1000 Genomes data) of 43 worldwide populations is a useful resource for forensic applications and disease association studies. PMID:26932865

  19. Kuwaiti population subgroup of nomadic Bedouin ancestry-Whole genome sequence and analysis.

    PubMed

    John, Sumi Elsa; Thareja, Gaurav; Hebbar, Prashantha; Behbehani, Kazem; Thanaraj, Thangavel Alphonse; Alsmadi, Osama

    2015-03-01

    Kuwaiti native population comprises three distinct genetic subgroups of Persian, "city-dwelling" Saudi Arabian tribe, and nomadic "tent-dwelling" Bedouin ancestry. Bedouin subgroup is characterized by presence of 17% African ancestry; it owes it origin to nomadic tribes of the deserts of Arabian Peninsula and North Africa. By sequencing whole genome of a Kuwaiti male from this subgroup at 41X coverage, we report 3,752,878 SNPs, 411,839 indels, and 8451 structural variations. Neighbor-joining tree, based on shared variant positions carrying disease-risk alleles between the Bedouin and other continental genomes, places Bedouin genome at the nexus of African, Asian, and European genomes in concordance with geographical location of Kuwait and Peninsula. In congruence with participant's medical history for morbid obesity and bronchial asthma, risk alleles are seen at deleterious SNPs associated with obesity and asthma. Many of the observed deleterious 'novel' variants lie in genes associated with autosomal recessive disorders characteristic of the region. PMID:26484159

  20. Ancestry assessment using random forest modeling.

    PubMed

    Hefner, Joseph T; Spradley, M Kate; Anderson, Bruce

    2014-05-01

    A skeletal assessment of ancestry relies on morphoscopic traits and skeletal measurements. Using a sample of American Black (n = 38), American White (n = 39), and Southwest Hispanics (n = 72), the present study investigates whether these data provide similar biological information and combines both data types into a single classification using a random forest model (RFM). Our results indicate that both data types provide similar information concerning the relationships among population groups. Also, by combining both in an RFM, the correct allocation of ancestry for an unknown cranium increases. The distribution of cross-validated grouped cases correctly classified using discriminant analyses and RFMs ranges between 75.4% (discriminant function analysis, morphoscopic data only) and 89.6% (RFM). Unlike the traditional, experience-based approach using morphoscopic traits, the inclusion of both data types in a single analysis is a quantifiable approach accounting for more variation within and between groups, reducing misclassification rates, and capturing aspects of cranial shape, size, and morphology. PMID:24502438

  1. MtDNA ancestry of Rio de Janeiro population, Brazil.

    PubMed

    Bernardo, Suellen; Hermida, Rose; Desidério, Márcia; Silva, Dayse A; de Carvalho, Elizeu F

    2014-01-01

    Polymorphism studies concerning HVI and HVII regions of mitochondrial DNA (mtDNA) have improved the understanding of the admixture genetic process related to the occupation of the continents by human population groups. We have analyzed the mtDNA lineages of 190 healthy and maternally unrelated individuals born in the metropolitan region of the Rio de Janeiro city, the capital of the State of Rio de Janeiro, southeastern Brazil. The data showing that 57.9, 25.3 and 16.8 % of the matrilineages found in Rio de Janeiro come from African, Amerindian and European population groups. They are, respectively, in close agreement with historical records which indicate that the admixture population of Brazil is the resulting of interethnic asymmetry crosses between individuals from those population groups. The high proportion of African mtDNA lineages in the population of Rio de Janeiro is in accordance with studies related to other Brazilian states.

  2. Adaptation through proportion

    NASA Astrophysics Data System (ADS)

    Xiong, Liyang; Shi, Wenjia; Tang, Chao

    2016-08-01

    Adaptation is a ubiquitous feature in biological sensory and signaling networks. It has been suggested that adaptive systems may follow certain simple design principles across diverse organisms, cells and pathways. One class of networks that can achieve adaptation utilizes an incoherent feedforward control, in which two parallel signaling branches exert opposite but proportional effects on the output at steady state. In this paper, we generalize this adaptation mechanism by establishing a steady-state proportionality relationship among a subset of nodes in a network. Adaptation can be achieved by using any two nodes in the sub-network to respectively regulate the output node positively and negatively. We focus on enzyme networks and first identify basic regulation motifs consisting of two and three nodes that can be used to build small networks with proportional relationships. Larger proportional networks can then be constructed modularly similar to LEGOs. Our method provides a general framework to construct and analyze a class of proportional and/or adaptation networks with arbitrary size, flexibility and versatile functional features.

  3. Managed European-Derived Honey Bee, Apis mellifera sspp, Colonies Reduce African-Matriline Honey Bee, A. m. scutellata, Drones at Regional Mating Congregations

    PubMed Central

    Mortensen, Ashley N.; Ellis, James D.

    2016-01-01

    African honey bees (Apis mellifera scutellata) dramatically changed the South American beekeeping industry as they rapidly spread through the Americas following their introduction into Brazil. In the present study, we aimed to determine if the management of European-derived honey bees (A. mellifera sspp.) could reduce the relative abundance of African-matriline drones at regional mating sites known as drone congregation areas (DCAs). We collected 2,400 drones at six DCAs either 0.25 km or >2.8 km from managed European-derived honey bee apiaries. The maternal ancestry of each drone was determined by Bgl II enzyme digestion of an amplified portion of the mitochondrial Cytochrome b gene. Furthermore, sibship reconstruction via nuclear microsatellites was conducted for a subset of 1,200 drones to estimate the number of colonies contributing drones to each DCA. Results indicate that DCAs distant to managed European apiaries (>2.8 km) had significantly more African−matriline drones (34.33% of the collected drones had African mitochondrial DNA) than did DCAs close (0.25 km) to managed European apiaries (1.83% of the collected drones had African mitochondrial DNA). Furthermore, nuclear sibship reconstruction demonstrated that the reduction in the proportion of African matriline drones at DCAs near apiaries was not simply an increase in the number of European matriline drones at the DCAs but also the result of fewer African matriline colonies contributing drones to the DCAs. Our data demonstrate that the management of European honey bee colonies can dramatically influence the proportion of drones with African matrilines at nearby drone congregation areas, and would likely decreasing the probability that virgin European queens will mate with African drones at those drone congregation areas. PMID:27518068

  4. Robust inference of population structure for ancestry prediction and correction of stratification in the presence of relatedness.

    PubMed

    Conomos, Matthew P; Miller, Michael B; Thornton, Timothy A

    2015-05-01

    Population structure inference with genetic data has been motivated by a variety of applications in population genetics and genetic association studies. Several approaches have been proposed for the identification of genetic ancestry differences in samples where study participants are assumed to be unrelated, including principal components analysis (PCA), multidimensional scaling (MDS), and model-based methods for proportional ancestry estimation. Many genetic studies, however, include individuals with some degree of relatedness, and existing methods for inferring genetic ancestry fail in related samples. We present a method, PC-AiR, for robust population structure inference in the presence of known or cryptic relatedness. PC-AiR utilizes genome-screen data and an efficient algorithm to identify a diverse subset of unrelated individuals that is representative of all ancestries in the sample. The PC-AiR method directly performs PCA on the identified ancestry representative subset and then predicts components of variation for all remaining individuals based on genetic similarities. In simulation studies and in applications to real data from Phase III of the HapMap Project, we demonstrate that PC-AiR provides a substantial improvement over existing approaches for population structure inference in related samples. We also demonstrate significant efficiency gains, where a single axis of variation from PC-AiR provides better prediction of ancestry in a variety of structure settings than using 10 (or more) components of variation from widely used PCA and MDS approaches. Finally, we illustrate that PC-AiR can provide improved population stratification correction over existing methods in genetic association studies with population structure and relatedness.

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

    PubMed Central

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

    2016-01-01

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

  6. Native American Ancestry Is Associated With Severe Diabetic Retinopathy in Latinos

    PubMed Central

    Gao, Xiaoyi; Gauderman, W. James; Marjoram, Paul; Torres, Mina; Chen, Yii-Der I.; Taylor, Kent D.; Rotter, Jerome I.; Varma, Rohit

    2014-01-01

    Purpose. Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. Studies have observed that Latinos have a higher prevalence of DR than whites. The purpose of this study is to test the association between genetic admixture and severe DR in Latinos with type 2 diabetes mellitus (T2DM). Methods. We conducted a case–control study using 944 T2DM subjects from the Los Angeles Latino Eye Study. Cases (n = 135) were defined as proliferative or severe nonproliferative DR subjects. Controls (n = 809) were other diabetic subjects in the cohort. Genotyping was performed on the Illumina OmniExpress BeadChip. We estimated genetic ancestry in Latinos using STRUCTURE with the HapMap reference panels. Univariate and multivariate logistic regression analyses were used to test the relationship between the proportions of genetic ancestry and severe DR. Results. Native American ancestry (NAA) in Latino T2DM subjects is associated significantly with severe DR (P = 0.002). The association remained significant (P = 0.005) after adjusting for age, sex, duration of diabetes, hemoglobin A1c, body mass index, systolic blood pressure, education, and income. We also validated the NAA estimates in Latinos using ADMIXTURE with the 1000 Genomes Project reference panels and obtained consistent results. Conclusions. Our results demonstrate for the first time to our knowledge that NAA is a significant risk factor for severe DR in Latinos. PMID:25146985

  7. Beta-globin haplotype analysis suggests that a major source of Malagasy ancestry is derived from Bantu-speaking Negroids.

    PubMed Central

    Hewitt, R.; Krause, A.; Goldman, A.; Campbell, G.; Jenkins, T.

    1996-01-01

    The origins of the inhabitants of Madagascar have not been fully resolved. Anthropological studies and preliminary genetic data point to two main sources of ancestry of the Malagasy, namely, Indonesian and African, with additional contributions from India and Arabia. The sickle-cell (beta s) mutation is found in populations of African and Indian origin. The frequency of the beta s-globin gene, derived from 1,425 Malagasy individuals, varies from 0 in some highland populations to .25 in some coastal populations. The beta s mutation is thought to have arisen at least five times, on the basis of the presence of five distinct beta s-associated haplotypes, each found in a separate geographic area. Twenty-five of the 35 Malagasy beta s haplotypes were of the typical "Bantu" type, 1 "Senegal" haplotype was found, and 2 rare or atypical haplotypes were observed; the remaining 7 haplotypes were consistent with the Bantu haplotype. The Bantu beta s mutation is thought to have been introduced into Madagascar by Bantu-speaking immigrants (colonists or slaves) from central or east Africa. The Senegal beta s mutation may have been introduced to the island via Portuguese naval explorers. This study provides the first definitive biological evidence that a major component of Malagasy ancestry is derived from African populations, in particular, Bantu-speaking Negroids. beta A haplotypes are also consistent with the claim for a significant African contribution to Malagasy ancestry but are also suggestive of Asian/Oceanic and Caucasoid admixture within the Malagasy population. PMID:8651308

  8. 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.

  9. 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.

  10. Keep It in Proportion.

    ERIC Educational Resources Information Center

    Snider, Richard G.

    1985-01-01

    The ratio factors approach involves recognizing a given fraction, then multiplying so that units cancel. This approach, which is grounded in concrete operational thinking patterns, provides a standard for science ratio and proportion problems. Examples are included for unit conversions, mole problems, molarity, speed/density problems, and…

  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. Genome-wide analysis reveals the ancient and recent admixture history of East African Shorthorn Zebu from Western Kenya

    PubMed Central

    Mbole-Kariuki, M N; Sonstegard, T; Orth, A; Thumbi, S M; Bronsvoort, B M de C; Kiara, H; Toye, P; Conradie, I; Jennings, A; Coetzer, K; Woolhouse, M E J; Hanotte, O; Tapio, M

    2014-01-01

    The Kenyan East African zebu cattle are valuable and widely used genetic resources. Previous studies using microsatellite loci revealed the complex history of these populations with the presence of taurine and zebu genetic backgrounds. Here, we estimate at genome-wide level the genetic composition and population structure of the East African Shorthorn Zebu (EASZ) of western Kenya. A total of 548 EASZ from 20 sub-locations were genotyped using the Illumina BovineSNP50 v. 1 beadchip. STRUCTURE analysis reveals admixture with Asian zebu, African and European taurine cattle. The EASZ were separated into three categories: substantial (⩾12.5%), moderate (1.56%proportion. The non-European taurine introgressed animals (n=425) show an unfluctuating zebu and taurine ancestry of 0.84±0.009 s.d. and 0.16±0.009 s.d., respectively, with significant differences in African taurine (AT) and Asian zebu backgrounds across chromosomes (P<0.0001). In contrast, no such differences are observed for the European taurine ancestry (P=0.1357). Excluding European introgressed animals, low and nonsignificant genetic differentiation and isolation by distance are observed among sub-locations (Fst=0.0033, P=0.09; r=0.155, P=0.07). Following a short population expansion, a major reduction in effective population size (Ne) is observed from approximately 240 years ago to present time. Our results support ancient zebu × AT admixture in the EASZ population, subsequently shaped by selection and/or genetic drift, followed by a more recent exotic European cattle introgression. PMID:24736786

  13. Genome-wide analysis reveals the ancient and recent admixture history of East African Shorthorn Zebu from Western Kenya.

    PubMed

    Mbole-Kariuki, M N; Sonstegard, T; Orth, A; Thumbi, S M; Bronsvoort, B M de C; Kiara, H; Toye, P; Conradie, I; Jennings, A; Coetzer, K; Woolhouse, M E J; Hanotte, O; Tapio, M

    2014-10-01

    The Kenyan East African zebu cattle are valuable and widely used genetic resources. Previous studies using microsatellite loci revealed the complex history of these populations with the presence of taurine and zebu genetic backgrounds. Here, we estimate at genome-wide level the genetic composition and population structure of the East African Shorthorn Zebu (EASZ) of western Kenya. A total of 548 EASZ from 20 sub-locations were genotyped using the Illumina BovineSNP50 v. 1 beadchip. STRUCTURE analysis reveals admixture with Asian zebu, African and European taurine cattle. The EASZ were separated into three categories: substantial (⩾12.5%), moderate (1.56%proportion. The non-European taurine introgressed animals (n=425) show an unfluctuating zebu and taurine ancestry of 0.84±0.009 s.d. and 0.16±0.009 s.d., respectively, with significant differences in African taurine (AT) and Asian zebu backgrounds across chromosomes (P<0.0001). In contrast, no such differences are observed for the European taurine ancestry (P=0.1357). Excluding European introgressed animals, low and nonsignificant genetic differentiation and isolation by distance are observed among sub-locations (Fst=0.0033, P=0.09; r=0.155, P=0.07). Following a short population expansion, a major reduction in effective population size (Ne) is observed from approximately 240 years ago to present time. Our results support ancient zebu × AT admixture in the EASZ population, subsequently shaped by selection and/or genetic drift, followed by a more recent exotic European cattle introgression. PMID:24736786

  14. Genomic ancestry and somatic alterations correlate with age at diagnosis in Hispanic children with B-cell ALL

    PubMed Central

    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.

    2014-01-01

    Background 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. Methods 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. Results 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=2.0×10−4 and 12.4 months, P=0.011, respectively), while CDKN2A and IKZF1 deletions were associated with older age at diagnosis (19.7 months, P=7.0×10−4 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. Conclusion 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. PMID:24753091

  15. Soft tissue thickness values for black and coloured South African children aged 6-13 years.

    PubMed

    Briers, N; Briers, T M; Becker, P J; Steyn, M

    2015-07-01

    In children, craniofacial changes due to facial growth complicate facial approximations and require specific knowledge of soft tissue thicknesses (STT). The lack of South African juvenile STT standards of particular age groups, sex and ancestry is problematic. According to forensic artists in the South African Police Service the use of African-American values to reconstruct faces of Black South African children yields poor results. In order to perform a facial approximation that presents a true reflection of the child in question, information regarding differences in facial soft tissue at different ages, sexes and ancestry groups is needed. The aims of this study were to provide data on STT of South African Black and Coloured children and to assess differences in STT with respect to age, sex and ancestry. STT was measured using cephalograms of South African children (n=388), aged 6-13 years. After digitizing the images, STT measurements were taken at ten mid-facial landmarks from each image using the iTEM measuring program. STT comparisons between groups per age, sex and ancestry were statistically analyzed. The results showed that STT differences at lower face landmarks are more pronounced in age groups per ancestry as opposed to differences per age and sex. Generally, an increase in STT was seen between 6-10 year old groups and 11-13 year old groups, regardless of ancestry and sex, at the midphiltrum, labiale inferius, pogonion, and beneath chin landmarks. This research created a reference dataset for STT of South African children of Black and Coloured ancestry per age and sex that will be useful for facial reconstruction/approximation of juvenile remains.

  16. Multiwire proportional chamber development

    NASA Technical Reports Server (NTRS)

    Doolittle, R. F.; Pollvogt, U.; Eskovitz, A. J.

    1973-01-01

    The development of large area multiwire proportional chambers, to be used as high resolution spatial detectors in cosmic ray experiments is described. A readout system was developed which uses a directly coupled, lumped element delay-line whose characteristics are independent of the MWPC design. A complete analysis of the delay-line and the readout electronic system shows that a spatial resolution of about 0.1 mm can be reached with the MWPC operating in the strictly proportional region. This was confirmed by measurements with a small MWPC and Fe-55 X-rays. A simplified analysis was carried out to estimate the theoretical limit of spatial resolution due to delta-rays, spread of the discharge along the anode wire, and inclined trajectories. To calculate the gas gain of MWPC's of different geometrical configurations a method was developed which is based on the knowledge of the first Townsend coefficient of the chamber gas.

  17. Monitor proportional counter

    NASA Technical Reports Server (NTRS)

    Weisskopf, M. C.

    1979-01-01

    An Uhuru class Ar-CO2 gas filled proportional counter sealed with a 1.5 mil beryllium window and sensitive to X-rays in the energy bandwidth from 1.5 to 22 keV is presented. This device is coaligned with the X-ray telescope aboard the Einstein Observatory and takes data as a normal part of the Observatory operations.

  18. How probable is common ancestry according to different evolutionary processes?

    PubMed

    Sober, Elliott; Steel, Mike

    2015-05-21

    Darwin and contemporary biologists argue that all present-day life traces back to one or a few common ancestors. Here we investigate the relationship of different evolutionary processes to this hypothesis of common ancestry. We identify the property of an evolutionary process that determines what its probabilistic impact on the common ancestry thesis will be. The point of this exercise is to understand how the parts of Darwin׳s powerful theory fit together, not to call into question common ancestry or natural selection, since these two pillars of Darwin׳s theory enjoy strong support.

  19. A continuum of admixture in the Western Hemisphere revealed by the African Diaspora genome

    PubMed Central

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

    2016-01-01

    The African Diaspora in the Western Hemisphere represents one of the largest forced migrations in history and had a profound impact on genetic diversity in modern populations. To date, the fine-scale population structure of descendants of the African Diaspora remains largely uncharacterized. Here we present genetic variation from deeply sequenced genomes of 642 individuals from North and South American, Caribbean and West African populations, substantially increasing the lexicon of human genomic variation and suggesting much variation remains to be discovered in African-admixed populations in the Americas. We summarize genetic variation in these populations, quantifying the postcolonial sex-biased European gene flow across multiple regions. Moreover, we refine estimates on the burden of deleterious variants carried across populations and how this varies with African ancestry. Our data are an important resource for empowering disease mapping studies in African-admixed individuals and will facilitate gene discovery for diseases disproportionately affecting individuals of African ancestry. PMID:27725671

  20. Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms (SNPs) Associated With the Development of Erectile Dysfunction in African-American Men After Radiotherapy for Prostate Cancer

    SciTech Connect

    Kerns, Sarah L.; Ostrer, Harry; Stock, Richard; Li, William; Pearlman, Alexander; Campbell, Christopher; Shao Yongzhao; Stone, Nelson; Kusnetz, Lynda; Rosenstein, Barry S.

    2010-12-01

    Purpose: To identify single nucleotide polymorphisms (SNPs) associated with erectile dysfunction (ED) among African-American prostate cancer patients treated with external beam radiation therapy. Methods and Materials: A cohort of African-American prostate cancer patients treated with external beam radiation therapy was observed for the development of ED by use of the five-item Sexual Health Inventory for Men (SHIM) questionnaire. Final analysis included 27 cases (post-treatment SHIM score {<=}7) and 52 control subjects (post-treatment SHIM score {>=}16). A genome-wide association study was performed using approximately 909,000 SNPs genotyped on Affymetrix 6.0 arrays (Affymetrix, Santa Clara, CA). Results: We identified SNP rs2268363, located in the follicle-stimulating hormone receptor (FSHR) gene, as significantly associated with ED after correcting for multiple comparisons (unadjusted p = 5.46 x 10{sup -8}, Bonferroni p = 0.028). We identified four additional SNPs that tended toward a significant association with an unadjusted p value < 10{sup -6}. Inference of population substructure showed that cases had a higher proportion of African ancestry than control subjects (77% vs. 60%, p = 0.005). A multivariate logistic regression model that incorporated estimated ancestry and four of the top-ranked SNPs was a more accurate classifier of ED than a model that included only clinical variables. Conclusions: To our knowledge, this is the first genome-wide association study to identify SNPs associated with adverse effects resulting from radiotherapy. It is important to note that the SNP that proved to be significantly associated with ED is located within a gene whose encoded product plays a role in male gonad development and function. Another key finding of this project is that the four SNPs most strongly associated with ED were specific to persons of African ancestry and would therefore not have been identified had a cohort of European ancestry been screened. This study

  1. Y Chromosome Lineages in Men of West African Descent

    PubMed Central

    Keita, Shomarka O. Y.; Kittles, Rick A.

    2012-01-01

    The early African experience in the Americas is marked by the transatlantic slave trade from ∼1619 to 1850 and the rise of the plantation system. The origins of enslaved Africans were largely dependent on European preferences as well as the availability of potential laborers within Africa. Rice production was a key industry of many colonial South Carolina low country plantations. Accordingly, rice plantations owners within South Carolina often requested enslaved Africans from the so-called “Grain Coast” of western Africa (Senegal to Sierra Leone). Studies on the African origins of the enslaved within other regions of the Americas have been limited. To address the issue of origins of people of African descent within the Americas and understand more about the genetic heterogeneity present within Africa and the African Diaspora, we typed Y chromosome specific markers in 1,319 men consisting of 508 west and central Africans (from 12 populations), 188 Caribbeans (from 2 islands), 532 African Americans (AAs from Washington, DC and Columbia, SC), and 91 European Americans. Principal component and admixture analyses provide support for significant Grain Coast ancestry among African American men in South Carolina. AA men from DC and the Caribbean showed a closer affinity to populations from the Bight of Biafra. Furthermore, 30–40% of the paternal lineages in African descent populations in the Americas are of European ancestry. Diverse west African ancestries and sex-biased gene flow from EAs has contributed greatly to the genetic heterogeneity of African populations throughout the Americas and has significant implications for gene mapping efforts in these populations. PMID:22295064

  2. Proportional counter radiation camera

    DOEpatents

    Borkowski, C.J.; Kopp, M.K.

    1974-01-15

    A gas-filled proportional counter camera that images photon emitting sources is described. A two-dimensional, positionsensitive proportional multiwire counter is provided as the detector. The counter consists of a high- voltage anode screen sandwiched between orthogonally disposed planar arrays of multiple parallel strung, resistively coupled cathode wires. Two terminals from each of the cathode arrays are connected to separate timing circuitry to obtain separate X and Y coordinate signal values from pulse shape measurements to define the position of an event within the counter arrays which may be recorded by various means for data display. The counter is further provided with a linear drift field which effectively enlarges the active gas volume of the counter and constrains the recoil electrons produced from ionizing radiation entering the counter to drift perpendicularly toward the planar detection arrays. A collimator is interposed between a subject to be imaged and the counter to transmit only the radiation from the subject which has a perpendicular trajectory with respect to the planar cathode arrays of the detector. (Official Gazette)

  3. Analyses of genetic ancestry enable key insights for molecular ecology.

    PubMed

    Gompert, Zachariah; Buerkle, C Alex

    2013-11-01

    Gene flow and recombination in admixed populations produce genomes that are mosaic combinations of chromosome segments inherited from different source populations, that is, chromosome segments with different genetic ancestries. The statistical problem of estimating genetic ancestry from DNA sequence data has been widely studied, and analyses of genetic ancestry have facilitated research in molecular ecology and ecological genetics. In this review, we describe and compare different model-based statistical methods used to infer genetic ancestry. We describe the conceptual and mathematical structure of these models and highlight some of their key differences and shared features. We then discuss recent empirical studies that use estimates of genetic ancestry to analyse population histories, the nature and genetic basis of species boundaries, and the genetic architecture of traits. These diverse studies demonstrate the breadth of applications that rely on genetic ancestry estimates and typify the genomics-enabled research that is becoming increasingly common in molecular ecology. We conclude by identifying key research areas where future studies might further advance this field. PMID:24103088

  4. Accurate Inference of Local Phased Ancestry of Modern Admixed Populations

    PubMed Central

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

    2014-01-01

    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. PMID:25052506

  5. 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

    2014-01-01

    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. PMID:25052506

  6. Masked Proportional Routing

    NASA Technical Reports Server (NTRS)

    Wolpert, David

    2004-01-01

    Masked proportional routing is an improved procedure for choosing links between adjacent nodes of a network for the purpose of transporting an entity from a source node ("A") to a destination node ("B"). The entity could be, for example, a physical object to be shipped, in which case the nodes would represent waypoints and the links would represent roads or other paths between waypoints. For another example, the entity could be a message or packet of data to be transmitted from A to B, in which case the nodes could be computer-controlled switching stations and the links could be communication channels between the stations. In yet another example, an entity could represent a workpiece while links and nodes could represent, respectively, manufacturing processes and stages in the progress of the workpiece towards a finished product. More generally, the nodes could represent states of an entity and the links could represent allowed transitions of the entity. The purpose of masked proportional routing and of related prior routing procedures is to schedule transitions of entities from their initial states ("A") to their final states ("B") in such a manner as to minimize a cost or to attain some other measure of optimality or efficiency. Masked proportional routing follows a distributed (in the sense of decentralized) approach to probabilistically or deterministically choosing the links. It was developed to satisfy a need for a routing procedure that 1. Does not always choose the same link(s), even for two instances characterized by identical estimated values of associated cost functions; 2. Enables a graceful transition from one set of links to another set of links as the circumstances of operation of the network change over time; 3. Is preferably amenable to separate optimization of different portions of the network; 4. Is preferably usable in a network in which some of the routing decisions are made by one or more other procedure(s); 5. Preferably does not cause an

  7. 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

  8. Gated strip proportional detector

    DOEpatents

    Morris, Christopher L.; Idzorek, George C.; Atencio, Leroy G.

    1987-01-01

    A gated strip proportional detector includes a gas tight chamber which encloses a solid ground plane, a wire anode plane, a wire gating plane, and a multiconductor cathode plane. The anode plane amplifies the amount of charge deposited in the chamber by a factor of up to 10.sup.6. The gating plane allows only charge within a narrow strip to reach the cathode. The cathode plane collects the charge allowed to pass through the gating plane on a set of conductors perpendicular to the open-gated region. By scanning the open-gated region across the chamber and reading out the charge collected on the cathode conductors after a suitable integration time for each location of the gate, a two-dimensional image of the intensity of the ionizing radiation incident on the detector can be made.

  9. Gated strip proportional detector

    DOEpatents

    Morris, C.L.; Idzorek, G.C.; Atencio, L.G.

    1985-02-19

    A gated strip proportional detector includes a gas tight chamber which encloses a solid ground plane, a wire anode plane, a wire gating plane, and a multiconductor cathode plane. The anode plane amplifies the amount of charge deposited in the chamber by a factor of up to 10/sup 6/. The gating plane allows only charge within a narrow strip to reach the cathode. The cathode plane collects the charge allowed to pass through the gating plane on a set of conductors perpendicular to the open-gated region. By scanning the open-gated region across the chamber and reading out the charge collected on the cathode conductors after a suitable integration time for each location of the gate, a two-dimensional image of the intensity of the ionizing radiation incident on the detector can be made.

  10. Intrahepatic Cholestasis of Pregnancy (ICP) in U.S. Latinas and Chileans: Clinical features, Ancestry Analysis, and Admixture Mapping.

    PubMed

    Bull, Laura N; Hu, Donglei; Shah, Sohela; Temple, Luisa; Silva, Karla; Huntsman, Scott; Melgar, Jennifer; Geiser, Mary T; Sanford, Ukina; Ortiz, Juan A; Lee, Richard H; Kusanovic, Juan P; Ziv, Elad; Vargas, Juan E

    2015-01-01

    In the Americas, women with Indigenous American ancestry are at increased risk of intrahepatic cholestasis of pregnancy (ICP), relative to women of other ethnicities. We hypothesized that ancestry-related genetic factors contribute to this increased risk. We collected clinical and laboratory data, and performed biochemical assays on samples from U.S. Latinas and Chilean women, with and without ICP. The study sample included 198 women with ICP (90 from California, U.S., and 108 from Chile) and 174 pregnant control women (69 from California, U.S., and 105 from Chile). SNP genotyping was performed using Affymetrix arrays. We compared overall genetic ancestry between cases and controls, and used a genome-wide admixture mapping approach to screen for ICP susceptibility loci. We identified commonalities and differences in features of ICP between the 2 countries and determined that cases had a greater proportion of Indigenous American ancestry than did controls (p = 0.034). We performed admixture mapping, taking country of origin into account, and identified one locus for which Native American ancestry was associated with increased risk of ICP at a genome-wide level of significance (P = 3.1 x 10(-5), Pcorrected = 0.035). This locus has an odds ratio of 4.48 (95% CI: 2.21-9.06) for 2 versus zero Indigenous American chromosomes. This locus lies on chromosome 2, with a 10 Mb 95% confidence interval which does not contain any previously identified hereditary 'cholestasis genes.' Our results indicate that genetic factors contribute to the risk of developing ICP in the Americas, and support the utility of clinical and genetic studies of ethnically mixed populations for increasing our understanding of ICP. PMID:26126184

  11. Intrahepatic Cholestasis of Pregnancy (ICP) in U.S. Latinas and Chileans: Clinical features, Ancestry Analysis, and Admixture Mapping

    PubMed Central

    Bull, Laura N.; Hu, Donglei; Shah, Sohela; Temple, Luisa; Silva, Karla; Huntsman, Scott; Melgar, Jennifer; Geiser, Mary T.; Sanford, Ukina; Ortiz, Juan A.; Lee, Richard H.; Kusanovic, Juan P.

    2015-01-01

    In the Americas, women with Indigenous American ancestry are at increased risk of intrahepatic cholestasis of pregnancy (ICP), relative to women of other ethnicities. We hypothesized that ancestry-related genetic factors contribute to this increased risk. We collected clinical and laboratory data, and performed biochemical assays on samples from U.S. Latinas and Chilean women, with and without ICP. The study sample included 198 women with ICP (90 from California, U.S., and 108 from Chile) and 174 pregnant control women (69 from California, U.S., and 105 from Chile). SNP genotyping was performed using Affymetrix arrays. We compared overall genetic ancestry between cases and controls, and used a genome-wide admixture mapping approach to screen for ICP susceptibility loci. We identified commonalities and differences in features of ICP between the 2 countries and determined that cases had a greater proportion of Indigenous American ancestry than did controls (p = 0.034). We performed admixture mapping, taking country of origin into account, and identified one locus for which Native American ancestry was associated with increased risk of ICP at a genome-wide level of significance (P = 3.1 x 10-5, Pcorrected = 0.035). This locus has an odds ratio of 4.48 (95% CI: 2.21-9.06) for 2 versus zero Indigenous American chromosomes. This locus lies on chromosome 2, with a 10 Mb 95% confidence interval which does not contain any previously identified hereditary ‘cholestasis genes.’ Our results indicate that genetic factors contribute to the risk of developing ICP in the Americas, and support the utility of clinical and genetic studies of ethnically mixed populations for increasing our understanding of ICP. PMID:26126184

  12. Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives.

    PubMed

    Brutsaert, Tom D; Parra, Esteban J; Shriver, Mark D; Gamboa, Alfredo; Rivera-Ch, Maria; León-Velarde, Fabiola

    2005-07-01

    Andean high-altitude (HA) natives have a low (blunted) hypoxic ventilatory response (HVR), lower effective alveolar ventilation, and lower ventilation (VE) at rest and during exercise compared with acclimatized newcomers to HA. Despite blunted chemosensitivity and hypoventilation, Andeans maintain comparable arterial O(2) saturation (Sa(O(2))). This study was designed to evaluate the influence of ancestry on these trait differences. At sea level, we measured the HVR in both acute (HVR-A) and sustained (HVR-S) hypoxia in a sample of 32 male Peruvians of mainly Quechua and Spanish origins who were born and raised at sea level. We also measured resting and exercise VE after 10-12 h of exposure to altitude at 4,338 m. Native American ancestry proportion (NAAP) was assessed for each individual using a panel of 80 ancestry-informative molecular markers (AIMs). NAAP was inversely related to HVR-S after 10 min of isocapnic hypoxia (r = -0.36, P = 0.04) but was not associated with HVR-A. In addition, NAAP was inversely related to exercise VE (r = -0.50, P = 0.005) and ventilatory equivalent (VE/Vo(2), r = -0.51, P = 0.004) measured at 4,338 m. Thus Quechua ancestry may partly explain the well-known blunted HVR (10, 35, 36, 57, 62) at least to sustained hypoxia, and the relative exercise hypoventilation at altitude of Andeans compared with European controls. Lower HVR-S and exercise VE could reflect improved gas exchange and/or attenuated chemoreflex sensitivity with increasing NAAP. On the basis of these ancestry associations and on the fact that developmental effects were completely controlled by study design, we suggest both a genetic basis and an evolutionary origin for these traits in Quechua.

  13. 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

  14. The ancestry and affiliations of Kennewick Man.

    PubMed

    Rasmussen, Morten; Sikora, Martin; Albrechtsen, Anders; Korneliussen, Thorfinn Sand; Moreno-Mayar, J Víctor; Poznik, G David; Zollikofer, Christoph P E; Ponce de León, Marcia S; 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

    2015-07-23

    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 8,340-9,200 calibrated years before present (BP). His population affinities have been the subject of scientific debate and legal controversy. Based on an 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 permitted. 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 Americans. 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 for 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 are available for comparison, several seem 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 genome-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.

  15. The ancestry and affiliations of Kennewick Man.

    PubMed

    Rasmussen, Morten; Sikora, Martin; Albrechtsen, Anders; Korneliussen, Thorfinn Sand; Moreno-Mayar, J Víctor; Poznik, G David; Zollikofer, Christoph P E; Ponce de León, Marcia S; 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

    2015-07-23

    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 8,340-9,200 calibrated years before present (BP). His population affinities have been the subject of scientific debate and legal controversy. Based on an 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 permitted. 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 Americans. 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 for 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 are available for comparison, several seem 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 genome-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. 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

  17. 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. PMID:26092716

  18. 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

  19. 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. PMID:27603370

  20. Generalization and dilution of association results from European GWAS in populations of non-European ancestry: the PAGE study.

    PubMed

    Carlson, Christopher S; Matise, Tara C; North, Kari E; Haiman, Christopher A; Fesinmeyer, Megan D; Buyske, Steven; Schumacher, Fredrick R; Peters, Ulrike; Franceschini, Nora; Ritchie, Marylyn D; Duggan, David J; Spencer, Kylee L; Dumitrescu, Logan; Eaton, Charles B; Thomas, Fridtjof; Young, Alicia; Carty, Cara; Heiss, Gerardo; Le Marchand, Loic; Crawford, Dana C; Hindorff, Lucia A; Kooperberg, Charles L

    2013-09-01

    The vast majority of genome-wide association study (GWAS) findings reported to date are from populations with European Ancestry (EA), and it is not yet clear how broadly the genetic associations described will generalize to populations of diverse ancestry. The Population Architecture Using Genomics and Epidemiology (PAGE) study is a consortium of multi-ancestry, population-based studies formed with the objective of refining our understanding of the genetic architecture of common traits emerging from GWAS. In the present analysis of five common diseases and traits, including body mass index, type 2 diabetes, and lipid levels, we compare direction and magnitude of effects for GWAS-identified variants in multiple non-EA populations against EA findings. We demonstrate that, in all populations analyzed, a significant majority of GWAS-identified variants have allelic associations in the same direction as in EA, with none showing a statistically significant effect in the opposite direction, after adjustment for multiple testing. However, 25% of tagSNPs identified in EA GWAS have significantly different effect sizes in at least one non-EA population, and these differential effects were most frequent in African Americans where all differential effects were diluted toward the null. We demonstrate that differential LD between tagSNPs and functional variants within populations contributes significantly to dilute effect sizes in this population. Although most variants identified from GWAS in EA populations generalize to all non-EA populations assessed, genetic models derived from GWAS findings in EA may generate spurious results in non-EA populations due to differential effect sizes. Regardless of the origin of the differential effects, caution should be exercised in applying any genetic risk prediction model based on tagSNPs outside of the ancestry group in which it was derived. Models based directly on functional variation may generalize more robustly, but the identification

  1. 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

  2. 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.

  3. Genome-wide Analysis of Body Proportion Classifies Height-Associated Variants by Mechanism of Action and Implicates Genes Important for Skeletal Development

    PubMed Central

    Chan, Yingleong; Salem, Rany M.; Hsu, Yu-Han H.; McMahon, George; Pers, Tune H.; Vedantam, Sailaja; Esko, Tonu; Guo, Michael H.; Lim, Elaine T.; Franke, Lude; Smith, George Davey; Strachan, David P.; Hirschhorn, Joel N.

    2015-01-01

    Human height is a composite measurement, reflecting the sum of leg, spine, and head lengths. Many common variants influence total height, but the effects of these or other variants on the components of height (body proportion) remain largely unknown. We studied sitting height ratio (SHR), the ratio of sitting height to total height, to identify such effects in 3,545 African Americans and 21,590 individuals of European ancestry. We found that SHR is heritable: 26% and 39% of the total variance of SHR can be explained by common variants in European and African Americans, respectively, and global European admixture is negatively correlated with SHR in African Americans (r2 ≈ 0.03). Six regions reached genome-wide significance (p < 5 × 10−8) for association with SHR and overlapped biological candidate genes, including TBX2 and IGFBP3. We found that 130 of 670 height-associated variants are nominally associated (p < 0.05) with SHR, more than expected by chance (p = 5 × 10−40). At these 130 loci, the height-increasing alleles are associated with either a decrease (71 loci) or increase (59 loci) in SHR, suggesting that different height loci disproportionally affect either leg length or spine/head length. Pathway analyses via DEPICT revealed that height loci affecting SHR, and especially those affecting leg length, show enrichment of different biological pathways (e.g., bone/cartilage/growth plate pathways) than do loci with no effect on SHR (e.g., embryonic development). These results highlight the value of using a pair of related but orthogonal phenotypes, in this case SHR with height, as a prism to dissect the biology underlying genetic associations in polygenic traits and diseases. PMID:25865494

  4. Genome-wide Scan of 29,141 African Americans Finds No Evidence of Directional Selection since Admixture

    PubMed Central

    Bhatia, Gaurav; Tandon, Arti; Patterson, Nick; Aldrich, Melinda C.; Ambrosone, Christine B.; Amos, Christopher; Bandera, Elisa V.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Bock, Cathryn H.; Caporaso, Neil; Casey, Graham; Deming, Sandra L.; Diver, W. Ryan; Gapstur, Susan M.; Gillanders, Elizabeth M.; Harris, Curtis C.; Henderson, Brian E.; Ingles, Sue A.; Isaacs, William; De Jager, Phillip L.; John, Esther M.; Kittles, Rick A.; Larkin, Emma; McNeill, Lorna H.; Millikan, Robert C.; Murphy, Adam; Neslund-Dudas, Christine; Nyante, Sarah; Press, Michael F.; Rodriguez-Gil, Jorge L.; Rybicki, Benjamin A.; Schwartz, Ann G.; Signorello, Lisa B.; Spitz, Margaret; Strom, Sara S.; Tucker, Margaret A.; Wiencke, John K.; Witte, John S.; Wu, Xifeng; Yamamura, Yuko; Zanetti, Krista A.; Zheng, Wei; Ziegler, Regina G.; Chanock, Stephen J.; Haiman, Christopher A.; Reich, David; Price, Alkes L.

    2014-01-01

    The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study’s conclusion of selection in African Americans before admixture is also subject to doubt. This is because the FST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas. PMID:25242497

  5. Genome-wide scan of 29,141 African Americans finds no evidence of directional selection since admixture.

    PubMed

    Bhatia, Gaurav; Tandon, Arti; Patterson, Nick; Aldrich, Melinda C; Ambrosone, Christine B; Amos, Christopher; Bandera, Elisa V; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Bock, Cathryn H; Caporaso, Neil; Casey, Graham; Deming, Sandra L; Diver, W Ryan; Gapstur, Susan M; Gillanders, Elizabeth M; Harris, Curtis C; Henderson, Brian E; Ingles, Sue A; Isaacs, William; De Jager, Phillip L; John, Esther M; Kittles, Rick A; Larkin, Emma; McNeill, Lorna H; Millikan, Robert C; Murphy, Adam; Neslund-Dudas, Christine; Nyante, Sarah; Press, Michael F; Rodriguez-Gil, Jorge L; Rybicki, Benjamin A; Schwartz, Ann G; Signorello, Lisa B; Spitz, Margaret; Strom, Sara S; Tucker, Margaret A; Wiencke, John K; Witte, John S; Wu, Xifeng; Yamamura, Yuko; Zanetti, Krista A; Zheng, Wei; Ziegler, Regina G; Chanock, Stephen J; Haiman, Christopher A; Reich, David; Price, Alkes L

    2014-10-01

    The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study's conclusion of selection in African Americans before admixture is also subject to doubt. This is because the FST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas.

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

    PubMed Central

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

    2008-01-01

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

  7. Genetic ancestry and indigenous heritage in a Native American descendant community in Bermuda.

    PubMed

    Gaieski, Jill B; Owings, Amanda C; Vilar, Miguel G; Dulik, Matthew C; Gaieski, David F; Gittelman, Rachel M; Lindo, John; Gau, Lydia; Schurr, Theodore G

    2011-11-01

    Discovered in the early 16th century by European colonists, Bermuda is an isolated set of islands located in the mid-Atlantic. Shortly after its discovery, Bermuda became the first English colony to forcibly import its labor by trafficking in enslaved Africans, white ethnic minorities, and indigenous Americans. Oral traditions circulating today among contemporary tribes from the northeastern United States recount these same events, while, in Bermuda, St. David's Islanders consider their histories to be linked to a complex Native American, European, and African past. To investigate the influence of historical events on biological ancestry and native cultural identity, we analyzed genetic variation in 111 members of Bermuda's self-proclaimed St. David's Island Native Community. Our results reveal that the majority of mitochondrial DNA (mtDNA) and Y-chromosome haplotypes are of African and West Eurasian origin. However, unlike other English-speaking New World colonies, most African mtDNA haplotypes appear to derive from central and southeast Africa, reflecting the extent of maritime activities in the region. In light of genealogical and oral historical data from the St. David's community, the low frequency of Native American mtDNA and NRY lineages may reflect the influence of genetic drift, the demographic impact of European colonization, and historical admixture with persons of non-native backgrounds, which began with the settlement of the islands. By comparing the genetic data with genealogical and historical information, we are able to reconstruct the complex history of this Bermudian community, which is unique among New World populations. PMID:21994016

  8. Genetic ancestry and indigenous heritage in a Native American descendant community in Bermuda.

    PubMed

    Gaieski, Jill B; Owings, Amanda C; Vilar, Miguel G; Dulik, Matthew C; Gaieski, David F; Gittelman, Rachel M; Lindo, John; Gau, Lydia; Schurr, Theodore G

    2011-11-01

    Discovered in the early 16th century by European colonists, Bermuda is an isolated set of islands located in the mid-Atlantic. Shortly after its discovery, Bermuda became the first English colony to forcibly import its labor by trafficking in enslaved Africans, white ethnic minorities, and indigenous Americans. Oral traditions circulating today among contemporary tribes from the northeastern United States recount these same events, while, in Bermuda, St. David's Islanders consider their histories to be linked to a complex Native American, European, and African past. To investigate the influence of historical events on biological ancestry and native cultural identity, we analyzed genetic variation in 111 members of Bermuda's self-proclaimed St. David's Island Native Community. Our results reveal that the majority of mitochondrial DNA (mtDNA) and Y-chromosome haplotypes are of African and West Eurasian origin. However, unlike other English-speaking New World colonies, most African mtDNA haplotypes appear to derive from central and southeast Africa, reflecting the extent of maritime activities in the region. In light of genealogical and oral historical data from the St. David's community, the low frequency of Native American mtDNA and NRY lineages may reflect the influence of genetic drift, the demographic impact of European colonization, and historical admixture with persons of non-native backgrounds, which began with the settlement of the islands. By comparing the genetic data with genealogical and historical information, we are able to reconstruct the complex history of this Bermudian community, which is unique among New World populations.

  9. Surgical anatomy of the pudendal nerve and its branches in South Africans.

    PubMed

    van der Walt, S; Oettlé, A C; Patel, H R H

    2015-07-01

    Dissection of the pudendal nerve (PN) and its branches in 71 cadavers revealed anatomic variations not previously described. Knowledge of this variation is necessary to prevent nerve injury resulting in sexual of sensory dysfunction. Because descriptions vary, this study re-evaluated the anatomy of the PN as implicated in perineal procedures in South Africans. The course of the PN from the gluteal region into the perineum was dissected in an adult sample of both sexes and of African and European ancestry. Distances between PN and branches to applicable landmarks were measured. Basic descriptive statistics and comparisons were carried out between groups. In 5/13 African females, the inferior rectal nerve (IRN) entered the gluteal region separately and in 12/13 cases it passed medial to the ischial spine with the PN. The dorsal nerve of the clitoris or penis (DNC/DNP) was closer to the bony frame in those of European ancestry. The IRN branches were more superficial in females, but deeper in males of European ancestry. In African females, a PN block and Richter stitch should be placed more medial. Outside-in transobturator tape procedures might endanger the DNC/DNP in obese individuals. In females of European ancestry the IRN branches are compromised during ischioanal abscess drainage. In males of European ancestry, the dorsal penile nerve block might be less effective. Predictions should be verified clinically.

  10. Ancestry of the Iban Is Predominantly Southeast Asian: Genetic Evidence from Autosomal, Mitochondrial, and Y Chromosomes

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2011-01-01

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

  12. Suicidal ideation in Hispanic and mixed-ancestry adolescents.

    PubMed

    Olvera, R L

    2001-01-01

    This survey examined differences in suicidal ideation, depressive symptomatology, acculturation, and coping strategies based on ethnicity. The author gathered data from a self-report questionnaire administered to students in an ethnically diverse middle school (grades 6-8, N= 158). Hispanic (predominantly Mexican American) and mixed-ancestry adolescents displayed significantly higher risk of suicidal ideation compared to Anglo peers, even when socioeconomic status, age, and gender were controlled for. Suicidal ideation was associated with depressive symptoms, family problems, lower levels of acculturation, and various coping strategies. Using multivariate analysis, Hispanic ancestry, depressive symptoms, family problems, and the use of social coping remained in the model. PMID:11775717

  13. Visual Manipulatives for Proportional Reasoning.

    ERIC Educational Resources Information Center

    Moore, Joyce L.; Schwartz, Daniel L.

    The use of a visual representation in learning about proportional relations was studied, examining students' understandings of the invariance of a multiplicative relation on both sides of a proportion equation and the invariance of the structural relations that exist in different semantic types of proportion problems. Subjects were 49 high-ability…

  14. 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; van Oorschot, R A H; Zatkalikova, L; Carracedo, Á; Phillips, C

    2015-11-01

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

  15. Pyle metaphyseal dysplasia in an African child: Case report and review of the literature.

    PubMed

    Wonkam, A; Makubalo, N; Roberts, T; Chetty, M

    2016-06-01

    Pyle disease (OMIM 265900), also known as metaphyseal dysplasia, is a rare autosomal recessive disorder with no known gene mutation. We report a case of Pyle disease in a 7-year-old African boy of mixed ancestry who presented with finger and wrist fractures following minor trauma. The radiological findings revealed abnormally broad metaphyses of the tubular bones, known as Erlenmeyer-flask bone deformity, and mild cranial sclerosis, both hallmarks of the condition. We report the first case in a patient with African ancestry, which could help in the gene discovery of this rare autosomal recessive skeletal dysplasia with unknown mutations. PMID:27245543

  16. Suicidal Ideation in Hispanic and Mixed-Ancestry Adolescents.

    ERIC Educational Resources Information Center

    Olvera, Rene L.

    2001-01-01

    Examined differences in suicidal ideation, depressive symptomatology, acculturation, and coping strategies based on ethnicity. Hispanic (predominantly Mexican American) and mixed-ancestry adolescents displayed significantly higher risk of suicidal ideation compared to Anglo peers, even when controlling for socioeconomic status, age, and gender.…

  17. Assessing Patterns of Admixture and Ancestry in Canadian Honey Bees

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    PubMed Central

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

    2016-01-01

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

  19. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis.

    PubMed

    Paternoster, Lavinia; Standl, Marie; Waage, Johannes; Baurecht, Hansjörg; Hotze, Melanie; Strachan, David P; Curtin, John A; Bønnelykke, Klaus; Tian, Chao; Takahashi, Atsushi; Esparza-Gordillo, Jorge; Alves, Alexessander Couto; Thyssen, Jacob P; den Dekker, Herman T; Ferreira, Manuel A; Altmaier, Elisabeth; Sleiman, Patrick M A; Xiao, Feng Li; Gonzalez, Juan R; Marenholz, Ingo; Kalb, Birgit; Pino-Yanes, Maria; Xu, Cheng-Jian; Carstensen, Lisbeth; Groen-Blokhuis, Maria M; Venturini, Cristina; Pennell, Craig E; Barton, Sheila J; Levin, Albert M; Curjuric, Ivan; Bustamante, Mariona; Kreiner-Møller, Eskil; Lockett, Gabrielle A; Bacelis, Jonas; Bunyavanich, Supinda; Myers, Rachel A; Matanovic, Anja; Kumar, Ashish; Tung, Joyce Y; Hirota, Tomomitsu; Kubo, Michiaki; McArdle, Wendy L; Henderson, A John; Kemp, John P; Zheng, Jie; Smith, George Davey; Rüschendorf, Franz; Bauerfeind, Anja; Lee-Kirsch, Min Ae; Arnold, Andreas; Homuth, Georg; Schmidt, Carsten O; Mangold, Elisabeth; Cichon, Sven; Keil, Thomas; Rodríguez, Elke; Peters, Annette; Franke, Andre; Lieb, Wolfgang; Novak, Natalija; Fölster-Holst, Regina; Horikoshi, Momoko; Pekkanen, Juha; Sebert, Sylvain; Husemoen, Lise L; Grarup, Niels; de Jongste, Johan C; Rivadeneira, Fernando; Hofman, Albert; Jaddoe, Vincent W V; Pasmans, Suzanne G M A; Elbert, Niels J; Uitterlinden, André G; Marks, Guy B; Thompson, Philip J; Matheson, Melanie C; Robertson, Colin F; Ried, Janina S; Li, Jin; Zuo, Xian Bo; Zheng, Xiao Dong; Yin, Xian Yong; Sun, Liang Dan; McAleer, Maeve A; O'Regan, Grainne M; Fahy, Caoimhe M R; Campbell, Linda E; Macek, Milan; Kurek, Michael; Hu, Donglei; Eng, Celeste; Postma, Dirkje S; Feenstra, Bjarke; Geller, Frank; Hottenga, Jouke Jan; Middeldorp, Christel M; Hysi, Pirro; Bataille, Veronique; Spector, Tim; Tiesler, Carla M T; Thiering, Elisabeth; Pahukasahasram, Badri; Yang, James J; Imboden, Medea; Huntsman, Scott; Vilor-Tejedor, Natàlia; Relton, Caroline L; Myhre, Ronny; Nystad, Wenche; Custovic, Adnan; Weiss, Scott T; Meyers, Deborah A; Söderhäll, Cilla; Melén, Erik; Ober, Carole; Raby, Benjamin A; Simpson, Angela; Jacobsson, Bo; Holloway, John W; Bisgaard, Hans; Sunyer, Jordi; Probst-Hensch, Nicole M; Williams, L Keoki; Godfrey, Keith M; Wang, Carol A; Boomsma, Dorret I; Melbye, Mads; Koppelman, Gerard H; Jarvis, Deborah; McLean, W H Irwin; Irvine, Alan D; Zhang, Xue Jun; Hakonarson, Hakon; Gieger, Christian; Burchard, Esteban G; Martin, Nicholas G; Duijts, Liesbeth; Linneberg, Allan; Jarvelin, Marjo-Riitta; Nöthen, Markus M; Lau, Susanne; Hübner, Norbert; Lee, Young-Ae; Tamari, Mayumi; Hinds, David A; Glass, Daniel; Brown, Sara J; Heinrich, Joachim; Evans, David M; Weidinger, Stephan

    2015-12-01

    Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis. PMID:26482879

  20. Analysis of Prostate Cancer Susceptibility Variants in South African Men: Replicating Associations on Chromosomes 8q24 and 10q11.

    PubMed

    Fernandez, Pedro; Salie, Muneeb; du Toit, Danielle; van der Merwe, Andre

    2015-01-01

    Genome-wide association studies (GWAS) have implicated single nucleotide polymorphisms (SNPs) on chromosomes 2p15, 6q25, 7p15.2, 7q21, 8q24, 10q11, 10q26, 11q13, 17q12, 17q24, 19q13, and Xp11, with prostate cancer (PCa) susceptibility and/or tumour aggressiveness, in populations of African, European, and Asian ancestry. The objective of this study was to confirm these associations in South African Mixed Ancestry and White men. We evaluated 17 prioritised GWAS SNPs in South African cases (331 Mixed Ancestry and 155 White) and controls (178 Mixed Ancestry and 145 White). The replicated SNP associations for the different South African ethnic groups were rs7008482 (8q24) (p = 2.45 × 10(-5)), rs6983267 (8q24) (p = 4.48 × 10(-7)), and rs10993994 (10q11) (p = 1.40 × 10(-3)) in Mixed Ancestry men and rs10993994 (p = 1.56 × 10(-9)) in White men. No significant associations were observed for the analyses stratified by disease aggressiveness in the individual and the combined population group analysis. The present study demonstrates that a number of known PCa susceptibility variants may contribute to disease susceptibility in South African men. Larger genetic investigations extended to other South African population groups are warranted to confirm the role of these and other SNPs in disease susceptibility.

  1. Analysis of Prostate Cancer Susceptibility Variants in South African Men: Replicating Associations on Chromosomes 8q24 and 10q11

    PubMed Central

    Fernandez, Pedro; Salie, Muneeb; du Toit, Danielle; van der Merwe, Andre

    2015-01-01

    Genome-wide association studies (GWAS) have implicated single nucleotide polymorphisms (SNPs) on chromosomes 2p15, 6q25, 7p15.2, 7q21, 8q24, 10q11, 10q26, 11q13, 17q12, 17q24, 19q13, and Xp11, with prostate cancer (PCa) susceptibility and/or tumour aggressiveness, in populations of African, European, and Asian ancestry. The objective of this study was to confirm these associations in South African Mixed Ancestry and White men. We evaluated 17 prioritised GWAS SNPs in South African cases (331 Mixed Ancestry and 155 White) and controls (178 Mixed Ancestry and 145 White). The replicated SNP associations for the different South African ethnic groups were rs7008482 (8q24) (p = 2.45 × 10−5), rs6983267 (8q24) (p = 4.48 × 10−7), and rs10993994 (10q11) (p = 1.40 × 10−3) in Mixed Ancestry men and rs10993994 (p = 1.56 × 10−9) in White men. No significant associations were observed for the analyses stratified by disease aggressiveness in the individual and the combined population group analysis. The present study demonstrates that a number of known PCa susceptibility variants may contribute to disease susceptibility in South African men. Larger genetic investigations extended to other South African population groups are warranted to confirm the role of these and other SNPs in disease susceptibility. PMID:26347821

  2. The landscape of recombination in African Americans

    PubMed Central

    Hinch, Anjali G.; Tandon, Arti; Patterson, Nick; Song, Yunli; Rohland, Nadin; Palmer, Cameron D.; Chen, Gary K.; Wang, Kai; Buxbaum, Sarah G.; Akylbekova, Meggie; Aldrich, Melinda C.; Ambrosone, Christine B.; Amos, Christopher; Bandera, Elisa V.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Bock, Cathryn H.; Boerwinkle, Eric; Cai, Qiuyin; Caporaso, Neil; Casey, Graham; Cupples, L. Adrienne; Deming, Sandra L.; Diver, W. Ryan; Divers, Jasmin; Fornage, Myriam; Gillanders, Elizabeth M.; Glessner, Joseph; Harris, Curtis C.; Hu, Jennifer J.; Ingles, Sue A.; Isaacs, Williams; John, Esther M.; Kao, W. H. Linda; Keating, Brendan; Kittles, Rick A.; Kolonel, Laurence N.; Larkin, Emma; Le Marchand, Loic; McNeill, Lorna H.; Millikan, Robert C.; Murphy, Adam; Musani, Solomon; Neslund-Dudas, Christine; Nyante, Sarah; Papanicolaou, George J.; Press, Michael F.; Psaty, Bruce M.; Reiner, Alex P.; Rich, Stephen S.; Rodriguez-Gil, Jorge L.; Rotter, Jerome I.; Rybicki, Benjamin A.; Schwartz, Ann G.; Signorello, Lisa B.; Spitz, Margaret; Strom, Sara S.; Thun, Michael J.; Tucker, Margaret A.; Wang, Zhaoming; Wiencke, John K.; Witte, John S.; Wrensch, Margaret; Wu, Xifeng; Yamamura, Yuko; Zanetti, Krista A.; Zheng, Wei; Ziegler, Regina G.; Zhu, Xiaofeng; Redline, Susan; Hirschhorn, Joel N.; Henderson, Brian E.; Taylor, Herman A.; Price, Alkes L.; Hakonarson, Hakon; Chanock, Stephen J.; Haiman, Christopher A.; Wilson, James G.; Reich, David; Myers, Simon R.

    2011-01-01

    Recombination, together with mutation, is the ultimate source of genetic variation in populations. We leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing-over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P<10−245). We identify a 17 base pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of African-enriched alleles of PRDM9. PMID:21775986

  3. The landscape of recombination in African Americans.

    PubMed

    Hinch, Anjali G; Tandon, Arti; Patterson, Nick; Song, Yunli; Rohland, Nadin; Palmer, Cameron D; Chen, Gary K; Wang, Kai; Buxbaum, Sarah G; Akylbekova, Ermeg L; Aldrich, Melinda C; Ambrosone, Christine B; Amos, Christopher; Bandera, Elisa V; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Bock, Cathryn H; Boerwinkle, Eric; Cai, Qiuyin; Caporaso, Neil; Casey, Graham; Cupples, L Adrienne; Deming, Sandra L; Diver, W Ryan; Divers, Jasmin; Fornage, Myriam; Gillanders, Elizabeth M; Glessner, Joseph; Harris, Curtis C; Hu, Jennifer J; Ingles, Sue A; Isaacs, William; John, Esther M; Kao, W H Linda; Keating, Brendan; Kittles, Rick A; Kolonel, Laurence N; Larkin, Emma; Le Marchand, Loic; McNeill, Lorna H; Millikan, Robert C; Murphy, Adam; Musani, Solomon; Neslund-Dudas, Christine; Nyante, Sarah; Papanicolaou, George J; Press, Michael F; Psaty, Bruce M; Reiner, Alex P; Rich, Stephen S; Rodriguez-Gil, Jorge L; Rotter, Jerome I; Rybicki, Benjamin A; Schwartz, Ann G; Signorello, Lisa B; Spitz, Margaret; Strom, Sara S; Thun, Michael J; Tucker, Margaret A; Wang, Zhaoming; Wiencke, John K; Witte, John S; Wrensch, Margaret; Wu, Xifeng; Yamamura, Yuko; Zanetti, Krista A; Zheng, Wei; Ziegler, Regina G; Zhu, Xiaofeng; Redline, Susan; Hirschhorn, Joel N; Henderson, Brian E; Taylor, Herman A; Price, Alkes L; Hakonarson, Hakon; Chanock, Stephen J; Haiman, Christopher A; Wilson, James G; Reich, David; Myers, Simon R

    2011-07-20

    Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P value < 10(-245)). We identify a 17-base-pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of PRDM9 alleles common in West Africans and rare in Europeans. Sites of this motif are predicted to be risk loci for disease-causing genomic rearrangements in individuals carrying these alleles. More generally, this map provides a resource for research in human genetic variation and evolution.

  4. Distinct Transcript Isoforms of the Atypical Chemokine Receptor 1 (ACKR1)/Duffy Antigen Receptor for Chemokines (DARC) Gene Are Expressed in Lymphoblasts and Altered Isoform Levels Are Associated with Genetic Ancestry and the Duffy-Null Allele.

    PubMed

    Davis, Melissa B; Walens, Andrea; Hire, Rupali; Mumin, Kauthar; Brown, Andrea M; Ford, DeJuana; Howerth, Elizabeth W; Monteil, Michele

    2015-01-01

    The Atypical ChemoKine Receptor 1 (ACKR1) gene, better known as Duffy Antigen Receptor for Chemokines (DARC or Duffy), is responsible for the Duffy Blood Group and plays a major role in regulating the circulating homeostatic levels of pro-inflammatory chemokines. Previous studies have shown that one common variant, the Duffy Null (Fy-) allele that is specific to African Ancestry groups, completely removes expression of the gene on erythrocytes; however, these individuals retain endothelial expression. Additional alleles are associated with a myriad of clinical outcomes related to immune responses and inflammation. In addition to allele variants, there are two distinct transcript isoforms of DARC which are expressed from separate promoters, and very little is known about the distinct transcriptional regulation or the distinct functionality of these protein isoforms. Our objective was to determine if the African specific Fy- allele alters the expression pattern of DARC isoforms and therefore could potentially result in a unique signature of the gene products, commonly referred to as antigens. Our work is the first to establish that there is expression of DARC on lymphoblasts. Our data indicates that people of African ancestry have distinct relative levels of DARC isoforms expressed in these cells. We conclude that the expression of both isoforms in combination with alternate alleles yields multiple Duffy antigens in ancestry groups, depending upon the haplotypes across the gene. Importantly, we hypothesize that DARC isoform expression patterns will translate into ancestry-specific inflammatory responses that are correlated with the axis of pro-inflammatory chemokine levels and distinct isoform-specific interactions with these chemokines. Ultimately, this work will increase knowledge of biological mechanisms underlying disparate clinical outcomes of inflammatory-related diseases among ethnic and geographic ancestry groups. PMID:26473357

  5. Multiple Ways to Solve Proportions

    ERIC Educational Resources Information Center

    Ercole, Leslie K.; Frantz, Marny; Ashline, George

    2011-01-01

    When solving problems involving proportions, students may intuitively draw on strategies that connect to their understanding of fractions, decimals, and percents. These two statements--"Instruction in solving proportions should include methods that have a strong intuitive basis" and "Teachers should begin instruction with more intuitive…

  6. Lack of Association of the APOL1 G3 Haplotype in African Americans with ESRD

    PubMed Central

    Ng, Maggie C.Y.; Langefeld, Carl D.; Divers, Jasmin; Lea, Janice P.; Okusa, Mark D.; Kimberly, Robert P.; Bowden, Donald W.

    2015-01-01

    Apolipoprotein L1 gene (APOL1) G1 and G2 variants are strongly associated with progressive nondiabetic nephropathy in populations with recent African ancestry. Selection for these variants occurred as a result of protection from human African trypanosomiasis (HAT). Resequencing of this region in 10 genetically and geographically distinct African populations residing in HAT endemic regions identified eight single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium and comprising a novel G3 haplotype. To determine whether the APOL1 G3 haplotype was associated with nephropathy, G1, G2, and G3 SNPs and 70 ancestry informative markers spanning the genome were genotyped in 937 African Americans with nondiabetic ESRD, 965 African Americans with type 2 diabetes–associated ESRD, and 1029 non-nephropathy controls. In analyses adjusting for age, sex, APOL1 G1/G2 risk (recessive), and global African ancestry, the G3 haplotype was not significantly associated with ESRD (P=0.05 for nondiabetic ESRD, P=0.57 for diabetes-associated ESRD, and P=0.27 for all-cause ESRD). We conclude that variation in APOL1 G3 makes a nominal, if any, contribution to ESRD in African Americans; G1 and G2 variants explain the vast majority of nondiabetic nephropathy susceptibility. PMID:25249559

  7. Lack of Association of the APOL1 G3 Haplotype in African Americans with ESRD.

    PubMed

    Palmer, Nicholette D; Ng, Maggie C Y; Langefeld, Carl D; Divers, Jasmin; Lea, Janice P; Okusa, Mark D; Kimberly, Robert P; Bowden, Donald W; Freedman, Barry I

    2015-05-01

    Apolipoprotein L1 gene (APOL1) G1 and G2 variants are strongly associated with progressive nondiabetic nephropathy in populations with recent African ancestry. Selection for these variants occurred as a result of protection from human African trypanosomiasis (HAT). Resequencing of this region in 10 genetically and geographically distinct African populations residing in HAT endemic regions identified eight single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium and comprising a novel G3 haplotype. To determine whether the APOL1 G3 haplotype was associated with nephropathy, G1, G2, and G3 SNPs and 70 ancestry informative markers spanning the genome were genotyped in 937 African Americans with nondiabetic ESRD, 965 African Americans with type 2 diabetes-associated ESRD, and 1029 non-nephropathy controls. In analyses adjusting for age, sex, APOL1 G1/G2 risk (recessive), and global African ancestry, the G3 haplotype was not significantly associated with ESRD (P=0.05 for nondiabetic ESRD, P=0.57 for diabetes-associated ESRD, and P=0.27 for all-cause ESRD). We conclude that variation in APOL1 G3 makes a nominal, if any, contribution to ESRD in African Americans; G1 and G2 variants explain the vast majority of nondiabetic nephropathy susceptibility.

  8. Admixture mapping of quantitative trait loci for blood lipids in African-Americans.

    PubMed

    Basu, Analabha; Tang, Hua; Lewis, Cora E; North, Kari; Curb, J David; Quertermous, Thomas; Mosley, Thomas H; Boerwinkle, Eric; Zhu, Xiaofeng; Risch, Neil J

    2009-06-01

    Blood lipid levels, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), are highly heritable traits and major risk factors for atherosclerotic cardiovascular disease (CVD). Using individual ancestry estimates at marker locations across the genome, we present a novel quantitative admixture mapping analysis of all three lipid traits in a large sample of African-Americans from the Family Blood Pressure Program. Regression analysis was performed with both total and marker-location-specific European ancestry as explanatory variables, along with demographic covariates. Robust permutation analysis was used to assess statistical significance. Overall European ancestry was significantly correlated with HDL-C (negatively) and TG (positively), but not with LDL-C. We found strong evidence for a novel locus underlying HDL-C on chromosome 8q, which correlated negatively with European ancestry (P = .0014); the same location also showed positive correlation of European ancestry with TG levels. A region on chromosome 14q also showed significant negative correlation between HDL-C levels and European ancestry. On chromosome 15q, a suggestive negative correlation of European ancestry with TG and positive correlation with HDL-C was observed. Results with LDL-C were less significant overall. We also found significant evidence for genome-wide ancestry effects underlying the joint distribution of HDL-C and TG, not fully explained by the locus on chromosome 8. Our results are consistent with a genetic contribution to and may explain the healthier HDL-C and TG profiles found in Blacks versus Whites. The identified regions provide locations for follow-up studies of genetic variants underlying lipid variation in African-Americans and possibly other populations.

  9. 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

  10. Statistical classification methods for estimating ancestry using morphoscopic traits.

    PubMed

    Hefner, Joseph T; Ousley, Stephen D

    2014-07-01

    Ancestry assessments using cranial morphoscopic traits currently rely on subjective trait lists and observer experience rather than empirical support. The trait list approach, which is untested, unverified, and in many respects unrefined, is relied upon because of tradition and subjective experience. Our objective was to examine the utility of frequently cited morphoscopic traits and to explore eleven appropriate and novel methods for classifying an unknown cranium into one of several reference groups. Based on these results, artificial neural networks (aNNs), OSSA, support vector machines, and random forest models showed mean classification accuracies of at least 85%. The aNNs had the highest overall classification rate (87.8%), and random forests show the smallest difference between the highest (90.4%) and lowest (76.5%) classification accuracies. The results of this research demonstrate that morphoscopic traits can be successfully used to assess ancestry without relying only on the experience of the observer.

  11. Reconstruction of Genome Ancestry Blocks in Multiparental Populations

    PubMed Central

    Zheng, Chaozhi; Boer, Martin P.; van Eeuwijk, Fred A.

    2015-01-01

    We present a general hidden Markov model framework called reconstructing ancestry blocks bit by bit (RABBIT) for reconstructing genome ancestry blocks from single-nucleotide polymorphism (SNP) array data, a required step for quantitative trait locus (QTL) mapping. The framework can be applied to a wide range of mapping populations such as the Arabidopsis multiparent advanced generation intercross (MAGIC), the mouse Collaborative Cross (CC), and the diversity outcross (DO) for both autosomes and X chromosomes if they exist. The model underlying RABBIT accounts for the joint pattern of recombination breakpoints between two homologous chromosomes and missing data and allelic typing errors in the genotype data of both sampled individuals and founders. Studies on simulated data of the MAGIC and the CC and real data of the MAGIC, the DO, and the CC demonstrate that RABBIT is more robust and accurate in reconstructing recombination bin maps than some commonly used methods. PMID:26048018

  12. 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.

  13. Facial asymmetry and genetic ancestry in Latin American admixed populations.

    PubMed

    Quinto-Sánchez, Mirsha; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Cintas, Celia; Silva de Cerqueira, Caio Cesar; Ramallo, Virginia; Castillo, Lucia; Farrera, Arodi; Jaramillo, Claudia; Arias, Williams; Fuentes, Macarena; Everardo, Paola; de Avila, Francisco; Gomez-Valdés, Jorge; Hünemeier, Tábita; Gibbon, Shara; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Bortolini, Maria Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Ruiz-Linares, Andres; González-José, Rolando

    2015-05-01

    Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer environmental and genetic factors affecting facial phenotypes. However, the genetic basis and environmental determinants of both asymmetry types is far from being completely known. The analysis of facial asymmetries in admixed individuals can be of help to characterize the impact of a genome's heterozygosity on the developmental basis of both fluctuating and directional asymmetries. Here we characterize the association between genetic ancestry and individual asymmetry on a sample of Latin-American admixed populations. To do so, three-dimensional (3D) facial shape attributes were explored on a sample of 4,104 volunteers aged between 18 and 85 years. Individual ancestry and heterozygosity was estimated using more than 730,000 genome-wide markers. Multivariate techniques applied to geometric morphometric data were used to evaluate the magnitude and significance of directional and fluctuating asymmetry (FA), as well as correlations and multiple regressions aimed to estimate the relationship between facial FA scores and heterozygosity and a set of covariates. Results indicate that directional and FA are both significant, the former being the strongest expression of asymmetry in this sample. In addition, our analyses suggest that there are some specific patterns of facial asymmetries characterizing the different ancestry groups. Finally, we find that more heterozygous individuals exhibit lower levels of asymmetry. Our results highlight the importance of including ancestry-admixture estimators, especially when the analyses are aimed to compare levels of asymmetries on groups differing on socioeconomic levels, as a proxy to estimate developmental noise. PMID:25582401

  14. A Quasi-Exclusive European Ancestry in the Senepol Tropical Cattle Breed Highlights the Importance of the slick Locus in Tropical Adaptation

    PubMed Central

    Flori, Laurence; Gonzatti, Mary Isabel; Thevenon, Sophie; Chantal, Isabelle; Pinto, Joar; Berthier, David; Aso, Pedro M.; Gautier, Mathieu

    2012-01-01

    Background The Senepol cattle breed (SEN) was created in the early XXth century from a presumed cross between a European (EUT) breed (Red Poll) and a West African taurine (AFT) breed (N’Dama). Well adapted to tropical conditions, it is also believed trypanotolerant according to its putative AFT ancestry. However, such origins needed to be verified to define relevant husbandry practices and the genetic background underlying such adaptation needed to be characterized. Methodology/Principal Findings We genotyped 153 SEN individuals on 47,365 SNPs and combined the resulting data with those available on 18 other populations representative of EUT, AFT and Zebu (ZEB) cattle. We found on average 89% EUT, 10.4% ZEB and 0.6% AFT ancestries in the SEN genome. We further looked for footprints of recent selection using standard tests based on the extent of haplotype homozygosity. We underlined i) three footprints on chromosome (BTA) 01, two of which are within or close to the polled locus underlying the absence of horns and ii) one footprint on BTA20 within the slick hair coat locus, involved in thermotolerance. Annotation of these regions allowed us to propose three candidate genes to explain the observed signals (TIAM1, GRIK1 and RAI14). Conclusions/Significance Our results do not support the accepted concept about the AFT origin of SEN breed. Initial AFT ancestry (if any) might have been counter-selected in early generations due to breeding objectives oriented in particular toward meat production and hornless phenotype. Therefore, SEN animals are likely susceptible to African trypanosomes which questions the importation of SEN within the West African tsetse belt, as promoted by some breeding societies. Besides, our results revealed that SEN breed is predominantly a EUT breed well adapted to tropical conditions and confirmed the importance in thermotolerance of the slick locus. PMID:22675421

  15. APOL1 renal-risk genotypes associate with longer hemodialysis survival in prevalent nondiabetic African American patients with end-stage renal disease.

    PubMed

    Ma, Lijun; Langefeld, Carl D; Comeau, Mary E; Bonomo, Jason A; Rocco, Michael V; Burkart, John M; Divers, Jasmin; Palmer, Nicholette D; Hicks, Pamela J; Bowden, Donald W; Lea, Janice P; Krisher, Jenna O; Clay, Margo J; Freedman, Barry I

    2016-08-01

    Relative to European Americans, evidence supports that African Americans with end-stage renal disease (ESRD) survive longer on dialysis. Renal-risk variants in the apolipoprotein L1 gene (APOL1), associated with nondiabetic nephropathy and less subclinical atherosclerosis, may contribute to dialysis outcomes. Here, APOL1 renal-risk variants were assessed for association with dialytic survival in 450 diabetic and 275 nondiabetic African American hemodialysis patients from Wake Forest and Emory School of Medicine outpatient facilities. Outcomes were provided by the ESRD Network 6-Southeastern Kidney Council Standardized Information Management System. Dates of death, receipt of a kidney transplant, and loss to follow-up were recorded. Outcomes were censored at the date of transplantation or through 1 July 2015. Multivariable Cox proportional hazards models were computed separately in patients with nondiabetic and diabetic ESRD, adjusting for the covariates age, gender, comorbidities, ancestry, and presence of an arteriovenous fistula or graft at dialysis initiation. In nondiabetic ESRD, patients with 2 (vs. 0/1) APOL1 renal-risk variants had significantly longer dialysis survival (hazard ratio 0.57), a pattern not observed in patients with diabetes-associated ESRD (hazard ratio 1.29). Thus, 2 APOL1 renal-risk variants are associated with longer dialysis survival in African Americans without diabetes, potentially relating to presence of renal-limited disease or less atherosclerosis. PMID:27157696

  16. Vitamin D status of older adults of diverse ancestry living in the greater Toronto area

    PubMed Central

    2013-01-01

    Background Physiological and lifestyle factors put older adults at an increased risk of vitamin D insufficiency and resulting negative health outcomes. Here we explore the vitamin D status in a sample of community dwelling older adults of diverse ancestry living in the Greater Toronto area (GTA). Methods Two hundred and twenty-four (224) adults over 60 years of age were recruited from the Square One Older Adult Centre, in Mississauga, Ontario. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations were measured from dried blood spot cards. Dietary and supplemental intakes of vitamin D were assessed via questionnaires. Skin pigmentation was assessed quantitatively by measuring melanin levels using a reflectometer. Results The mean 25(OH)D concentration in the total sample was 82.4 nmol/L. There were no statistically significant differences in serum 25(OH)D concentrations, supplemental or dietary vitamin D intakes between the three major ancestral groups (East Asians, Europeans and South Asians). Females had significantly higher 25(OH)D concentrations than males (84.5 nmol/L vs. 72.2 nmol/L, p = 0.012). The proportion of participants with 25(OH)D concentrations below 50 nmol/L and 75 nmol/L were 12.1%, and 38.8%, respectively. The mean daily supplemental intake of vitamin D was 917 IU/day. Vitamin D intake from supplements was the major factor determining 25(OH)D concentrations (p < 0.001). Conclusions Mean concentration of 25(OH)D in a sample of older adults of diverse ancestry living in the GTA exceeded 80 nmol/L, and there were no significant differences in 25(OH)D levels between ancestral groups. These results sharply contrast with our recent study focused on young adults of diverse ancestry living in the same geographic area, in which we found substantially lower 25(OH)D concentrations (mean 39.5 nmol/L), low supplemental vitamin D intake (114 IU/day), and significant differences in 25(OH)D levels between ancestral groups. High daily intake

  17. Proportional smile design using the recurring esthetic dental (red) proportion.

    PubMed

    Ward, D H

    2001-01-01

    Dentists have needed an objective way in which to evaluate a smile. A method for determining the ideal size and position of the anterior teeth has been presented here. Use of the FIVE to evaluate the RED proportion and the width-to-height ratio, tempered with sound clinical judgment, gives pleasing and consistent results. With the diversity that exists in nature, rarely does the final result follow all the mathematical rules of proportional smile design. This approach may serve as a foundation on which to base initial smile design, however. When one begins to understand the relationship between beauty, mathematics, and the surrounding world, one begins to appreciate their interdependence.

  18. Meta-analysis of loci associated with age at natural menopause in African-American women

    PubMed Central

    Chen, Christina T.L.; Liu, Ching-Ti; Chen, Gary K.; Andrews, Jeanette S.; Arnold, Alice M.; Dreyfus, Jill; Franceschini, Nora; Garcia, Melissa E.; Kerr, Kathleen F.; Li, Guo; Lohman, Kurt K.; Musani, Solomon K.; Nalls, Michael A.; Raffel, Leslie J.; Smith, Jennifer; Ambrosone, Christine B.; Bandera, Elisa V.; Bernstein, Leslie; Britton, Angela; Brzyski, Robert G.; Cappola, Anne; Carlson, Christopher S.; Couper, David; Deming, Sandra L.; Goodarzi, Mark O.; Heiss, Gerardo; John, Esther M.; Lu, Xiaoning; Le Marchand, Loic; Marciante, Kristin; Mcknight, Barbara; Millikan, Robert; Nock, Nora L.; Olshan, Andrew F.; Press, Michael F.; Vaiyda, Dhananjay; Woods, Nancy F.; Taylor, Herman A.; Zhao, Wei; Zheng, Wei; Evans, Michele K.; Harris, Tamara B.; Henderson, Brian E.; Kardia, Sharon L.R.; Kooperberg, Charles; Liu, Yongmei; Mosley, Thomas H.; Psaty, Bruce; Wellons, Melissa; Windham, Beverly G.; Zonderman, Alan B.; Cupples, L. Adrienne; Demerath, Ellen W.; Haiman, Christopher; Murabito, Joanne M.; Rajkovic, Aleksandar

    2014-01-01

    Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA. PMID:24493794

  19. Meta-analysis of loci associated with age at natural menopause in African-American women.

    PubMed

    Chen, Christina T L; Liu, Ching-Ti; Chen, Gary K; Andrews, Jeanette S; Arnold, Alice M; Dreyfus, Jill; Franceschini, Nora; Garcia, Melissa E; Kerr, Kathleen F; Li, Guo; Lohman, Kurt K; Musani, Solomon K; Nalls, Michael A; Raffel, Leslie J; Smith, Jennifer; Ambrosone, Christine B; Bandera, Elisa V; Bernstein, Leslie; Britton, Angela; Brzyski, Robert G; Cappola, Anne; Carlson, Christopher S; Couper, David; Deming, Sandra L; Goodarzi, Mark O; Heiss, Gerardo; John, Esther M; Lu, Xiaoning; Le Marchand, Loic; Marciante, Kristin; Mcknight, Barbara; Millikan, Robert; Nock, Nora L; Olshan, Andrew F; Press, Michael F; Vaiyda, Dhananjay; Woods, Nancy F; Taylor, Herman A; Zhao, Wei; Zheng, Wei; Evans, Michele K; Harris, Tamara B; Henderson, Brian E; Kardia, Sharon L R; Kooperberg, Charles; Liu, Yongmei; Mosley, Thomas H; Psaty, Bruce; Wellons, Melissa; Windham, Beverly G; Zonderman, Alan B; Cupples, L Adrienne; Demerath, Ellen W; Haiman, Christopher; Murabito, Joanne M; Rajkovic, Aleksandar

    2014-06-15

    Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA.

  20. Population ancestry and genetic risk for diabetes and kidney, cardiovascular, and bone disease: modifiable environmental factors may produce the cures.

    PubMed

    Freedman, Barry I; Divers, Jasmin; Palmer, Nicholette D

    2013-12-01

    Variable rates of disease observed between members of different continental population groups may be mediated by inherited factors, environmental exposures, or their combination. This article provides evidence in support of differential allele frequency distributions that underlie the higher rates of nondiabetic kidney disease in the focal segmental glomerulosclerosis spectrum of disease and lower rates of coronary artery calcified atherosclerotic plaque and osteoporosis in populations of African ancestry. With recognition that these and other common complex diseases are affected by biological factors comes the realization that targeted manipulation of environmental exposures and pharmacologic treatments will have different effects based on genotype. The present era of precision medicine will couple one's genetic makeup with specific therapies to reduce rates of disease based on the presence of disease-specific alleles.

  1. Population Ancestry and Genetic Risk for Diabetes and Kidney, Cardiovascular, and Bone Disease: Modifiable Environmental Factors May Produce the Cures

    PubMed Central

    Freedman, Barry I.; Divers, Jasmin; Palmer, Nicholette D.

    2013-01-01

    Variable rates of disease observed between members of different continental population groups may be mediated by inherited factors, environmental exposures, or their combination. This manuscript provides evidence in support of differential allele frequency distributions that underlie the higher rates of non-diabetic kidney disease in the focal segmental glomerulosclerosis spectrum of disease and lower rates of coronary artery calcified atherosclerotic plaque and osteoporosis in populations of African ancestry. With recognition that these and other common complex diseases are affected by biologic factors comes the realization that targeted manipulation of environmental exposures and pharmacologic treatments will have different effects based on genotype. The current era of precision medicine will couple one’s genetic make-up with specific therapies to reduce rates of disease based on presence of disease-specific alleles. PMID:23896482

  2. 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

  3. The Potential for Enhancing the Power of Genetic Association Studies in African Americans through the Reuse of Existing Genotype Data

    PubMed Central

    Chen, Gary K.; Millikan, Robert C.; John, Esther M.; Ambrosone, Christine B.; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer J.; Chanock, Stephen J.; Ziegler, Regina G.; Bandera, Elisa V.; Henderson, Brian E.; Haiman, Christopher A.; Stram, Daniel O.

    2010-01-01

    We consider the feasibility of reusing existing control data obtained in genetic association studies in order to reduce costs for new studies. We discuss controlling for the population differences between cases and controls that are implicit in studies utilizing external control data. We give theoretical calculations of the statistical power of a test due to Bourgain et al (Am J Human Genet 2003), applied to the problem of dealing with case-control differences in genetic ancestry related to population isolation or population admixture. Theoretical results show that there may exist bounds for the non-centrality parameter for a test of association that places limits on study power even if sample sizes can grow arbitrarily large. We apply this method to data from a multi-center, geographically-diverse, genome-wide association study of breast cancer in African-American women. Our analysis of these data shows that admixture proportions differ by center with the average fraction of European admixture ranging from approximately 20% for participants from study sites in the Eastern United States to 25% for participants from West Coast sites. However, these differences in average admixture fraction between sites are largely counterbalanced by considerable diversity in individual admixture proportion within each study site. Our results suggest that statistical correction for admixture differences is feasible for future studies of African-Americans, utilizing the existing controls from the African-American Breast Cancer study, even if case ascertainment for the future studies is not balanced over the same centers or regions that supplied the controls for the current study. PMID:20824062

  4. Bayesian inference on proportional elections.

    PubMed

    Brunello, Gabriel Hideki Vatanabe; Nakano, Eduardo Yoshio

    2015-01-01

    Polls for majoritarian voting systems usually show estimates of the percentage of votes for each candidate. However, proportional vote systems do not necessarily guarantee the candidate with the most percentage of votes will be elected. Thus, traditional methods used in majoritarian elections cannot be applied on proportional elections. In this context, the purpose of this paper was to perform a Bayesian inference on proportional elections considering the Brazilian system of seats distribution. More specifically, a methodology to answer the probability that a given party will have representation on the chamber of deputies was developed. Inferences were made on a Bayesian scenario using the Monte Carlo simulation technique, and the developed methodology was applied on data from the Brazilian elections for Members of the Legislative Assembly and Federal Chamber of Deputies in 2010. A performance rate was also presented to evaluate the efficiency of the methodology. Calculations and simulations were carried out using the free R statistical software.

  5. Bayesian Inference on Proportional Elections

    PubMed Central

    Brunello, Gabriel Hideki Vatanabe; Nakano, Eduardo Yoshio

    2015-01-01

    Polls for majoritarian voting systems usually show estimates of the percentage of votes for each candidate. However, proportional vote systems do not necessarily guarantee the candidate with the most percentage of votes will be elected. Thus, traditional methods used in majoritarian elections cannot be applied on proportional elections. In this context, the purpose of this paper was to perform a Bayesian inference on proportional elections considering the Brazilian system of seats distribution. More specifically, a methodology to answer the probability that a given party will have representation on the chamber of deputies was developed. Inferences were made on a Bayesian scenario using the Monte Carlo simulation technique, and the developed methodology was applied on data from the Brazilian elections for Members of the Legislative Assembly and Federal Chamber of Deputies in 2010. A performance rate was also presented to evaluate the efficiency of the methodology. Calculations and simulations were carried out using the free R statistical software. PMID:25786259

  6. Africanization of a feral honey bee (Apis mellifera) population in South Texas: does a decade make a difference?

    PubMed

    Rangel, Juliana; Giresi, Melissa; Pinto, Maria Alice; Baum, Kristen A; Rubink, William L; Coulson, Robert N; Johnston, John Spencer

    2016-04-01

    The arrival to the United States of the Africanized honey bee, a hybrid between European subspecies and the African subspecies Apis mellifera scutellata, is a remarkable model for the study of biological invasions. This immigration has created an opportunity to study the dynamics of secondary contact of honey bee subspecies from African and European lineages in a feral population in South Texas. An 11-year survey of this population (1991-2001) showed that mitochondrial haplotype frequencies changed drastically over time from a resident population of eastern and western European maternal ancestry, to a population dominated by the African haplotype. A subsequent study of the nuclear genome showed that the Africanization process included bidirectional gene flow between European and Africanized honey bees, giving rise to a new panmictic mixture of A. m. scutellata- and European-derived genes. In this study, we examined gene flow patterns in the same population 23 years after the first hybridization event occurred. We found 28 active colonies inhabiting 92 tree cavities surveyed in a 5.14 km(2) area, resulting in a colony density of 5.4 colonies/km(2). Of these 28 colonies, 25 were of A. m. scutellata maternal ancestry, and three were of western European maternal ancestry. No colonies of eastern European maternal ancestry were detected, although they were present in the earlier samples. Nuclear DNA revealed little change in the introgression of A. m. scutellata-derived genes into the population compared to previous surveys. Our results suggest this feral population remains an admixed swarm with continued low levels of European ancestry and a greater presence of African-derived mitochondrial genetic composition.

  7. Africanization of a feral honey bee (Apis mellifera) population in South Texas: does a decade make a difference?

    PubMed

    Rangel, Juliana; Giresi, Melissa; Pinto, Maria Alice; Baum, Kristen A; Rubink, William L; Coulson, Robert N; Johnston, John Spencer

    2016-04-01

    The arrival to the United States of the Africanized honey bee, a hybrid between European subspecies and the African subspecies Apis mellifera scutellata, is a remarkable model for the study of biological invasions. This immigration has created an opportunity to study the dynamics of secondary contact of honey bee subspecies from African and European lineages in a feral population in South Texas. An 11-year survey of this population (1991-2001) showed that mitochondrial haplotype frequencies changed drastically over time from a resident population of eastern and western European maternal ancestry, to a population dominated by the African haplotype. A subsequent study of the nuclear genome showed that the Africanization process included bidirectional gene flow between European and Africanized honey bees, giving rise to a new panmictic mixture of A. m. scutellata- and European-derived genes. In this study, we examined gene flow patterns in the same population 23 years after the first hybridization event occurred. We found 28 active colonies inhabiting 92 tree cavities surveyed in a 5.14 km(2) area, resulting in a colony density of 5.4 colonies/km(2). Of these 28 colonies, 25 were of A. m. scutellata maternal ancestry, and three were of western European maternal ancestry. No colonies of eastern European maternal ancestry were detected, although they were present in the earlier samples. Nuclear DNA revealed little change in the introgression of A. m. scutellata-derived genes into the population compared to previous surveys. Our results suggest this feral population remains an admixed swarm with continued low levels of European ancestry and a greater presence of African-derived mitochondrial genetic composition. PMID:27069571

  8. Population genomic analysis uncovers African and European admixture in Drosophila melanogaster populations from the south-eastern United States and Caribbean Islands.

    PubMed

    Kao, Joyce Y; Zubair, Asif; Salomon, Matthew P; Nuzhdin, Sergey V; Campo, Daniel

    2015-04-01

    Drosophila melanogaster is postulated to have colonized North America in the past several 100 years in two waves. Flies from Europe colonized the east coast United States while flies from Africa inhabited the Caribbean, which if true, make the south-east US and Caribbean Islands a secondary contact zone for African and European D. melanogaster. This scenario has been proposed based on phenotypes and limited genetic data. In our study, we have sequenced individual whole genomes of flies from populations in the south-east US and Caribbean Islands and examined these populations in conjunction with population sequences from the west coast US, Africa, and Europe. We find that west coast US populations are closely related to the European population, likely reflecting a rapid westward expansion upon first settlements into North America. We also find genomic evidence of African and European admixture in south-east US and Caribbean populations, with a clinal pattern of decreasing proportions of African ancestry with higher latitude. Our genomic analysis of D. melanogaster populations from the south-east US and Caribbean Islands provides more evidence for the Caribbean Islands as the source of previously reported novel African alleles found in other east coast US populations. We also find the border between the south-east US and the Caribbean island to be the admixture hot zone where distinctly African-like Caribbean flies become genomically more similar to European-like south-east US flies. Our findings have important implications for previous studies examining the generation of east coast US clines via selection.

  9. Genome-wide association studies in Africans and African Americans: expanding the framework of the genomics of human traits and disease.

    PubMed

    Peprah, Emmanuel; Xu, Huichun; Tekola-Ayele, Fasil; Royal, Charmaine D

    2015-01-01

    Genomic research is one of the tools for elucidating the pathogenesis of diseases of global health relevance and paving the research dimension to clinical and public health translation. Recent advances in genomic research and technologies have increased our understanding of human diseases, genes associated with these disorders, and the relevant mechanisms. Genome-wide association studies (GWAS) have proliferated since the first studies were published several years ago and have become an important tool in helping researchers comprehend human variation and the role genetic variants play in disease. However, the need to expand the diversity of populations in GWAS has become increasingly apparent as new knowledge is gained about genetic variation. Inclusion of diverse populations in genomic studies is critical to a more complete understanding of human variation and elucidation of the underpinnings of complex diseases. In this review, we summarize the available data on GWAS in recent African ancestry populations within the western hemisphere (i.e. African Americans and peoples of the Caribbean) and continental African populations. Furthermore, we highlight ways in which genomic studies in populations of recent African ancestry have led to advances in the areas of malaria, HIV, prostate cancer, and other diseases. Finally, we discuss the advantages of conducting GWAS in recent African ancestry populations in the context of addressing existing and emerging global health conditions.

  10. Genome-wide association studies in Africans and African Americans: Expanding the Framework of the Genomics of Human Traits and Disease

    PubMed Central

    Peprah, Emmanuel; Xu, Huichun; Tekola-Ayele, Fasil; Royal, Charmaine D.

    2014-01-01

    Genomic research is one of the tools for elucidating the pathogenesis of diseases of global health relevance, and paving the research dimension to clinical and public health translation. Recent advances in genomic research and technologies have increased our understanding of human diseases, genes associated with these disorders, and the relevant mechanisms. Genome-wide association studies (GWAS) have proliferated since the first studies were published several years ago, and have become an important tool in helping researchers comprehend human variation and the role genetic variants play in disease. However, the need to expand the diversity of populations in GWAS has become increasingly apparent as new knowledge is gained about genetic variation. Inclusion of diverse populations in genomic studies is critical to a more complete understanding of human variation and elucidation of the underpinnings of complex diseases. In this review, we summarize the available data on GWAS in recent-African ancestry populations within the western hemisphere (i.e. African Americans and peoples of the Caribbean) and continental African populations. Furthermore, we highlight ways in which genomic studies in populations of recent African ancestry have led to advances in the areas of malaria, HIV, prostate cancer, and other diseases. Finally, we discuss the advantages of conducting GWAS in recent African ancestry populations in the context of addressing existing and emerging global health conditions. PMID:25427668

  11. Proportional Reasoning with a Pyramid

    ERIC Educational Resources Information Center

    Mamolo, Ami; Sinclair, Margaret; Whiteley, Walter J.

    2011-01-01

    Proportional reasoning pops up in math class in a variety of places, such as while making scaled drawings; finding equivalent fractions; converting units of measurement; comparing speeds, prices, and rates; and comparing lengths, areas, and volume. Students need to be exposed to a variety of representations to develop a sound understanding of this…

  12. Proportional Hazards Models of Graduation

    ERIC Educational Resources Information Center

    Chimka, Justin R.; Reed-Rhoads, Teri; Barker, Kash

    2008-01-01

    Survival analysis is a statistical tool used to describe the duration between events. Many processes in medical research, engineering, and economics can be described using survival analysis techniques. This research involves studying engineering college student graduation using Cox proportional hazards models. Among male students with American…

  13. Social Justice and Proportional Reasoning

    ERIC Educational Resources Information Center

    Simic-Muller, Ksenija

    2015-01-01

    Ratio and proportional reasoning tasks abound that have connections to real-world situations. Examples in this article demonstrate how textbook tasks can easily be transformed into authentic real-world problems that shed light on issues of equity and fairness, such as population growth and crime rates. A few ideas are presented on how teachers can…

  14. Saving Money Using Proportional Reasoning

    ERIC Educational Resources Information Center

    de la Cruz, Jessica A.; Garney, Sandra

    2016-01-01

    It is beneficial for students to discover intuitive strategies, as opposed to the teacher presenting strategies to them. Certain proportional reasoning tasks are more likely to elicit intuitive strategies than other tasks. The strategies that students are apt to use when approaching a task, as well as the likelihood of a student's success or…

  15. Multiple sclerosis susceptibility alleles in African Americans

    PubMed Central

    Johnson, Britt A.; Wang, Joanne; Taylor, Elise M.; Caillier, Stacy J.; Herbert, Joseph; Khan, Omar A.; Cross, Anne H.; De Jager, Philip L.; Gourraud, Pierre-Antoine F.; Cree, Bruce C.A.; Hauser, Stephen L.; Oksenberg, Jorge R.

    2009-01-01

    Multiple sclerosis (MS) is an autoimmune demyelinating disease characterized by complex genetics and multifaceted gene-environment interactions. Compared to whites, African Americans have a lower risk for developing MS, but African Americans with MS have a greater risk of disability. These differences between African Americans and whites may represent differences in genetic susceptibility and/or environmental factors. SNPs from 12 candidate genes have recently been identified and validated with MS risk in white populations. We performed a replication study using 918 cases and 656 unrelated controls to test whether these candidate genes are also associated with MS risk in African Americans. CD6, CLEC16a, EVI5, GPC5, and TYK2 contained SNPs that are associated with MS risk in the African American dataset. EVI5 showed the strongest association outside the MHC (rs10735781, OR = 1.233, 95% CI = 1.06–1.43, P value = 0.006). In addition, RGS1 appears to affect age of onset whereas TNFRSF1A appears to be associated with disease progression. None of the tested variants showed results that were statistically in-consistent with the effects established in whites. The results are consistent with shared disease genetic mechanisms among individuals of European and African ancestry. PMID:19865102

  16. 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. PMID:23667324

  17. 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

  18. Genomewide ancestry and divergence patterns from low-coverage sequencing data reveal a complex history of admixture in wild baboons.

    PubMed

    Wall, Jeffrey D; Schlebusch, Stephen A; Alberts, Susan C; Cox, Laura A; Snyder-Mackler, Noah; Nevonen, Kimberly A; Carbone, Lucia; Tung, Jenny

    2016-07-01

    Naturally occurring admixture has now been documented in every major primate lineage, suggesting its key role in primate evolutionary history. Active primate hybrid zones can provide valuable insight into this process. Here, we investigate the history of admixture in one of the best-studied natural primate hybrid zones, between yellow baboons (Papio cynocephalus) and anubis baboons (Papio anubis) in the Amboseli ecosystem of Kenya. We generated a new genome assembly for yellow baboon and low-coverage genomewide resequencing data from yellow baboons, anubis baboons and known hybrids (n = 44). Using a novel composite likelihood method for estimating local ancestry from low-coverage data, we found high levels of genetic diversity and genetic differentiation between the parent taxa, and excellent agreement between genome-scale ancestry estimates and a priori pedigree, life history and morphology-based estimates (r(2)  = 0.899). However, even putatively unadmixed Amboseli yellow individuals carried a substantial proportion of anubis ancestry, presumably due to historical admixture. Further, the distribution of shared vs. fixed differences between a putatively unadmixed Amboseli yellow baboon and an unadmixed anubis baboon, both sequenced at high coverage, is inconsistent with simple isolation-migration or equilibrium migration models. Our findings suggest a complex process of intermittent contact that has occurred multiple times in baboon evolutionary history, despite no obvious fitness costs to hybrids or major geographic or behavioural barriers. In combination with the extensive phenotypic data available for baboon hybrids, our results provide valuable context for understanding the history of admixture in primates, including in our own lineage.

  19. Genomewide ancestry and divergence patterns from low-coverage sequencing data reveal a complex history of admixture in wild baboons.

    PubMed

    Wall, Jeffrey D; Schlebusch, Stephen A; Alberts, Susan C; Cox, Laura A; Snyder-Mackler, Noah; Nevonen, Kimberly A; Carbone, Lucia; Tung, Jenny

    2016-07-01

    Naturally occurring admixture has now been documented in every major primate lineage, suggesting its key role in primate evolutionary history. Active primate hybrid zones can provide valuable insight into this process. Here, we investigate the history of admixture in one of the best-studied natural primate hybrid zones, between yellow baboons (Papio cynocephalus) and anubis baboons (Papio anubis) in the Amboseli ecosystem of Kenya. We generated a new genome assembly for yellow baboon and low-coverage genomewide resequencing data from yellow baboons, anubis baboons and known hybrids (n = 44). Using a novel composite likelihood method for estimating local ancestry from low-coverage data, we found high levels of genetic diversity and genetic differentiation between the parent taxa, and excellent agreement between genome-scale ancestry estimates and a priori pedigree, life history and morphology-based estimates (r(2)  = 0.899). However, even putatively unadmixed Amboseli yellow individuals carried a substantial proportion of anubis ancestry, presumably due to historical admixture. Further, the distribution of shared vs. fixed differences between a putatively unadmixed Amboseli yellow baboon and an unadmixed anubis baboon, both sequenced at high coverage, is inconsistent with simple isolation-migration or equilibrium migration models. Our findings suggest a complex process of intermittent contact that has occurred multiple times in baboon evolutionary history, despite no obvious fitness costs to hybrids or major geographic or behavioural barriers. In combination with the extensive phenotypic data available for baboon hybrids, our results provide valuable context for understanding the history of admixture in primates, including in our own lineage. PMID:27145036

  20. What is proportional reasoning, anyway?

    NASA Astrophysics Data System (ADS)

    Subero, Keron; Kanim, Stephen

    2007-10-01

    There appears to be a correlation between some measures of scientific reasoning skills and gain on conceptual measures of student understanding of introductory physics such as the Force Concept Inventory. At NMSU, we have established a correlation between pretest scores on proportional reasoning tasks and student performance on conceptual post-tests in the introductory lab. Proponents of a Piagetian model of cognitive development would call these scientific reasoning skills `operational capacities'' that signal the last transition in human intellectual growth from ``Concrete Operational'' to ``Formal'' reasoning. Seen in this light, the correlations described above suggest a cognitive ``deficit'' associated with development. We are exploring the possibility that proportional reasoning may in fact be a blanket term to describe many smaller elements of skills which students often seem to lack. In this talk, I will present some initial results from our investigation.

  1. 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

  2. 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

  3. The role of targeted BRCA1/BRCA2 mutation analysis in hereditary breast/ovarian cancer families of Portuguese ancestry.

    PubMed

    Peixoto, A; Santos, C; Pinto, P; Pinheiro, M; Rocha, P; Pinto, C; Bizarro, S; Veiga, I; Principe, A S; Maia, S; Castro, F; Couto, R; Gouveia, A; Teixeira, M R

    2015-07-01

    We report the analysis of altogether 1050 suspected hereditary breast/ovarian cancer (HBOC) families, 524 fully screened for BRCA1/BRCA2 mutations and 526 tested only for the most common mutations. Of the 119 families with pathogenic mutations, 40 (33.6%) had the BRCA2 c.156_157insAlu rearrangement and 15 (12.6%) the BRCA1 c.3331_3334del mutation, the former being specific of Portuguese ancestry and the latter showing a founder effect in Portugal. Interestingly, the two most common mutations were found in a significant proportion of the HBOC families with an a priori BRCAPRO mutation probability <10%. We recommend that all suspected HBOC families from Portugal or with Portuguese ancestry, even those fulfilling moderately stringent clinical-criteria for genetic testing, should be specifically analyzed for the two most common BRCA1/BRCA2 founder mutations, and we here present a simple method for this first tier test. Screening of the entire coding regions of BRCA1 and BRCA2 should subsequently be offered to those families with a mutation probability ≥10% if none of those founder mutations are found. PMID:24916970

  4. Admixture and genetic diversity distribution patterns of non-recombining lineages of Native American ancestry in Colombian populations.

    PubMed

    Xavier, Catarina; Builes, Juan José; Gomes, Verónica; Ospino, Jose Miguel; Aquino, Juliana; Parson, Walther; Amorim, António; Gusmão, Leonor; Goios, Ana

    2015-01-01

    Genetic diversity of present American populations results from very complex demographic events involving different types and degrees of admixture. Through the analysis of lineage markers such as mtDNA and Y chromosome it is possible to recover the original Native American haplotypes, which remained identical since the admixture events due to the absence of recombination. However, the decrease in the effective population sizes and the consequent genetic drift effects suffered by these populations during the European colonization resulted in the loss or under-representation of a substantial fraction of the Native American lineages. In this study, we aim to clarify how the diversity and distribution of uniparental lineages vary with the different demographic characteristics (size, degree of isolation) and the different levels of admixture of extant Native groups in Colombia. We present new data resulting from the analyses of mtDNA whole control region, Y chromosome SNP haplogroups and STR haplotypes, and autosomal ancestry informative insertion-deletion polymorphisms in Colombian individuals from different ethnic and linguistic groups. The results demonstrate that populations presenting a high proportion of non-Native American ancestry have preserved nevertheless a substantial diversity of Native American lineages, for both mtDNA and Y chromosome. We suggest that, by maintaining the effective population sizes high, admixture allowed for a decrease in the effects of genetic drift due to Native population size reduction and thus resulting in an effective preservation of the Native American non-recombining lineages.

  5. The role of targeted BRCA1/BRCA2 mutation analysis in hereditary breast/ovarian cancer families of Portuguese ancestry.

    PubMed

    Peixoto, A; Santos, C; Pinto, P; Pinheiro, M; Rocha, P; Pinto, C; Bizarro, S; Veiga, I; Principe, A S; Maia, S; Castro, F; Couto, R; Gouveia, A; Teixeira, M R

    2015-07-01

    We report the analysis of altogether 1050 suspected hereditary breast/ovarian cancer (HBOC) families, 524 fully screened for BRCA1/BRCA2 mutations and 526 tested only for the most common mutations. Of the 119 families with pathogenic mutations, 40 (33.6%) had the BRCA2 c.156_157insAlu rearrangement and 15 (12.6%) the BRCA1 c.3331_3334del mutation, the former being specific of Portuguese ancestry and the latter showing a founder effect in Portugal. Interestingly, the two most common mutations were found in a significant proportion of the HBOC families with an a priori BRCAPRO mutation probability <10%. We recommend that all suspected HBOC families from Portugal or with Portuguese ancestry, even those fulfilling moderately stringent clinical-criteria for genetic testing, should be specifically analyzed for the two most common BRCA1/BRCA2 founder mutations, and we here present a simple method for this first tier test. Screening of the entire coding regions of BRCA1 and BRCA2 should subsequently be offered to those families with a mutation probability ≥10% if none of those founder mutations are found.

  6. 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

  7. 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.

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  9. Photodetectors for Scintillator Proportionality Measurement

    SciTech Connect

    Moses, William W.; Choong, Woon-Seng; Hull, Giulia; Payne, Steve; Cherepy, Nerine; Valentine, J.D.

    2010-10-18

    We evaluate photodetectors for use in a Compton Coincidence apparatus designed for measuring scintillator proportionality. There are many requirements placed on the photodetector in these systems, including active area, linearity, and the ability to accurately measure low light levels (which implies high quantum efficiency and high signal-to-noise ratio). Through a combination of measurement and Monte Carlo simulation, we evaluate a number of potential photodetectors, especially photomultiplier tubes and hybrid photodetectors. Of these, we find that the most promising devices available are photomultiplier tubes with high ({approx}50%) quantum efficiency, although hybrid photodetectors with high quantum efficiency would be preferable.

  10. Admixture mapping of lung cancer in 1812 African-Americans.

    PubMed

    Schwartz, Ann G; Wenzlaff, Angela S; Bock, Cathryn H; Ruterbusch, Julie J; Chen, Wei; Cote, Michele L; Artis, Amanda S; Van Dyke, Alison L; Land, Susan J; Harris, Curtis C; Pine, Sharon R; Spitz, Margaret R; Amos, Christopher I; Levin, Albert M; McKeigue, Paul M

    2011-03-01

    Lung cancer continues to be the leading cause of cancer death in the USA and the best example of a cancer with undisputed evidence of environmental risk. However, a genetic contribution to lung cancer has also been demonstrated by studies of familial aggregation, family-based linkage, candidate gene studies and most recently genome-wide association studies (GWAS). The African-American population has been underrepresented in these genetic studies and has patterns of cigarette use and linkage disequilibrium that differ from patterns in other populations. Therefore, studies in African-Americans can provide complementary data to localize lung cancer susceptibility genes and explore smoking dependence-related genes. We used admixture mapping to further characterize genetic risk of lung cancer in a series of 837 African-American lung cancer cases and 975 African-American controls genotyped at 1344 ancestry informative single-nucleotide polymorphisms. Both case-only and case-control analyses were conducted using ADMIXMAP adjusted for age, sex, pack-years of smoking, family history of lung cancer, history of emphysema and study site. In case-only analyses, excess European ancestry was observed over a wide region on chromosome 1 with the largest excess seen at rs6587361 for non-small-cell lung cancer (NSCLC) (Z-score = -4.33; P = 1.5 × 10⁻⁵) and for women with NSCLC (Z-score = -4.82; P = 1.4 × 10⁻⁶). Excess African ancestry was also observed on chromosome 3q with a peak Z-score of 3.33 (P = 0.0009) at rs181696 among ever smokers with NSCLC. These results add to the findings from the GWAS in Caucasian populations and suggest novel regions of interest.

  11. Race and Ancestry in the Age of Inclusion: Technique and Meaning in Post-Genomic Science

    PubMed Central

    Shim, Janet K.; Ackerman, Sara L.; Darling, Katherine Weatherford; Hiatt, Robert A.; Lee, Sandra Soo-Jin

    2015-01-01

    This paper examines how race and ancestry are taken up in gene-environment interaction (GEI) research on complex diseases such as heart disease, diabetes, and cancer. Using 54 in-depth interviews of 33 scientists and over 200 hours of observation at scientific conferences, we explore how GEI researchers use and interpret race, ethnicity, and ancestry in their work. We find that the use of self-identified race and ethnicity (SIRE) exists alongside ancestry informative markers (AIMs) to ascertain genetic ancestry. Our participants assess the utility of these two techniques in relative terms, downplaying the accuracy and value of SIRE compared to the precision and necessity of AIMs. In doing so, we argue that post-genomic scientists seeking to understand the interactions of genetic and environmental disease determinants actually undermine their ability to do so, by valorizing precise characterizations of individuals’ genetic ancestry over measurement of the social processes and relations that differentiate social groups. PMID:25378251

  12. Race and ancestry in the age of inclusion: technique and meaning in post-genomic science.

    PubMed

    Shim, Janet K; Ackerman, Sara L; Darling, Katherine Weatherford; Hiatt, Robert A; Lee, Sandra Soo-Jin

    2014-12-01

    This article examines how race and ancestry are taken up in gene-environment interaction (GEI) research on complex diseases such as heart disease, diabetes, and cancer. Using 54 in-depth interviews of 33 scientists and over 200 hours of observation at scientific conferences, we explore how GEI researchers use and interpret race, ethnicity, and ancestry in their work. We find that the use of self-identified race and ethnicity (SIRE) exists alongside ancestry informative markers (AIMs) to ascertain genetic ancestry. Our participants assess the utility of these two techniques in relative terms, downplaying the accuracy and value of SIRE compared to the precision and necessity of AIMs. In doing so, we argue that post-genomic scientists seeking to understand the interactions of genetic and environmental disease determinants actually undermine their ability to do so by valorizing precise characterizations of individuals' genetic ancestry over measurement of the social processes and relations that differentiate social groups. PMID:25378251

  13. Incisors’ proportions in smile esthetics

    PubMed Central

    Alsulaimani, Fahad F; Batwa, Waeil

    2013-01-01

    Aims: To determine whether alteration of the maxillary central and lateral incisors’ length and width, respectively, would affect perceived smile esthetics and to validate the most esthetic length and width, respectively, for the central and lateral incisors. Materials and Methods: Photographic manipulation was undertaken to produce two sets of photographs, each set of four photographs showing the altered width of the lateral incisor and length of the central length. The eight produced photographs were assessed by laypeople, dentists and orthodontists. Results: Alteration in the incisors’ proportion affected the relative smile attractiveness for laypeople (n=124), dentists (n=115) and orthodontists (n=68); dentists and orthodontists did not accept lateral width reduction of more than 0.5 mm (P<0.01), which suggests that the lateral to central incisor width ratio ranges from 54% to 62%. However, laypeople did not accept lateral width reduction of more than 1 mm (P<0.01), widening the range to be from 48% to 62%. All groups had zero tolerance for changes in central crown length (P<0.01). Conclusion: All participants recognized that the central incisors’ length changes. For lateral incisors, laypeople were more tolerant than dentists and orthodontists. This suggests that changing incisors’ proportions affects the relative smile attractiveness. PMID:24987650

  14. A comprehensive examination of breast cancer risk loci in African American women.

    PubMed

    Feng, Ye; Stram, Daniel O; Rhie, Suhn Kyong; Millikan, Robert C; Ambrosone, Christine B; John, Esther M; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah; Bandera, Elisa V; Ingles, Sue A; Press, Michael F; Deming, Sandra L; Rodriguez-Gil, Jorge L; Palmer, Julie R; Olopade, Olufunmilayo I; Huo, Dezheng; Adebamowo, Clement A; Ogundiran, Temidayo; Chen, Gary K; Stram, Alex; Park, Karen; Rand, Kristin A; Chanock, Stephen J; Le Marchand, Loic; Kolonel, Laurence N; Conti, David V; Easton, Douglas; Henderson, Brian E; Haiman, Christopher A

    2014-10-15

    Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. In this study of breast cancer in African American women (3016 cases, 2745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) were found to have an association with breast cancer in the same direction as previously reported, with eight (15%) replicating at P < 0.05. Through fine-mapping, in three regions (1q32, 3p24, 10q25), we identified variants that better captured associations with overall breast cancer or estrogen receptor positive disease. We also observed suggestive associations with variants (at P < 5 × 10(-6)) in three separate regions (6q25, 14q13, 22q12) that may represent novel risk variants. Directional consistency of association observed for ∼65-70% of currently known genetic variants for breast cancer in women of African ancestry implies a shared functional common variant at most loci. To validate and enhance the spectrum of alleles that define associations at the known breast cancer risk loci, as well as genome-wide, will require even larger collaborative efforts in women of African ancestry.

  15. A comprehensive examination of breast cancer risk loci in African American women

    PubMed Central

    Feng, Ye; Stram, Daniel O.; Rhie, Suhn Kyong; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F.; Hu, Jennifer J.; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue A.; Press, Michael F.; Deming, Sandra L.; Rodriguez-Gil, Jorge L.; Palmer, Julie R.; Olopade, Olufunmilayo I.; Huo, Dezheng; Adebamowo, Clement A.; Ogundiran, Temidayo; Chen, Gary K.; Stram, Alex; Park, Karen; Rand, Kristin A.; Chanock, Stephen J.; Le Marchand, Loic; Kolonel, Laurence N.; Conti, David V.; Easton, Douglas; Henderson, Brian E.; Haiman, Christopher A.

    2014-01-01

    Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. In this study of breast cancer in African American women (3016 cases, 2745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) were found to have an association with breast cancer in the same direction as previously reported, with eight (15%) replicating at P < 0.05. Through fine-mapping, in three regions (1q32, 3p24, 10q25), we identified variants that better captured associations with overall breast cancer or estrogen receptor positive disease. We also observed suggestive associations with variants (at P < 5 × 10−6) in three separate regions (6q25, 14q13, 22q12) that may represent novel risk variants. Directional consistency of association observed for ∼65–70% of currently known genetic variants for breast cancer in women of African ancestry implies a shared functional common variant at most loci. To validate and enhance the spectrum of alleles that define associations at the known breast cancer risk loci, as well as genome-wide, will require even larger collaborative efforts in women of African ancestry. PMID:24852375

  16. 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

    2015-06-01

    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

  17. 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

  18. Celtic ancestry, HLA phenotype and increased risk of skin cancer.

    PubMed

    Long, C C; Darke, C; Marks, R

    1998-04-01

    Individuals of Celtic ancestry are claimed to be at greater risk of skin cancer than non-Celts, and various positive and negative associations between certain human leucocyte antigen (HLA) phenotypes and the development of skin cancer have been described. The aims of this study were to determine whether any HLA phenotypes are associated either with Celtic or non-Celtic ancestry, or skin type. One thousand and ten members of the Welsh Bone Marrow Donor Registry (WBMDR), whose HLA phenotypes are known, were asked to complete a questionnaire which enquired as to their family origins and their 'Index of Celtic Ancestry' scored out of 12. Three groups were identified: non-Celts (score < 3), Celts (score > 9), and a subset of the Celts--'high scoring' Celts (score > 10). Details of hair and eye colour and skin type were also requested. Skin type and HLA-A, -B, -DR and -DQ frequencies were compared between the three groups (Celts, non-Celts and 'high scoring' Celts), and a random indigenous population of 9196 members of the WBMDR. Seven hundred and thirty-six replies were received (279 male, 457 female, mean age 31 years). One hundred and forty-four Celts, 51 'high scoring' Celts and 170 non-Celts were identified. Forty-six (32%) Celts had skin type I or II compared with 36 (21%) non-Celts (P = 0.039), and 37 (73%) 'high scoring' Celts had skin type I or II (P < 0.0001). However, there were no significant differences between the groups with regard to hair colour, eye colour or number of episodes of painful sunburn. The frequency of HLA-DR4 was 32% in the non-Celtic group, 44% in the Celtic group (not significant), and 53% in the 'high scoring' Celts (P = 0.008). However, the difference was not significant after correction. There were no significant associations between skin type and HLA phenotype. HLA-DR4 is known to be associated with an increased risk of both basal cell carcinoma and malignant melanoma and its increased frequency in Celts may be an independent risk

  19. The cancer caregiving experience of caregivers of Mexican ancestry.

    PubMed

    Juarez, Gloria; Branin, Joan J; Rosales, Monica

    2014-01-01

    The act of providing care may be the same in all ethnic groups, but the way caregiving is defined by family members is influenced by cultural values and beliefs. This study describes the caregiving experience and challenges of caregivers of Mexican ancestry. Qualitative interviews of 20 family caregivers and thematic analysis of transcribed audiotapes identified four themes that characterized their caregiving experience. These themes include an emphasis on family values, a strong commitment to care, difficulties dealing with everyday life realities, and a reliance on spirituality, all of which added to the meaningfulness and burden of caregiving. Further investigation within a cultural context is warranted in the development of interventions and programs to better assist caregivers in coping with the challenges of providing cancer care.

  20. Genetics, Ancestry, and Hypertension: Implications for Targeted Antihypertensive Therapies

    PubMed Central

    Chasman, Daniel I.; Cooper-DeHoff, Rhonda M.; Arnett, Donna K.

    2016-01-01

    Hypertension is the most common chronic condition seen by physicians in ambulatory care and a condition for which life-long medications are commonly prescribed. There is evidence for genetic factors influencing blood pressure variation in populations and response to medications. This review summarizes recent genetic discoveries that surround blood pressure, hypertension, and antihypertensive drug response from genome-wide association studies, while highlighting ancestry-specific findings and any potential implication for drug therapy targets. Genome-wide association studies have identified several novel loci for inter-individual variation of blood pressure and hypertension risk in the general population. Evidence from pharmacogenetic studies suggests that genes influence the blood pressure response to antihypertensive drugs, although results are somewhat inconsistent across studies. There is still much work that remains to be done to identify genes both for efficacy and adverse events of antihypertensive medications. PMID:24903233

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

    PubMed

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

    2016-04-01

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

  2. Assessment of Azorean ancestry by Alu insertion polymorphisms.

    PubMed

    Branco, Claudia C; Palla, Raquel; Lino, Sílvia; Pacheco, Paula R; Cabral, Rita; De Fez, Laura; Peixoto, Bernardo R; Mota-Vieira, Luisa

    2006-01-01

    Knowledge of population ancestry from genetic markers is essential, for example, to understand the history of human migration and to carry out admixture and association studies. Here we assess the genome ancestry of the Azorean population through analysis of six Alu polymorphic sites (TPA-25, ACE, APO, B65, PV92, and D1) in 65 Azoreans and 30 Portuguese unrelated blood donors and compare data for the Y-chromosome and mtDNA. Allele frequencies were calculated by direct counting. Statistical analysis was performed using Arlequin 2.0. Nei's genetic distance was calculated with DISPAN software, and trees were constructed by neighbor joining (NJ) using PHYLIP 3.63. The results show that all Alu insertions were polymorphic. APO is the closest to fixation. The less frequent insertions are PV92 and D1 in the Azores and Portugal, respectively. ACE and TPA-25 show the highest values of heterozygosity in both populations. Allele frequencies are very similar to those obtained in European populations. These results are validated by the Y-chromosome and mtDNA data, where the majority of the maternal and paternal lineages are European. Overall, these data are reflected in the phylogenetic tree, in which the Azoreans and the Portuguese branch with Catalans, Andalusians, Moroccans, and Algerians. We conclude that the population of the Azores shows no significant genetic differences from that of mainland Portugal and that it is an outbred population. Moreover, the data validate the use of Alu insertion polymorphisms to assess the origin and history of human populations. PMID:16493635

  3. 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

  4. Challenging the principle of proportionality.

    PubMed

    Andersson, Anna-Karin Margareta

    2016-04-01

    The first objective of this article is to examine one aspect of the principle of proportionality (PP) as advanced by Alan Gewirth in his 1978 bookReason and Morality Gewirth claims that being capable of exercising agency to some minimal degree is a property that justifies having at least prima facie rights not to get killed. However, according to the PP, before the being possesses the capacity for exercising agency to that minimal degree, the extent of her rights depends on to what extent she approaches possession of agential capacities. One interpretation of PP holds that variations in degree of possession of the physical constitution necessary to exercise agency are morally relevant. The other interpretation holds that only variations in degree of actual mental capacity are morally relevant. The first of these interpretations is vastly more problematic than the other. The second objective is to argue that according to the most plausible interpretation of the PP, the fetus' level of development before at least the 20th week of pregnancy does not affect the fetus' moral rights status. I then suggest that my argument is not restricted to such fetuses, although extending my argument to more developed fetuses requires caution. PMID:26839114

  5. African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era.

    PubMed

    Kasembeli, Alex N; Duarte, Raquel; Ramsay, Michèle; Naicker, Saraladevi

    2015-05-01

    Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus (HIV) infection are the major causes of CKD. HIV-associated nephropathy (HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1 risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits (including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era.

  6. The African Diaspora: Mitochondrial DNA and the Atlantic Slave Trade

    PubMed Central

    Salas, Antonio; Richards, Martin; Lareu, María-Victoria; Scozzari, Rosaria; Coppa, Alfredo; Torroni, Antonio; Macaulay, Vincent; Carracedo, Ángel

    2004-01-01

    Between the 15th and 19th centuries ad, the Atlantic slave trade resulted in the forced movement of ∼13 million people from Africa, mainly to the Americas. Only ∼11 million survived the passage, and many more died in the early years of captivity. We have studied 481 mitochondrial DNAs (mtDNAs) of recent African ancestry in the Americas and in Eurasia, in an attempt to trace them back to particular regions of Africa. Our results show that mtDNAs in America and Eurasia can, in many cases, be traced to broad geographical regions within Africa, largely in accordance with historical evidence, and raise the possibility that a greater resolution may be possible in the future. However, they also indicate that, at least for the moment, considerable caution is warranted when assessing claims to be able to trace the ancestry of particular lineages to a particular locality within modern-day Africa. PMID:14872407

  7. 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

    2014-01-01

    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

  8. 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

    2014-01-01

    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

  9. Common Variation in Vitamin D Pathway Genes Predicts Circulating 25-Hydroxyvitamin D Levels among African Americans

    PubMed Central

    Signorello, Lisa B.; Shi, Jiajun; Cai, Qiuyin; Zheng, Wei; Williams, Scott M.; Long, Jirong; Cohen, Sarah S.; Li, Guoliang; Hollis, Bruce W.; Smith, Jeffrey R.; Blot, William J.

    2011-01-01

    Vitamin D is implicated in a wide range of health outcomes, and although environmental predictors of vitamin D levels are known, the genetic drivers of vitamin D status remain to be clarified. African Americans are a group at particularly high risk for vitamin D insufficiency but to date have been virtually absent from studies of genetic predictors of circulating vitamin D levels. Within the Southern Community Cohort Study, we investigated the association between 94 single nucleotide polymorphisms (SNPs) in five vitamin D pathway genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1) and serum 25-hydroxyvitamin D (25(OH)D) levels among 379 African American and 379 Caucasian participants. We found statistically significant associations with three SNPs (rs2298849 and rs2282679 in the GC gene, and rs10877012 in the CYP27B1 gene), although only for African Americans. A genotype score, representing the number of risk alleles across the three SNPs, alone accounted for 4.6% of the variation in serum vitamin D among African Americans. A genotype score of 5 (vs. 1) was also associated with a 7.1 ng/mL reduction in serum 25(OH)D levels and a six-fold risk of vitamin D insufficiency (<20 ng/mL) (odds ratio 6.0, p = 0.01) among African Americans. With African ancestry determined from a panel of 276 ancestry informative SNPs, we found that high risk genotypes did not cluster among those with higher African ancestry. This study is one of the first to investigate common genetic variation in relation to vitamin D levels in African Americans, and the first to evaluate how vitamin D-associated genotypes vary in relation to African ancestry. These results suggest that further evaluation of genetic contributors to vitamin D status among African Americans may help provide insights regarding racial health disparities or enable the identification of subgroups especially in need of vitamin D-related interventions. PMID:22205958

  10. Worldwide patterns of ancestry, divergence, and admixture in domesticated cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The domestication and development of cattle has considerably impacted human societies, but the histories of cattle breeds have been poorly understood especially for African, Asian, and American breeds. Using genotypes from 43,043 autosomal single nucleotide polymorphism markers scored in 1,543 anima...

  11. The frequency of an IL-18-associated haplotype in Africans.

    PubMed

    Thompson, Simon R; Humphries, Steve E; Thomas, Mark G; Ekong, Rosemary; Tarekegn, Ayele; Bekele, Endeshaw; Creemer, Olivia; Bradman, Neil; Veeramah, Krishna R

    2013-04-01

    Variation within the gene for the proinflammatory cytokine interleukin (IL)-18 has been associated with inter-individual differences in levels of free protein and disease risk. We investigated the frequency of function-associated IL18 gene haplotypes in an extensive sample (n=2357) of African populations from across the continent. A previously identified five tagging SNP (single-nucleotide polymorphism) haplotype (here designated hGTATA), known to be associated with lower levels of IL-18, was observed at a frequency of 27% in a British population of recent European ancestry, but was found at low frequency (<8%) or completely absent in African populations. Potentially protective variants may, as a consequence, be found at low frequency in African individuals and may confer a difference in disease risk.

  12. Inference of Ancestry in Forensic Analysis II: Analysis of Genetic Data.

    PubMed

    Santos, Carla; Phillips, Chris; Gomez-Tato, A; Alvarez-Dios, J; Carracedo, Ángel; Lareu, Maria Victoria

    2016-01-01

    Three approaches applicable to the analysis of forensic ancestry-informative marker data-STRUCTURE, principal component analysis, and the Snipper Bayesian classification system-are reviewed. Detailed step-by-step guidance is provided for adjusting parameter settings in STRUCTURE with particular regard to their effect when differentiating populations. Several enhancements to the Snipper online forensic classification portal are described, highlighting the added functionality they bring to particular aspects of ancestry-informative SNP analysis in a forensic context.

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

    PubMed

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

    2015-01-01

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

  14. A Genealogical Look at Shared Ancestry on the X Chromosome.

    PubMed

    Buffalo, Vince; Mount, Stephen M; Coop, Graham

    2016-09-01

    Close relatives can share large segments of their genome identical by descent (IBD) that can be identified in genome-wide polymorphism data sets. There are a range of methods to use these IBD segments to identify relatives and estimate their relationship. These methods have focused on sharing on the autosomes, as they provide a rich source of information about genealogical relationships. We hope to learn additional information about recent ancestry through shared IBD segments on the X chromosome, but currently lack the theoretical framework to use this information fully. Here, we fill this gap by developing probability distributions for the number and length of X chromosome segments shared IBD between an individual and an ancestor k generations back, as well as between half- and full-cousin relationships. Due to the inheritance pattern of the X and the fact that X homologous recombination occurs only in females (outside of the pseudoautosomal regions), the number of females along a genealogical lineage is a key quantity for understanding the number and length of the IBD segments shared among relatives. When inferring relationships among individuals, the number of female ancestors along a genealogical lineage will often be unknown. Therefore, our IBD segment length and number distributions marginalize over this unknown number of recombinational meioses through a distribution of recombinational meioses we derive. By using Bayes' theorem to invert these distributions, we can estimate the number of female ancestors between two relatives, giving us details about the genealogical relations between individuals not possible with autosomal data alone. PMID:27356612

  15. Race and ancestry in biomedical research: exploring the challenges

    PubMed Central

    2009-01-01

    The use of race in biomedical research has, for decades, been a source of social controversy. However, recent events, such as the adoption of racially targeted pharmaceuticals, have raised the profile of the race issue. In addition, we are entering an era in which genomic research is increasingly focused on the nature and extent of human genetic variation, often examined by population, which leads to heightened potential for misunderstandings or misuse of terms concerning genetic variation and race. Here, we draw together the perspectives of participants in a recent interdisciplinary workshop on ancestry and health in medicine in order to explore the use of race in research issue from the vantage point of a variety of disciplines. We review the nature of the race controversy in the context of biomedical research and highlight several challenges to policy action, including restrictions resulting from commercial or regulatory considerations, the difficulty in presenting precise terminology in the media, and drifting or ambiguous definitions of key terms. PMID:19348695

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

    PubMed

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

    2015-01-01

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

  17. Genetic Ancestry of the Extinct Javan and Bali Tigers

    PubMed Central

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

    2015-01-01

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

  18. 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.

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2016-08-01

    Increased susceptibility to cleft lip, with or without cleft palate (CL±P) has been observed in South America, as related to Amerindian ancestry, using epidemiological data, uniparental markers, and blood groups. In this study, it was evaluated whether this increased risk remains when Amerindian ancestry is estimated using autosomal markers and considered in the predictive model. Ancestry was estimated through genotyping 62 insertion and deletion (INDEL) markers in sample sets of patients with CL±P, patients with cleft palate (CP), and controls, from Patagonia in southern Argentina and Belém in northern Brazil. The Amerindian ancestry in patients from Patagonia with CL±P was greater than in controls although it did not reach statistical significance. The European ancestry in patients with CL±P from Belém and in patients with CP from Belém and Patagonia was higher than in controls and statistically significant for patients with CP who were from Belém. This high contribution of European genetic ancestry among patients with CP who were from Belém has not been previously observed in American populations. Our results do not corroborate the currently accepted risks for CL±P and CP estimated by epidemiological studies in the North American populations and probably reflect the higher admixture found in South American ethnic groups when compared with the same ethnic groups from the North American populations. PMID:27105611

  1. 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.

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

    PubMed

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

    2016-07-01

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

  3. Influence of Genetic Ancestry on INDEL Markers of NFKβ1, CASP8, PAR1, IL4 and CYP19A1 Genes in Leprosy Patients

    PubMed Central

    Pinto, Pablo; Salgado, Claudio; Santos, Ney Pereira Carneiro; Santos, Sidney; Ribeiro-dos-Santos, Ândrea

    2015-01-01

    Background Leprosy is an insidious infectious disease caused by the obligate intracellular bacteria Mycobacterium leprae, and host genetic factors can modulate the immune response and generate distinct categories of leprosy susceptibility that are also influenced by genetic ancestry. Methodology/Principal Findings We investigated the possible effects of CYP19A1 [rs11575899], NFKβ1 [rs28362491], IL1α [rs3783553], CASP8 [rs3834129], UGT1A1 [rs8175347], PAR1 [rs11267092], CYP2E1 [INDEL 96pb] and IL4 [rs79071878] genes in a group of 141 leprosy patients and 180 healthy individuals. The INDELs were typed by PCR Multiplex in ABI PRISM 3130 and analyzed with GeneMapper ID v3.2. The NFKβ1, CASP8, PAR1 and IL4 INDELs were associated with leprosy susceptibility, while NFKβ1, CASP8, PAR1 and CYP19A1 were associated with the MB (Multibacilary) clinical form of leprosy. Conclusions/Significance NFKβ1 [rs28362491], CASP8 [rs3834129], PAR1 [rs11267092] and IL4 [rs79071878] genes are potential markers for susceptibility to leprosy development, while the INDELs in NFKβ1, CASP8, PAR1 and CYP19A1 (rs11575899) are potential markers for the severe clinical form MB. Moreover, all of these markers are influenced by genetic ancestry, and European contribution increases the risk to leprosy development, in other hand an increase in African contribution generates protection against leprosy. PMID:26367014

  4. Mythology to reality: case report on a giant cutaneous horn of the scalp in an African American female.

    PubMed

    Leppard, William; Loungani, Rahul; Saylors, Bradley; Delaney, Kevin

    2014-01-01

    We present a case study of a patient with a rare and disfiguring dermatologic condition known as cornu cutaneum, or giant cutaneous horn (GCH). While this condition has been well described in people of European and Asian ancestry, its presence in African populations is perceived to be rare and has not been reported in the literature until recently. We present the case of cornu cutaneum in a woman of African descent, contributing to the recent evidence that this condition may not be as rare in African populations as believed. Etiologic factors, epidemiology and management are also reviewed.

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

    PubMed

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

    2015-09-01

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

  6. An ancestry informative marker set for determining continental origin: validation and extension using human genome diversity panels

    PubMed Central

    Nassir, Rami; Kosoy, Roman; Tian, Chao; White, Phoebe A; Butler, Lesley M; Silva, Gabriel; Kittles, Rick; Alarcon-Riquelme, Marta E; Gregersen, Peter K; Belmont, John W; De La Vega, Francisco M; Seldin, Michael F

    2009-01-01

    Background Case-control genetic studies of complex human diseases can be confounded by population stratification. This issue can be addressed using panels of ancestry informative markers (AIMs) that can provide substantial population substructure information. Previously, we described a panel of 128 SNP AIMs that were designed as a tool for ascertaining the origins of subjects from Europe, Sub-Saharan Africa, Americas, and East Asia. Results In this study, genotypes from Human Genome Diversity Panel populations were used to further evaluate a 93 SNP AIM panel, a subset of the 128 AIMS set, for distinguishing continental origins. Using both model-based and relatively model-independent methods, we here confirm the ability of this AIM set to distinguish diverse population groups that were not previously evaluated. This study included multiple population groups from Oceana, South Asia, East Asia, Sub-Saharan Africa, North and South America, and Europe. In addition, the 93 AIM set provides population substructure information that can, for example, distinguish Arab and Ashkenazi from Northern European population groups and Pygmy from other Sub-Saharan African population groups. Conclusion These data provide additional support for using the 93 AIM set to efficiently identify continental subject groups for genetic studies, to identify study population outliers, and to control for admixture in association studies. PMID:19630973

  7. Ancestry, Temporality, and Potentiality: Engaging Cancer Genetics in Southern Brazil.

    PubMed

    Gibbon, Sahra

    2013-10-01

    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.

  8. Genome-wide detection of natural selection in African Americans pre- and post-admixture

    PubMed Central

    Jin, Wenfei; Xu, Shuhua; Wang, Haifeng; Yu, Yongguo; Shen, Yiping; Wu, Bailin; Jin, Li

    2012-01-01

    It is particularly meaningful to investigate natural selection in African Americans (AfA) due to the high mortality their African ancestry has experienced in history. In this study, we examined 491,526 autosomal single nucleotide polymorphisms (SNPs) genotyped in 5210 individuals and conducted a genome-wide search for selection signals in 1890 AfA. Several genomic regions showing an excess of African or European ancestry, which were considered the footprints of selection since population admixture, were detected based on a commonly used approach. However, we also developed a new strategy to detect natural selection both pre- and post-admixture by reconstructing an ancestral African population (AAF) from inferred African components of ancestry in AfA and comparing it with indigenous African populations (IAF). Interestingly, many selection-candidate genes identified by the new approach were associated with AfA-specific high-risk diseases such as prostate cancer and hypertension, suggesting an important role these disease-related genes might have played in adapting to a new environment. CD36 and HBB, whose mutations confer a degree of protection against malaria, were also located in the highly differentiated regions between AAF and IAF. Further analysis showed that the frequencies of alleles protecting against malaria in AAF were lower than those in IAF, which is consistent with the relaxed selection pressure of malaria in the New World. There is no overlap between the top candidate genes detected by the two approaches, indicating the different environmental pressures AfA experienced pre- and post-population admixture. We suggest that the new approach is reasonably powerful and can also be applied to other admixed populations such as Latinos and Uyghurs. PMID:22128132

  9. Genome-wide detection of natural selection in African Americans pre- and post-admixture.

    PubMed

    Jin, Wenfei; Xu, Shuhua; Wang, Haifeng; Yu, Yongguo; Shen, Yiping; Wu, Bailin; Jin, Li

    2012-03-01

    It is particularly meaningful to investigate natural selection in African Americans (AfA) due to the high mortality their African ancestry has experienced in history. In this study, we examined 491,526 autosomal single nucleotide polymorphisms (SNPs) genotyped in 5210 individuals and conducted a genome-wide search for selection signals in 1890 AfA. Several genomic regions showing an excess of African or European ancestry, which were considered the footprints of selection since population admixture, were detected based on a commonly used approach. However, we also developed a new strategy to detect natural selection both pre- and post-admixture by reconstructing an ancestral African population (AAF) from inferred African components of ancestry in AfA and comparing it with indigenous African populations (IAF). Interestingly, many selection-candidate genes identified by the new approach were associated with AfA-specific high-risk diseases such as prostate cancer and hypertension, suggesting an important role these disease-related genes might have played in adapting to a new environment. CD36 and HBB, whose mutations confer a degree of protection against malaria, were also located in the highly differentiated regions between AAF and IAF. Further analysis showed that the frequencies of alleles protecting against malaria in AAF were lower than those in IAF, which is consistent with the relaxed selection pressure of malaria in the New World. There is no overlap between the top candidate genes detected by the two approaches, indicating the different environmental pressures AfA experienced pre- and post-population admixture. We suggest that the new approach is reasonably powerful and can also be applied to other admixed populations such as Latinos and Uyghurs.

  10. African Aesthetics

    ERIC Educational Resources Information Center

    Abiodun, Rowland

    2001-01-01

    No single traditional discipline can adequately supply answers to the many unresolved questions in African art history. Because of the aesthetic, cultural, historical, and, not infrequently, political biases, already built into the conception and development of Western art history, the discipline of art history as defined and practiced in the West…

  11. "African Connection."

    ERIC Educational Resources Information Center

    Adelman, Cathy; And Others

    This interdisciplinary unit provides students in grades kindergarten through seventh grade an opportunity to understand diversity through a study of Africa as a diverse continent. The project is designed to provide all elementary students with cultural enrichment by exposing them to African music, art, storytelling, and movement. This project can…

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

    PubMed

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

    2008-04-01

    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

  13. Replication of 6 Obesity Genes in a Meta-Analysis of Genome-Wide Association Studies from Diverse Ancestries

    PubMed Central

    Tan, Li-Jun; Zhu, Hu; He, Hao; Wu, Ke-Hao; Li, Jian; Chen, Xiang-Ding; Zhang, Ji-Gang; Shen, Hui; Tian, Qing; Krousel-Wood, Marie; Papasian, Christopher J.; Bouchard, Claude; Pérusse, Louis; Deng, Hong-Wen

    2014-01-01

    Obesity is a major public health problem with a significant genetic component. Multiple DNA polymorphisms/genes have been shown to be strongly associated with obesity, typically in populations of European descent. The aim of this study was to verify the extent to which 6 confirmed obesity genes (FTO, CTNNBL1, ADRB2, LEPR, PPARG and UCP2 genes) could be replicated in 8 different samples (n = 11,161) and to explore whether the same genes contribute to obesity-susceptibility in populations of different ancestries (five Caucasian, one Chinese, one African-American and one Hispanic population). GWAS-based data sets with 1000 G imputed variants were tested for association with obesity phenotypes individually in each population, and subsequently combined in a meta-analysis. Multiple variants at the FTO locus showed significant associations with BMI, fat mass (FM) and percentage of body fat (PBF) in meta-analysis. The strongest association was detected at rs7185735 (P-value = 1.01×10−7 for BMI, 1.80×10−6 for FM, and 5.29×10−4 for PBF). Variants at the CTNNBL1, LEPR and PPARG loci demonstrated nominal association with obesity phenotypes (meta-analysis P-values ranging from 1.15×10−3 to 4.94×10−2). There was no evidence of association with variants at ADRB2 and UCP2 genes. When stratified by sex and ethnicity, FTO variants showed sex-specific and ethnic-specific effects on obesity traits. Thus, it is likely that FTO has an important role in the sex- and ethnic-specific risk of obesity. Our data confirmed the role of FTO, CTNNBL1, LEPR and PPARG in obesity predisposition. These findings enhanced our knowledge of genetic associations between these genes and obesity-related phenotypes, and provided further justification for pursuing functional studies of these genes in the pathophysiology of obesity. Sex and ethnic differences in genetic susceptibility across populations of diverse ancestries may contribute to a more targeted prevention and customized

  14. Replication of 6 obesity genes in a meta-analysis of genome-wide association studies from diverse ancestries.

    PubMed

    Tan, Li-Jun; Zhu, Hu; He, Hao; Wu, Ke-Hao; Li, Jian; Chen, Xiang-Ding; Zhang, Ji-Gang; Shen, Hui; Tian, Qing; Krousel-Wood, Marie; Papasian, Christopher J; Bouchard, Claude; Pérusse, Louis; Deng, Hong-Wen

    2014-01-01

    Obesity is a major public health problem with a significant genetic component. Multiple DNA polymorphisms/genes have been shown to be strongly associated with obesity, typically in populations of European descent. The aim of this study was to verify the extent to which 6 confirmed obesity genes (FTO, CTNNBL1, ADRB2, LEPR, PPARG and UCP2 genes) could be replicated in 8 different samples (n = 11,161) and to explore whether the same genes contribute to obesity-susceptibility in populations of different ancestries (five Caucasian, one Chinese, one African-American and one Hispanic population). GWAS-based data sets with 1000 G imputed variants were tested for association with obesity phenotypes individually in each population, and subsequently combined in a meta-analysis. Multiple variants at the FTO locus showed significant associations with BMI, fat mass (FM) and percentage of body fat (PBF) in meta-analysis. The strongest association was detected at rs7185735 (P-value = 1.01×10(-7) for BMI, 1.80×10(-6) for FM, and 5.29×10(-4) for PBF). Variants at the CTNNBL1, LEPR and PPARG loci demonstrated nominal association with obesity phenotypes (meta-analysis P-values ranging from 1.15×10(-3) to 4.94×10(-2)). There was no evidence of association with variants at ADRB2 and UCP2 genes. When stratified by sex and ethnicity, FTO variants showed sex-specific and ethnic-specific effects on obesity traits. Thus, it is likely that FTO has an important role in the sex- and ethnic-specific risk of obesity. Our data confirmed the role of FTO, CTNNBL1, LEPR and PPARG in obesity predisposition. These findings enhanced our knowledge of genetic associations between these genes and obesity-related phenotypes, and provided further justification for pursuing functional studies of these genes in the pathophysiology of obesity. Sex and ethnic differences in genetic susceptibility across populations of diverse ancestries may contribute to a more targeted prevention and customized

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

    PubMed

    Tallman, Sean D; Winburn, Allysha P

    2015-09-01

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

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

    PubMed

    Katherine Spradley, M; Jantz, Richard L

    2016-07-01

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

  17. Translating Population Difference: The Use and Re-Use of Genetic Ancestry in Brazilian Cancer Genetics

    PubMed Central

    Gibbon, Sahra

    2016-01-01

    ABSTRACT In the past ten years, there has been an expansion of scientific interest in population genetics linked to both understanding histories of human migration and the way that population difference and diversity may account for and/or be implicated in health and disease. In this article, I examine how particular aspects of a globalizing research agenda related to population differences and genetic ancestry are taken up in locally variant ways in the nascent field of Brazilian cancer genetics. Drawing on a broad range of ethnographic data from clinical and nonclinical contexts in the south of Brazil, I examine the ambiguities that attention to genetic ancestry generates, so revealing the disjunctured and diverse ways a global research agenda increasingly orientated to questions of population difference and genetic ancestry is being used and reused. PMID:26452039

  18. Translating Population Difference: The Use and Re-Use of Genetic Ancestry in Brazilian Cancer Genetics.

    PubMed

    Gibbon, Sahra

    2016-01-01

    In the past ten years, there has been an expansion of scientific interest in population genetics linked to both understanding histories of human migration and the way that population difference and diversity may account for and/or be implicated in health and disease. In this article, I examine how particular aspects of a globalizing research agenda related to population differences and genetic ancestry are taken up in locally variant ways in the nascent field of Brazilian cancer genetics. Drawing on a broad range of ethnographic data from clinical and nonclinical contexts in the south of Brazil, I examine the ambiguities that attention to genetic ancestry generates, so revealing the disjunctured and diverse ways a global research agenda increasingly orientated to questions of population difference and genetic ancestry is being used and reused.

  19. Fighting through Resistance: Challenges Faced by African American Women Principals in Predominately White School Settings

    ERIC Educational Resources Information Center

    Jackson, Alicia D.

    2013-01-01

    African American women represented a growing proportion within the field of education in attaining leadership roles as school principals. As the numbers continued to rise slowly, African American women principals found themselves leading in diverse or even predominately White school settings. Leading in such settings encouraged African American…

  20. The Ball Curve: Calculated Racism and the Stereotype of African American Men.

    ERIC Educational Resources Information Center

    Hall, Ronald E.

    2001-01-01

    Discusses the impact of racial stereotyping on the performance of African American and European American athletes, providing an alternative to race-based intelligence differentials. Focuses on stereotypes of African American men; the Bell Curve; the high proportion of African Americans in U.S. athletics; and masculinity and the stereotype of the…

  1. Proportional Reasoning and the Visually Impaired

    ERIC Educational Resources Information Center

    Hilton, Geoff; Hilton, Annette; Dole, Shelley L.; Goos, Merrilyn; O'Brien, Mia

    2012-01-01

    Proportional reasoning is an important aspect of formal thinking that is acquired during the developmental years that approximate the middle years of schooling. Students who fail to acquire sound proportional reasoning often experience difficulties in subjects that require quantitative thinking, such as science, technology, engineering, and…

  2. CCSSM Challenge: Graphing Ratio and Proportion

    ERIC Educational Resources Information Center

    Kastberg, Signe E.; D'Ambrosio, Beatriz S.; Lynch-Davis, Kathleen; Mintos, Alexia; Krawczyk, Kathryn

    2013-01-01

    A renewed emphasis was placed on ratio and proportional reasoning in the middle grades in the Common Core State Standards for Mathematics (CCSSM). The expectation for students includes the ability to not only compute and then compare and interpret the results of computations in context but also interpret ratios and proportions as they are…

  3. Working Memory Mechanism in Proportional Quantifier Verification

    ERIC Educational Resources Information Center

    Zajenkowski, Marcin; Szymanik, Jakub; Garraffa, Maria

    2014-01-01

    The paper explores the cognitive mechanisms involved in the verification of sentences with proportional quantifiers (e.g. "More than half of the dots are blue"). The first study shows that the verification of proportional sentences is more demanding than the verification of sentences such as: "There are seven blue and eight yellow…

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  6. Genetic ancestry of participants in the National Children’s Study

    PubMed Central

    2014-01-01

    Background 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. Results 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. Conclusions 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. PMID:24490717

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

    PubMed

    Campbell, Desmond D; Parra, Maria V; Duque, Constanza; Gallego, Natalia; Franco, Liliana; Tandon, Arti; Hünemeier, Tábita; Bortolini, Cátira; Villegas, Alberto; Bedoya, Gabriel; McCarthy, Mark I; Price, Alkes; Reich, David; Ruiz-Linares, Andrés

    2012-01-01

    The "thrifty genotype" hypothesis proposes that the high prevalence of type 2 diabetes (T2D) in Native Americans and admixed Latin Americans has a genetic basis and reflects an evolutionary adaptation to a past low calorie/high exercise lifestyle. However, identification of the gene variants underpinning this hypothesis remains elusive. Here we assessed the role of Native American ancestry, socioeconomic status (SES) and 21 candidate gene loci in susceptibility to T2D in a sample of 876 T2D cases and 399 controls from Antioquia (Colombia). Although mean Native American ancestry is significantly higher in T2D cases than in controls (32% v 29%), this difference is confounded by the correlation of ancestry with SES, which is a stronger predictor of disease status. Nominally significant association (P<0.05) was observed for markers in: TCF7L2, RBMS1, CDKAL1, ZNF239, KCNQ1 and TCF1 and a significant bias (P<0.05) towards OR>1 was observed for markers selected from previous T2D genome-wide association studies, consistent with a role for Old World variants in susceptibility to T2D in Latin Americans. No association was found to the only known Native American-specific gene variant previously associated with T2D in a Mexican sample (rs9282541 in ABCA1). An admixture mapping scan with 1,536 ancestry informative markers (AIMs) did not identify genome regions with significant deviation of ancestry in Antioquia. Exclusion analysis indicates that this scan rules out ~95% of the genome as harboring loci with ancestry risk ratios >1.22 (at P < 0.05). PMID:22529894

  8. Amerind Ancestry, Socioeconomic Status and the Genetics of Type 2 Diabetes in a Colombian Population

    PubMed Central

    Campbell, Desmond D.; Parra, Maria V.; Duque, Constanza; Gallego, Natalia; Franco, Liliana; Tandon, Arti; Hünemeier, Tábita; Bortolini, Cátira; Villegas, Alberto; Bedoya, Gabriel; McCarthy, Mark I.; Price, Alkes; Reich, David; Ruiz-Linares, Andrés

    2012-01-01

    The “thrifty genotype” hypothesis proposes that the high prevalence of type 2 diabetes (T2D) in Native Americans and admixed Latin Americans has a genetic basis and reflects an evolutionary adaptation to a past low calorie/high exercise lifestyle. However, identification of the gene variants underpinning this hypothesis remains elusive. Here we assessed the role of Native American ancestry, socioeconomic status (SES) and 21 candidate gene loci in susceptibility to T2D in a sample of 876 T2D cases and 399 controls from Antioquia (Colombia). Although mean Native American ancestry is significantly higher in T2D cases than in controls (32% v 29%), this difference is confounded by the correlation of ancestry with SES, which is a stronger predictor of disease status. Nominally significant association (P<0.05) was observed for markers in: TCF7L2, RBMS1, CDKAL1, ZNF239, KCNQ1 and TCF1 and a significant bias (P<0.05) towards OR>1 was observed for markers selected from previous T2D genome-wide association studies, consistent with a role for Old World variants in susceptibility to T2D in Latin Americans. No association was found to the only known Native American-specific gene variant previously associated with T2D in a Mexican sample (rs9282541 in ABCA1). An admixture mapping scan with 1,536 ancestry informative markers (AIMs) did not identify genome regions with significant deviation of ancestry in Antioquia. Exclusion analysis indicates that this scan rules out ∼95% of the genome as harboring loci with ancestry risk ratios >1.22 (at P < 0.05). PMID:22529894

  9. Neanderthal ancestry drives evolution of lipid catabolism in contemporary Europeans

    PubMed Central

    Khrameeva, Ekaterina E.; Bozek, Katarzyna; He, Liu; Yan, Zheng; Jiang, Xi; Wei, Yuning; Tang, Kun; Gelfand, Mikhail S.; Prufer, Kay; Kelso, Janet; Paabo, Svante; Giavalisco, Patrick; Lachmann, Michael; Khaitovich, Philipp

    2014-01-01

    Although Neanderthals are extinct, fragments of their genomes persist in contemporary humans. Here we show that while the genome-wide frequency of Neanderthal-like sites is approximately constant across all contemporary out-of-Africa populations, genes involved in lipid catabolism contain more than threefold excess of such sites in contemporary humans of European descent. Evolutionally, these genes show significant association with signatures of recent positive selection in the contemporary European, but not Asian or African populations. Functionally, the excess of Neanderthal-like sites in lipid catabolism genes can be linked with a greater divergence of lipid concentrations and enzyme expression levels within this pathway, seen in contemporary Europeans, but not in the other populations. We conclude that sequence variants that evolved in Neanderthals may have given a selective advantage to anatomically modern humans that settled in the same geographical areas. PMID:24690587

  10. Genome-wide meta-analyses of smoking behaviors in African Americans.

    PubMed

    David, S P; Hamidovic, A; Chen, G K; Bergen, A W; Wessel, J; Kasberger, J L; Brown, W M; Petruzella, S; Thacker, E L; Kim, Y; Nalls, M A; Tranah, G J; Sung, Y J; Ambrosone, C B; Arnett, D; Bandera, E V; Becker, D M; Becker, L; Berndt, S I; Bernstein, L; Blot, W J; Broeckel, U; Buxbaum, S G; Caporaso, N; Casey, G; Chanock, S J; Deming, S L; Diver, W R; Eaton, C B; Evans, D S; Evans, M K; Fornage, M; Franceschini, N; Harris, T B; Henderson, B E; Hernandez, D G; Hitsman, B; Hu, J J; Hunt, S C; Ingles, S A; John, E M; Kittles, R; Kolb, S; Kolonel, L N; Le Marchand, L; Liu, Y; Lohman, K K; McKnight, B; Millikan, R C; Murphy, A; Neslund-Dudas, C; Nyante, S; Press, M; Psaty, B M; Rao, D C; Redline, S; Rodriguez-Gil, J L; Rybicki, B A; Signorello, L B; Singleton, A B; Smoller, J; Snively, B; Spring, B; Stanford, J L; Strom, S S; Swan, G E; Taylor, K D; Thun, M J; Wilson, A F; Witte, J S; Yamamura, Y; Yanek, L R; Yu, K; Zheng, W; Ziegler, R G; Zonderman, A B; Jorgenson, E; Haiman, C A; Furberg, H

    2012-01-01

    The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (β = 0.040, s.e. = 0.007, P = 1.84 × 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans. PMID:22832964

  11. Genome-wide meta-analyses of smoking behaviors in African Americans.

    PubMed

    David, S P; Hamidovic, A; Chen, G K; Bergen, A W; Wessel, J; Kasberger, J L; Brown, W M; Petruzella, S; Thacker, E L; Kim, Y; Nalls, M A; Tranah, G J; Sung, Y J; Ambrosone, C B; Arnett, D; Bandera, E V; Becker, D M; Becker, L; Berndt, S I; Bernstein, L; Blot, W J; Broeckel, U; Buxbaum, S G; Caporaso, N; Casey, G; Chanock, S J; Deming, S L; Diver, W R; Eaton, C B; Evans, D S; Evans, M K; Fornage, M; Franceschini, N; Harris, T B; Henderson, B E; Hernandez, D G; Hitsman, B; Hu, J J; Hunt, S C; Ingles, S A; John, E M; Kittles, R; Kolb, S; Kolonel, L N; Le Marchand, L; Liu, Y; Lohman, K K; McKnight, B; Millikan, R C; Murphy, A; Neslund-Dudas, C; Nyante, S; Press, M; Psaty, B M; Rao, D C; Redline, S; Rodriguez-Gil, J L; Rybicki, B A; Signorello, L B; Singleton, A B; Smoller, J; Snively, B; Spring, B; Stanford, J L; Strom, S S; Swan, G E; Taylor, K D; Thun, M J; Wilson, A F; Witte, J S; Yamamura, Y; Yanek, L R; Yu, K; Zheng, W; Ziegler, R G; Zonderman, A B; Jorgenson, E; Haiman, C A; Furberg, H

    2012-05-22

    The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (β = 0.040, s.e. = 0.007, P = 1.84 × 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.

  12. Evaluation of fall Sun Exposure Score in predicting vitamin D status in young Canadian adults, and the influence of ancestry.

    PubMed

    Sham, Lauren; Yeh, E Ann; Magalhaes, Sandra; Parra, Esteban J; Gozdzik, Agnes; Banwell, Brenda; Hanwell, Heather E

    2015-04-01

    Query of sun-related habits or ancestry could help screen for risk of vitamin D insufficiency (serum 25-hydroxyvitamin D<75nmol/L). We evaluated the association between Sun Exposure Score (calculated from recall of Time Exposed to Sun and Skin Exposed to Sun in the previous week), demographics and anthropometrics (including self-reported ancestry and skin melanin reflectometry), and serum 25(OH)D levels in healthy young Canadian adults in the Greater Toronto Area (GTA; 43°N) during fall. 310 adults (67% female) of European, East Asian, and South Asian ancestries were evaluated. The median (interquartile range) 25(OH)D level was 49.7nmol/L (36.7-70.3) and 80% of participants were vitamin D insufficient. The vast majority of those of East and South Asian ancestry were vitamin D insufficient (91% and 97%, respectively), as were 55% of those of European ancestry. Sun Exposure Score and 25(OH)D concentrations were not associated after accounting for confounders. A multivariable model showed ancestry, recent summer sun exposure, sex, melanin, vitamin D intake, age and year of study significantly predicted 25(OH)D concentration; ancestry was the strongest independent predictor (adjusted R(2)=43%). Although Sun Exposure Score was not a significant predictor of serum 25(OH)D levels, inquiry of ancestry has potential use in screening for vitamin D insufficiency.

  13. Obesity and African Americans

    MedlinePlus

    ... Data > Minority Population Profiles > Black/African American > Obesity Obesity and African Americans African American women have the ... ss6304.pdf [PDF | 3.38MB] HEALTH IMPACT OF OBESITY More than 80 percent of people with type ...

  14. The ancestry and cumulative evolution of immune reactions.

    PubMed

    Dzik, Jolanta M

    2010-01-01

    functional convergence was presumably enabled by the general similarity of the lectin-like recognition domain three-dimensional structure. Sponges contain molecules with SCR/CCP domains that show high homology to the mammalian regulators of complement activation (RCA family). A multi-component complement system comprising at least the central molecule of the complement system, C3, Factor B, and MASP developed in the cnidarians and evolved into the multilevel cascade engaged in innate and acquired immunity of vertebrates. The adaptive immune system of mammals is also deeply rooted in the metazoan evolution. Some its precursors have been traced as deep as in sponges, namely, two classes of receptors that comprise Ig-like domains, the receptor tyrosine kinases (RTK), and the non-enzymic sponge adhesion molecules (SAM). The antibody-based immune system defined by the presence of the major histocompatibility complex (MHC), T-cell receptor (TCR), B-cell receptor (BCR) or recombination activating genes (RAGs) is known beginning from jawed fishes. However, genes closely resembling RAG1 and RAG2 have been uncovered in the genome of a see urchin. The ancestry of MHC gene remains unknown. Similarly, no homologue of the protein binding domain (PBD) in MHC molecules has been found in invertebrates. The pathway by which endogenous peptides are degraded for presentation with class I MHC molecules utilizes mechanisms similar to those involved in the normal turnover of intracellular proteins, apparently recruited to work also for the immune system. Several cDNAs coding for lysosomal enzymes, e.g., cathepsin, have been isolated from sponges. All chromosomal duplication events in the MHC region occurred after the origin of the agnathans but before the gnathostomes split from them. The V-domains of the subtype found in the receptors of T and B-cells are known from both agnathans and cephalochordates, although they do not rearrange. The rearrangement mechanism of the lymphocyte V

  15. Proportion of recovered waterfowl bands reported

    USGS Publications Warehouse

    Geis, A.D.; Atwood, E.L.

    1961-01-01

    Data from the annual mail survey of waterfowl hunters in the United States were used to estimate the total numbers of banded waterfowl that were shot. These estimates were compared with Banding Office records to estimate the proportion of recovered bands that was reported. On the average, about two banded birds were recovered for each one reported. The proportion reported was higher for some areas and for some species than for others. The proportion reported was higher when more of the reports came through employees of conservation agencies.

  16. Blood quantum and perceptions of black-white biracial targets: the black ancestry prototype model of affirmative action.

    PubMed

    Sanchez, Diana T; Good, Jessica J; Chavez, George

    2011-01-01

    The present study examined the causal role of amount of Black ancestry in targets' perceived fit with Black prototypes and perceivers' categorization of biracial targets. Greater Black ancestry increased the likelihood that perceivers categorized biracial targets as Black and perceived targets as fitting Black prototypes (e.g., experiencing racial discrimination, possessing stereotypic traits). These results persisted, controlling for perceptions of phenotype that stem from ancestry information. Perceivers' beliefs about how society would categorize the biracial targets predicted perceptions of discrimination, whereas perceivers' beliefs about the targets' self-categorization predicted trait perceptions. The results of this study support the Black ancestry prototype model of affirmative action, which reveals the downstream consequences of Black ancestry for the distribution of minority resources (e.g., affirmative action) to biracial targets. PMID:21088283

  17. Working memory mechanism in proportional quantifier verification.

    PubMed

    Zajenkowski, Marcin; Szymanik, Jakub; Garraffa, Maria

    2014-12-01

    The paper explores the cognitive mechanisms involved in the verification of sentences with proportional quantifiers (e.g., "More than half of the dots are blue"). The first study shows that the verification of proportional sentences is more demanding than the verification of sentences such as: "There are seven blue and eight yellow dots". The second study reveals that both types of sentences are correlated with memory storage, however, only proportional sentences are associated with the cognitive control. This result suggests that the cognitive mechanism underlying the verification of proportional quantifiers is crucially related to the integration process, in which an individual has to compare in memory the cardinalities of two sets. In the third study we find that the numerical distance between two cardinalities that must be compared significantly influences the verification time and accuracy. The results of our studies are discussed in the broader context of processing complex sentences. PMID:24374596

  18. Proportionality, just war theory and weapons innovation.

    PubMed

    Forge, John

    2009-03-01

    Just wars are supposed to be proportional responses to aggression: the costs of war must not greatly exceed the benefits. This proportionality principle raises a corresponding 'interpretation problem': what are the costs and benefits of war, how are they to be determined, and a 'measurement problem': how are costs and benefits to be balanced? And it raises a problem about scope: how far into the future do the states of affairs to be measured stretch? It is argued here that weapons innovation always introduces costs, and that these costs cannot be determined in advance of going to war. Three examples, the atomic bomb, the AK-47 and the ancient Greek catapult, are given as examples. It is therefore argued that the proportionality principle is inapplicable prospectively. Some replies to the argument are discussed and rejected. Some more general defences of the proportionality principle are considered and also rejected. Finally, the significance of the argument for Just War Theory as a whole is discussed.

  19. Using Resampling to Compare Two Proportions

    ERIC Educational Resources Information Center

    Stephenson, W. Robert; Froelich, Amy G.; Duckworth, William M.

    2010-01-01

    This article shows that when applying resampling methods to the problem of comparing two proportions, students can discover that whether you resample with or without replacement can make a big difference.

  20. RECENT ADVANCES OF GENETIC ANCESTRY TESTING IN BIOMEDICAL RESEARCH AND DIRECT TO CONSUMER TESTING

    PubMed Central

    Via, Marc; Ziv, Elad; Burchard, Esteban González

    2010-01-01

    In the post-Human Genome Project era, the debate on the concept of race/ethnicity and its implications for biomedical research are dependent on two critical issues: whether and how to classify individuals and whether biological factors play a role in health disparities. The advent of reliable estimates of genetic (or biogeographic) ancestry has provided this debate with a quantitative and more objective tool. The estimation of genetic ancestry allows investigators to control for population stratification in association studies and helps to detect biological causation behind population-specific differences in disease and drug response. New techniques such as admixture mapping can specifically detect population-specific risk alleles for a disease in admixed populations. However, researchers have to be mindful of the correlation between genetic ancestry and socioeconomic and environmental factors that could underlie these differences. More importantly, researchers must avoid the stigmatization of individuals based on perceived or real genetic risks. The latter point will become increasingly sensitive as several “for profit companies” are offering ancestry and genetic testing directly to consumers and the consequences of the spread of the services of these companies is still unforeseeable. PMID:19793051

  1. 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. PMID:25051225

  2. Panmixia postponed: ancestry-related assortative mating in contemporary human populations

    PubMed Central

    2009-01-01

    A study of two different populations reveals that in both the choice of a spouse is non-random not only in respect of broad ethnic group but also in regard to specific ancestries within that group. The cause of this surprising bias remains unclear. PMID:19951396

  3. Resiliency and Collateral Learning in Science in Some Students of Cree Ancestry

    ERIC Educational Resources Information Center

    Sutherland, Dawn

    2005-01-01

    In the context of schooling, resiliency refers to the ability to thrive academically despite adverse circumstances. In this study the relationship between academic resilience and student's collateral learning is explored in 20 students of Cree ancestry. The individual resilience of each student was examined by identifying protective factors for…

  4. I too, am America: a review of research on systemic lupus erythematosus in African-Americans.

    PubMed

    Williams, Edith M; Bruner, Larisa; Adkins, Alyssa; Vrana, Caroline; Logan, Ayaba; Kamen, Diane; Oates, James C

    2016-01-01

    Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder that can cause significant morbidity and mortality. A large body of evidence has shown that African-Americans experience the disease more severely than other racial-ethnic groups. Relevant literature for the years 2000 to August 2015 were obtained from systematic searches of PubMed, Scopus, and the EBSCOHost platform that includes MEDLINE, CINAHL, etc. to evaluate research focused on SLE in African-Americans. Thirty-six of the 1502 articles were classified according to their level of evidence. The systematic review of the literature reported a wide range of adverse outcomes in African-American SLE patients and risk factors observed in other mono and multi-ethnic investigations. Studies limited to African-Americans with SLE identified novel methods for more precise ascertainment of risk and observed novel findings that hadn't been previously reported in African-Americans with SLE. Both environmental and genetic studies included in this review have highlighted unique African-American populations in an attempt to isolate risk attributable to African ancestry and observed increased genetic influence on overall disease in this cohort. The review also revealed emerging research in areas of quality of life, race-tailored interventions, and self-management. This review reemphasizes the importance of additional studies to better elucidate the natural history of SLE in African-Americans and optimize therapeutic strategies for those who are identified as being at high risk. PMID:27651918

  5. I too, am America: a review of research on systemic lupus erythematosus in African-Americans

    PubMed Central

    Williams, Edith M; Bruner, Larisa; Adkins, Alyssa; Vrana, Caroline; Logan, Ayaba; Kamen, Diane; Oates, James C

    2016-01-01

    Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder that can cause significant morbidity and mortality. A large body of evidence has shown that African-Americans experience the disease more severely than other racial-ethnic groups. Relevant literature for the years 2000 to August 2015 were obtained from systematic searches of PubMed, Scopus, and the EBSCOHost platform that includes MEDLINE, CINAHL, etc. to evaluate research focused on SLE in African-Americans. Thirty-six of the 1502 articles were classified according to their level of evidence. The systematic review of the literature reported a wide range of adverse outcomes in African-American SLE patients and risk factors observed in other mono and multi-ethnic investigations. Studies limited to African-Americans with SLE identified novel methods for more precise ascertainment of risk and observed novel findings that hadn't been previously reported in African-Americans with SLE. Both environmental and genetic studies included in this review have highlighted unique African-American populations in an attempt to isolate risk attributable to African ancestry and observed increased genetic influence on overall disease in this cohort. The review also revealed emerging research in areas of quality of life, race-tailored interventions, and self-management. This review reemphasizes the importance of additional studies to better elucidate the natural history of SLE in African-Americans and optimize therapeutic strategies for those who are identified as being at high risk.

  6. I too, am America: a review of research on systemic lupus erythematosus in African-Americans

    PubMed Central

    Williams, Edith M; Bruner, Larisa; Adkins, Alyssa; Vrana, Caroline; Logan, Ayaba; Kamen, Diane; Oates, James C

    2016-01-01

    Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder that can cause significant morbidity and mortality. A large body of evidence has shown that African-Americans experience the disease more severely than other racial-ethnic groups. Relevant literature for the years 2000 to August 2015 were obtained from systematic searches of PubMed, Scopus, and the EBSCOHost platform that includes MEDLINE, CINAHL, etc. to evaluate research focused on SLE in African-Americans. Thirty-six of the 1502 articles were classified according to their level of evidence. The systematic review of the literature reported a wide range of adverse outcomes in African-American SLE patients and risk factors observed in other mono and multi-ethnic investigations. Studies limited to African-Americans with SLE identified novel methods for more precise ascertainment of risk and observed novel findings that hadn't been previously reported in African-Americans with SLE. Both environmental and genetic studies included in this review have highlighted unique African-American populations in an attempt to isolate risk attributable to African ancestry and observed increased genetic influence on overall disease in this cohort. The review also revealed emerging research in areas of quality of life, race-tailored interventions, and self-management. This review reemphasizes the importance of additional studies to better elucidate the natural history of SLE in African-Americans and optimize therapeutic strategies for those who are identified as being at high risk. PMID:27651918

  7. Association of Genetic Ancestry with Breast Cancer in Ethnically Diverse Women from Chicago

    PubMed Central

    Al-Alem, Umaima; Rauscher, Garth; Shah, Ebony; Batai, Ken; Mahmoud, Abeer; Beisner, Erin; Silva, Abigail; Peterson, Caryn; Kittles, Rick

    2014-01-01

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

  8. B cells from African American lupus patients exhibit an activated phenotype

    PubMed Central

    Menard, Laurence C.; Habte, Sium; Gonsiorek, Waldemar; Lee, Deborah; Banas, Dana; Holloway, Deborah A.; Cunningham, Mark; Stetsko, Dawn; Casano, Francesca; Kansal, Selena; Davis, Patricia M.; Carman, Julie; Zhang, Clarence K.; Abidi, Ferva; Furie, Richard; Nadler, Steven G.; Suchard, Suzanne J.

    2016-01-01

    Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease driven by both innate and adaptive immune cells. African Americans tend to present with more severe disease at an earlier age compared with patients of European ancestry. In order to better understand the immunological differences between African American and European American patients, we analyzed the frequencies of B cell subsets and the expression of B cell activation markers from a total of 68 SLE patients and 69 normal healthy volunteers. We found that B cells expressing the activation markers CD86, CD80, PD1, and CD40L, as well as CD19+CD27–IgD– double-negative B cells, were enriched in African American patients vs. patients of European ancestry. In addition to increased expression of CD40L, surface levels of CD40 on B cells were lower, suggesting the engagement of the CD40 pathway. In vitro experiments confirmed that CD40L expressed by B cells could lead to CD40 activation and internalization on adjacent B cells. To conclude, these results indicate that, compared with European American patients, African American SLE patients present with a particularly active B cell component, possibly via the activation of the CD40/CD40L pathway. These data may help guide the development of novel therapies.

  9. B cells from African American lupus patients exhibit an activated phenotype

    PubMed Central

    Menard, Laurence C.; Habte, Sium; Gonsiorek, Waldemar; Lee, Deborah; Banas, Dana; Holloway, Deborah A.; Cunningham, Mark; Stetsko, Dawn; Casano, Francesca; Kansal, Selena; Davis, Patricia M.; Carman, Julie; Zhang, Clarence K.; Abidi, Ferva; Furie, Richard; Nadler, Steven G.; Suchard, Suzanne J.

    2016-01-01

    Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease driven by both innate and adaptive immune cells. African Americans tend to present with more severe disease at an earlier age compared with patients of European ancestry. In order to better understand the immunological differences between African American and European American patients, we analyzed the frequencies of B cell subsets and the expression of B cell activation markers from a total of 68 SLE patients and 69 normal healthy volunteers. We found that B cells expressing the activation markers CD86, CD80, PD1, and CD40L, as well as CD19+CD27–IgD– double-negative B cells, were enriched in African American patients vs. patients of European ancestry. In addition to increased expression of CD40L, surface levels of CD40 on B cells were lower, suggesting the engagement of the CD40 pathway. In vitro experiments confirmed that CD40L expressed by B cells could lead to CD40 activation and internalization on adjacent B cells. To conclude, these results indicate that, compared with European American patients, African American SLE patients present with a particularly active B cell component, possibly via the activation of the CD40/CD40L pathway. These data may help guide the development of novel therapies. PMID:27699274

  10. Spectrum of mitochondrial genomic variation and associated clinical presentation of prostate cancer in South African men

    PubMed Central

    McCrow, John P.; Petersen, Desiree C.; Louw, Melanie; Chan, Eva K. F.; Harmeyer, Katherine; Vecchiarelli, Stefano; Lyons, Ruth J.; Bornman, M. S. Riana

    2015-01-01

    BACKGROUND Prostate cancer incidence and mortality rates are significantly increased in African–American men, but limited studies have been performed within Sub–Saharan African populations. As mitochondria control energy metabolism and apoptosis we speculate that somatic mutations within mitochondrial genomes are candidate drivers of aggressive prostate carcinogenesis. METHODS We used matched blood and prostate tissue samples from 87 South African men (77 with African ancestry) to perform deep sequencing of complete mitochondrial genomes. Clinical presentation was biased toward aggressive disease (Gleason score >7, 64%), and compared with men without prostate cancer either with or without benign prostatic hyperplasia. RESULTS We identified 144 somatic mtDNA single nucleotide variants (SNVs), of which 80 were observed in 39 men presenting with aggressive disease. Both the number and frequency of somatic mtDNA SNVs were associated with higher pathological stage. CONCLUSIONS Besides doubling the total number of somatic PCa‐associated mitochondrial genome mutations identified to date, we associate mutational load with aggressive prostate cancer status in men of African ancestry. Prostate 76:349–358, 2016. © 2015 The Authors. The Prostate published by Wiley Periodicals, Inc. PMID:26660354

  11. Temporal pattern of africanization in a feral honeybee population from Texas inferred from mitochondrial DNA.

    PubMed

    Pinto, M Alice; Rubink, William L; Coulson, Robert N; Patton, John C; Johnston, J Spencer

    2004-05-01

    The invasion of Africanized honeybees (Apis mellifera L.) in the Americas provides a window of opportunity to study the dynamics of secondary contact of subspecies of bees that evolved in allopatry in ecologically distinctive habitats of the Old World. We report here the results of an 11-year mitochondrial DNA survey of a feral honeybee population from southern United States (Texas). The mitochondrial haplotype (mitotype) frequencies changed radically during the 11-year study period. Prior to immigration of Africanized honeybees, the resident population was essentially of eastern and western European maternal ancestry. Three years after detection of the first Africanized swarm there was a mitotype turnover in the population from predominantly eastern European to predominantly A. m. scutellata (ancestor of Africanized honeybees). This remarkable change in the mitotype composition coincided with arrival of the parasitic mite Varroa destructor, which was likely responsible for severe losses experienced by colonies of European ancestry. From 1997 onward the population stabilized with most colonies of A. m. scutellata maternal origin.

  12. Progress in studying scintillator proportionality: Phenomenological model

    SciTech Connect

    Bizarri, Gregory; Cherepy, Nerine; Choong, Woon-Seng; Hull, Giulia; Moses, William; Payne, Sephen; Singh, Jai; Valentine, John; Vasilev, Andrey; Williams, Richard

    2009-04-30

    We present a model to describe the origin of non-proportional dependence of scintillator light yield on the energy of an ionizing particle. The non-proportionality is discussed in terms of energy relaxation channels and their linear and non-linear dependences on the deposited energy. In this approach, the scintillation response is described as a function of the deposited energy deposition and the kinetic rates of each relaxation channel. This mathematical framework allows both a qualitative interpretation and a quantitative fitting representation of scintillation non-proportionality response as function of kinetic rates. This method was successfully applied to thallium doped sodium iodide measured with SLYNCI, a new facility using the Compton coincidence technique. Finally, attention is given to the physical meaning of the dominant relaxation channels, and to the potential causes responsible for the scintillation non-proportionality. We find that thallium doped sodium iodide behaves as if non-proportionality is due to competition between radiative recombinations and non-radiative Auger processes.

  13. Evaluation of Genome Wide Association Study Associated Type 2 Diabetes Susceptibility Loci in Sub Saharan Africans

    PubMed Central

    Adeyemo, Adebowale A.; Tekola-Ayele, Fasil; Doumatey, Ayo P.; Bentley, Amy R.; Chen, Guanjie; Huang, Hanxia; Zhou, Jie; Shriner, Daniel; Fasanmade, Olufemi; Okafor, Godfrey; Eghan, Benjamin; Agyenim-Boateng, Kofi; Adeleye, Jokotade; Balogun, Williams; Elkahloun, Abdel; Chandrasekharappa, Settara; Owusu, Samuel; Amoah, Albert; Acheampong, Joseph; Johnson, Thomas; Oli, Johnnie; Adebamowo, Clement; Collins, Francis; Dunston, Georgia; Rotimi, Charles N.

    2015-01-01

    Genome wide association studies (GWAS) for type 2 diabetes (T2D) undertaken in European and Asian ancestry populations have yielded dozens of robustly associated loci. However, the genomics of T2D remains largely understudied in sub-Saharan Africa (SSA), where rates of T2D are increasing dramatically and where the environmental background is quite different than in these previous studies. Here, we evaluate 106 reported T2D GWAS loci in continental Africans. We tested each of these SNPs, and SNPs in linkage disequilibrium (LD) with these index SNPs, for an association with T2D in order to assess transferability and to fine map the loci leveraging the generally reduced LD of African genomes. The study included 1775 unrelated Africans (1035 T2D cases, 740 controls; mean age 54 years; 59% female) enrolled in Nigeria, Ghana, and Kenya as part of the Africa America Diabetes Mellitus (AADM) study. All samples were genotyped on the Affymetrix Axiom PanAFR SNP array. Forty-one of the tested loci showed transferability to this African sample (p < 0.05, same direction of effect), 11 at the exact reported SNP and 30 others at SNPs in LD with the reported SNP (after adjustment for the number of tested SNPs). TCF7L2 SNP rs7903146 was the most significant locus in this study (p = 1.61 × 10−8). Most of the loci that showed transferability were successfully fine-mapped, i.e., localized to smaller haplotypes than in the original reports. The findings indicate that the genetic architecture of T2D in SSA is characterized by several risk loci shared with non-African ancestral populations and that data from African populations may facilitate fine mapping of risk loci. The study provides an important resource for meta-analysis of African ancestry populations and transferability of novel loci. PMID:26635871

  14. Africans in America.

    ERIC Educational Resources Information Center

    Hart, Ayanna; Spangler, Earl

    This book introduces African-American history and culture to children. The first Africans in America came from many different regions and cultures, but became united in this country by being black, African, and slaves. Once in America, Africans began a long struggle for freedom which still continues. Slavery, the Civil War, emancipation, and the…

  15. Therapy with African Families.

    ERIC Educational Resources Information Center

    Nwadiora, Emeka

    1996-01-01

    Informs helping professionals about the unique history and challenges of African families to guide them toward providing ethnically sensitive psychological services to African immigrant families in need. African families undergo great stress when faced with the alienation of being Black and African in a Euro-American culture. (SLD)

  16. African Outreach Workshop 1974.

    ERIC Educational Resources Information Center

    Schmidt, Nancy J.

    This report discusses the 1974 African Outreach Workshop planned and coordinated by the African Studies Program at the University of Illinois at Urbana-Champaign. Its major aim was to assist teachers in developing curriculum units on African using materials available in their local community. A second aim was for the African Studies Program to…

  17. Microevolution of African American dental morphology.

    PubMed

    Edgar, Heather J H

    2007-04-01

    The African American (AA) gene pool is primarily the result of gene flow between two biologically disparate groups: West Africans (WA) and Americans of western European descent (EA). This research utilizes characteristics of dental morphology to trace genetic relationships among WA, western Europeans (EU), AA, and European Americans. Dental morphological traits are useful for this purpose because they are heritable, do not remodel during life (although they can be lost to wear or pathology), and can be compared equally among samples from past and present populations. The results of this research provide new information about human microevolution through time and space in a biocultural setting. The mean measure of divergence is used to analyze dental morphological data from 1,265 individuals in 25 samples grouped by ancestry and time. Three hypotheses associated with admixture in AA are tested. When compared with known history, results from dental morphological data are equivocal in documenting admixture in AA. Dental morphological traits do appear to reflect admixture in AA. However, changes in trait frequencies do not closely correspond with important cultural events and trends such as the institutionalized racism of the Civil War and Jim Crow era. Results are mixed concerning whether AA with greater admixture were more likely to take part in the Great Migration to southern urban centers and to the North.

  18. Boron-10 Lined Proportional Counter Wall Effects

    SciTech Connect

    Siciliano, Edward R.; Kouzes, Richard T.

    2012-05-01

    The Department of Energy Office of Nuclear Safeguards (NA-241) is supporting the project 'Coincidence Counting With Boron-Based Alternative Neutron Detection Technology' at Pacific Northwest National Laboratory (PNNL) for development of an alternative neutron coincidence counter. The goal of this project is to design, build and demonstrate a boron-lined proportional tube based system in the configuration of a coincidence counter. This report provides information about how variations in proportional counter radius and gas pressure in a typical coincident counter design might affect the observed signal from boron-lined tubes. A discussion comparing tubes to parallel plate counters is also included.

  19. Proportional hazards models with discrete frailty.

    PubMed

    Caroni, Chrys; Crowder, Martin; Kimber, Alan

    2010-07-01

    We extend proportional hazards frailty models for lifetime data to allow a negative binomial, Poisson, Geometric or other discrete distribution of the frailty variable. This might represent, for example, the unknown number of flaws in an item under test. Zero frailty corresponds to a limited failure model containing a proportion of units that never fail (long-term survivors). Ways of modifying the model to avoid this are discussed. The models are illustrated on a previously published set of data on failures of printed circuit boards and on new data on breaking strengths of samples of cord.

  20. Ratio, Proportion and Scaling. Mathematics Resource Project.

    ERIC Educational Resources Information Center

    Hoffer, Shirley Ann, Ed.

    The Mathematics Resource Project has as its goal the production of topical resources for teachers, drawn from the vast amounts of available material. This experimental edition on Ratio, Proportion, and Scaling, contains a teaching emphasis section, a classroom materials section, and teacher commentaries. The teaching emphasis section stresses…

  1. Augmented mixed models for clustered proportion data

    PubMed Central

    Bandyopadhyay, Dipankar; Galvis, Diana M; Lachos, Victor H

    2015-01-01

    Often in biomedical research, we deal with continuous (clustered) proportion responses ranging between zero and one quantifying the disease status of the cluster units. Interestingly, the study population might also consist of relatively disease-free as well as highly diseased subjects, contributing to proportion values in the interval [0, 1]. Regression on a variety of parametric densities with support lying in (0, 1), such as beta regression, can assess important covariate effects. However, they are deemed inappropriate due to the presence of zeros and/or ones. To evade this, we introduce a class of general proportion density, and further augment the probabilities of zero and one to this general proportion density, controlling for the clustering. Our approach is Bayesian and presents a computationally convenient framework amenable to available freeware. Bayesian case-deletion influence diagnostics based on q-divergence measures are automatic from the Markov chain Monte Carlo output. The methodology is illustrated using both simulation studies and application to a real dataset from a clinical periodontology study. PMID:25491718

  2. Golden Proportions for the Generalized Tribonacci Numbers

    ERIC Educational Resources Information Center

    Shah, Devbhadra V.; Mehta, Darshana A.

    2009-01-01

    It is known that the ratios of consecutive terms of Fibonacci and Tribonacci sequences converge to the fixed ratio. In this article, we consider the generalized form of Tribonacci numbers and derive the "golden proportion" for the whole family of this generalized sequence. (Contains 2 tables.)

  3. Indices of body proportionality in neonates.

    PubMed

    Tsou Yau, K I; Chang, M H

    1993-01-01

    The inadequacy of using body weight alone to evaluate fetal skeletal and soft-tissue growth has long been recognized. Body proportionality indices could identify symptomatic newborn infants better than size-for-date classification. Lack of normative data precludes its being used, practically, in Chinese newborns. Thus body weight, body length, head circumference and mid-arm circumference were measured in 240 neonates appropriate for gestational age, 27-42 weeks, 960-3918 g, to construct reference indices of body proportionality: ponderal index (PI), body mass index (BMI), weight/length ratio (W/L), head circumference/body length ratio (HC/L) and mid-arm circumference/head circumference ratio (MAC/HC). All the five indices of body proportionality but HC/L were statistically correlated with gestational age (GA). For full-term newborns, PI did not correlate with GA. Furthers, the MAC/HC ratio decreased after 40 weeks' gestation. Therefore, when these indices of body proportionality are used to evaluate intrauterine nutritional status of a newborn, the appropriate standard for GA should be considered. PMID:8372678

  4. Canine Conjectures: Using Data for Proportional Reasoning

    ERIC Educational Resources Information Center

    Westenskow, Arla; Moyer-Packenham, Patricia S.

    2011-01-01

    No person, place, or thing can capture the attention of a class of sixth graders like "man's best friend." To prompt students' interest in a series of lessons on proportional relationships, the authors brought in a unique teaching aid--a dog. A family dog was used to supply the measurements for scatter plots and variables so that students could…

  5. Kitchen Gardens: Contexts for Developing Proportional Reasoning

    ERIC Educational Resources Information Center

    Hilton, Annette; Hilton, Geoff; Dole, Shelley; Goos, Merrilyn; O'Brien, Mia

    2013-01-01

    It is great to see how the sharing of ideas sparks new ideas. In 2011 Lyon and Bragg wrote an "Australian Primary Mathematics Classroom" (APMC) article on the mathematics of kitchen gardens. In this article the authors show how the kitchen garden may be used as a starting point for proportional reasoning. The authors highlight different…

  6. Intermediate Moral Respect and Proportionality Reasoning.

    PubMed

    Finegan, Thomas

    2016-10-01

    In a recent article in this journal Jonathan Pugh critiques the idea of intermediate 'moral respect' which some say is owed to embryos. This concept is inherent within the 'principle of proportionality', the principle that destructive research on embryos is permissable only if the research serves an important purpose. Pugh poses two specific questions to proponents of the idea of intermediate moral respect. This article argues that while the questions posed by Pugh are