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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. PMID:25846634

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

    PubMed Central

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

    2012-01-01

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

  3. Relationship of Pain and Ancestry in African American Women

    PubMed Central

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

    2015-01-01

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

  4. Estimating Genetic Ancestry Proportions from Faces

    PubMed Central

    Klimentidis, Yann C.; Shriver, Mark D.

    2009-01-01

    Ethnicity can be a means by which people identify themselves and others. This type of identification mediates many kinds of social interactions and may reflect adaptations to a long history of group living in humans. Recent admixture in the US between groups from different continents, and the historically strong emphasis on phenotypic differences between members of these groups, presents an opportunity to examine the degree of concordance between estimates of group membership based on genetic markers and on visually-based estimates of facial features. We first measured the degree of Native American, European, African and East Asian genetic admixture in a sample of 14 self-identified Hispanic individuals, chosen to cover a broad range of Native American and European genetic admixture proportions. We showed frontal and side-view photographs of the 14 individuals to 241 subjects living in New Mexico, and asked them to estimate the degree of NA admixture for each individual. We assess the overall concordance for each observer based on an aggregated measure of the difference between the observer and the genetic estimates. We find that observers reach a significantly higher degree of concordance than expected by chance, and that the degree of concordance as well as the direction of the discrepancy in estimates differs based on the ethnicity of the observer, but not on the observers' age or sex. This study highlights the potentially high degree of discordance between physical appearance and genetic measures of ethnicity, as well as how perceptions of ethnic affiliation are context-specific. We compare our findings to those of previous studies and discuss their implications. PMID:19223962

  5. Effect of Genetic African Ancestry on eGFR and Kidney Disease

    PubMed Central

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

    2015-01-01

    Self-reported ancestry, genetically determined ancestry, and APOL1 polymorphisms are associated with variation in kidney function and related disease risk, but the relative importance of these factors remains unclear. We estimated the global proportion of African ancestry for 9048 individuals at Mount Sinai Medical Center in Manhattan (3189 African Americans, 1721 European Americans, and 4138 Hispanic/Latino Americans by self-report) using genome-wide genotype data. CKD-EPI eGFR and genotypes of three APOL1 coding variants were available. In admixed African Americans and Hispanic/Latino Americans, serum creatinine values increased as African ancestry increased (per 10% increase in African ancestry, creatinine values increased 1% in African Americans and 0.9% in Hispanic/Latino Americans; P≤1x10−7). eGFR was likewise significantly associated with African genetic ancestry in both populations. In contrast, APOL1 risk haplotypes were significantly associated with CKD, eGFR<45 ml/min per 1.73 m2, and ESRD, with effects increasing with worsening disease states and the contribution of genetic African ancestry decreasing in parallel. Using genetic ancestry in the eGFR equation to reclassify patients as black on the basis of ≥50% African ancestry resulted in higher eGFR for 14.7% of Hispanic/Latino Americans and lower eGFR for 4.1% of African Americans, affecting CKD staging in 4.3% and 1% of participants, respectively. Reclassified individuals had electrolyte values consistent with their newly assigned CKD stage. In summary, proportion of African ancestry was significantly associated with normal-range creatinine and eGFR, whereas APOL1 risk haplotypes drove the associations with CKD. Recalculation of eGFR on the basis of genetic ancestry affected CKD staging and warrants additional investigation. PMID:25349204

  6. Charting the ancestry of African Americans.

    PubMed

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

    2005-10-01

    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

  7. 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

  8. Ancestry of African Americans with Sickle Cell Disease

    PubMed Central

    Solovieff, Nadia; Hartley, Stephen W.; Baldwin, Clinton T.; Klings, Elizabeth S.; Gladwin, Mark T.; Taylor, James G.; Kato, Gregory J.; Farrer, Lindsay A.; Steinberg, Martin H.; Sebastiani, Paola

    2011-01-01

    The inheritance of genetic disease depends on ancestry that must be considered when interpreting genetic association studies and can provide insights when comparing traits in a population. We compared the genetic profiles of African Americans with sickle cell disease to those of Black Africans and Caucasian populations of European descent and found that they are less genetically admixed than other African Americans and have an ancestry similar to Yorubans, Mandenkas and Bantu. PMID:21546286

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2011-07-15

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

  11. 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

  12. 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

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

    PubMed

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

    2014-06-01

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

  14. 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

  15. 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

  16. European Ancestry as a Risk Factor for Atrial Fibrillation in African Americans

    PubMed Central

    Marcus, Gregory M.; Alonso, Alvaro; Peralta, Carmen A.; Lettre, Guillaume; Vittinghoff, Eric; Lubitz, Steven A.; Fox, Ervin R.; Levitzky, Yamini S.; Mehra, Reena; Kerr, Kathleen F.; Deo, Rajat; Sotoodehnia, Nona; Akylbekova, Meggie; Ellinor, Patrick T.; Paltoo, Dina N.; Soliman, Elsayed Z.; Benjamin, Emelia J.; Heckbert, Susan R.

    2010-01-01

    Background Despite a higher burden of standard atrial fibrillation (AF) risk factors, African Americans have a lower risk of AF than whites. It is unknown if the higher riskis due to genetic or environmental factors. As African Americans have varying degrees of European ancestry, we sought to test the hypothesis that European ancestry is an independent risk factor for AF. Methods and Results We studied whites (n=4,543) and African Americans (n=822) in the Cardiovascular Health Study (CHS) and whites (n=10,902) and Africa Americans (n=3,517) in the Atherosclerosis Risk in Communities (ARIC) Study (n=3,517). Percent European ancestry in African Americans was estimated using 1,747 ancestry informative markers (AIMs) from the Illumina custom ITMAT-Broad-CARe (IBC) array. Among African Americans without baseline AF, 120 of 804 CHS participants and 181 of 3,517 ARIC participants developed incident AF. A meta-analysis from the two studies revealed that every 10% increase in European ancestry increased the risk of AF by 13% (HR 1.13, 95% CI 1.03–1.23, p=0.007). After adjusting for potential confounders, European ancestry remained a predictor of incident AF in each cohort alone, with a combined estimated hazard ratio for each 10% increase in European ancestry of 1.17 (95% CI 1.07–1.29, p=0.001). A second analysis using 3,192 AIMs from a genome wide Affymetrix 6.0 array in ARIC African Americans yielded similar results. Conclusion European ancestry predicted risk of incident AF. Our study suggests that investigating genetic variants contributing to differential AF risk in individuals of African versus European ancestry will be informative. PMID:21098467

  17. 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

  18. 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

  19. 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

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

    PubMed Central

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

    2013-01-01

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

  1. 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

  2. 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

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

    PubMed Central

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

    2012-01-01

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

  4. Comparing Genetic Ancestry and Self-Described Race in African Americans Born in the United States and in Africa

    PubMed Central

    Yaeger, Rona; Avila-Bront, Alexa; Abdul, Kazeem; Nolan, Patricia C.; Grann, Victor R.; Birchette, Mark G.; Choudhry, Shweta; Burchard, Esteban G.; Beckman, Kenneth B.; Gorroochurn, Prakash; Ziv, Elad; Consedine, Nathan S.; Joe, Andrew K.

    2008-01-01

    Genetic association studies can be used to identify factors that may contribute to disparities in disease evident across different racial and ethnic populations. However, such studies may not account for potential confounding if study populations are genetically heterogeneous. Racial and ethnic classifications have been used as proxies for genetic relatedness. We investigated genetic admixture and developed a questionnaire to explore variables used in constructing racial identity in two cohorts – 50 African Americans (AAs) and 40 Nigerians. Genetic ancestry was determined by genotyping 107 ancestry informative markers. Ancestry estimates calculated with maximum likelihood estimation were compared with population stratification detected with principal component analysis. Ancestry was approximately 95% west African, 4% European, and 1% Native American in the Nigerian cohort and 83% west African, 15% European, and 2% Native American in the AA cohort. Therefore, self-identification as AA agreed well with inferred west African ancestry. However, the cohorts differed significantly in mean percentage west African and European ancestries (P < 0.0001) and in the variance for individual ancestry (P ≤ 0.01). Among AAs, no set of questionnaire items effectively estimated degree of west African ancestry, and self-report of a high degree of African ancestry in a three-generation family tree did not accurately predict degree of African ancestry. Our findings suggest that self-reported race and ancestry can predict ancestral clusters, but do not reveal the extent of admixture. Genetic classifications of ancestry may provide a more objective and accurate method of defining homogenous populations for the investigation of specific population-disease associations. PMID:18559547

  5. Is the observed association between dairy intake and fibroids in African Americans explained by genetic ancestry?

    PubMed

    Wise, Lauren A; Palmer, Julie R; Ruiz-Narvaez, Edward; Reich, David E; Rosenberg, Lynn

    2013-10-01

    Uterine leiomyomata are a major source of gynecological morbidity and are 2-3 times more prevalent in African Americans than European Americans. In an earlier report, we found that dairy intake was inversely associated with uterine leiomyomata among African Americans. Because African Americans are more likely to have lactose intolerance and avoid dairy products, the observed association might have been confounded by genetic ancestry. This report reevaluates the dairy-uterine leiomyomata association after accounting for genetic ancestry among 1,968 cases and 2,183 noncases from the Black Women's Health Study (1997-2007). Dairy intake was estimated by using food frequency questionnaires in 1995 and 2001. Percent European ancestry was estimated by using a panel of ancestry informative markers. Incidence rate ratios and 95% confidence intervals were estimated by using Cox regression, with adjustment for potential confounders and percent European ancestry. Incidence rate ratios comparing 1, 2, 3, and ≥4 servings/day with <1 serving/day of dairy products were 0.95 (95% confidence interval (CI): 0.85, 1.06), 0.75 (95% CI: 0.61, 0.92), 0.77 (95% CI: 0.57, 1.04), and 0.59 (95% CI: 0.41, 0.86), respectively (Ptrend = 0.0003). These effect estimates were similar to those obtained without control for ancestry. The findings suggest that the observed inverse association between dairy consumption and uterine leiomyomata in African Americans is not explained by percent European ancestry. PMID:23825169

  6. Is the Observed Association Between Dairy Intake and Fibroids in African Americans Explained by Genetic Ancestry?

    PubMed Central

    Wise, Lauren A.; Palmer, Julie R.; Ruiz-Narvaez, Edward; Reich, David E.; Rosenberg, Lynn

    2013-01-01

    Uterine leiomyomata are a major source of gynecological morbidity and are 2–3 times more prevalent in African Americans than European Americans. In an earlier report, we found that dairy intake was inversely associated with uterine leiomyomata among African Americans. Because African Americans are more likely to have lactose intolerance and avoid dairy products, the observed association might have been confounded by genetic ancestry. This report reevaluates the dairy-uterine leiomyomata association after accounting for genetic ancestry among 1,968 cases and 2,183 noncases from the Black Women's Health Study (1997–2007). Dairy intake was estimated by using food frequency questionnaires in 1995 and 2001. Percent European ancestry was estimated by using a panel of ancestry informative markers. Incidence rate ratios and 95% confidence intervals were estimated by using Cox regression, with adjustment for potential confounders and percent European ancestry. Incidence rate ratios comparing 1, 2, 3, and ≥4 servings/day with <1 serving/day of dairy products were 0.95 (95% confidence interval (CI): 0.85, 1.06), 0.75 (95% CI: 0.61, 0.92), 0.77 (95% CI: 0.57, 1.04), and 0.59 (95% CI: 0.41, 0.86), respectively (Ptrend = 0.0003). These effect estimates were similar to those obtained without control for ancestry. The findings suggest that the observed inverse association between dairy consumption and uterine leiomyomata in African Americans is not explained by percent European ancestry. PMID:23825169

  7. 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

  8. 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

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

    PubMed

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

    2010-06-01

    Understanding genetic variation between populations is important because it affects the portability of human genome-wide analytical methods. We compared genetic variation and substructure between Malawians and other African and non-African HapMap populations. Allele frequencies and adjacent linkage disequilibrium (LD) were measured for 617 715 single nucleotide polymorphisms (SNPs) across subject genomes. Allele frequencies in the Malawian population (N=226) were highly correlated with allele frequencies in HapMap populations of African ancestry (AFA, N=376), namely Yoruban in Ibadan, Nigeria (Spearman's r(2)=0.97), Luhya in Webuye, Kenya (r(2)=0.97), African Americans in the southwest United States (r(2)=0.94) and Maasai in Kinyawa, Kenya (r(2)=0.91). This correlation was much lower between Malawians and other ancestry populations (r(2)<0.52). LD correlations between Malawians and HapMap populations were strongest for the populations of AFA (AFA r(2)>0.82, other ancestries r(2)<0.57). Principal components analyses revealed little population substructure within our Malawi sample but provided clear distinction between Malawians, AFA populations and two European populations. Five SNPs within the lactase gene (LCT) had substantially different allele frequencies between the Malawi population and Maasai in Kenyawa, Kenya (rs3769013, rs730005, rs3769012, rs2304370; P-values <1 x 10(-33)). PMID:20485449

  10. 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 (

  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. 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

  13. 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. PMID:23475944

  14. 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

  15. 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. PMID:26823525

  16. Molecular Variation in Neuropeptide Y and Bone Mineral Density Among Men of African Ancestry

    PubMed Central

    Goodrich, Louis J.; Yerges-Armstrong, Laura M.; Miljkovic, Iva; Nestlerode, Cara S.; Kuipers, Allison L.; Bunker, Clareann H.; Patrick, Alan L.; Wheeler, Victor W.

    2016-01-01

    Neuropeptide Y (NPY) is a physiological candidate gene for the regulation of body weight and has more recently been implicated in regulating bone mass. The current study sought to test if inherited variation in NPY might influence BMD in a population of African-ancestry men who have high bone mineral density (BMD). We genotyped 17 tagging single-nucleotide polymorphisms (SNPs) across the NPY gene region in 1,113 randomly selected men of African ancestry aged ≥40 years and tested for association with anthropometric characteristics and proximal femur BMD. The homozygous rare genotype of four SNPs was associated with a 0.92–1.59% decrease in stature (corrected P < 0.05). No SNP was associated with body mass index or body weight. Two SNPs in a 5-kb linkage disequilibrium block encompassing exons 3 and 4 were associated with proximal femur BMD, adjusted for age, body weight, and height (corrected P < 0.05). These results suggest that genetic variation at the NPY locus may contribute to bone density, independently of body weight. PMID:19865784

  17. 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

  18. Genome-wide Association Analysis of Blood-Pressure Traits in African-Ancestry Individuals Reveals Common Associated Genes in African and Non-African Populations

    PubMed Central

    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; Go, Min Jin; Kim, Young Jin; Lee, Jong-Young; Jeon, Jae-Pil; Kim, Sung Soo; Han, Bok-Ghee; Cho, Yoon Shin; Sim, Xueling; Tay, Wan Ting; Ong, Rick Twee Hee; Seielstad, Mark; Liu, Jian Jun; Aung, Tin; Wong, Tien Yin; Teo, Yik Ying; Tai, E. Shyong; Chen, Chien-Hsiun; Chang, Li-ching; Chen, Yuan-Tsong; Wu, Jer-Yuarn; Kelly, Tanika N.; Gu, Dongfeng; Hixson, James E.; Sung, Yun Ju; He, Jiang; Tabara, Yasuharu; Kokubo, Yoshihiro; Miki, Tetsuro; Iwai, Naoharu; Kato, Norihiro; Takeuchi, Fumihiko; Katsuya, Tomohiro; Nabika, Toru; Sugiyama, Takao; Zhang, Yi; Huang, Wei; Zhang, Xuegong; Zhou, Xueya; Jin, Li; Zhu, Dingliang; 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

    2013-01-01

    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. PMID:23972371

  19. 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. PMID:23583978

  20. 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

  1. 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

  2. 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. PMID:26079385

  3. 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

  4. 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

  5. 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

  6. 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

  7. Genome-wide Ancestry Association Testing Identifies a Common European Variant on 6q14.1 as a Risk Factor for Asthma in African Americans

    PubMed Central

    Torgerson, Dara G.; Capurso, Daniel; Ampleford, Elizabeth J.; Li, Xingnan; Moore, Wendy C.; Gignoux, Christopher R.; Hu, Donglei; Eng, Celeste; Mathias, Rasika A.; Busse, William W.; Castro, Mario; Erzurum, Serpil C.; Fitzpatrick, Anne M.; Gaston, Benjamin; Israel, Elliot; Jarjour, Nizar N.; Teague, W. Gerald; Wenzel, Sally E.; Rodríguez-Santana, José R.; Rodríguez-Cintrón, William; Avila, Pedro C.; Ford, Jean G.; Barnes, Kathleen C.; Burchard, Esteban G.; Howard, Timothy D.; Bleecker, Eugene R.; Meyers, Deborah A.; Cox, Nancy J.; Ober, Carole; Nicolae, Dan L.

    2012-01-01

    Background Genetic variants that contribute to asthma susceptibility may be present at varying frequencies in different populations, which is an important consideration and advantage for performing genetic association studies in admixed populations. Objective To identify asthma-associated loci in African Americans. Methods We compared local African and European ancestry estimated from dense single nucleotide polymorphism (SNP) genotype data in African American adults with asthma and non-asthmatic controls. Allelic tests of association were performed within the candidate regions identified, correcting for local European admixture. Results We identified a significant ancestry association peak on chromosomes 6q. Allelic tests for association within this region identified a SNP (rs1361549) on 6q14.1 that was associated with asthma exclusively in African Americans with local European admixture (OR=2.2). The risk allele is common in Europe (42% in the HapMap CEU) but absent in West Africa (0% in the HapMap YRI), suggesting the allele is present in African Americans due to recent European admixture. We replicated our findings in Puerto Ricans and similarly found that the signal of association is largely specific to individuals who are heterozygous for African and non-African ancestry at 6q14.1. However, we found no evidence for association in European Americans or in Puerto Ricans in the absence of local African ancestry, suggesting that the association with asthma at rs1361549 is due to an environmental or genetic interaction. Conclusion We identified a novel asthma-associated locus that is relevant to admixed populations with African ancestry, and highlight the importance of considering local ancestry in genetic association studies of admixed populations. PMID:22607992

  8. 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 (bothP<0.01). There were also significant genetic correlations between renin activity and whole-body bone mineral density. There were no associations with aldosterone concentration in any model and results for aldosterone/renin ratio were similar to those for renin activity. This is the first study to report a significant association between renin activity and a marker of bone turnover and bone mineral density in generally healthy individuals. Also, there is evidence for significant genetic pleiotropy and, thus, there may be a shared biological mechanism underlying both the renin-angiotensin-aldosterone system and bone metabolism that is independent of hypertension. PMID:26975710

  9. Genome-Wide Local Ancestry Approach Identifies Genes and Variants Associated with Chemotherapeutic Susceptibility in African Americans

    PubMed Central

    Wheeler, Heather E.; Gorsic, Lidija K.; Welsh, Marleen; Stark, Amy L.; Gamazon, Eric R.; Cox, Nancy J.; Dolan, M. Eileen

    2011-01-01

    Chemotherapeutic agents are used in the treatment of many cancers, yet variable resistance and toxicities among individuals limit successful outcomes. Several studies have indicated outcome differences associated with ancestry among patients with various cancer types. Using both traditional SNP-based and newly developed gene-based genome-wide approaches, we investigated the genetics of chemotherapeutic susceptibility in lymphoblastoid cell lines derived from 83 African Americans, a population for which there is a disparity in the number of genome-wide studies performed. To account for population structure in this admixed population, we incorporated local ancestry information into our association model. We tested over 2 million SNPs and identified 325, 176, 240, and 190 SNPs that were suggestively associated with cytarabine-, 5′-deoxyfluorouridine (5′-DFUR)-, carboplatin-, and cisplatin-induced cytotoxicity, respectively (p≤10−4). Importantly, some of these variants are found only in populations of African descent. We also show that cisplatin-susceptibility SNPs are enriched for carboplatin-susceptibility SNPs. Using a gene-based genome-wide association approach, we identified 26, 11, 20, and 41 suggestive candidate genes for association with cytarabine-, 5′-DFUR-, carboplatin-, and cisplatin-induced cytotoxicity, respectively (p≤10−3). Fourteen of these genes showed evidence of association with their respective chemotherapeutic phenotypes in the Yoruba from Ibadan, Nigeria (p<0.05), including TP53I11, COPS5 and GAS8, which are known to be involved in tumorigenesis. Although our results require further study, we have identified variants and genes associated with chemotherapeutic susceptibility in African Americans by using an approach that incorporates local ancestry information. PMID:21755009

  10. 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

  11. Body fatness and breast cancer risk in women of African ancestry

    PubMed Central

    2013-01-01

    Background Obesity has been shown to be inversely associated with breast cancer risk in premenopausal women, while increasing risk in postmenopausal women. However, the current evidence is largely based on studies in Caucasian populations. Associations in women of African ancestry (AA), who have a higher prevalence of obesity, have been evaluated in few studies and results suggest different effects. Methods We evaluated the impact of body size, body fat distribution, and body composition on breast cancer risk among AA women (978 cases and 958 controls) participating in the Women’s Circle of Health Study, a multi-site case–control study in New York City (NYC) and New Jersey (NJ). Cases were newly diagnosed with histologically confirmed ductal carcinoma in situ or invasive breast cancer, age 20–75 yrs. In NYC, cases were recruited through hospitals with the largest referral patterns for AA women and controls through random digit dialing (RDD). In NJ, cases were identified in seven counties in NJ thorough the NJ State Cancer Registry, and controls through RDD and community-based recruitment. During in-person interviews, questionnaires were administered and detailed anthropometric measurements were obtained. Body composition was assessed by bioelectrical impedance analysis. Results BMI did not have a major impact on pre- or post-menopausal breast cancer, but was significantly associated with reduced risk of ER-/PR- tumors among postmenopausal women (OR: 0.37; 95% CI: 0.15-0.96 for BMI > 30 vs. BMI < 25). Furthermore, increased premenopausal breast cancer risk was found for higher waist and hip circumferences after adjusting for BMI, with ORs of 2.25 (95% CI: 1.07-4.74) and 2.91 (95% CI: 1.39-6.10), respectively, comparing the highest vs. lowest quartile. While ORs for higher fat mass and percent body fat among postmenopausal women were above one, confidence intervals included the null value. Conclusions Our study suggests that in AA women BMI is

  12. Rates of and Risk factors for trabecular and cortical BMD loss in middle-aged and elderly African Ancestry men

    PubMed Central

    Sheu, Yahtyng; Bunker, Clareann H.; Jonnalagadda, Pallavi; Cvejkus, Ryan K.; Patrick, Allen L.; Wheeler, Victor W.; Gordon, Christopher L.; Zmuda, Joseph M.

    2014-01-01

    Low trabecular (Tb) and cortical (Ct) volumetric BMD (vBMD) are related to increased fracture risk, but little is known about the patterns and correlates of Tb and Ct vBMD loss with aging. We examined the rates of change in total, Tb.vBMD and Ct.vBMD at the radius and tibia, and identified factors associated with vBMD loss among 1,569 men of African descent aged 40 years and older. Quantitative computed tomography was used to measure vBMD 6 years apart. The annualized rate of loss in Tb.vBMD was significant at the radius (−0.047%/yr, p=0.016) but not tibia. At the radius, a significant loss of Tb.vBMD was observed in men aged 40-49 that appeared to be attenuated and not statistically significant among older age men. In contrast, the decline in Ct.vBMD was similar at both skeletal sites (−0.254 to −0.264%/yr, p<0.0001) and was consistent across all age groups. Positive associations were found for vBMD changes with body weight (all but radius Ct.vBMD) and diabetes (Ct.vBMD only), while negative associations were found with hypertension (all but radius Tb.vBMD), smoking (Ct.vBMD only), and androgen deprivation therapy (cortical vBMD only). Trabecular and cortical vBMD loss appears to follow different patterns among middle- and older-aged men of African ancestry. Factors associated with the decline in vBMD also varied by compartment and anatomical site. Additional studies are needed to better understand the physiological mechanisms underlying early BMD loss among African ancestry men. PMID:25213918

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

    PubMed Central

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

    2008-01-01

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

  14. 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

  15. 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. PMID:23040495

  16. 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

  17. 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

  18. Differences in coronary heart disease risk markers among apparently healthy individuals of African ancestry.

    PubMed Central

    Davis, Errol E.; Huffman, Fatma G.

    2007-01-01

    OBJECTIVE: This study identified and compared coronary heart disease (CHD) risk factors among foreign-born Afro Caribbeans (FBAC), U.S.-born Afro-Caribbean Americans (USBAC) and African Americans. METHODS: Sixty-six FBAC living in the United States for <10 years, 62 USBAC and 61 African-American adults (18-40 years) were recruited. Sociodemographic, behavioral and biochemical data were collected and analyzed. RESULTS: More USBAC (26.2%) and African-American (23.7%) participants compared to the FBAC (10.8%) participants had significantly (p < 0.05) poorer diet scores and were significantly (p < 0.05) more obese (17.7% and 23.0% vs. 7.6%). These differences remained significant between the male ethnic groups but not the females. Also, more USBAC and African-American participants compared to FBAC participants watched television often/very often (54.8% and 49.2% vs. 45.5%), played less sports (56.5% and 55.7% vs. 40.9%) and smoked cigarettes (4.8% and 6.6% vs. 0.0%). In general, USBAC and African-American participants were more likely to have elevated blood glucose (BG), total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP) levels compared to FBAC participants. More FBAC than USBAC and African-American participants had elevated blood pressure (BP) and low levels of high-density-lipoprotein cholesterol (HDL-C). However, the differences were not significant. CONCLUSION: This study demonstrated that there are differences in risk factors for CHD among ethnic groups (FBAC, USBAC and African-American participants) of persons with African ancestory. PMID:17595935

  19. 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

  20. Genome-wide patterns of population structure and admixture in West Africans and African Americans.

    PubMed

    Bryc, Katarzyna; Auton, Adam; Nelson, Matthew R; Oksenberg, Jorge R; Hauser, Stephen L; Williams, Scott; Froment, Alain; Bodo, Jean-Marie; Wambebe, Charles; Tishkoff, Sarah A; Bustamante, Carlos D

    2010-01-12

    Quantifying patterns of population structure in Africans and African Americans illuminates the history of human populations and is critical for undertaking medical genomic studies on a global scale. To obtain a fine-scale genome-wide perspective of ancestry, we analyze Affymetrix GeneChip 500K genotype data from African Americans (n = 365) and individuals with ancestry from West Africa (n = 203 from 12 populations) and Europe (n = 400 from 42 countries). We find that population structure within the West African sample reflects primarily language and secondarily geographical distance, echoing the Bantu expansion. Among African Americans, analysis of genomic admixture by a principal component-based approach indicates that the median proportion of European ancestry is 18.5% (25th-75th percentiles: 11.6-27.7%), with very large variation among individuals. In the African-American sample as a whole, few autosomal regions showed exceptionally high or low mean African ancestry, but the X chromosome showed elevated levels of African ancestry, consistent with a sex-biased pattern of gene flow with an excess of European male and African female ancestry. We also find that genomic profiles of individual African Americans afford personalized ancestry reconstructions differentiating ancient vs. recent European and African ancestry. Finally, patterns of genetic similarity among inferred African segments of African-American genomes and genomes of contemporary African populations included in this study suggest African ancestry is most similar to non-Bantu Niger-Kordofanian-speaking populations, consistent with historical documents of the African Diaspora and trans-Atlantic slave trade. PMID:20080753

  1. 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

  2. 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

  3. The evolution of skin pigmentation and hair texture in people of African ancestry.

    PubMed

    Jablonski, Nina G; Chaplin, George

    2014-04-01

    Our species, Homo sapiens, evolved in Africa, and humanity's highest levels of genetic diversity are maintained there today. Underlying genetic diversity combined with the great range of solar regimes and climatic conditions found in Africa has contributed to a wide range of human integumentary phenotypes within the continent. Millions of Africans have moved, voluntarily and involuntarily, to other continents in the past 2000 years, and the range of integumentary phenotypes among admixed African diaspora populations is enormous. In this contribution, we do not catalog this variation, but provide basic evolutionary background as to how it developed in the first place. PMID:24679998

  4. Recurrent BRCA1 and BRCA2 mutations in breast cancer patients of African ancestry.

    PubMed

    Zhang, Jing; Fackenthal, James D; Zheng, Yonglan; Huo, Dezheng; Hou, Ningqi; Niu, Qun; Zvosec, Cecilia; Ogundiran, Temidayo O; Hennis, Anselm J; Leske, Maria Cristina; Nemesure, Barbara; Wu, Suh-Yuh; Olopade, Olufunmilayo I

    2012-07-01

    Recurrent mutations constituted nearly three quarters of all BRCA1 mutations and almost half of all BRCA2 mutations identified in the first cohort of the Nigerian Breast Cancer Study. To further characterize breast/ovarian cancer risks associated with BRCA1/BRCA2 mutations in the African diaspora, we genotyped recurrent mutations among Nigerian, African American, and Barbadian breast cancer patients. A replication cohort of 356 Nigerian breast cancer patients was genotyped for 12 recurrent BRCA1/2 mutant alleles (Y101X, 1742insG, 4241delTG, M1775R, 4359insC, C64Y, 1623delTTAAA, Q1090X, and 943ins10 from BRCA1, and 1538delAAGA, 2630del11, and 9045delGAAA from BRCA2) by means of SNaPshot followed by direct sequencing or by direct sequencing alone. In addition, 260 African Americans and 118 Barbadians were genotyped for six of the recurrent BRCA1 mutations by SNaPshot assay. Of all the BRCA1/2 recurrent mutations we identified in the first cohort, six were identified in 11 patients in the replication study. These mutation carriers constitute 3.1 % [95 % Confidence Interval (CI) 1.6-5.5 %] of the replication cohort. By comparison, 6.9 % (95 % CI 4.7-9.7 %) of the discovery cohort carried BRCA1/2 recurrent mutations. For the subset of recurrent mutations we tested in breast cancer cases from Barbados or the United States, only two 943ins10 carriers were identified in African Americans. Nigerian breast cancer patients from Ibadan carry a broad and unique spectrum of BRCA1/2 mutations. Our data suggest that BRCA1/2 mutation testing limited to recurrent mutations is not sufficient to understand the BRCA1/2-associated breast cancer risk in African populations in the diaspora. As the cost of Sanger sequencing is considerably reduced, deploying innovative technologies such as high throughput DNA sequencing of BRCA1/2 and other cancer susceptibility genes will be essential for identifying high-risk individuals and families to reduce the burden of aggressive early onset breast

  5. Association Analysis of WNT10B With Bone Mass and Structure Among Individuals of African Ancestry

    PubMed Central

    Zmuda, Joseph M; Yerges, Laura M; Kammerer, Candace M; Cauley, Jane A; Wang, Xiaojing; Nestlerode, Cara S; Wheeler, Victor W; Patrick, Alan L; Bunker, ClareAnn H; Moffett, Susan P; Ferrell, Robert E

    2009-01-01

    Wnts comprise a family of secreted growth factors that regulate the development and maintenance of many organs. Recently, Wnt10b was shown to stimulate osteoblastogenesis and bone formation in mice. To evaluate further the role of Wnt10b in bone health in humans, we performed bidirectional sequencing of ∼8 kb of the WNT10B gene region in 192 individuals (96 African, 96 white) to identify single nucleotide polymorphisms (SNPs). We identified 19 SNPs with minor allele frequency (MAF) ≥0.01. Ten of these SNPs were not present in the NCBI dbSNP database (build 127), whereas 10 of the 20 SNPs (50%) reported in dbSNP were not verified. We initially genotyped seven tagging SNPs that captured common (MAF ≥ 0.05) variation in the region with r 2 > 0.80 and a potentially functional SNP in exon 5 in 1035 Afro-Caribbean men ≥40 yr of age. Association analysis showed three SNPs in a 3′ region of linkage disequilibrium that were associated with DXA measures of hip BMD. Associations between two of these three SNPs (rs1051886, rs3741627) with hip BMD were replicated in an additional 980 Afro-Caribbean men (p < 0.05), in the combined sample of 2015 men (p ≤ 0.006), and in 416 individuals ≥18 yr of age (mean, 44 yr) belonging to eight extended, multigenerational Afro-Caribbean families with mean family size >50 (3535 relative pairs; p < 0.05). Further analysis showed that rs1051886 and rs3741627 were associated with cortical cross-sectional area, periosteal circumference, and BMC in the radius, such that individuals with the minor alleles had lower biomechanical indices of long-bone bending strength. This analysis implicates the WNT10B locus as a genetic element in the regulation of bone mass and structural geometry. PMID:19016593

  6. Molar proportions of volatile fatty acids in the gastrointestinal tract of East African wild ruminants.

    PubMed

    Clemens, E T; Maloiy, G M; Sutton, J D

    1983-01-01

    The molar proportions of seven individual VFA's were determined at select sites along the gastrointestinal tract of sixteen species of East African wild ruminants. The resulting data were statistically analyzed for species effect, and for effects due to major feeding groups (browsers, grazers, fresh grass grazers, etc.) and for body weight groups (5-750 kg animals). Present data suggest that body weight, rather than diet, is the more influential factor in reticulo-rumen fermentation rate, and in the molar proportion of fatty acids present. The molar proportions of VFA's observed in the mid and hindgut of these wild ruminants appeared more responsive to diet and body weight of the animal than did foregut VFA values. PMID:6139202

  7. Assessment of the Relationship between Self-Declared Ethnicity, Mitochondrial Haplogroups and Genomic Ancestry in Brazilian Individuals

    PubMed Central

    Cardena, Mari M. S. G.; Ribeiro-dos-Santos, Ândrea; Santos, Sidney; Mansur, Alfredo J.; Pereira, Alexandre C.; Fridman, Cintia

    2013-01-01

    In populations that have a high degree of admixture, such as in Brazil, the sole use of ethnicity self-declaration information is not a good method for classifying individuals regarding their ethnicity. Here, we evaluate the relationship of self-declared ethnicities with genomic ancestry and mitochondrial haplogroups in 492 individuals from southeastern Brazil. Mitochondrial haplogroups were obtained by analyzing the hypervariable regions of the mitochondrial DNA (mtDNA), and the genomic ancestry was obtained using 48 autosomal insertion-deletion ancestry informative markers (AIM). Of the 492 individuals, 74.6% self-declared as White, 13.8% as Brown and 10.4% as Black. Classification of the mtDNA haplogroups showed that 46.3% had African mtDNA, and the genomic ancestry analysis showed that the main contribution was European (57.4%). When we looked at the distribution of mtDNA and genomic ancestry according to the self-declared ethnicities from 367 individuals who self-declared as White, 37.6% showed African mtDNA, and they had a high contribution of European genomic ancestry (63.3%) but also a significant contribution of African ancestry (22.2%). Of the 68 individuals who self-declared as Brown, 25% showed Amerindian mtDNA and similar contribution of European and African genomic ancestries. Of the 51 subjects who self-declared as black, 80.4% had African mtDNA, and the main contribution of genomic ancestry was African (55.6%), but they also had a significant proportion of European ancestry (32.1%). The Brazilian population had a uniform degree of Amerindian genomic ancestry, and it was only with the use of genetic markers (autosomal or mitochondrial) that we were able to capture Amerindian ancestry information. Additionally, it was possible to observe a high degree of heterogeneity in the ancestry for both types of genetic markers, which shows the high genetic admixture that is present in the Brazilian population. We suggest that in epidemiological studies, the use

  8. 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

  9. 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

  10. 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

  11. 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

  12. Skin pigmentation, biogeographical ancestry and admixture mapping.

    PubMed

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

    2003-04-01

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

  13. 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. PMID:18622492

  14. Genetic ancestry and risk of mortality among U.S. Latinas with breast cancer

    PubMed Central

    Fejerman, Laura; Hu, Donglei; Huntsman, Scott; John, Esther M.; Stern, Mariana C.; Haiman, Christopher A.; Pérez-Stable, Eliseo J.; Ziv, Elad

    2013-01-01

    Multiple studies have reported that Latina women in the U.S. are diagnosed with breast cancer at more advanced stages and have poorer survival than non-Latina White women. However, Latinas are a heterogeneous group with individuals having different proportions of European, Indigenous American and African genetic ancestry. In this study we evaluated the association between genetic ancestry and survival after breast cancer diagnosis among 899 Latina women from the San Francisco Bay Area. Genetic ancestry was estimated from single nucleotide polymorphisms from an Affymetrix 6.0 array and we used Cox proportional hazards models to evaluate the association between genetic ancestry and breast cancer-specific mortality (tests were two-sided). Women were followed for an average of 9 years during which 75 died from breast cancer. Our results showed that Individuals with higher Indigenous American ancestry had increased risk of breast cancer-specific mortality [hazard ratio (HR): 1.57 per 25% increase in Indigenous American ancestry; 95% confidence interval (CI): 1.08–2.29]. Adjustment for demographic factors, tumor characteristics, and some treatment information did not explain the observed association [HR: 1.75, 95%CI: 1.12–2.74]. In an analysis in which ancestry was dichotomized, the hazard of mortality showed a two-fold increase when comparing women with <50% Indigenous American ancestry to women with ≥50% [HR: 1.89, 95%CI: 1.10–3.24]. This was also reflected by Kaplan-Meier survival estimates (P for Log-Rank test of 0.003). Overall, results suggest that genetic factors and/or unmeasured differences in treatment or access to care should be further explored to understand and reduce ethnic disparities in breast cancer outcomes. PMID:24177181

  15. Genome-wide comparison of African-ancestry populations from CARe and other cohorts reveals signals of natural selection.

    PubMed

    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

    2011-09-01

    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 (F(ST) < 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

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

    PubMed Central

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

    2013-01-01

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

  17. Both serum 25-hydroxyvitamin D and calcium levels may increase the risk of incident prostate cancer in Caribbean men of African ancestry.

    PubMed

    Jackson, Maria D; Tulloch-Reid, Marshall K; Lindsay, Carole M; Smith, Garrett; Bennett, Franklyn I; McFarlane-Anderson, Norma; Aiken, William; Coard, Kathleen C M

    2015-06-01

    Circulating 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with both higher and lower risk of prostate cancer (PCa), whereas elevated levels of circulating calcium has been related to higher risks. However, there are few studies that account for effects of both calcium and 25(OH)D concentrations on incident PCa in a black population. We examined these relationships in a case-control study of men 40-80 years old with newly diagnosed, histologically confirmed PCa in Jamaica, a tropical country. Mean serum calcium concentrations was higher among cases (2.32 ± 0.19 mmol/L) than controls, (2.27 ± 0.30 mmol/L) (P = 0.023) however, there were no differences in 25(OH)D by cancer status (cases, 33.67 ± 12.71 ng/mL; controls (32.25 ± 12.59 ng/mL). Serum calcium was not correlated with 25(OH)D (partial correlation: r, 0.06; P = 0.287). Multivariable-adjusted models showed a positive linear relationship between PCa and serum calcium (OR, 1.12; CI, 1.00-1.25 per 0.1 nmol/L). Serum 25(OH)D concentration also showed a positive association with PCa (OR, 1.23; CI, 1.01-1.49 per 10 ng/mL). The odds of PCa in men with serum 25(OH)D tertile 2 was OR, 2.18; CI, 1.04-4.43 and OR, 2.47 CI, 1.20-4.90 for tertile 3 (P(trend) = 0.013). Dietary intakes of calcium showed no relationship with PCa. Despite the strong relationship between serum calcium and vitamin D the mechanism by which each affects prostate cancer risk in men of African ancestry needs additional investigation. PMID:25858172

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

    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. PMID:24259553

  19. Investigation of the locus near MC4R with childhood obesity in Americans of European and African ancestry.

    PubMed

    Grant, Struan F A; Bradfield, Jonathan P; Zhang, Haitao; Wang, Kai; Kim, Cecilia E; Annaiah, Kiran; Santa, Erin; Glessner, Joseph T; Thomas, Kelly; Garris, Maria; Frackelton, Edward C; Otieno, F George; Shaner, Julie L; Smith, Ryan M; Imielinski, Marcin; Chiavacci, Rosetta M; Li, Mingyao; Berkowitz, Robert I; Hakonarson, Hakon

    2009-07-01

    Recently a modest, but consistently, replicated association was demonstrated between obesity and the single-nucleotide polymorphism (SNP), rs17782313, 3' of the MC4R locus as a consequence of a meta-analysis of genome-wide association (GWA) studies of the disease in white populations. We investigated the association in the context of the childhood form of the disease utilizing data from our ongoing GWA study in a cohort of 728 European-American (EA) obese children (BMI > or =95th percentile) and 3,960 EA controls (BMI <95th percentile), as well as 1,008 African-American (AA) obese children and 2,715 AA controls. rs571312, rs10871777, and rs476828 (perfect surrogates for rs17782313) yielded odds ratios in the EA cohort of 1.142 (P = 0.045), 1.137 (P = 0.054), and 1.145 (P = 0.042); however, there was no significant association with these SNPs in the AA cohort. When investigating all 30 SNPs present on the Illumina BeadChip at this locus, again there was no evidence for association in AA cases when correcting for the number of tests employed. As such, variants 3' to the MC4R locus present on the genotyping platform utilized confer a similar magnitude of risk of obesity in white children as to their adult white counterparts but this observation did not extend to AAs. PMID:19265794

  20. Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP.

    PubMed

    Grant, Struan F A; Li, Mingyao; Bradfield, Jonathan P; Kim, Cecilia E; Annaiah, Kiran; Santa, Erin; Glessner, Joseph T; Casalunovo, Tracy; Frackelton, Edward C; Otieno, F George; Shaner, Julie L; Smith, Ryan M; Imielinski, Marcin; Eckert, Andrew W; Chiavacci, Rosetta M; Berkowitz, Robert I; Hakonarson, Hakon

    2008-01-01

    Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs9939609, within the FTO locus and obesity as a consequence of a genome wide association (GWA) study of type 2 diabetes in adults. We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA). Utilizing data from our ongoing GWA study in our cohort of 418 Caucasian obese children (BMI>or=95th percentile), 2,270 Caucasian controls (BMI<95th percentile), 578 AA obese children and 1,424 AA controls, we investigated the association of the previously reported variation at the FTO locus with the childhood form of this disease in both ethnicities. The minor allele frequencies (MAF) of rs8050136 and rs3751812 (perfect surrogates for rs9939609 i.e. both r(2) = 1) in the Caucasian cases were 0.448 and 0.443 respectively while they were 0.391 and 0.386 in Caucasian controls respectively, yielding for both an odds ratio (OR) of 1.27 (95% CI 1.08-1.47; P = 0.0022). Furthermore, the MAFs of rs8050136 and rs3751812 in the AA cases were 0.449 and 0.115 respectively while they were 0.436 and 0.090 in AA controls respectively, yielding an OR of 1.05 (95% CI 0.91-1.21; P = 0.49) and of 1.31 (95% CI 1.050-1.643; P = 0.017) respectively. Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA. We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation. As such, variants in the FTO gene confer a similar magnitude of risk of obesity to children as to their adult counterparts and appear to have a global impact. PMID:18335027

  1. Population analysis of vitamin D receptor polymorphisms and the role of genetic ancestry in an admixed population

    PubMed Central

    Lins, Tulio C.; Vieira, Rodrigo G.; Grattapaglia, Dario; Pereira, Rinaldo W.

    2011-01-01

    The vitamin D receptor (VDR) is an essential protein related to bone metabolism. Some VDR alleles are differentially distributed among ethnic populations and display variable patterns of linkage disequilibrium (LD). In this study, 200 unrelated Brazilians were genotyped using 21 VDR single nucleotide polymorphisms (SNPs) and 28 ancestry informative markers. The patterns of LD and haplotype distribution were compared among Brazilian and the HapMap populations of African (YRI), European (CEU) and Asian (JPT+CHB) origins. Conditional regression and haplotype-specific analysis were performed using estimates of individual genetic ancestry in Brazilians as a quantitative trait. Similar patterns of LD were observed in the 5′ and 3′ gene regions. However, the frequency distribution of haplotype blocks varied among populations. Conditional regression analysis identified haplotypes associated with European and Amerindian ancestry, but not with the proportion of African ancestry. Individual ancestry estimates were associated with VDR haplotypes. These findings reinforce the need to correct for population stratification when performing genetic association studies in admixed populations. PMID:21931507

  2. Both serum 25-hydroxyvitamin D and calcium levels may increase the risk of incident prostate cancer in Caribbean men of African ancestry

    PubMed Central

    Jackson, Maria D; Tulloch-Reid, Marshall K; Lindsay, Carole M; Smith, Garrett; Bennett, Franklyn I; McFarlane-Anderson, Norma; Aiken, William; Coard, Kathleen C M

    2015-01-01

    Circulating 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with both higher and lower risk of prostate cancer (PCa), whereas elevated levels of circulating calcium has been related to higher risks. However, there are few studies that account for effects of both calcium and 25(OH)D concentrations on incident PCa in a black population. We examined these relationships in a case–control study of men 40–80 years old with newly diagnosed, histologically confirmed PCa in Jamaica, a tropical country. Mean serum calcium concentrations was higher among cases (2.32 ± 0.19 mmol/L) than controls, (2.27 ± 0.30 mmol/L) (P = 0.023) however, there were no differences in 25(OH)D by cancer status (cases, 33.67 ± 12.71 ng/mL; controls (32.25 ± 12.59 ng/mL). Serum calcium was not correlated with 25(OH)D (partial correlation: r, 0.06; P = 0.287). Multivariable-adjusted models showed a positive linear relationship between PCa and serum calcium (OR, 1.12; CI, 1.00–1.25 per 0.1 nmol/L). Serum 25(OH)D concentration also showed a positive association with PCa (OR, 1.23; CI, 1.01–1.49 per 10 ng/mL). The odds of PCa in men with serum 25(OH)D tertile 2 was OR, 2.18; CI, 1.04–4.43 and OR, 2.47 CI, 1.20–4.90 for tertile 3 (Ptrend = 0.013). Dietary intakes of calcium showed no relationship with PCa. Despite the strong relationship between serum calcium and vitamin D the mechanism by which each affects prostate cancer risk in men of African ancestry needs additional investigation. PMID:25858172

  3. Results from a Prostate Cancer Admixture Mapping Study in African American Men

    PubMed Central

    Bock, Cathryn H.; 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.

    2010-01-01

    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. PMID:19568772

  4. African and non-African admixture components in African Americans and an African Caribbean population.

    PubMed

    Murray, Tanda; Beaty, Terri H; Mathias, Rasika A; Rafaels, Nicholas; Grant, Audrey Virginia; Faruque, Mezbah U; Watson, Harold R; Ruczinski, Ingo; Dunston, Georgia M; Barnes, Kathleen C

    2010-09-01

    Admixture is a potential source of confounding in genetic association studies, so it becomes important to detect and estimate admixture in a sample of unrelated individuals. Populations of African descent in the US and the Caribbean share similar historical backgrounds but the distributions of African admixture may differ. We selected 416 ancestry informative markers (AIMs) to estimate and compare admixture proportions using STRUCTURE in 906 unrelated African Americans (AAs) and 294 Barbadians (ACs) from a study of asthma. This analysis showed AAs on average were 72.5% African, 19.6% European and 8% Asian, while ACs were 77.4% African, 15.9% European, and 6.7% Asian which were significantly different. A principal components analysis based on these AIMs yielded one primary eigenvector that explained 54.04% of the variation and captured a gradient from West African to European admixture. This principal component was highly correlated with African vs. European ancestry as estimated by STRUCTURE (r(2)=0.992, r(2)=0.912, respectively). To investigate other African contributions to African American and Barbadian admixture, we performed PCA on approximately 14,000 (14k) genome-wide SNPs in AAs, ACs, Yorubans, Luhya and Maasai African groups, and estimated genetic distances (F(ST)). We found AAs and ACs were closest genetically (F(ST)=0.008), and both were closer to the Yorubans than the other East African populations. In our sample of individuals of African descent, approximately 400 well-defined AIMs were just as good for detecting substructure as approximately 14,000 random SNPs drawn from a genome-wide panel of markers. PMID:20717976

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    Pool, John E.

    2015-01-01

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

  7. 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

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

    PubMed

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

    2011-10-01

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

  9. Genomic ancestry evaluated by ancestry-informative markers in patients with sickle cell disease.

    PubMed

    Nascimento, A F; Oliveira, J S; Silva Junior, J C; Barbosa, A A L

    2016-01-01

    The β(s) mutation is responsible for the most aggressive form of sickle cell disease, has a predominantly African origin, and arrived in Brazil through the slave trade. However, the Brazilian population is highly miscegenated, underscoring the importance of ancestry-informative markers (AIMs) for the identification of the genetic structure of a population. In this study, we have estimated the genetic contributions of various ethnicities in individuals with sickle cell disease in the microregion of Jequié, Bahia, in Brazil, by using AIMs, and compared the findings to those from a phenotypic characterization. Eight AIMs were analyzed: AT3 (rs3138521), DRD2 (rs1079598), APO (rs3138522), PV92, Sb19.3 (rs3138524), CKM (rs4884), LPL (rs285), and CCR5Δ32 (rs333). Samples were subjected to polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism. The amplified products were electrophoresed on agarose gels, and the data were statistically analyzed using Genepop, FSTAT 2.9, and Admix3. Phenotypic classification showed a high frequency of mulattos  (85%) in the Brazilian population; however, ancestry-informative markers indicated that 44, 42, and 11% of the population had European, African, and native American ancestries, respectively. The phenotypic classification is justified as a complementary method for the characterization of the genetic ancestry in patients with sickle cell disease, as it confirms the molecular findings regarding ancestry. PMID:27051031

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. The History of African Gene Flow into Southern Europeans, Levantines, and Jews

    PubMed Central

    Moorjani, Priya; Patterson, Nick; Hirschhorn, Joel N.; Keinan, Alon; Hao, Li; Atzmon, Gil; Burns, Edward; Ostrer, Harry; Price, Alkes L.; Reich, David

    2011-01-01

    Previous genetic studies have suggested a history of sub-Saharan African gene flow into some West Eurasian populations after the initial dispersal out of Africa that occurred at least 45,000 years ago. However, there has been no accurate characterization of the proportion of mixture, or of its date. We analyze genome-wide polymorphism data from about 40 West Eurasian groups to show that almost all Southern Europeans have inherited 1%–3% African ancestry with an average mixture date of around 55 generations ago, consistent with North African gene flow at the end of the Roman Empire and subsequent Arab migrations. Levantine groups harbor 4%–15% African ancestry with an average mixture date of about 32 generations ago, consistent with close political, economic, and cultural links with Egypt in the late middle ages. We also detect 3%–5% sub-Saharan African ancestry in all eight of the diverse Jewish populations that we analyzed. For the Jewish admixture, we obtain an average estimated date of about 72 generations. This may reflect descent of these groups from a common ancestral population that already had some African ancestry prior to the Jewish Diasporas. PMID:21533020

  17. The history of African gene flow into Southern Europeans, Levantines, and Jews.

    PubMed

    Moorjani, Priya; Patterson, Nick; Hirschhorn, Joel N; Keinan, Alon; Hao, Li; Atzmon, Gil; Burns, Edward; Ostrer, Harry; Price, Alkes L; Reich, David

    2011-04-01

    Previous genetic studies have suggested a history of sub-Saharan African gene flow into some West Eurasian populations after the initial dispersal out of Africa that occurred at least 45,000 years ago. However, there has been no accurate characterization of the proportion of mixture, or of its date. We analyze genome-wide polymorphism data from about 40 West Eurasian groups to show that almost all Southern Europeans have inherited 1%-3% African ancestry with an average mixture date of around 55 generations ago, consistent with North African gene flow at the end of the Roman Empire and subsequent Arab migrations. Levantine groups harbor 4%-15% African ancestry with an average mixture date of about 32 generations ago, consistent with close political, economic, and cultural links with Egypt in the late middle ages. We also detect 3%-5% sub-Saharan African ancestry in all eight of the diverse Jewish populations that we analyzed. For the Jewish admixture, we obtain an average estimated date of about 72 generations. This may reflect descent of these groups from a common ancestral population that already had some African ancestry prior to the Jewish Diasporas. PMID:21533020

  18. Archaic human ancestry in East Asia.

    PubMed

    Skoglund, Pontus; Jakobsson, Mattias

    2011-11-01

    Recent studies of ancient genomes have suggested that gene flow from archaic hominin groups to the ancestors of modern humans occurred on two separate occasions during the modern human expansion out of Africa. At the same time, decreasing levels of human genetic diversity have been found at increasing distance from Africa as a consequence of human expansion out of Africa. We analyzed the signal of archaic ancestry in modern human populations, and we investigated how serial founder models of human expansion affect the signal of archaic ancestry using simulations. For descendants of an archaic admixture event, we show that genetic drift coupled with ascertainment bias for common alleles can cause artificial but largely predictable differences in similarity to archaic genomes. In genotype data from non-Africans, this effect results in a biased genetic similarity to Neandertals with increasing distance from Africa. However, in addition to the previously reported gene flow between Neandertals and non-Africans as well as gene flow between an archaic human population from Siberia ("Denisovans") and Oceanians, we found a significant affinity between East Asians, particularly Southeast Asians, and the Denisova genome--a pattern that is not expected under a model of solely Neandertal admixture in the ancestry of East Asians. These results suggest admixture between Denisovans or a Denisova-related population and the ancestors of East Asians, and that the history of anatomically modern and archaic humans might be more complex than previously proposed. PMID:22042846

  19. 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

  20. 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

  1. AncesTrees: ancestry estimation with randomized decision trees.

    PubMed

    Navega, David; Coelho, Catarina; Vicente, Ricardo; Ferreira, Maria Teresa; Wasterlain, Sofia; Cunha, Eugénia

    2015-09-01

    In forensic anthropology, ancestry estimation is essential in establishing the individual biological profile. The aim of this study is to present a new program--AncesTrees--developed for assessing ancestry based on metric analysis. AncesTrees relies on a machine learning ensemble algorithm, random forest, to classify the human skull. In the ensemble learning paradigm, several models are generated and co-jointly used to arrive at the final decision. The random forest algorithm creates ensembles of decision trees classifiers, a non-linear and non-parametric classification technique. The database used in AncesTrees is composed by 23 craniometric variables from 1,734 individuals, representative of six major ancestral groups and selected from the Howells' craniometric series. The program was tested in 128 adult crania from the following collections: the African slaves' skeletal collection of Valle da Gafaria; the Medical School Skull Collection and the Identified Skeletal Collection of 21st Century, both curated at the University of Coimbra. The first step of the test analysis was to perform ancestry estimation including all the ancestral groups of the database. The second stage of our test analysis was to conduct ancestry estimation including only the European and the African ancestral groups. In the first test analysis, 75% of the individuals of African ancestry and 79.2% of the individuals of European ancestry were correctly identified. The model involving only African and European ancestral groups had a better performance: 93.8% of all individuals were correctly classified. The obtained results show that AncesTrees can be a valuable tool in forensic anthropology. PMID:25053239

  2. Uniparental ancestry markers in Chilean populations.

    PubMed

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

    2016-08-01

    The presence of Native Americans, Europeans, and Africans has led to the development of a multi-ethnic, admixed population in Chile. This study aimed to contribute to the characterization of the uniparental genetic structure of three Chilean regions. Newborns from seven hospitals in Independencia, Providencia, Santiago, Curicó, Cauquenes, Valdívia, and Puerto Montt communes, belonging to the Chilean regions of Santiago, Maule, and Los Lagos, were studied. The presence of Native American mitochondrial DNA (mtDNA) haplogroups and two markers present in the non-recombinant region of the Y chromosome, DYS199 and DYS287, indicative of Native American and African ancestry, respectively, was determined. A high Native American matrilineal contribution and a low Native American and African patrilineal contributions were found in all three studied regions. As previously found in Chilean admixed populations, the Native American matrilineal contribution was lower in Santiago than in the other studied regions. However, there was an unexpectedly higher contribution of Native American ancestry in one of the studied communes in Santiago, probably due to the high rate of immigration from other regions of the country. The population genetic sub-structure we detected in Santiago using few uniparental markers requires further confirmation, owing to possible stratification for autosomal and X-chromosome markers. PMID:27494198

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

    PubMed Central

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

    2015-01-01

    Motivation: A basic problem of broad public and scientific interest is to use the DNA of an individual to infer the genomic ancestries of the parents. In particular, we are often interested in the fraction of each parent’s genome that comes from specific ancestries (e.g. European, African, Native American, etc). This has many applications ranging from understanding the inheritance of ancestry-related risks and traits to quantifying human assortative mating patterns. Results: We model the problem of parental genomic ancestry inference as a pooled semi-Markov process. We develop a general mathematical framework for pooled semi-Markov processes and construct efficient inference algorithms for these models. Applying our inference algorithm to genotype data from 231 Mexican trios and 258 Puerto Rican trios where we have the true genomic ancestry of each parent, we demonstrate that our method accurately infers parameters of the semi-Markov processes and parents’ genomic ancestries. We additionally validated the method on simulations. Our model of pooled semi-Markov process and inference algorithms may be of independent interest in other settings in genomics and machine learning. Contact: jazo@microsoft.com PMID:26072482

  4. [The selection of 30 ancestry informative markers and its application in ancestry inference].

    PubMed

    Li, Caixia; Jia, Jing; Wei, Yiliang; Wan, Lihua; Hu, Lan; Ye, Jiang

    2014-08-01

    A panel of ancestry informative markers (AIMs) can be used to describe the genetic components of a population and infer the ancestral origin of a DNA sample. In this study, we selected 30 AIMs from 282 SNPs screened from 30 phenotype-related genes based on the genotyping data of 658 samples from nine populations in the HapMap database. Then,a multiplex assay was developed based on micro-sequencing general chip technologies, and a population allele frequency database was established. This system was utilized to ascertain the origin of subjects from East Asian, European, and African.First, 658 HapMap samples were analyzed using this panel of AIMs, and then 194 unrelated DNA samples from five populations were used for further validation of the system. Finally, population genetic components and individual genetic composition were generated using Structure software, and individual ancestry inferences were made. The 30-AIM assay was well balanced for Hardy-Weinberg equilibrium (P > 0.01), and there was no linkage disequilibrium (l < 0.1). Ancestry component analyses for the 658 HapMap samples and 194 recruited samples were consistent with their known origins. The established panel filtered and developed by the 30 AIMs can be applied to analyze the genetic components of Asian, European,and African populations, as well as individual genetic composition. PMID:25143275

  5. Unravelling the hidden ancestry of American admixed populations

    PubMed Central

    Montinaro, Francesco; Busby, George B.J.; Pascali, Vincenzo L.; Myers, Simon; Hellenthal, Garrett; Capelli, Cristian

    2015-01-01

    The movement of people into the Americas has brought different populations into contact, and contemporary American genomes are the product of a range of complex admixture events. Here we apply a haplotype-based ancestry identification approach to a large set of genome-wide SNP data from a variety of American, European and African populations to determine the contributions of different ancestral populations to the Americas. Our results provide a fine-scale characterization of the source populations, identify a series of novel, previously unreported contributions from Africa and Europe and highlight geohistorical structure in the ancestry of American admixed populations. PMID:25803618

  6. 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

  7. 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. PMID:26984822

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

    PubMed Central

    Salam, Muhammad T.; Avoundjian, Tigran; Knight, Wendy M.; Gilliland, Frank D.

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    The association between a geographical region and an mtDNA haplogroup(s) has provided the basis for using mtDNA haplogroups to infer an individual’s place of origin and genetic ancestry. Although it is well known that ancestry inferences using mtDNA haplogroups and those using genome-wide markers are frequently discrepant, little empirical information exists on the magnitude and scope of such discrepancies between multiple mtDNA haplogroups and worldwide populations. We compared genetic-ancestry inferences made by mtDNA-haplogroup membership to those made by autosomal SNPs in ∼940 samples of the Human Genome Diversity Panel and recently admixed populations from the 1000 Genomes Project. Continental-ancestry proportions often varied widely among individuals sharing the same mtDNA haplogroup. For only half of mtDNA haplogroups did the highest average continental-ancestry proportion match the highest continental-ancestry proportion of a majority of individuals with that haplogroup. Prediction of an individual’s mtDNA haplogroup from his or her continental-ancestry proportions was often incorrect. Collectively, these results indicate that for most individuals in the worldwide populations sampled, mtDNA-haplogroup membership provides limited information about either continental ancestry or continental region of origin. PMID:25620206

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

    PubMed Central

    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

  11. 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

  12. Copy number variation signature to predict human ancestry

    PubMed Central

    2012-01-01

    Background Copy number variations (CNVs) are genomic structural variants that are found in healthy populations and have been observed to be associated with disease susceptibility. Existing methods for CNV detection are often performed on a sample-by-sample basis, which is not ideal for large datasets where common CNVs must be estimated by comparing the frequency of CNVs in the individual samples. Here we describe a simple and novel approach to locate genome-wide CNVs common to a specific population, using human ancestry as the phenotype. Results We utilized our previously published Genome Alteration Detection Analysis (GADA) algorithm to identify common ancestry CNVs (caCNVs) and built a caCNV model to predict population structure. We identified a 73 caCNV signature using a training set of 225 healthy individuals from European, Asian, and African ancestry. The signature was validated on an independent test set of 300 individuals with similar ancestral background. The error rate in predicting ancestry in this test set was 2% using the 73 caCNV signature. Among the caCNVs identified, several were previously confirmed experimentally to vary by ancestry. Our signature also contains a caCNV region with a single microRNA (MIR270), which represents the first reported variation of microRNA by ancestry. Conclusions We developed a new methodology to identify common CNVs and demonstrated its performance by building a caCNV signature to predict human ancestry with high accuracy. The utility of our approach could be extended to large case–control studies to identify CNV signatures for other phenotypes such as disease susceptibility and drug response. PMID:23270563

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

    PubMed Central

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

    2014-01-01

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

  14. Genetic ancestries in northwest Cambodia.

    PubMed

    Black, M L; Dufall, K; Wise, C; Sullivan, S; Bittles, A H

    2006-01-01

    A survey of the genetic ancestry of 125 Cambodian children resident in Siem Reap province was undertaken, based on eight Y-chromosome binary polymorphisms and sequencing of the mtDNA HV1 region. The data indicated a largely East Asian paternal ancestry and a local Southeast Asian maternal ancestry. The presence of Y-chromosomes P* and R1al* was suggestive of a small but significant Indo-European male ancestral component, which probably reflects the history of Indian, and later European, influences on Cambodia. PMID:17381059

  15. 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

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

    PubMed

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

    2015-12-15

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

  17. 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

  18. 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

  19. Biogeographical ancestry and race.

    PubMed

    Gannett, Lisa

    2014-09-01

    The use of racial and ethnic categories in biological and biomedical research is controversial-for example, in the comparison of disease risk in different groups or as a means of making use of or controlling for population structure in the mapping of genes to chromosomes. Biogeographical ancestry (BGA) has been recommended as a more accurate and appropriate category. BGA is a product of the collaboration between biological anthropologist Mark Shriver from Pennsylvania State University and molecular biologist Tony Frudakis from the now-defunct biotechnology start-up company DNAPrint genomics, Inc. Shriver and Frudakis portray BGA as a measure of the 'biological', 'genetic', 'natural', and 'objective' components of race and ethnicity, what philosophers of science would call a natural kind. This paper argues that BGA is not a natural kind that escapes social and political connotations of race and ethnicity, as Shriver and Frudakis and other proponents believe, but a construction that is built upon race-as race has been socially constructed in the European scientific and philosophical traditions. More specifically, BGA is not a global category of biological and anthropological classification but a local category shaped by the U.S. context of its production, especially the forensic aim of being able to predict the race or ethnicity of an unknown suspect based on DNA found at the crime scene. Therefore, caution needs to be exercised in the embrace of BGA as an alternative to the use of racial and ethnic categories in biological and biomedical research. PMID:24989973

  20. Modern human ancestry at the peripheries: a test of the replacement theory.

    PubMed

    Wolpoff, M H; Hawks, J; Frayer, D W; Hunley, K

    2001-01-12

    The replacement theory of modern human origins stipulates that populations outside of Africa were replaced by a new African species of modern humans. Here we test the replacement theory in two peripheral areas far from Africa by examining the ancestry of early modern Australians and Central Europeans. Analysis of pairwise differences was used to determine if dual ancestry in local archaic populations and earlier modern populations from the Levant and/or Africa could be rejected. The data imply that both have a dual ancestry. The diversity of recent humans cannot result exclusively from a single Late Pleistocene dispersal. PMID:11209077

  1. Proportional Reasoning.

    ERIC Educational Resources Information Center

    Miller, Jane Lincoln; Fey, James T.

    2000-01-01

    Explores strategies to encourage students' understanding of proportional reasoning. Conducts a study to compare the proportional reasoning of students studying one of the new standards-based curricula with that of students from a control group. (ASK)

  2. 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

  3. 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

  4. 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

  5. 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.

  6. CoAIMs: A Cost-Effective Panel of Ancestry Informative Markers for Determining Continental Origins

    PubMed Central

    Londin, Eric R.; Keller, Margaret A.; Maista, Cathleen; Smith, Gretchen; Mamounas, Laura A.; Zhang, Ran; Madore, Steven J.; Gwinn, Katrina; Corriveau, Roderick A.

    2010-01-01

    Background Genetic ancestry is known to impact outcomes of genotype-phenotype studies that are designed to identify risk for common diseases in human populations. Failure to control for population stratification due to genetic ancestry can significantly confound results of disease association studies. Moreover, ancestry is a critical factor in assessing lifetime risk of disease, and can play an important role in optimizing treatment. As modern medicine moves towards using personal genetic information for clinical applications, it is important to determine genetic ancestry in an accurate, cost-effective and efficient manner. Self-identified race is a common method used to track and control for population stratification; however, social constructs of race are not necessarily informative for genetic applications. The use of ancestry informative markers (AIMs) is a more accurate method for determining genetic ancestry for the purposes of population stratification. Methodology/Principal Findings Here we introduce a novel panel of 36 microsatellite (MSAT) AIMs that determines continental admixture proportions. This panel, which we have named Continental Ancestry Informative Markers or CoAIMs, consists of MSAT AIMs that were chosen based upon their measure of genetic variance (Fst), allele frequencies and their suitability for efficient genotyping. Genotype analysis using CoAIMs along with a Bayesian clustering method (STRUCTURE) is able to discern continental origins including Europe/Middle East (Caucasians), East Asia, Africa, Native America, and Oceania. In addition to determining continental ancestry for individuals without significant admixture, we applied CoAIMs to ascertain admixture proportions of individuals of self declared race. Conclusion/Significance CoAIMs can be used to efficiently and effectively determine continental admixture proportions in a sample set. The CoAIMs panel is a valuable resource for genetic researchers performing case-control genetic

  7. 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

  8. 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

  9. Genome-Wide Linkage Scan for Primary Open Angle Glaucoma: Influences of Ancestry and Age at Diagnosis

    PubMed Central

    Qin, Xuejun; Liu, Yutao; Gibson, Jason R.; Santiago-Turla, Cecilia; Larocque-Abramson, Karen R.; Del Bono, Elizabeth; Challa, Pratap; Herndon, Leon W.; Akafo, Stephen; Wiggs, Janey L.; Schmidt, Silke; Hauser, Michael A.

    2011-01-01

    Primary open-angle glaucoma (POAG) is the most common form of glaucoma and one of the leading causes of vision loss worldwide. The genetic etiology of POAG is complex and poorly understood. The purpose of this work is to identify genomic regions of interest linked to POAG. This study is the largest genetic linkage study of POAG performed to date: genomic DNA samples from 786 subjects (538 Caucasian ancestry, 248 African ancestry) were genotyped using either the Illumina GoldenGate Linkage 4 Panel or the Illumina Infinium Human Linkage-12 Panel. A total of 5233 SNPs was analyzed in 134 multiplex POAG families (89 Caucasian ancestry, 45 African ancestry). Parametric and non-parametric linkage analyses were performed on the overall dataset and within race-specific datasets (Caucasian ancestry and African ancestry). Ordered subset analysis was used to stratify the data on the basis of age of glaucoma diagnosis. Novel linkage regions were identified on chromosomes 1 and 20, and two previously described loci—GLC1D on chromosome 8 and GLC1I on chromosome 15—were replicated. These data will prove valuable in the context of interpreting results from genome-wide association studies for POAG. PMID:21765929

  10. Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia.

    PubMed

    Yang, Jun J; Cheng, Cheng; Devidas, Meenakshi; Cao, Xueyuan; Fan, Yiping; Campana, Dario; Yang, Wenjian; Neale, Geoff; Cox, Nancy J; Scheet, Paul; Borowitz, Michael J; Winick, Naomi J; Martin, Paul L; Willman, Cheryl L; Bowman, W Paul; Camitta, Bruce M; Carroll, Andrew; Reaman, Gregory H; Carroll, William L; Loh, Mignon; Hunger, Stephen P; Pui, Ching-Hon; Evans, William E; Relling, Mary V

    2011-03-01

    Although five-year survival rates for childhood acute lymphoblastic leukemia (ALL) are now over 80% in most industrialized countries, not all children have benefited equally from this progress. Ethnic differences in survival after childhood ALL have been reported in many clinical studies, with poorer survival observed among African Americans or those with Hispanic ethnicity when compared with European Americans or Asians. The causes of ethnic differences remain uncertain, although both genetic and non-genetic factors are likely important. Interrogating genome-wide germline SNP genotypes in an unselected large cohort of children with ALL, we observed that the component of genomic variation that co-segregated with Native American ancestry was associated with risk of relapse (P = 0.0029) even after adjusting for known prognostic factors (P = 0.017). Ancestry-related differences in relapse risk were abrogated by the addition of a single extra phase of chemotherapy, indicating that modifications to therapy can mitigate the ancestry-related risk of relapse. PMID:21297632

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

    PubMed

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

    2010-09-01

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

  12. 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

  13. Analysis of paternal lineages in Brazilian and African populations

    PubMed Central

    2010-01-01

    The present-day Brazilian population is a consequence of the admixture of various peoples of very different origins, namely, Amerindians, Europeans and Africans. The proportion of each genetic contribution is known to be very heterogeneous throughout the country. The aim of the present study was to compare the male lineages present in two distinct Brazilian populations, as well as to evaluate the African contribution to their male genetic substrate. Thus, two Brazilian population samples from Manaus (State of Amazon) and Ribeirão Preto (State of São Paulo) and three African samples from Guinea Bissau, Angola and Mozambique were typed for a set of nine Y chromosome specific STRs. The data were compared with those from African, Amerindian and European populations. By using Y-STR haplotype information, low genetic distances were found between the Manaus and Ribeirão Preto populations, as well as between these and others from Iberia. Likewise, no significant distances were observed between any of the African samples from Angola, Mozambique and Guinea Bissau. Highly significant Rst values were found between both Brazilian samples and all the African and Amerindian populations. The absence of a significant Sub-Saharan African male component resulting from the slave trade, and the low frequency in Amerindian ancestry Y-lineages in the Manaus and Ribeirão Preto population samples are in accordance with the accentuated gender asymmetry in admixture processes that has been systematically reported in colonial South American populations. PMID:21637407

  14. The Ancestry of Brazilian mtDNA Lineages

    PubMed Central

    Alves-Silva, Juliana; da Silva Santos, Magda; Guimarães, Pedro E. M.; Ferreira, Alessandro C. S.; Bandelt, Hans-Jürgen; Pena, Sérgio D. J.; Prado, Vania Ferreira

    2000-01-01

    We have analyzed 247 Brazilian mtDNAs for hypervariable segment (HVS)–I and selected restriction fragment-length–polymorphism sites, to assess their ancestry in different continents. The total sample showed nearly equal amounts of Native American, African, and European matrilineal genetic contribution but with regional differences within Brazil. The mtDNA pool of present-day Brazilians clearly reflects the imprints of the early Portuguese colonization process (involving directional mating), as well as the recent immigrant waves (from Europe) of the last century. The subset of 99 mtDNAs from the southeastern region encompasses nearly all mtDNA haplogroups observed in the total Brazilian sample; for this regional subset, HVS-II was analyzed, providing, in particular, some novel details of the African mtDNA phylogeny. PMID:10873790

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

    PubMed

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

    2013-09-01

    In order to investigate the underlying genetic structure and genomic ancestry proportions of Peruvian subpopulations, we analyzed 551 human samples of 25 localities from the Andean, Amazonian, and Coastal regions of Peru with a set of 40 ancestry informative insertion-deletion polymorphisms. Using genotypes of reference populations from different continents for comparison, our analysis indicated that populations from all 25 Peruvian locations had predominantly Amerindian genetic ancestry. Among populations from the Titicaca Lake islands of Taquile, Amantani, Anapia, and Uros, and the Yanque locality from the southern Peruvian Andes, there was no significant proportion of non-autochthonous genomes, indicating that their genetic background is effectively derived from the first settlers of South America. However, the Andean populations from San Marcos, Cajamarca, Characato and Chogo, and coastal populations from Lambayeque and Lima displayed a low but significant European ancestry proportion. Furthermore, Amazonian localities of Pucallpa, Lamas, Chachapoyas, and Andean localities of Ayacucho and Huancayo displayed intermediate levels of non-autochthonous ancestry, mostly from Europe. These results are in close agreement with the documented history of post-Columbian immigrations in Peru and with several reports suggesting a larger effective size of indigenous inhabitants during the formation of the current country's population. PMID:23863748

  16. 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

  17. 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

  18. Evaluating Self-declared Ancestry of U.S. Americans with Autosomal, Y-chromosomal and Mitochondrial DNA

    PubMed Central

    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

    2010-01-01

    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. © 2010 Wiley-Liss, Inc. PMID:20886636

  19. 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

  20. 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

  1. 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

  2. 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. PMID:25833170

  3. 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. PMID:26259114

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

    PubMed

    Zhang, Jianqi; Stram, Daniel O

    2014-09-01

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

  5. 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

  6. 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

  7. To what extent does genealogical ancestry imply genetic ancestry?

    PubMed

    Matsen, Frederick A; Evans, Steven N

    2008-09-01

    Recent statistical and computational analyses have shown that a genealogical most recent common ancestor (MRCA) may have lived in the recent past [Chang, J.T., 1999. Recent common ancestors of all present-day individuals. Adv. Appl. Probab. 31, 1002-1026. 1027-1038; Rohde, D.L.T., Olson, S., Chang, J.T., 2004. Modelling the recent common ancestry of all living humans. Nature 431, 562-566]. However, coalescent-based approaches show that genetic most recent common ancestors for a given non-recombining locus are typically much more ancient [Kingman, J.F.C., 1982a. The coalescent. Stochastic Process Appl. 13, 235-248; Kingman, J.F.C., 1982b. On the genealogy of large populations. J. Appl. Probab. 19A, 27-43]. It is not immediately clear how these two perspectives interact. This paper investigates relationships between the number of descendant alleles of an ancestor allele and the number of genealogical descendants of the individual who possessed that allele for a simple diploid genetic model extending the genealogical model of [Chang, J.T., 1999. Recent common ancestors of all present-day individuals. Adv. Appl. Probab. 31, 1002-1026. 1027-1038]. PMID:18634815

  8. Early hominin limb proportions.

    PubMed

    Richmond, Brian G; Aiello, Leslie C; Wood, Bernard A

    2002-10-01

    Recent analyses and new fossil discoveries suggest that the evolution of hominin limb length proportions is complex, with evolutionary reversals and a decoupling of proportions within and between limbs. This study takes into account intraspecific variation to test whether or not the limb proportions of four early hominin associated skeletons (AL 288-1, OH 62, BOU-VP-12/1, and KNM-WT 15000) can be considered to be significantly different from one another. Exact randomization methods were used to compare the differences between pairs of fossil skeletons to the differences observed between all possible pairs of individuals within large samples of Gorilla gorilla, Pan troglodytes, Pongo pygmaeus, and Homo sapiens. Although the difference in humerofemoral proportions between OH 62 and AL 288-1 does not exceed variation in the extant samples, it is rare. When humerofemoral midshaft circumferences are compared, the difference between OH 62 and AL 288-1 is fairly common in extant species. This, in combination with error associated with the limb lengths estimates, suggests that it may be premature to consider H. (or Australopithecus) habilis as having more apelike limb proportions than those in A. afarensis. The humerofemoral index of BOU-VP-12/1 differs significantly from both OH 62 and AL 288-1, but not from KNM-WT 15000. Published length estimates, if correct, suggest that the relative forearm length of BOU-VP-12/1 is unique among hominins, exceeding those of the African apes and resembling the proportions in Pongo. Evidence that A. afarensis exhibited a less apelike upper:lower limb design than A. africanus (and possibly H. habilis) suggests that, if A. afarensis is broadly ancestral to A. africanus, the latter did not simply inherit primitive morphology associated with arboreality, but is derived in this regard. The fact that the limb proportions of OH 62 (and possibly KNM-ER 3735) are no more human like than those of AL 288-1 underscores the primitive body design of H

  9. 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

  10. 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

  11. 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

  12. Women of African Descent: Persistence in Completing Doctorates

    ERIC Educational Resources Information Center

    Iddrisu, Vannetta Bailey

    2010-01-01

    This study examines the educational persistence of women of African descent (WOAD) in pursuit of a doctorate degree at universities in the southeastern United States. WOAD are women of African ancestry born outside the African continent. These women are heirs to an inner dogged determination and spirit to survive despite all odds (Pulliam, 2003,…

  13. 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

  14. 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

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

    PubMed

    Hall, Jacob B; Dumitrescu, Logan; Dilks, Holli H; Crawford, Dana C; Bush, William S

    2014-01-01

    Recently, the development of biobanks linked to electronic medical records has presented new opportunities for genetic and epidemiological research. Studies based on these resources, however, present unique challenges, including the accurate assignment of individual-level population ancestry. In this work we examine the accuracy of administratively-assigned race in diverse populations by comparing assigned races to genetically-defined ancestry estimates. Using 220 ancestry informative markers, we generated principal components for patients in our dataset, which were used to cluster patients into groups based on genetic ancestry. Consistent with other studies, we find a strong overall agreement (Kappa  = 0.872) between genetic ancestry and assigned race, with higher rates of agreement for African-descent and European-descent assignments, and reduced agreement for Hispanic, East Asian-descent, and South Asian-descent assignments. These results suggest caution when selecting study samples of non-African and non-European backgrounds when administratively-assigned race from biobanks is used. PMID:24896101

  16. 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

  17. 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

  18. 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

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

    PubMed

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

    2015-01-01

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

  20. 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

  1. 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

  2. Vitamin D in African Americans with multiple sclerosis

    PubMed Central

    Gelfand, J.M.; Cree, B.A.C.; McElroy, J.; Oksenberg, J.; Green, R.; Mowry, E.M.; Miller, J.W.; Hauser, S.L.

    2011-01-01

    Objective: To evaluate whether vitamin D is associated with multiple sclerosis (MS) status and disease severity in African Americans. Methods: Serum 25-hydroxyvitamin D was compared in a cross-sectional sample of 339 African Americans with MS and 342 African American controls. Correlations between disease severity (Multiple Sclerosis Severity Score [MSSS]) and 25-hydroxyvitamin D levels were sought. Results: A total of 71% of controls and 77% of patients with MS were vitamin D deficient (<50 nmol/L; <20 ng/mL), and 93% of controls and 94% of patients with MS were vitamin D insufficient (<75 nmol/L; <30 ng/mL). Median unadjusted (29.7 vs 36.6 nmol/L, p = 0.0001) and deseasonalized (p = 0.0013) 25-hydroxyvitamin D levels were lower in the MS group. Multivariable analysis revealed that differences in latitude and ultraviolet index accounted for much of this association. The median (interquartile range) MSSS was 6.1 (4.8–8.1). There was no apparent association between the MSSS and vitamin D status. A greater proportion of European genetic ancestry, a measure of genetic admixture, was positively correlated with 25-hydroxyvitamin D (p = 0.007). Conclusions: Levels of 25-hydroxyvitamin D were lower in African Americans with MS than controls, an observation primarily explained by differences in climate and geography. There was no apparent association between vitamin D status and disease severity. These results are consistent with observations in other populations that lower 25-hydroxyvitamin D is associated with having MS, but also highlight the importance of climate and ancestry in determining vitamin D status. PMID:21606454

  3. 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

  4. 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

  5. Susceptibility loci for heroin and cocaine addiction in the serotonergic and adrenergic pathways in populations of different ancestry

    PubMed Central

    Levran, Orna; Peles, Einat; Randesi, Matthew; Correa da Rosa, Joel; Ott, Jurg; Rotrosen, John; Adelson, Miriam; Kreek, Mary Jeanne

    2016-01-01

    Background Drug addiction is influenced by genetic factors. Aim To determine if genetic variants in the serotonergic and adrenergic pathways are associated with heroin and/or cocaine addiction. Subjects & methods The study examined 140 polymorphisms in 19 genes in 1855 subjects with predominantly European or African ancestries. Results A total of 38 polymorphisms (13 genes) showed nominal associations, including novel associations in S100A10 (p11) and SLC18A2 (VMAT2). The association of HTR3B SNP rs11606194 with heroin addiction in the European ancestry subgroup remained significant after correction for multiple testing (pcorrected = 0.04). Conclusion The study strengthens our previous findings of association of polymorphisms in HTR3A, HTR3B and ADRA1A. The study suggests partial overlap in genetic susceptibility between populations of different ancestry and between heroin and cocaine addiction. PMID:26227246

  6. 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…

  7. 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. PMID:23555287

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Multiple Loci Associated with Renal Function in African Americans

    PubMed Central

    Shriner, Daniel; Herbert, Alan; Doumatey, Ayo P.; Zhou, Jie; Huang, Hanxia; Erdos, Michael R.; Chen, Guanjie; Gerry, Norman P.; Christman, Michael F.; Adeyemo, Adebowale; Rotimi, Charles N.

    2012-01-01

    The incidence of chronic kidney disease varies by ethnic group in the USA, with African Americans displaying a two-fold higher rate than European Americans. One of the two defining variables underlying staging of chronic kidney disease is the glomerular filtration rate. Meta-analysis in individuals of European ancestry has identified 23 genetic loci associated with the estimated glomerular filtration rate (eGFR). We conducted a follow-up study of these 23 genetic loci using a population-based sample of 1,018 unrelated admixed African Americans. We included in our follow-up study two variants in APOL1 associated with end-stage kidney disease discovered by admixture mapping in admixed African Americans. To address confounding due to admixture, we estimated local ancestry at each marker and global ancestry. We performed regression analysis stratified by local ancestry and combined the resulting regression estimates across ancestry strata using an inverse variance-weighted fixed effects model. We found that 11 of the 24 loci were significantly associated with eGFR in our sample. The effect size estimates were not significantly different between the subgroups of individuals with two copies of African ancestry vs. two copies of European ancestry for any of the 11 loci. In contrast, allele frequencies were significantly different at 10 of the 11 loci. Collectively, the 11 loci, including four secondary signals revealed by conditional analyses, explained 14.2% of the phenotypic variance in eGFR, in contrast to the 1.4% explained by the 24 loci in individuals of European ancestry. Our findings provide insight into the genetic basis of variation in renal function among admixed African Americans. PMID:23028791

  15. Multiple loci associated with renal function in African Americans.

    PubMed

    Shriner, Daniel; Herbert, Alan; Doumatey, Ayo P; Zhou, Jie; Huang, Hanxia; Erdos, Michael R; Chen, Guanjie; Gerry, Norman P; Christman, Michael F; Adeyemo, Adebowale; Rotimi, Charles N

    2012-01-01

    The incidence of chronic kidney disease varies by ethnic group in the USA, with African Americans displaying a two-fold higher rate than European Americans. One of the two defining variables underlying staging of chronic kidney disease is the glomerular filtration rate. Meta-analysis in individuals of European ancestry has identified 23 genetic loci associated with the estimated glomerular filtration rate (eGFR). We conducted a follow-up study of these 23 genetic loci using a population-based sample of 1,018 unrelated admixed African Americans. We included in our follow-up study two variants in APOL1 associated with end-stage kidney disease discovered by admixture mapping in admixed African Americans. To address confounding due to admixture, we estimated local ancestry at each marker and global ancestry. We performed regression analysis stratified by local ancestry and combined the resulting regression estimates across ancestry strata using an inverse variance-weighted fixed effects model. We found that 11 of the 24 loci were significantly associated with eGFR in our sample. The effect size estimates were not significantly different between the subgroups of individuals with two copies of African ancestry vs. two copies of European ancestry for any of the 11 loci. In contrast, allele frequencies were significantly different at 10 of the 11 loci. Collectively, the 11 loci, including four secondary signals revealed by conditional analyses, explained 14.2% of the phenotypic variance in eGFR, in contrast to the 1.4% explained by the 24 loci in individuals of European ancestry. Our findings provide insight into the genetic basis of variation in renal function among admixed African Americans. PMID:23028791

  16. Stable Patterns of Gene Expression Regulating Carbohydrate Metabolism Determined by Geographic Ancestry

    PubMed Central

    Schisler, Jonathan C.; Charles, Peter C.; Parker, Joel S.; Hilliard, Eleanor G.; Mapara, Sabeen; Meredith, Dane; Lineberger, Robert E.; Wu, Samuel S.; Alder, Brian D.; Stouffer, George A.; Patterson, Cam

    2009-01-01

    Background Individuals of African descent in the United States suffer disproportionately from diseases with a metabolic etiology (obesity, metabolic syndrome, and diabetes), and from the pathological consequences of these disorders (hypertension and cardiovascular disease). Methodology/Principal Findings Using a combination of genetic/genomic and bioinformatics approaches, we identified a large number of genes that were both differentially expressed between American subjects self-identified to be of either African or European ancestry and that also contained single nucleotide polymorphisms that distinguish distantly related ancestral populations. Several of these genes control the metabolism of simple carbohydrates and are direct targets for the SREBP1, a metabolic transcription factor also differentially expressed between our study populations. Conclusions/Significance These data support the concept of stable patterns of gene transcription unique to a geographic ancestral lineage. Differences in expression of several carbohydrate metabolism genes suggest both genetic and transcriptional mechanisms contribute to these patterns and may play a role in exacerbating the disproportionate levels of obesity, diabetes, and cardiovascular disease observed in Americans with African ancestry. PMID:20016837

  17. 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

  18. 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

  19. 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)

  20. A high-density admixture scan in 1,670 African Americans with hypertension.

    PubMed

    Deo, Rahul C; Patterson, Nick; Tandon, Arti; McDonald, Gavin J; Haiman, Christopher A; Ardlie, Kristin; Henderson, Brian E; Henderson, Sean O; Reich, David

    2007-11-01

    Hypertension (HTN) is a devastating disease with a higher incidence in African Americans than European Americans, inspiring searches for genetic variants that contribute to this difference. We report the results of a large-scale admixture scan for genes contributing HTN risk, in which we screened 1,670 African Americans with HTN and 387 control individuals for regions of the genome with elevated proportion of African or European ancestry. No loci were identified that were significantly associated with HTN. We also searched for evidence of an admixture signal at 40 candidate genes and eight previously reported linkage peaks, but none appears to contribute substantially to the differential HTN risk between African and European Americans. Finally, we observed nominal association at one of the loci detected in the admixture scan of Zhu et al. 2005 (p = 0.016 at 6q24.3 correcting for four hypotheses tested), although we caution that the significance is marginal and the estimated odds ratio of 1.19 per African allele is less than what would be expected from the original report; thus, further work is needed to follow up this locus. PMID:18020707

  1. A High-Density Admixture Scan in 1,670 African Americans with Hypertension

    PubMed Central

    Deo, Rahul C; Patterson, Nick; Tandon, Arti; McDonald, Gavin J; Haiman, Christopher A; Ardlie, Kristin; Henderson, Brian E; Henderson, Sean O; Reich, David

    2007-01-01

    Hypertension (HTN) is a devastating disease with a higher incidence in African Americans than European Americans, inspiring searches for genetic variants that contribute to this difference. We report the results of a large-scale admixture scan for genes contributing HTN risk, in which we screened 1,670 African Americans with HTN and 387 control individuals for regions of the genome with elevated proportion of African or European ancestry. No loci were identified that were significantly associated with HTN. We also searched for evidence of an admixture signal at 40 candidate genes and eight previously reported linkage peaks, but none appears to contribute substantially to the differential HTN risk between African and European Americans. Finally, we observed nominal association at one of the loci detected in the admixture scan of Zhu et al. 2005 (p = 0.016 at 6q24.3 correcting for four hypotheses tested), although we caution that the significance is marginal and the estimated odds ratio of 1.19 per African allele is less than what would be expected from the original report; thus, further work is needed to follow up this locus. PMID:18020707

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

    PubMed Central

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

    2013-01-01

    Many studies provide evidence relating lower human arsenic (As) methylation efficiency, represented by high % urinary monomethylarsonic acid (MMA(V)), with several arsenic-induced diseases, possibly due to the fact that MMA(V) serves as a proxy for MMA(III), the most toxic arsenic metabolite. Some epidemiological studies have 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 arsenic 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 arsenic in northwest Mexico. Total urinary As (TAs) mean and range were 170.4 and 2.3–1053.5 μg/L, while %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 associated with lower %uMMA excretion in this population (p <0.01). The data also showed a significant interaction between BMI and gender indicating negative association between BMI and %uMMA, stronger in women than men (p <0.01). Moreover age and the AS3MT variants 7388 (intronic) and M287T (non-synonymous) were also significantly associated with As methylation efficiency (p = 0.01). 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. PMID:22047162

  3. 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

  4. KIR Genotypic Diversity Can Track Ancestries in Heterogeneous Populations: A Potential Confounder for Disease Association Studies

    PubMed Central

    Singh, Komal Manpreet; Phung, Yume T.; Kohla, Mohamed S.; Lan, Billy Y-A; Chan, Sharon; Suen, Diana L.; Murad, Sahar; Rheault, Shana; Davidson, Peter; Evans, Jennifer; Singh, Manpreet; Dohil, Sofie; Osorio, Robert W.; Wakil, Adil E.; Page, Kimberly; Feng, Sandy; Cooper, Stewart L.

    2014-01-01

    Killer cell immunoglobulin-like receptors (KIR) are encoded by highly polymorphic genes that regulate the activation of natural killer (NK) cells and other lymphocyte subsets, and likely play key roles in innate and adaptive immunity. Association studies increasingly implicate KIR in disease predisposition and outcome but could be confounded by unknown KIR genetic structure in heterogeneous populations. To examine this we characterized the diversity of 16 KIR genes in 712 Northern Californians (NC) stratified by selfassigned ethnicities, and compared the profiles of KIR polymorphism with other US and global populations using a reference database. Sixty-eight distinct KIR genotypes were characterized: 58 in 457 Caucasians (NCC); 17 in 47 African Americans (NCAA); 21 in 80 Asians (NCA); 20 in 74 Hispanics (NCH) and 18 in 54 “other” ethnicities (NCO). KIR genotype patterns and frequencies in the 4 defined ethnicities were compared with each other and with 34 global populations by phylogenetic analysis. Although there were no population-specific genotypes, the KIR genotype frequency patterns faithfully traced the ancestry of NCC, NCAA and NCA but not of NCH whose ancestries are known to be more heterogeneous. KIR genotype frequencies can therefore track ethnic ancestries in modern urban populations. Our data emphasize the importance of selecting ethnically matched controls in KIR based studies to avert spurious associations. PMID:21898189

  5. Inferring ancestry from population genomic data and its applications

    PubMed Central

    Padhukasahasram, Badri

    2014-01-01

    Ancestry inference is a frequently encountered problem and has many applications such as forensic analyses, genetic association studies, and personal genomics. The main goal of ancestry inference is to identify an individual’s population of origin based on our knowledge of natural populations. Because both self-reported ancestry in humans or the sampling location of an organism can be inaccurate for this purpose, the use of genetic markers can facilitate accurate and reliable inference of an individual’s ancestral origins. At a higher level, there are two different paradigms in ancestry inference: global ancestry inference which tries to compute the genome-wide average of the population contributions and local ancestry inference which tries to identify the regional ancestry of a genomic segment. In this mini review, I describe the numerous approaches that are currently available for both kinds of ancestry inference from population genomic datasets. I first describe the general ideas underlying such inference methods and their relationship to one another. Then, I describe practical applications in which inference of ancestry has proven useful. Lastly, I discuss challenges and directions for future research work in this area. PMID:25071832

  6. 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,…

  7. 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

  8. 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

  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. PMID:24502438

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. Adaptation through proportion.

    PubMed

    Xiong, Liyang; Shi, Wenjia; Tang, Chao

    2016-01-01

    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. PMID:27526863

  17. 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

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

    PubMed Central

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

    2008-01-01

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

  19. Proportioning Cats and Rats

    ERIC Educational Resources Information Center

    Markworth, Kimberly A.

    2012-01-01

    Students may be able to set up a relevant proportion and solve through cross multiplication. However, this ability may not reflect the desired mathematical understanding of the covarying relationship that exists between two variables or the equivalent relationship that exists between two ratios. Students who lack this understanding are likely to…

  20. Selecting Proportional Reasoning Tasks

    ERIC Educational Resources Information Center

    de la Cruz, Jessica A.

    2013-01-01

    With careful consideration given to task selection, students can construct their own solution strategies to solve complex proportional reasoning tasks while the teacher's instructional goals are still met. Several aspects of the tasks should be considered including their numerical structure, context, difficulty level, and the strategies they are…

  1. 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…

  2. 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

  3. 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

  4. Genetic Architecture of Skin and Eye Color in an African-European Admixed Population

    PubMed Central

    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

    2013-01-01

    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. PMID:23555287

  5. 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

  6. Y chromosome lineages in men of west African descent.

    PubMed

    Torres, Jada Benn; Doura, Menahem B; 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. Glucose intolerance in the West African Diaspora: a skeletal muscle fibre type distribution hypothesis.

    PubMed

    Nielsen, J; Christensen, D L

    2011-08-01

    In the United States, Black Americans are largely descendants of West African slaves; they have a higher relative proportion of obesity and experience a higher prevalence of diabetes than White Americans. However, obesity rates alone cannot explain the higher prevalence of type 2 diabetes. Type 2 diabetes is characterized by insulin resistance and beta-cell dysfunction. We hypothesize that the higher prevalence of type 2 diabetes in African Americans (as compared to White Americans) is facilitated by an inherited higher percentage of skeletal muscle fibre type II and a lower percentage of skeletal muscle fibre type I. Skeletal muscle fibre type II is less oxidative and more glycolytic than skeletal muscle fibre type I. Lower oxidative capacity is associated with lower fat oxidation and a higher disposal of lipids, which are stored as muscular adipose tissue in higher amounts in Black compared to White Americans. In physically active individuals, the influence of muscle fibre composition will not be as detrimental as in physically inactive individuals. This discrepancy is caused by the plasticity in the skeletal muscle fibre characteristics towards a higher activity of oxidative enzymes as a consequence of physical activity. We suggest that a higher percentage of skeletal muscle fibre type II combined with physical inactivity has an impact on insulin sensitivity and high prevalence of type 2 diabetes in Blacks of West African ancestry. PMID:21382179

  13. Founder effect and prevalence of myotonic dystrophy in South Africans: molecular studies.

    PubMed Central

    Goldman, A.; Krause, A.; Ramsay, M.; Jenkins, T.

    1996-01-01

    A high prevalence of myotonic dystrophy (DM) has been described in South African Caucasoid Afrikaans-speaking families in the northern Transvaal. Evidence is presented for a strong founder effect, with a single haplotype occurring on 68% of all Caucasoid DM chromosomes; among the Afrikaans speakers, the proportion was 83%. In addition to this major haplotype, five minor DM haplotypes in the Caucasoids and two minor haplotypes in DM individuals of mixed ancestry were found. All DM chromosomes, however, had a common haplotype core, namely, Alu (ins), HinfI-2 (intron 9), and TaqI-2 (D19S463). We have detected significant linkage disequilibrium between the DM mutation and particular alleles of the extragenic markers D19S112 and D19S207. Significant differences were found in allele and haplotype distributions in the Caucasoid DM and non-DM chromosomes and Negroid non-DM chromosomes. These findings together with the strong association of allele 3 at the D19S63 locus on 93% (14/15) of the South African DM chromosomes suggest that the majority of present-day DM mutations in South African Caucasoids may have originated from a common initial founder who introduced one of the European ancestral mutations. PMID:8755933

  14. 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

  15. 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

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

    PubMed

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

    2013-05-01

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

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

    PubMed Central

    Brown, Robert; Pasaniuc, Bogdan

    2014-01-01

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

  18. 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

  19. 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

  20. Evaluating a subset of ancestry informative SNPs for discriminating among Southwest Asian and circum-Mediterranean populations.

    PubMed

    Bulbul, Ozlem; Cherni, Lotfi; Khodjet-El-Khil, Houssein; Rajeevan, Haseena; Kidd, Kenneth K

    2016-07-01

    Many different published sets of single nucleotide polymorphisms (SNPs) and/or insertion-deletion polymorphisms (InDels) can serve as ancestry informative markers (AIMs) to distinguish among continental regions of the world. For a focus on Southwest Asian ancestry we chose to start with the Kidd Lab panel of 55 ancestry-informative SNPs (AISNPs) because it already provided good global reference data (FROG-kb: frog.med.yale.edu) in a set of 73 population samples distinguishing at least 8 biogeographic clusters of populations. This panel serves as a good first tier ancestry panel. We are now interested in identifying region-specific second tier panels for more refined distinction among populations within each of the global regions. We have begun studying the global region centered on Southwest Asia and the region encompassing the Mediterranean Sea. We have incorporated 10 populations from North Africa, Turkey and Iran and included 31 of the original 73 populations and eleven 1000 Genomes Phase3 populations for a total of 3129 individuals from 52 populations, all typed for the 55 AISNPs. We have then identified the subset of the 55 AISNPs that are most informative for this region of the world using Heatmap, Fst, and Informativeness analyses to eliminate those SNPs essentially redundant or providing no information among populations in this region, reducing the number of SNPs to 32. STRUCTURE and PCA analyses show the remaining 32 SNPs identify the North African cluster and appropriately include the Turkish and Iranian samples with the Southwest Asian cluster. These markers provide the basis for building an improved, optimized panel of AISNPs that provides additional information on differences among populations in this part of the world. The data have also allowed an examination of the accuracy of the ancestry inference based on 32 SNPs for the newly studied populations from this region. The likelihood ratio approach to ancestry inference embodied in FROG-kb provides

  1. 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

  2. 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

  3. 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)

  4. 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

  5. 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.

  6. 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.

  7. Load proportional safety brake

    NASA Technical Reports Server (NTRS)

    Cacciola, M. J.

    1979-01-01

    This brake is a self-energizing mechanical friction brake and is intended for use in a rotary drive system. It incorporates a torque sensor which cuts power to the power unit on any overload condition. The brake is capable of driving against an opposing load or driving, paying-out, an aiding load in either direction of rotation. The brake also acts as a no-back device when torque is applied to the output shaft. The advantages of using this type of device are: (1) low frictional drag when driving; (2) smooth paying-out of an aiding load with no runaway danger; (3) energy absorption proportional to load; (4) no-back activates within a few degrees of output shaft rotation and resets automatically; and (5) built-in overload protection.

  8. Masked Proportional Routing

    NASA Technical Reports Server (NTRS)

    Wolpert, David H. (Inventor)

    2003-01-01

    Distributed approach for determining a path connecting adjacent network nodes, for probabilistically or deterministically transporting an entity, with entity characteristic mu from a source node to a destination node. Each node i is directly connected to an arbitrary number J(mu) of nodes, labeled or numbered j=jl, j2, .... jJ(mu). In a deterministic version, a J(mu)-component baseline proportion vector p(i;mu) is associated with node i. A J(mu)-component applied proportion vector p*(i;mu) is determined from p(i;mu) to preclude an entity visiting a node more than once. Third and fourth J(mu)-component vectors, with components iteratively determined by Target(i;n(mu);mu),=alpha(mu).Target(i;n(mu)-1;mu)j+beta(mu).p* (i;mu)j and Actual(i;n(mu);+a(mu)j. Actual(i;n(mu)-l;mu)j+beta(mu).Sent(i;j'(mu);n(mu)-1;mu)j, are computed, where n(mu) is an entity sequence index and alpha(mu) and beta(mu) are selected numbers. In one embodiment, at each node i, the node j=j'(mu) with the largest vector component difference, Target(i;n(mu);mu)j'- Actual (i;n(mu);mu)j'. is chosen for the next link for entity transport, except in special gap circumstances, where the same link is optionally used for transporting consecutively arriving entities. The network nodes may be computer-controlled routers that switch collections of packets, frames, cells or other information units. Alternatively, the nodes may be waypoints for movement of physical items in a network or for transformation of a physical item. The nodes may be states of an entity undergoing state transitions, where allowed transitions are specified by the network and/or the destination node.

  9. 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. PMID:25242497

  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. 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

  14. 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

  15. 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

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

    PubMed Central

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

    2011-01-01

    We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of over 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinese women [ORs (95%CI)=1.30(1.22–1.38) and 1.64(1.50–1.80) for the AG and AA genotypes, respectively, P for trend = 1.54 × 10−30], Japanese women [ORs (95%CI)=1.31(1.13–1.52) and 1.37(1.06–1.76), P for trend = 2.51 × 10−4], and European-ancestry American women [ORs (95%CI)=1.07(0.99–1.16) and 1.18(1.04–1.34), P for trend = 0.0069]. No association with this SNP, however, was observed in African American women [ORs (95%CI)=0.81(0.63–1.06) and 0.85(0.65–1.11) for the AG and AA genotypes, respectively, P for trend = 0.4027). In vitro functional genomic studies identified a putative functional variant, rs6913578. This SNP is 1,440 bp downstream of rs2046210 and is in high LD with rs2046210 in Chinese (r2=0.91) and European-ancestry (r2=0.83) populations, but not in Africans (r2=0.57). SNP rs6913578 was found to be associated with breast cancer risk in Chinese and European-ancestry American women. After adjusting for rs2046210, the association of rs6913578 with breast cancer risk in African Americans approached borderline significance. Results from this large consortium study confirmed the association of rs2046210 with breast cancer risk among women of Chinese, Japanese, and European ancestry. This association may be explained in part by a putatively functional variant (rs6913578) identified in the region. PMID:21303983

  17. Mutational Landscape of Aggressive Prostate Tumors in African American Men.

    PubMed

    Lindquist, Karla J; Paris, Pamela L; Hoffmann, Thomas J; Cardin, Niall J; Kazma, Rémi; Mefford, Joel A; Simko, Jeffrey P; Ngo, Vy; Chen, Yalei; Levin, Albert M; Chitale, Dhananjay; Helfand, Brian T; Catalona, William J; Rybicki, Benjamin A; Witte, John S

    2016-04-01

    Prostate cancer is the most frequently diagnosed and second most fatal nonskin cancer among men in the United States. African American men are two times more likely to develop and die of prostate cancer compared with men of other ancestries. Previous whole genome or exome tumor-sequencing studies of prostate cancer have primarily focused on men of European ancestry. In this study, we sequenced and characterized somatic mutations in aggressive (Gleason ≥7, stage ≥T2b) prostate tumors from 24 African American patients. We describe the locations and prevalence of small somatic mutations (up to 50 bases in length), copy number aberrations, and structural rearrangements in the tumor genomes compared with patient-matched normal genomes. We observed several mutation patterns consistent with previous studies, such as large copy number aberrations in chromosome 8 and complex rearrangement chains. However, TMPRSS2-ERG gene fusions and PTEN losses occurred in only 21% and 8% of the African American patients, respectively, far less common than in patients of European ancestry. We also identified mutations that appeared specific to or more common in African American patients, including a novel CDC27-OAT gene fusion occurring in 17% of patients. The genomic aberrations reported in this study warrant further investigation of their biologic significant role in the incidence and clinical outcomes of prostate cancer in African Americans. Cancer Res; 76(7); 1860-8. ©2016 AACR. PMID:26921337

  18. 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.…

  19. 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...

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

    PubMed

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

    2016-01-01

    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

  1. 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

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

    PubMed Central

    2013-01-01

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

  3. Palenque de San Basilio in Colombia: genetic data support an oral history of a paternal ancestry in Congo.

    PubMed

    Ansari-Pour, Naser; Moñino, Yves; Duque, Constanza; Gallego, Natalia; Bedoya, Gabriel; Thomas, Mark G; Bradman, Neil

    2016-03-30

    The Palenque, a black community in rural Colombia, have an oral history of fugitive African slaves founding a free village near Cartagena in the seventeenth century. Recently, linguists have identified some 200 words in regular use that originate in a Kikongo language, with Yombe, mainly spoken in the Congo region, being the most likely source. The non-recombining portion of the Y chromosome (NRY) and mitochondrial DNA were analysed to establish whether there was greater similarity between present-day members of the Palenque and Yombe than between the Palenque and 42 other African groups (for all individuals,n= 2799) from which forced slaves might have been taken. NRY data are consistent with the linguistic evidence that Yombe is the most likely group from which the original male settlers of Palenque came. Mitochondrial DNA data suggested substantial maternal sub-Saharan African ancestry and a strong founder effect but did not associate Palenque with any particular African group. In addition, based on cultural data including inhabitants' claims of linguistic differences, it has been hypothesized that the two districts of the village (Abajo and Arriba) have different origins, with Arriba founded by men originating in Congo and Abajo by those born in Colombia. Although significant genetic structuring distinguished the two from each other, no supporting evidence for this hypothesis was found. PMID:27030413

  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 Central

    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. What are our AIMs? Interdisciplinary Perspectives on the Use of Ancestry Estimation in Disease Research

    PubMed Central

    Taylor, Janelle S.; Edwards, Karen L.; Fullerton, Stephanie M.

    2014-01-01

    Background Ancestry estimation serves as a tool to identify genetic contributions to disease but may contribute to racial discrimination and stigmatization. We sought to understand user perspectives on the benefits and harms of ancestry estimation to inform research practice and contribute to debates about the use of race and ancestry in genetics. Methods Key informant interviews with 22 scientists were conducted to examine scientists’ understandings of the benefits and harms of ancestry estimation. Results Three main perspectives were observed among key informant scientists who use ancestry estimation in genetic epidemiology research. Population geneticists self identified as educators who controlled the meaning and application of ancestry estimation in research. Clinician-researchers were optimistic about the application of ancestry estimation to individualized risk assessment and personalized medicine. Epidemiologists remained ambivalent toward ancestry estimation and suggested a continued role for race in their research. Conclusions We observed an imbalance of control over the meaning and application of ancestry estimation among disciplines that may result in unwarranted or premature translation of ancestry estimation into medicine and public health. Differences in disciplinary perspectives need to be addressed if translational benefits of genetic ancestry estimation are to be realized. PMID:25419472

  6. 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…

  7. African American rhinoplasty.

    PubMed

    Boyette, Jennings R; Stucker, Fred J

    2014-08-01

    Rhinoplasty in patients of African descent requires a patient-specific approach, because the goals and ideal proportions differ from the white nose. This article discusses approaches to surgical correction of common anatomic variations. In addition, common pitfalls are outlined. PMID:25049123

  8. 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

    2011-08-11

    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. PMID:21775986

  9. 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

  10. 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

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

    PubMed

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

    2013-01-01

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

  12. 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. PMID:24646108

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

    PubMed Central

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

    2011-01-01

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

  15. 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

  16. Fine-Mapping in African Americans of Eight Recently Discovered Genetic Loci for Plasma Lipids: The Jackson Heart Study

    PubMed Central

    Keebler, Mary E.; Deo, Rahul C.; Surti, Aarti; Konieczkowski, David; Guiducci, Candace; Burtt, Noel; Buxbaum, Sarah G.; Sarpong, Daniel F.; Steffes, Michael W.; Wilson, James G.; Taylor, Herman A.; Kathiresan, Sekar

    2011-01-01

    Background Genome-wide association studies in cohorts of European descent have identified novel genomic regions as associated with lipids, but their relevance in African Americans remains unclear. Methods and Results We genotyped 8 index SNPs and 488 tagging SNPs across 8 novel lipid loci in the Jackson Heart Study, a community-based cohort of 4605 African Americans. For each trait, we calculated residuals adjusted for age, sex, and global ancestry and performed multivariable linear regression to detect genotype-phenotype association with adjustment for local ancestry. To explore admixture effects, we conducted stratified analyses in individuals with a high probability of 2 African ancestral alleles or at least 1 European allele at each locus. We confirmed 2 index SNPs as associated with lipid traits in African Americans, with suggestive association for 3 more. However, the effect sizes for 4 of the 5 associated SNPs were larger in the European local ancestry subgroup compared to the African local ancestry subgroup, suggesting that the replication is driven by European ancestry segments. Through fine-mapping, we discovered 3 new SNPs with significant associations, two with consistent effect on triglyceride levels across ancestral groups: rs636523 near DOCK7/ANGPTL3 and rs780093 in GCKR. African LD patterns did not assist in narrowing association signals. Conclusions We confirm that 5 genetic regions associated with lipid traits in European-derived populations are relevant in African Americans. To further evaluate these loci, fine-mapping in larger African American cohorts and/or resequencing will be required. PMID:20570916

  17. Lumbee Native American ancestry and the incidence of aggressive histologic subtypes of endometrial cancer

    PubMed Central

    Zhang, Chelsea; Roque, Dario; Ehrisman, Jessie A.; DiSanto, Nicola; Broadwater, Gloria; Doll, Kemi M.; Gehrig, Paola A.; Secord, Angeles Alvarez; Havrilesky, Laura J.

    2015-01-01

    Objective The Lumbee Indian tribe is the largest Native American tribe in North Carolina, with about 55,000 enrolled members who mostly reside in southeastern counties. We evaluated whether Lumbee heritage is associated with high-risk histologic subtypes of endometrial cancer. Methods We retrospectively analyzed the available records from IRB-approved endometrial cancer databases at two institutions of patients of Lumbee descent (year of diagnosis range 1980–2014). Each Lumbee case was matched by age, year of diagnosis, and BMI to two non-Lumbee controls. Chi-square test was used to compare categorical associations. Kaplan–Meier methods and log-rank test were used to display and compare disease-free survival (DFS) and overall survival (OS). Multivariate Cox proportional hazards regression was used to adjust for age and BMI while testing cohort as a predictor of DFS and OS. Results Among 108 subjects, 10/35 (29%) Lumbee and 19/72 (26%) non-Lumbee subjects had high-risk (serous/clear cell/carcinosarcoma) histologic types (p = 0.8). 12/35 (34%) Lumbee and 24/72 (33%) non-Lumbee subjects had grade 3 tumors (p = 0.9). 5/33 (15%) Lumbee and 13/72 (18%) non-Lumbee had advanced stage endometrial cancer at diagnosis (p = 0.7). Lumbee ancestry was not associated with worse survival outcomes. OS (p = 0.054) and DFS (p = 0.01) were both worse in Blacks compared to Lumbee and White subjects. Conclusion In this retrospective cohort analysis, Lumbee Native American ancestry was not a significant independent predictor of rates of high-risk histological subtypes of endometrial cancer or poor survival outcomes. PMID:26425722

  18. 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

  19. 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

  20. 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…

  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. 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

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

    PubMed

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

    2015-09-01

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

  4. The potential for enhancing the power of genetic association studies in African Americans through the reuse of existing genotype data.

    PubMed

    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

    2010-09-01

    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

  5. Genetic risk variants in African Americans with multiple sclerosis

    PubMed Central

    Isobe, Noriko; Gourraud, Pierre-Antoine; Harbo, Hanne F.; Caillier, Stacy J.; Santaniello, Adam; Khankhanian, Pouya; Maiers, Martin; Spellman, Stephen; Cereb, Nezih; Yang, SooYoung; Pando, Marcelo J.; Piccio, Laura; Cross, Anne H.; De Jager, Philip L.; Cree, Bruce A.C.; Hauser, Stephen L.

    2013-01-01

    Objectives: To assess the association of established multiple sclerosis (MS) risk variants in 3,254 African Americans (1,162 cases and 2,092 controls). Methods: Human leukocyte antigen (HLA)-DRB1, HLA-DQB1, and HLA-A alleles were typed by molecular techniques. Single nucleotide polymorphism (SNP) genotyping was conducted for 76 MS-associated SNPs and 52 ancestry informative marker SNPs selected throughout the genome. Self-declared ancestry was refined by principal component analysis of the ancestry informative marker SNPs. An ancestry-adjusted multivariate model was applied to assess genetic associations. Results: The following major histocompatibility complex risk alleles were replicated: HLA-DRB1*15:01 (odds ratio [OR] = 2.02 [95% confidence interval: 1.54–2.63], p = 2.50e-07), HLA-DRB1*03:01 (OR = 1.58 [1.29–1.94], p = 1.11e-05), as well as HLA-DRB1*04:05 (OR = 2.35 [1.26–4.37], p = 0.007) and the African-specific risk allele of HLA-DRB1*15:03 (OR = 1.26 [1.05–1.51], p = 0.012). The protective association of HLA-A*02:01 was confirmed (OR = 0.72 [0.55–0.93], p = 0.013). None of the HLA-DQB1 alleles were associated with MS. Using a significance threshold of p < 0.01, outside the major histocompatibility complex region, 8 MS SNPs were also found to be associated with MS in African Americans. Conclusion: MS genetic risk in African Americans only partially overlaps with that of Europeans and could explain the difference of MS prevalence between populations. PMID:23771490

  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. PMID:27069571

  7. 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

  8. 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

  9. 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

  10. 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. PMID:25735402

  11. Genome-wide admixture and association study of serum iron, ferritin, transferrin saturation and total iron binding capacity in African Americans

    PubMed Central

    Li, Jin; Lange, Leslie A.; Duan, Qing; Lu, Yurong; Singleton, Andrew B.; Zonderman, Alan B.; Evans, Michele K.; Li, Yun; Taylor, Herman A.; Willis, Monte S.; Nalls, Mike; Wilson, James G.; Lange, Ethan M.

    2015-01-01

    Iron is an essential component of many important proteins and enzymes, including hemoglobin, which is responsible for carrying oxygen to the cells. African Americans (AAs) have a greater prevalence of iron deficiency compared with European Americans. We conducted genome-wide admixture-mapping and association studies for serum iron, serum ferritin, transferrin saturation (SAT) and total iron binding capacity (TIBC) in 2347 AAs participating in the Jackson Heart Study (JHS). Follow-up replication analyses for JHS iron-trait associated SNPs were conducted in 329 AA participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study (HANDLS). Higher estimated proportions of global African ancestry were significantly associated with lower levels of iron (P = 2.4 × 10−5), SAT (P = 0.0019) and TIBC (P = 0.042). We observed significant associations (P < 5 × 10−8) between serum TIBC levels and two independent SNPs around TF on chromosome 3, the first report of a genome-wide significant second independent signal in this region, and SNPs near two novel genes: HDGFL1 on chromosome 6 and MAF on chromosome 16. We also observed significant associations between ferritin levels and SNPs near GAB3 on chromosome X. We replicated our two independent associations at TF and our association at GAB3 in HANDLS. Our study provides evidence for both shared and unique genetic risk factors that are associated with iron-related measures in AAs. The top two variants in TF explain 11.2% of the total variation in TIBC levels in AAs after accounting for age, gender, body mass index and background ancestry. PMID:25224454

  12. An Australasian test of the recent African origin theory using the WLH-50 calvarium.

    PubMed

    Hawks, J; Oh, S; Hunley, K; Dobson, S; Cabana, G; Dayalu, P; Wolpoff, M H

    2000-07-01

    This analysis investigates the ancestry of a single modern human specimen from Australia, WLH-50 (Thorne et al., in preparation; Webb, 1989). Evaluating its ancestry is important to our understanding of modern human origins in Australasia because the prevailing models of human origins make different predictions for the ancestry of this specimen, and others like it. Some authors believe in the validity of a complete replacement theory and propose that modern humans in Australasia descended solely from earlier modern human populations found in Late Pleistocene Africa and the Levant. These ancestral modern populations are believed to have completely replaced other archaic human populations, including the Ngandong hominids of Indonesia. According to this recent African origin theory, the archaic humans from Indonesia are classified as Homo erectus, a different evolutionary species that could not have contributed to the ancestry of modern Australasians. Therefore this theory of complete replacement makes clear predictions concerning the ancestry of the specimen WLH-50. We tested these predictions using two methods: a discriminant analysis of metric data for three samples that are potential ancestors of WLH-50 (Ngandong, Late Pleistocene Africans, Levant hominids from Skhul and Qafzeh) and a pairwise difference analysis of nonmetric data for individuals within these samples. The results of these procedures provide an unambiguous refutation of a model of complete replacement within this region, and indicate that the Ngandong hominids or a population like them may have contributed significantly to the ancestry of WLH-50. We therefore contend that Ngandong hominids should be classified within the evolutionary species, Homo sapiens. The Multiregional model of human evolution has the expectation that Australasian ancestry is in all three of the potentially ancestral groups and best explains modern Australasian origins. PMID:10896810

  13. 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

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

    PubMed

    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

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

    PubMed

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

    2001-01-01

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

  16. Statistical evidence for common ancestry: Application to primates.

    PubMed

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

    2016-06-01

    Since Darwin, biologists have come to recognize that the theory of descent from common ancestry (CA) is very well supported by diverse lines of evidence. However, while the qualitative evidence is overwhelming, we also need formal methods for quantifying the evidential support for CA over the alternative hypothesis of separate ancestry (SA). In this article, we explore a diversity of statistical methods using data from the primates. We focus on two alternatives to CA, species SA (the separate origin of each named species) and family SA (the separate origin of each family). We implemented statistical tests based on morphological, molecular, and biogeographic data and developed two new methods: one that tests for phylogenetic autocorrelation while correcting for variation due to confounding ecological traits and a method for examining whether fossil taxa have fewer derived differences than living taxa. We overwhelmingly rejected both species and family SA with infinitesimal P values. We compare these results with those from two companion papers, which also found tremendously strong support for the CA of all primates, and discuss future directions and general philosophical issues that pertain to statistical testing of historical hypotheses such as CA. PMID:27139421

  17. 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

  18. Admixture and Genetic Diversity Distribution Patterns of Non-Recombining Lineages of Native American Ancestry in Colombian Populations

    PubMed Central

    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. PMID:25775361

  19. 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

  20. 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. PMID:25786259

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  2. 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…

  3. People of Native Ancestry, A Resource Guide for the Primary and Junior Divisions.

    ERIC Educational Resources Information Center

    Ontario Dept. of Education, Toronto.

    Basic principles of primary-junior education as they pertain specifically to people of native ancestry in Ontario are elaborated in this resource guide. Intended for both native and non-native teachers, principals, and administrators responsible for curriculum for children of native ancestry and others, its aim is to help in development of a…

  4. 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

  5. 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

  6. 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

  7. North African Populations Carry the Signature of Admixture with Neandertals

    PubMed Central

    Civit, Sergi; Arenas, Conxita; Ávila-Arcos, María C.; Bustamante, Carlos D.; Comas, David; Lalueza-Fox, Carles

    2012-01-01

    One of the main findings derived from the analysis of the Neandertal genome was the evidence for admixture between Neandertals and non-African modern humans. An alternative scenario is that the ancestral population of non-Africans was closer to Neandertals than to Africans because of ancient population substructure. Thus, the study of North African populations is crucial for testing both hypotheses. We analyzed a total of 780,000 SNPs in 125 individuals representing seven different North African locations and searched for their ancestral/derived state in comparison to different human populations and Neandertals. We found that North African populations have a significant excess of derived alleles shared with Neandertals, when compared to sub-Saharan Africans. This excess is similar to that found in non-African humans, a fact that can be interpreted as a sign of Neandertal admixture. Furthermore, the Neandertal's genetic signal is higher in populations with a local, pre-Neolithic North African ancestry. Therefore, the detected ancient admixture is not due to recent Near Eastern or European migrations. Sub-Saharan populations are the only ones not affected by the admixture event with Neandertals. PMID:23082212

  8. A method for estimating proportions

    NASA Technical Reports Server (NTRS)

    Guseman, L. F., Jr.; Marion, B. P.

    1975-01-01

    A proportion estimation procedure is presented which requires only on set of ground truth data for determining the error matrix. The error matrix is then used to determine an unbiased estimate. The error matrix is shown to be directly related to the probability of misclassifications, and is more diagonally dominant with the increase in the number of passes used.

  9. 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…

  10. 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…

  11. 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…

  12. 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

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

    PubMed Central

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

    2015-01-01

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

  14. 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

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

    PubMed Central

    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.

    2011-01-01

    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. PMID:21115650

  16. 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. PMID:24852375

  17. Rhinoplasty in the patient of African descent.

    PubMed

    Harris, Monte O

    2010-02-01

    We are in the midst of truly changing times, as patients of African descent actively embrace facial cosmetic surgery. Gaining surgical consistency in patients of African descent has proven to be elusive and unpredictable for many rhinoplasty surgeons. Surgical success relies on the surgeon's ability precisely to identify anatomic variables and reconcile these anatomic realities with the patient's expectations for aesthetic improvement and ethnic identity. An appreciation for underlying heritage provides a link culturally to connect with prospective patients and serves as a tool for establishing realistic aesthetic goals. This article highlights the significance of exploring ancestry in the rhinoplasty consultation; identifies key anatomic variables in the nasal tip, dorsum, and alar base; and reviews surgical logic that has facilitated the achievement of consistent, balanced aesthetic outcomes. PMID:20206100

  18. 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

  19. Reconstruction of Genome Ancestry Blocks in Multiparental Populations.

    PubMed

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

    2015-08-01

    We present a general hidden Markov model framework called R: econstructing A: ncestry B: locks 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

  20. 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

  1. Proportional counter as neutron detector

    NASA Technical Reports Server (NTRS)

    Braby, L. A.; Badhwar, G. D.

    2001-01-01

    A technique to separate out the dose, and lineal energy spectra of neutrons and charged particles is described. It is based on using two proportional counters, one with a wall, and the other with similar characteristics but wall made from a non-hydrogen containing material. Results of a calibration in a neutron field are also shown. c2001 Elsevier Science Ltd. All rights reserved.

  2. Metacarpal proportions in Australopithecus africanus.

    PubMed

    Green, David J; Gordon, Adam D

    2008-05-01

    Recent work has shown that, despite being craniodentally more derived, Australopithecus africanus had more apelike limb-size proportions than A. afarensis. Here, we test whether the A. africanus hand, as judged by metacarpal shaft and articular proportions, was similarly apelike. More specifically, did A. africanus have a short and narrow first metacarpal (MC1) relative to the other metacarpals? Proportions of both MC breadth and length were considered: the geometric mean (GM) of articular and midshaft measurements of MC1 breadth was compared to those of MC2-4, and MC1 length was compared to MC3 length individually and also to the GM of MC2 and 3 lengths. To compare the extant hominoid sample with an incomplete A. africanus fossil record (11 attributed metacarpals), a resampling procedure imposed sampling constraints on the comparative groups that produced composite intrahand ratios. Resampled ratios in the extant sample are not significantly different from actual ratios based on associated elements, demonstrating the methodological appropriateness of this technique. Australopithecus africanus metacarpals do not differ significantly from the great apes in the comparison of breadth ratios but are significantly greater than chimpanzees and orangutans in both measures of relative length. Conversely, A. africanus has a significantly smaller breadth ratio than modern humans, but does not significantly differ from this group in either measure of relative length. We conclude that the first metacarpals of A. africanus are more apelike in relative breadth while also being more humanlike in relative length, a finding consistent with previous work on A. afarensis hand proportions. This configuration would have likely promoted a high degree of manipulative dexterity, but the relatively slender, apelike first metacarpal suggests that A. africanus did not place the same mechanical demands on the thumb as more recent, stone-tool-producing hominins. PMID:18191176

  3. 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

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

    PubMed

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

    2013-01-01

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

  5. 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

  6. 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.

  7. 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. PMID:25949944

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

    PubMed Central

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

    2015-01-01

    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. PMID:25949944

  9. The African diaspora: mitochondrial DNA and the Atlantic slave trade.

    PubMed

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

    2004-03-01

    Between the 15th and 19th centuries ad, the Atlantic slave trade resulted in the forced movement of approximately 13 million people from Africa, mainly to the Americas. Only approximately 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

  10. 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

  11. Drift and proportional tracking chambers

    NASA Astrophysics Data System (ADS)

    Jaros, J. A.

    1980-11-01

    The many techniques exploited in constructing tracking chambers, particle detectors which measure the trajectories and momenta of charged particles, are discussed. In high energy interactions, the final states are dominated by closely collimated jets of high multiplicity, requiring good track-pair resolution in the tracking chamber. High energy particles deflect very little in limited magnetic field volumes, necessitating good spatial resolution for accurate momentum measurements. The colliding beam technique requires a device easily adapted to full solid angle coverage, and the high event rates expected in some of these machines put a premium on good time resolution. Finally, the production and subsequent decays of the tau, charmed and beautiful mesons provide multiple vertex topologies. To reconstruct these vertices reliably requires improvements in spatial resolution and track pair resolution. The proportional counter and its descendant, the drift chamber, are considered as tracking chambers. The physics of this device are discussed in order to understand its performance limitations and promises.

  12. The Use of Femoral Neck Axis Length to Estimate Sex and Ancestry.

    PubMed

    Meeusen, Rebecca A; Christensen, Angi M; Hefner, Joseph T

    2015-09-01

    Having multiple reliable methods of estimating sex and ancestry from various skeletal features increases the likelihood of identifying skeletal remains. Femoral neck axis length (FNAL), as measured in living individuals, has been shown to vary by sex and ancestry. FNAL has not, however, been previously measured directly from skeletonized remains and investigated for its potential use in forensic anthropological applications. This research proposes a method for measuring FNAL from skeletal remains, determines the reliability and repeatability of the measurement, and assesses the validity of FNAL in sex and ancestry estimation. Results showed low interobserver error in the measurement of FNAL (TEM=0.33 mm, R=0.99). Significant differences in FNAL were found between sexes as well as between American Black, American White, and Native American groups. FNAL can correctly classify sex in ~86% of all cases and is considered valuable to sex estimation. The value of FNAL to ancestry estimation, however, is considered limited. PMID:26258403

  13. 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...

  14. 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

  15. 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

  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. PMID:26781090

  19. 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

  20. 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

  1. A Genomic Portrait of Haplotype Diversity and Signatures of Selection in Indigenous Southern African Populations

    PubMed Central

    Chimusa, Emile R.; Meintjies, Ayton; Tchanga, Milaine; Mulder, Nicola; Seoighe, Cathal; Soodyall, Himla; Ramesar, Rajkumar

    2015-01-01

    We report a study of genome-wide, dense SNP (∼900K) and copy number polymorphism data of indigenous southern Africans. We demonstrate the genetic contribution to southern and eastern African populations, which involved admixture between indigenous San, Niger-Congo-speaking and populations of Eurasian ancestry. This finding illustrates the need to account for stratification in genome-wide association studies, and that admixture mapping would likely be a successful approach in these populations. We developed a strategy to detect the signature of selection prior to and following putative admixture events. Several genomic regions show an unusual excess of Niger-Kordofanian, and unusual deficiency of both San and Eurasian ancestry, which were considered the footprints of selection after population admixture. Several SNPs with strong allele frequency differences were observed predominantly between the admixed indigenous southern African populations, and their ancestral Eurasian populations. Interestingly, many candidate genes, which were identified within the genomic regions showing signals for selection, were associated with southern African-specific high-risk, mostly communicable diseases, such as malaria, influenza, tuberculosis, and human immunodeficiency virus/AIDs. This observation suggests a potentially important role that these genes might have played in adapting to the environment. Additionally, our analyses of haplotype structure, linkage disequilibrium, recombination, copy number variation and genome-wide admixture highlight, and support the unique position of San relative to both African and non-African populations. This study contributes to a better understanding of population ancestry and selection in south-eastern African populations; and the data and results obtained will support research into the genetic contributions to infectious as well as non-communicable diseases in the region. PMID:25811879

  2. 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

  3. Methylation quantitative trait loci (meQTLs) are consistently detected across ancestry, developmental stage, and tissue type

    PubMed Central

    2014-01-01

    Background Individual genotypes at specific loci can result in different patterns of DNA methylation. These methylation quantitative trait loci (meQTLs) influence methylation across extended genomic regions and may underlie direct SNP associations or gene-environment interactions. We hypothesized that the detection of meQTLs varies with ancestral population, developmental stage, and tissue type. We explored this by analyzing seven datasets that varied by ancestry (African American vs. Caucasian), developmental stage (neonate vs. adult), and tissue type (blood vs. four regions of postmortem brain) with genome-wide DNA methylation and SNP data. We tested for meQTLs by constructing linear regression models of methylation levels at each CpG site on SNP genotypes within 50 kb under an additive model controlling for multiple tests. Results Most meQTLs mapped to intronic regions, although a limited number appeared to occur in synonymous or nonsynonymous coding SNPs. We saw significant overlap of meQTLs between ancestral groups, developmental stages, and tissue types, with the highest rates of overlap within the four brain regions. Compared with a random group of SNPs with comparable frequencies, meQTLs were more likely to be 1) represented among the most associated SNPs in the WTCCC bipolar disorder results and 2) located in microRNA binding sites. Conclusions These data give us insight into how SNPs impact gene regulation and support the notion that peripheral blood may be a reliable correlate of physiological processes in other tissues. PMID:24555763

  4. Fast spatial ancestry via flexible allele frequency surfaces

    PubMed Central

    Rañola, John Michael; Novembre, John; Lange, Kenneth

    2014-01-01

    Motivation: Unique modeling and computational challenges arise in locating the geographic origin of individuals based on their genetic backgrounds. Single-nucleotide polymorphisms (SNPs) vary widely in informativeness, allele frequencies change non-linearly with geography and reliable localization requires evidence to be integrated across a multitude of SNPs. These problems become even more acute for individuals of mixed ancestry. It is hardly surprising that matching genetic models to computational constraints has limited the development of methods for estimating geographic origins. We attack these related problems by borrowing ideas from image processing and optimization theory. Our proposed model divides the region of interest into pixels and operates SNP by SNP. We estimate allele frequencies across the landscape by maximizing a product of binomial likelihoods penalized by nearest neighbor interactions. Penalization smooths allele frequency estimates and promotes estimation at pixels with no data. Maximization is accomplished by a minorize–maximize (MM) algorithm. Once allele frequency surfaces are available, one can apply Bayes’ rule to compute the posterior probability that each pixel is the pixel of origin of a given person. Placement of admixed individuals on the landscape is more complicated and requires estimation of the fractional contribution of each pixel to a person’s genome. This estimation problem also succumbs to a penalized MM algorithm. Results: We applied the model to the Population Reference Sample (POPRES) data. The model gives better localization for both unmixed and admixed individuals than existing methods despite using just a small fraction of the available SNPs. Computing times are comparable with the best competing software. Availability and implementation: Software will be freely available as the OriGen package in R. Contact: ranolaj@uw.edu or klange@ucla.edu Supplementary information: Supplementary data are available at

  5. Body Mass Index (BMI) Trajectories in Infancy Differ by Population Ancestry and May Presage Disparities in Early Childhood Obesity

    PubMed Central

    Roy, Sani M.; Chesi, Alessandra; Mentch, Frank; Xiao, Rui; Chiavacci, Rosetta; Mitchell, Jonathan A.; Kelly, Andrea; Hakonarson, Hakon; Grant, Struan F.A.; Zemel, Babette S.

    2015-01-01

    Context: No consensus definition exists for excess adiposity during infancy. After age 2 years, high body mass index (BMI) is related to adverse cardiometabolic outcomes. Before age 2 years, the utility of BMI as a metric of excess adiposity is unknown. Objectives: The objective of the study was to characterize infant BMI trajectories in a diverse, longitudinal cohort and investigate the relationship between the infancy BMI trajectory and childhood obesity. Subjects: Healthy, nonpreterm infants (n = 2114) in the Genetic Causes for Complex Pediatric Disorders study (The Children's Hospital of Philadelphia) with six or more BMI measurements in the first 13.5 months participated in the study. Design: For each infant, the BMI trajectory was modeled using polynomial regression. Independent effects of clinical factors on magnitude and timing of peak BMI were assessed. The relationship between infancy BMI and early childhood BMI (age 4 y) was examined (n = 1075). Results: The cohort was 53% male and 61% African-American. Peak BMI was 18.6 ± 1.7 kg/m2 and occurred at 8.6 ± 1.4 months. In multivariate analysis, boys had a higher (0.50 kg/m2, P < .001) peak BMI than girls. The peak was higher (0.53 kg/m2, P ≤ .001) and occurred earlier (by 12 d, P < .001) in African-American vs white children. The odds of obesity at age 4 years increased among children with higher (odds ratio 2.02; P < .001) and later (odds ratio 1.26; P = .02) infancy peak BMI. Conclusions: We demonstrate sex- and ancestry-specific differences in infancy BMI and an association of infancy peak BMI with childhood BMI. These findings support the potential utility of infancy BMI to identify children younger than age 2 years with increased risk for later obesity. PMID:25636051

  6. Early-Onset Chronic Obstructive Pulmonary Disease Is Associated with Female Sex, Maternal Factors, and African American Race in the COPDGene Study

    PubMed Central

    Foreman, Marilyn G.; Zhang, Lening; Murphy, James; Hansel, Nadia N.; Make, Barry; Hokanson, John E.; Washko, George; Regan, Elizabeth A.; Crapo, James D.; Silverman, Edwin K.

    2011-01-01

    Rationale: The characterization of young adults who develop late-onset diseases may augment the detection of novel genes and promote new pathogenic insights. Methods: We analyzed data from 2,500 individuals of African and European ancestry in the COPDGene Study. Subjects with severe, early-onset chronic obstructive pulmonary disease (COPD) (n = 70, age < 55 yr, FEV1 < 50% predicted) were compared with older subjects with COPD (n = 306, age > 64 yr, FEV1 < 50% predicted). Measurements and Main Results: Subjects with severe, early-onset COPD were predominantly females (66%), P = 0.0004. Proportionally, early-onset COPD was seen in 42% (25 of 59) of African Americans versus 14% (45 of 317) of non-Hispanic whites, P < 0.0001. Other risk factors included current smoking (56 vs. 17%, P < 0.0001) and self-report of asthma (39 vs. 25%, P = 0.008). Maternal smoking (70 vs. 44%, P = 0.0001) and maternal COPD (23 vs. 12%, P = 0.03) were reported more commonly in subjects with early-onset COPD. Multivariable regression analysis found association with African American race, odds ratio (OR), 7.5 (95% confidence interval [CI], 2.3–24; P = 0.0007); maternal COPD, OR, 4.7 (95% CI, 1.3–17; P = 0.02); female sex, OR, 3.1 (95% CI, 1.1–8.7; P = 0.03); and each pack-year of smoking, OR, 0.98 (95% CI, 0.96–1.0; P = 0.03). Conclusions: These observations support the hypothesis that severe, early-onset COPD is prevalent in females and is influenced by maternal factors. Future genetic studies should evaluate (1) gene-by-sex interactions to address sex-specific genetic contributions and (2) gene-by-race interactions. PMID:21562134

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

    PubMed Central

    2011-01-01

    Background In recent years, phylogeographic studies have produced detailed knowledge on the worldwide distribution of mitochondrial DNA (mtDNA) variants, linking specific clades of the mtDNA phylogeny with certain geographic areas. However, a multiplex genotyping system for the detection of the mtDNA haplogroups of major continental distribution that would be desirable for efficient DNA-based bio-geographic ancestry testing in various applications is still missing. Results Three multiplex genotyping assays, based on single-base primer extension technology, were developed targeting a total of 36 coding-region mtDNA variants that together differentiate 43 matrilineal haplo-/paragroups. These include the major diagnostic haplogroups for Africa, Western Eurasia, Eastern Eurasia and Native America. The assays show high sensitivity with respect to the amount of template DNA: successful amplification could still be obtained when using as little as 4 pg of genomic DNA and the technology is suitable for medium-throughput analyses. Conclusions We introduce an efficient and sensitive multiplex genotyping system for bio-geographic ancestry inference from mtDNA that provides resolution on the continental level. The method can be applied in forensics, to aid tracing unknown suspects, as well as in population studies, genealogy and personal ancestry testing. For more complete inferences of overall bio-geographic ancestry from DNA, the mtDNA system provided here can be combined with multiplex systems for suitable autosomal and, in the case of males, Y-chromosomal ancestry-sensitive DNA markers. PMID:21429198

  8. Sparse principal component analysis for identifying ancestry-informative markers in genome-wide association studies.

    PubMed

    Lee, Seokho; Epstein, Michael P; Duncan, Richard; Lin, Xihong

    2012-05-01

    Genome-wide association studies (GWAS) routinely apply principal component analysis (PCA) to infer population structure within a sample to correct for confounding due to ancestry. GWAS implementation of PCA uses tens of thousands of single-nucleotide polymorphisms (SNPs) to infer structure, despite the fact that only a small fraction of such SNPs provides useful information on ancestry. The identification of this reduced set of ancestry-informative markers (AIMs) from a GWAS has practical value; for example, researchers can genotype the AIM set to correct for potential confounding due to ancestry in follow-up studies that utilize custom SNP or sequencing technology. We propose a novel technique to identify AIMs from genome-wide SNP data using sparse PCA. The procedure uses penalized regression methods to identify those SNPs in a genome-wide panel that significantly contribute to the principal components while encouraging SNPs that provide negligible loadings to vanish from the analysis. We found that sparse PCA leads to negligible loss of ancestry information compared to traditional PCA analysis of genome-wide SNP data. We further demonstrate the value of sparse PCA for AIM selection using real data from the International HapMap Project and a genomewide study of inflammatory bowel disease. We have implemented our approach in open-source R software for public use. PMID:22508067

  9. Estimating proportions of materials using mixture models

    NASA Technical Reports Server (NTRS)

    Heydorn, R. P.; Basu, R.

    1983-01-01

    An approach to proportion estimation based on the notion of a mixture model, appropriate parametric forms for a mixture model that appears to fit observed remotely sensed data, methods for estimating the parameters in these models, methods for labelling proportion determination from the mixture model, and methods which use the mixture model estimates as auxiliary variable values in some proportion estimation schemes are addressed.

  10. 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

  11. 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

  12. 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. PMID:27364267

  13. 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

  14. 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. PMID:26452039

  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. PMID:25845441

  16. 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…

  17. 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

  18. 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

  19. 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

  20. 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. PMID:25752862

  1. Genome-wide association of anthropometric traits in African- and African-derived populations.

    PubMed

    Kang, Sun J; Chiang, Charleston W K; Palmer, Cameron D; Tayo, Bamidele O; Lettre, Guillaume; Butler, Johannah L; Hackett, Rachel; Adeyemo, Adebowale A; Guiducci, Candace; Berzins, Ilze; Nguyen, Thutrang T; Feng, Tao; Luke, Amy; Shriner, Daniel; Ardlie, Kristin; Rotimi, Charles; Wilks, Rainford; Forrester, Terrence; McKenzie, Colin A; Lyon, Helen N; Cooper, Richard S; Zhu, Xiaofeng; Hirschhorn, Joel N

    2010-07-01

    Genome-wide association (GWA) studies have identified common variants that are associated with a variety of traits and diseases, but most studies have been performed in European-derived populations. Here, we describe the first genome-wide analyses of imputed genotype and copy number variants (CNVs) for anthropometric measures in African-derived populations: 1188 Nigerians from Igbo-Ora and Ibadan, Nigeria, and 743 African-Americans from Maywood, IL. To improve the reach of our study, we used imputation to estimate genotypes at approximately 2.1 million single-nucleotide polymorphisms (SNPs) and also tested CNVs for association. No SNPs or common CNVs reached a genome-wide significance level for association with height or body mass index (BMI), and the best signals from a meta-analysis of the two cohorts did not replicate in approximately 3700 African-Americans and Jamaicans. However, several loci previously confirmed in European populations showed evidence of replication in our GWA panel of African-derived populations, including variants near IHH and DLEU7 for height and MC4R for BMI. Analysis of global burden of rare CNVs suggested that lean individuals possess greater total burden of CNVs, but this finding was not supported in an independent European population. Our results suggest that there are not multiple loci with strong effects on anthropometric traits in African-derived populations and that sample sizes comparable to those needed in European GWA studies will be required to identify replicable associations. Meta-analysis of this data set with additional studies in African-ancestry populations will be helpful to improve power to detect novel associations. PMID:20400458

  2. 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

  3. 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

  4. 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…

  5. 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…

  6. Predictors of Cigarette Use Among South African Adolescents

    PubMed Central

    Brook, Judith S.; Morojele, Neo K.; Brook, David W.; Rosen, Zohn

    2005-01-01

    The present study assesses the interrelation among domains of ethnic factors, the individual’s sense of well-being, personality/attitudes/behaviors, sibling and peer smoking, and adolescent smoking behavior. The sample consisted of 1,468 South African adolescents selected from four ethnic groups self-identified as defined by current South African usage: Black (mainly Zulu and Xhosa), Indian, White, and Coloured (mixed ancestry). In accordance with Family Interactional Theory, there was a sequence of patterning from ethnic factors and the individual’s sense of well-being to adolescent personality/attitudes/behaviors and models of smoking. All of the four domains in the model also had a direct effect on adolescent smoking behavior. The findings suggest four possible targets of therapeutic or preventive intervention with regard to adolescent smoking: ethnic factors, the individual’s sense of well-being, personality/attitudes/behaviors, and smoking within the peer group. PMID:16262539

  7. Colloquium paper: phylogenomic evidence of adaptive evolution in the ancestry of humans.

    PubMed

    Goodman, Morris; Sterner, Kirstin N

    2010-05-11

    In Charles Darwin's tree model for life's evolution, natural selection adaptively modifies newly arisen species as they branch apart from their common ancestor. In accord with this Darwinian concept, the phylogenomic approach to elucidating adaptive evolution in genes and genomes in the ancestry of modern humans requires a well supported and well sampled phylogeny that accurately places humans and other primates and mammals with respect to one another. For more than a century, first from the comparative immunological work of Nuttall on blood sera and now from comparative genomic studies, molecular findings have demonstrated the close kinship of humans to chimpanzees. The close genetic correspondence of chimpanzees to humans and the relative shortness of our evolutionary separation suggest that most distinctive features of the modern human phenotype had already evolved during our ancestry with chimpanzees. Thus, a phylogenomic assessment of being human should examine earlier stages of human ancestry as well as later stages. In addition, with the availability of a number of mammalian genomes, similarities in phenotype between distantly related taxa should be explored for evidence of convergent or parallel adaptive evolution. As an example, recent phylogenomic evidence has shown that adaptive evolution of aerobic energy metabolism genes may have helped shape such distinctive modern human features as long life spans and enlarged brains in the ancestries of both humans and elephants. PMID:20445097

  8. 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

  9. 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

  10. 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

  11. 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 ...

  12. Estimating crop proportions from remotely sensed data

    NASA Technical Reports Server (NTRS)

    Feiveson, A. H. (Principal Investigator)

    1979-01-01

    The classification/pixel-count method for estimating the proportion of wheat in each segment is theoretically biased even if all distributional assumptions are met. Alternative ways to estimate crop proportions are examined and their performance testing is considered. Topics covered include general linear functional estimates, the method of moments, and maximum likelihood estimators.

  13. 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…

  14. 34 CFR 81.32 - Proportionality.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Proportionality. 81.32 Section 81.32 Education Office of the Secretary, Department of Education GENERAL EDUCATION PROVISIONS ACT-ENFORCEMENT Hearings for Recovery of Funds § 81.32 Proportionality. (a)(1) A recipient that made an unallowable expenditure...

  15. Prospective Elementary School Teachers' Proportional Reasoning

    ERIC Educational Resources Information Center

    Valverde, Gabriela; Castro, Encarnación

    2012-01-01

    We present the findings of a study on prospective elementary teachers' proportional reasoning. After describing some of the teachers' performance in solving multiplicative structure problems that involve ratios and relations of direct proportionality between quantities, we were able to establish classifications of their answers according to…

  16. 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…

  17. 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…

  18. Neonatal Variables, Altitude of Residence and Aymara Ancestry in Northern Chile

    PubMed Central

    Rothhammer, Francisco; Fuentes-Guajardo, Macarena; Chakraborty, Ranajit; Lorenzo Bermejo, Justo; Dittmar, Manuela

    2015-01-01

    Studies performed in the Andean plateau, one of the highest inhabited areas in the world, have reported that reduced availability of oxygen is associated to fetal growth retardation and lower birth weight, which are established predictors of morbidity and mortality during the first year of life. To test this hypothesis, perinatal variables of neonates born at the Juan Noé Hospital of Arica, Chile, were analyzed in relation to altitude of residence and Aymara ancestry of their mothers. The study population comprised the offspring of 5,295 mothers born between February 2004 and August 2010. Information included birth weight, height, head circumference, gestational age, altitude of residence and socioeconomic status, and was obtained from medical records. Mother´s ancestry was assessed based on surnames which were linked to percentages of Aymara admixture estimates relying on 40 selected ancestry informative markers. After correcting for the effect of multicollinearity among predictor variables, neonates born to mothers with an increased component of Aymara ancestry showed significantly higher birth weight and height at sea level, a marginally significant (p-value 0.06) decrease of birth weight and a significant decrease of height with altitude in comparison with the offspring of mothers with low Aymara ancestry. Since observed tendencies are suggestive of a possible genetic adaptation to hypoxia of the Chilean Aymara, we discuss briefly preliminary evidence related to fetal oxygen transport, particularly polymorphisms in the promoters of the HBG1 and HBG2 genes that are modulators of HbF synthesis, obtained in this ethnic group. PMID:25885573

  19. Abraham's children in the genome era: major Jewish diaspora populations comprise distinct genetic clusters with shared Middle Eastern Ancestry.

    PubMed

    Atzmon, Gil; Hao, Li; Pe'er, Itsik; Velez, Christopher; Pearlman, Alexander; Palamara, Pier Francesco; Morrow, Bernice; Friedman, Eitan; Oddoux, Carole; Burns, Edward; Ostrer, Harry

    2010-06-11

    For more than a century, Jews and non-Jews alike have tried to define the relatedness of contemporary Jewish people. Previous genetic studies of blood group and serum markers suggested that Jewish groups had Middle Eastern origin with greater genetic similarity between paired Jewish populations. However, these and successor studies of monoallelic Y chromosomal and mitochondrial genetic markers did not resolve the issues of within and between-group Jewish genetic identity. Here, genome-wide analysis of seven Jewish groups (Iranian, Iraqi, Syrian, Italian, Turkish, Greek, and Ashkenazi) and comparison with non-Jewish groups demonstrated distinctive Jewish population clusters, each with shared Middle Eastern ancestry, proximity to contemporary Middle Eastern populations, and variable degrees of European and North African admixture. Two major groups were identified by principal component, phylogenetic, and identity by descent (IBD) analysis: Middle Eastern Jews and European/Syrian Jews. The IBD segment sharing and the proximity of European Jews to each other and to southern European populations suggested similar origins for European Jewry and refuted large-scale genetic contributions of Central and Eastern European and Slavic populations to the formation of Ashkenazi Jewry. Rapid decay of IBD in Ashkenazi Jewish genomes was consistent with a severe bottleneck followed by large expansion, such as occurred with the so-called demographic miracle of population expansion from 50,000 people at the beginning of the 15th century to 5,000,000 people at the beginning of the 19th century. Thus, this study demonstrates that European/Syrian and Middle Eastern Jews represent a series of geographical isolates or clusters woven together by shared IBD genetic threads. PMID:20560205

  20. Abraham's Children in the Genome Era: Major Jewish Diaspora Populations Comprise Distinct Genetic Clusters with Shared Middle Eastern Ancestry

    PubMed Central

    Atzmon, Gil; Hao, Li; Pe'er, Itsik; Velez, Christopher; Pearlman, Alexander; Palamara, Pier Francesco; Morrow, Bernice; Friedman, Eitan; Oddoux, Carole; Burns, Edward; Ostrer, Harry

    2010-01-01

    For more than a century, Jews and non-Jews alike have tried to define the relatedness of contemporary Jewish people. Previous genetic studies of blood group and serum markers suggested that Jewish groups had Middle Eastern origin with greater genetic similarity between paired Jewish populations. However, these and successor studies of monoallelic Y chromosomal and mitochondrial genetic markers did not resolve the issues of within and between-group Jewish genetic identity. Here, genome-wide analysis of seven Jewish groups (Iranian, Iraqi, Syrian, Italian, Turkish, Greek, and Ashkenazi) and comparison with non-Jewish groups demonstrated distinctive Jewish population clusters, each with shared Middle Eastern ancestry, proximity to contemporary Middle Eastern populations, and variable degrees of European and North African admixture. Two major groups were identified by principal component, phylogenetic, and identity by descent (IBD) analysis: Middle Eastern Jews and European/Syrian Jews. The IBD segment sharing and the proximity of European Jews to each other and to southern European populations suggested similar origins for European Jewry and refuted large-scale genetic contributions of Central and Eastern European and Slavic populations to the formation of Ashkenazi Jewry. Rapid decay of IBD in Ashkenazi Jewish genomes was consistent with a severe bottleneck followed by large expansion, such as occurred with the so-called demographic miracle of population expansion from 50,000 people at the beginning of the 15th century to 5,000,000 people at the beginning of the 19th century. Thus, this study demonstrates that European/Syrian and Middle Eastern Jews represent a series of geographical isolates or clusters woven together by shared IBD genetic threads. PMID:20560205

  1. 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

  2. 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.

  3. Evaluation of Genome Wide Association Study Associated Type 2 Diabetes Susceptibility Loci in Sub Saharan Africans.

    PubMed

    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

  4. 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

  5. Prostate cancer disparities in Black men of African descent: a comparative literature review of prostate cancer burden among Black men in the United States, Caribbean, United Kingdom, and West Africa

    PubMed Central

    Odedina, Folakemi T; Akinremi, Titilola O; Chinegwundoh, Frank; Roberts, Robin; Yu, Daohai; Reams, R Renee; Freedman, Matthew L; Rivers, Brian; Green, B Lee; Kumar, Nagi

    2009-01-01

    Background African American men have the highest prostate cancer morbidity and mortality rates than any other racial or ethnic group in the US. Although the overall incidence of and mortality from prostate cancer has been declining in White men since 1991, the decline in African American men lags behind White men. Of particular concern is the growing literature on the disproportionate burden of prostate cancer among other Black men of West African ancestry in the Caribbean Islands, United Kingdom and West Africa. This higher incidence of prostate cancer observed in populations of African descent may be attributed to the fact that these populations share ancestral genetic factors. To better understand the burden of prostate cancer among men of West African Ancestry, we conducted a review of the literature on prostate cancer incidence, prevalence, and mortality in the countries connected by the Transatlantic Slave Trade. Results Several published studies indicate high prostate cancer burden in Nigeria and Ghana. There was no published literature for the countries Benin, Gambia and Senegal that met our review criteria. Prostate cancer morbidity and/or mortality data from the Caribbean Islands and the United Kingdom also provided comparable or worse prostate cancer burden to that of US Blacks. Conclusion The growing literature on the disproportionate burden of prostate cancer among other Black men of West African ancestry follows the path of the Transatlantic Slave Trade. To better understand and address the global prostate cancer disparities seen in Black men of West African ancestry, future studies should explore the genetic and environmental risk factors for prostate cancer among this group. PMID:19208207

  6. Proportion estimation using prior cluster purities

    NASA Technical Reports Server (NTRS)

    Terrell, G. R. (Principal Investigator)

    1980-01-01

    The prior distribution of CLASSY component purities is studied, and this information incorporated into maximum likelihood crop proportion estimators. The method is tested on Transition Year spring small grain segments.

  7. 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.

  8. 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…

  9. 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…

  10. Coalescent entanglement and the conditional dependence of the times to common ancestry of mutually exclusive pairs of individuals.

    PubMed

    Wu, Steven; Koelle, Katia; Rodrigo, Allen

    2013-01-01

    The Kingman coalescent is a continuous-time diffusion approximation of the times to common ancestry of a sample of individuals drawn from a Wright-Fisher population. Here, we use the coalescent to answer a simple question: if we know the ancestry of 2 randomly sampled individuals in the population, what does it tell us about the ancestry of 2 other randomly sampled individuals? We show that there is a conditional dependency between the times to common ancestry between pairs of randomly sampled individuals. We call this "coalescent entanglement," and we demonstrate its effects through simulation. The effects of entanglement extend beyond the coalescent to phylogenetic birth-death processes in general. Entanglement also exerts its effects when the pairs of individuals chosen share no common lineages in the paths that connect the individuals in each pair. PMID:23077234

  11. Reassessing manual proportions in Australopithecus afarensis.

    PubMed

    Rolian, Campbell; Gordon, Adam D

    2013-11-01

    Previous analyses of hand morphology in Australopithecus afarensis have concluded that this taxon had modern human-like manual proportions, with relatively long thumbs and short fingers. These conclusions are based on the A.L.333 composite fossil assemblage from Hadar, Ethiopia, and are premised on the ability to assign phalanges to a single individual, and to the correct side and digit. Neither assignment is secure, however, given the taphonomy and sample composition at A.L.333. We use a resampling approach that includes the entire assemblage of complete hand elements at Hadar, and takes into account uncertainties in identifying phalanges by individual, side and digit number. This approach provides the most conservative estimates of manual proportions in Au. afarensis. We resampled hand long bone lengths in Au. afarensis and extant hominoids, and obtained confidence limits for distributions of manual proportions in the latter. Results confirm that intrinsic manual proportions in Au. afarensis are dissimilar to Pan and Pongo. However, manual proportions in Au. afarensis often fall at the upper end of the distribution in Gorilla, and very lower end in Homo, corresponding to disproportionately short thumbs and long medial digits in Homo. This suggests that manual proportions in Au. afarensis, particularly metacarpal proportions, were not as derived towards Homo as previously described, but rather are intermediate between gorillas and humans. Functionally, these results suggest Au. afarensis could not produce precision grips with the same efficiency as modern humans, which may in part account for the absence of lithic technology in this fossil taxon. PMID:24104947

  12. Dissecting ancestry genomic background in substance dependence genome-wide association studies

    PubMed Central

    Polimanti, Renato; Yang, Can; Zhao, Hongyu; Gelernter, Joel

    2015-01-01

    Aims To understand the role of ancestral genomic background in substance dependence (SD) genome-wide association studies (GWAS), we analyzed population diversity at genetic loci associated with SD traits and evaluated its effect on GWAS outcomes. Materials & methods We investigated 24 genes with variants associated with SD by GWAS; and 82 loci with putative subordinate roles with respect to SD-associated genes. Results We observed high ancestry-related frequency differences in common functional alleles in GWAS relevant genes and their interactive partners. Common functional alleles with high frequency differences demonstrated significant effects on the GWAS outcomes. Conclusion Population differences in SD GWAS outcomes seem not to be influenced by general variation across the genome, but by ancestry-related local haplotype structures at SD-associated loci. PMID:26267224

  13. Pigment phenotype and biogeographical ancestry from ancient skeletal remains: inferences from multiplexed autosomal SNP analysis.

    PubMed

    Bouakaze, Caroline; Keyser, Christine; Crubézy, Eric; Montagnon, Daniel; Ludes, Bertrand

    2009-07-01

    In the present study, a multiplexed genotyping assay for ten single nucleotide polymorphisms (SNPs) located within six pigmentation candidate genes was developed on modern biological samples and applied to DNA retrieved from 25 archeological human remains from southern central Siberia dating from the Bronze and Iron Ages. SNP genotyping was successful for the majority of ancient samples and revealed that most probably had typical European pigment features, i.e., blue or green eye color, light hair color and skin type, and were likely of European individual ancestry. To our knowledge, this study reports for the first time the multiplexed typing of autosomal SNPs on aged and degraded DNA. By providing valuable information on pigment traits of an individual and allowing individual biogeographical ancestry estimation, autosomal SNP typing can improve ancient DNA studies and aid human identification in some forensic casework situations when used to complement conventional molecular markers. PMID:19415315

  14. Nasal aperture shape evaluation between black and white South Africans.

    PubMed

    McDowell, Jennifer L; L'Abbé, Ericka N; Kenyhercz, Michael W

    2012-10-10

    The purpose of this study was to combine morphoscopic and metric analyses to assess variation in nasal aperture size and shape of black and white South Africans. Thirteen landmarks were digitized from the bony nasal region of 152 crania using an electromechanic instrument for geometric morphometric (general procrustes analysis) and craniometric analyses. Elliptical Fourier analysis was used to assess shape of the nasal aperture via outlines applied through photographs. Both principal component and discriminant function analyses were applied to these statistical methods. Black South Africans were classified 95-96% correctly and white South Africans were classified 91-94% correctly. In a four-way analysis of sex and ancestry, classification accuracy ranged from 56 to 70%. Most misclassifications were between the sexes within each group which suggests an absence of sexual dimorphism. This study found that there is quantifiable variation in shape of the nasal aperture between black and white South African groups using all three statistical methods. In forensic application, standard craniometrics can be used to accurately classify an unknown person. PMID:22727267

  15. 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.

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

    PubMed

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

    2016-07-01

    The century-old use of genetic markers to determine population relationships has morphed in modern forensics into use of markers to determine the ancestry of an individual from a DNA sample. Researchers have identified sets of SNPs that have frequency differences among populations and many sets of SNPs have been published for the purpose of inferring ancestry. Such inference also requires reference datasets for the particular set of SNPs selected. We have identified 21 largely independent published panels of ancestry informative SNPs (AISNPs) and examined their union of 1397 SNPs. No SNP occurs in more than 6 panels. The 1397 SNPs in 21 panels yield a largely empty matrix that is inhibiting progress on more refined ability to infer ancestry for a forensic sample. The most common set of reference populations is the HGDP set of 52 small population samples totaling a thousand individuals. Only 46 (3%) of the 1397 SNPs occur in three or more panels. We assembled a new dataset for 44 of those SNPs involving 4,559 individuals from 73 populations. Analyses of this dataset provided clear differentiation of only five biogeographic regions: sub-Saharan Africa, Europe and SW Asia, South Asia, East Asia, and the Americas. This is an inadequate level of biogeographic resolution already exceeded by other panels. We conclude that more such AISNP panels are not needed and that the forensic community must collaborate to develop a common set of highly differentiating AISNPs typed on a very large number of population samples. How that can be accomplished will be the subject of future discussion. PMID:26977931

  17. Genetic ancestry inference using support vector machines, and the active emergence of a unique American population.

    PubMed

    Haasl, Ryan J; McCarty, Catherine A; Payseur, Bret A

    2013-05-01

    We use genotype data from the Marshfield Clinical Research Foundation Personalized Medicine Research Project to investigate genetic similarity and divergence between Europeans and the sampled population of European Americans in Central Wisconsin, USA. To infer recent genetic ancestry of the sampled Wisconsinites, we train support vector machines (SVMs) on the positions of Europeans along top principal components (PCs). Our SVM models partition continent-wide European genetic variance into eight regional classes, which is an improvement over the geographically broader categories of recent ancestry reported by personal genomics companies. After correcting for misclassification error associated with the SVMs (<10%, in all cases), we observe a >14% discrepancy between insular ancestries reported by Wisconsinites and those inferred by SVM. Values of FST as well as Mantel tests for correlation between genetic and European geographic distances indicate minimal divergence between Europe and the local Wisconsin population. However, we find that individuals from the Wisconsin sample show greater dispersion along higher-order PCs than individuals from Europe. Hypothesizing that this pattern is characteristic of nascent divergence, we run computer simulations that mimic the recent peopling of Wisconsin. Simulations corroborate the pattern in higher-order PCs, demonstrate its transient nature, and show that admixture accelerates the rate of divergence between the admixed population and its parental sources relative to drift alone. Together, empirical and simulation results suggest that genetic divergence between European source populations and European Americans in Central Wisconsin is subtle but already under way. PMID:23211701

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

    PubMed

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

    2014-01-01

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

  19. Turkish Population Structure and Genetic Ancestry Reveal Relatedness among Eurasian Populations

    PubMed Central

    Hodoğlugil, Uğur; Mahley, Robert W.

    2013-01-01

    Summary Turkey connects the Middle East, Europe, and Asia and has experienced major population movements. We examined the population structure and genetic relatedness of samples from three regions of Turkey using over 500,000 SNP genotypes. The data were analyzed together with Human Genome Diversity Panel data. To obtain a more representative sampling from Central Asia, Kyrgyz samples (Bishkek, Kyrgyzstan) were genotyped and analyzed. Principal component (PC) analysis reveals a significant overlap between Turks and Middle Easterners and a relationship with Europeans and South and Central Asians; however, the Turkish genetic structure is unique. FRAPPE, STRUCTURE, and phylogenetic analyses support the PC analysis depending upon the number of parental ancestry components chosen. For example, supervised STRUCTURE (K = 3) illustrates a genetic ancestry for the Turks of 45% Middle Eastern (95% CI, 42–49), 40% European (95% CI, 36–44), and 15% Central Asian (95% CI, 13–16), whereas at K = 4 the genetic ancestry of the Turks was 38% European (95% CI, 35–42), 35% Middle Eastern (95% CI, 33–38), 18% South Asian (95% CI, 16–19), and 9% Central Asian (95% CI, 7–11). PC analysis and FRAPPE/STRUCTURE results from three regions in Turkey (Aydin, Istanbul, and Kayseri) were superimposed, without clear subpopulation structure, suggesting the selected samples were rather homogeneous. Thus, this study demonstrates admixture of Turkish people reflecting the population migration patterns. PMID:22332727

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

    PubMed Central

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

    2014-01-01

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

  1. Proportion congruency effects: instructions may be enough.

    PubMed

    Entel, Olga; Tzelgov, Joseph; Bereby-Meyer, Yoella

    2014-01-01

    Learning takes time, namely, one needs to be exposed to contingency relations between stimulus dimensions in order to learn, whereas intentional control can be recruited through task demands. Therefore showing that control can be recruited as a function of experimental instructions alone, that is, adapting the processing according to the instructions before the exposure to the task, can be taken as evidence for existence of control recruitment in the absence of learning. This was done by manipulating the information given at the outset of the experiment. In the first experiment, we manipulated list-level congruency proportion. Half of the participants were informed that most of the stimuli would be congruent, whereas the other half were informed that most of the stimuli would be incongruent. This held true for the stimuli in the second part of each experiment. In the first part, however, the proportion of the two stimulus types was equal. A proportion congruent (PC) effect was found in both parts of the experiment, but it was larger in the second part. In our second experiment, we manipulated the proportion of the stimuli within participants by applying an item-specific design. This was done by presenting some color words most often in their congruent color, and other color words in incongruent colors. Participants were informed about the exact word-color pairings in advance. Similar to Experiment 1, this held true only for the second experimental part. In contrast to our first experiment, informing participants in advance did not result in an item-specific proportion effect, which was observed only in the second part. Thus our results support the hypothesis that instructions may be enough to trigger list-level control, yet learning does contribute to the PC effect under such conditions. The item-level proportion effect is apparently caused by learning or at least it is moderated by it. PMID:25339929

  2. 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.

  3. 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…

  4. 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.)

  5. 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. PMID:18802788

  6. 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…

  7. Research on fluidics, valves, and proportional amplifiers

    NASA Technical Reports Server (NTRS)

    1974-01-01

    Research and development being conducted at the Systems and Controls Laboratory is reviewed. Static characteristics (supply, input, transfer, output, and noise characteristics) of laminar proportional amplifiers were investigated. Other topics discussed include velocity profiles for laminar fluidic jets, speed control systems employing a jet pipe valve, and power amplification with a vortex valve.

  8. Body proportions of Homo habilis reviewed.

    PubMed

    Haeusler, Martin; McHenry, Henry M

    2004-04-01

    The ratio of fore- to hindlimb size plays an important role in our understanding of human evolution. Although Homo habilis was relatively modern craniodentally, its body proportions are commonly believed to have been more apelike than in the earlier Australopithecus afarensis. The evidence for this, however, rests, on two fragmentary skeletons, OH 62 and KNM-ER 3735. The upper limb of the better-preserved OH 62 from Olduvai Gorge is long and slender, but its hindlimb is represented mainly by the proximal portion of a thin femur of uncertain length. The present analysis shows that upper-to-lower limb shaft proportions of both OH 62 and AL 288-1 (A. afarensis) fall in the modern human range of variation, although OH 62 also falls inside that of chimpanzees due to their overlap in small individuals. Despite being more fragmentary, the larger-bodied KNM-ER 3735 lies outside the chimpanzee range and close to the human mean. Because the differences between any of the three individuals are compatible with the range of variation seen in extant hominoid groups, it is not legitimate to infer more primitive upper-to-lower limb shaft proportions for either H. habilis or A. afarensis. Femur length of OH 62 can only be estimated by comparison. Its closest match in size and morphology is with the gracile OH 34 specimen, which therefore provides a better analogue for the reconstruction of OH 62 than the stocky AL 288-1 femur that is traditionally used. OH 34's slender proportions are hardly due to abrasion, but match those of a modern human of that body-size, suggesting that the relative length of OH 62's leg may have been human-like. Brachial proportions, however, remained primitive. Long legs may imply long distance terrestrial travel. Perhaps this adaptation evolved early in the genus Homo, with H. habilis providing an early representative of this important change. PMID:15066379

  9. Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans.

    PubMed

    Olfson, E; Saccone, N L; Johnson, E O; Chen, L-S; Culverhouse, R; Doheny, K; Foltz, S M; Fox, L; Gogarten, S M; Hartz, S; Hetrick, K; Laurie, C C; Marosy, B; Amin, N; Arnett, D; Barr, R G; Bartz, T M; Bertelsen, S; Borecki, I B; Brown, M R; Chasman, D I; van Duijn, C M; Feitosa, M F; Fox, E R; Franceschini, N; Franco, O H; Grove, M L; Guo, X; Hofman, A; Kardia, S L R; Morrison, A C; Musani, S K; Psaty, B M; Rao, D C; Reiner, A P; Rice, K; Ridker, P M; Rose, L M; Schick, U M; Schwander, K; Uitterlinden, A G; Vojinovic, D; Wang, J-C; Ware, E B; Wilson, G; Yao, J; Zhao, W; Breslau, N; Hatsukami, D; Stitzel, J A; Rice, J; Goate, A; Bierut, L J

    2016-05-01

    The common nonsynonymous variant rs16969968 in the α5 nicotinic receptor subunit gene (CHRNA5) is the strongest genetic risk factor for nicotine dependence in European Americans and contributes to risk in African Americans. To comprehensively examine whether other CHRNA5 coding variation influences nicotine dependence risk, we performed targeted sequencing on 1582 nicotine-dependent cases (Fagerström Test for Nicotine Dependence score⩾4) and 1238 non-dependent controls, with independent replication of common and low frequency variants using 12 studies with exome chip data. Nicotine dependence was examined using logistic regression with individual common variants (minor allele frequency (MAF)⩾0.05), aggregate low frequency variants (0.05>MAF⩾0.005) and aggregate rare variants (MAF<0.005). Meta-analysis of primary results was performed with replication studies containing 12 174 heavy and 11 290 light smokers. Next-generation sequencing with 180 × coverage identified 24 nonsynonymous variants and 2 frameshift deletions in CHRNA5, including 9 novel variants in the 2820 subjects. Meta-analysis confirmed the risk effect of the only common variant (rs16969968, European ancestry: odds ratio (OR)=1.3, P=3.5 × 10(-11); African ancestry: OR=1.3, P=0.01) and demonstrated that three low frequency variants contributed an independent risk (aggregate term, European ancestry: OR=1.3, P=0.005; African ancestry: OR=1.4, P=0.0006). The remaining 22 rare coding variants were associated with increased risk of nicotine dependence in the European American primary sample (OR=12.9, P=0.01) and in the same risk direction in African Americans (OR=1.5, P=0.37). Our results indicate that common, low frequency and rare CHRNA5 coding variants are independently associated with nicotine dependence risk. These newly identified variants likely influence the risk for smoking-related diseases such as lung cancer. PMID:26239294

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

    PubMed Central

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

    2011-01-01

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

  11. The Effects of Socioeconomic Status, Clinical Factors, and Genetic Ancestry on Pulmonary Tuberculosis Disease in Northeastern Mexico

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  13. The genetics of East African populations: a Nilo-Saharan component in the African genetic landscape

    PubMed Central

    Dobon, Begoña; Hassan, Hisham Y.; Laayouni, Hafid; Luisi, Pierre; Ricaño-Ponce, Isis; Zhernakova, Alexandra; Wijmenga, Cisca; Tahir, Hanan; Comas, David; Netea, Mihai G.; Bertranpetit, Jaume

    2015-01-01

    East Africa is a strategic region to study human genetic diversity due to the presence of ethnically, linguistically, and geographically diverse populations. Here, we provide new insight into the genetic history of populations living in the Sudanese region of East Africa by analysing nine ethnic groups belonging to three African linguistic families: Niger-Kordofanian, Nilo-Saharan and Afro-Asiatic. A total of 500 individuals were genotyped for 200,000 single-nucleotide polymorphisms. Principal component analysis, clustering analysis using ADMIXTURE, FST statistics, and the three-population test were used to investigate the underlying genetic structure and ancestry of the different ethno-linguistic groups. Our analyses revealed a genetic component for Sudanese Nilo-Saharan speaking groups (Darfurians and part of Nuba populations) related to Nilotes of South Sudan, but not to other Sudanese populations or other sub-Saharan populations. Populations inhabiting the North of the region showed close genetic affinities with North Africa, with a component that could be remnant of North Africans before the migrations of Arabs from Arabia. In addition, we found very low genetic distances between populations in genes important for anti-malarial and anti-bacterial host defence, suggesting similar selective pressures on these genes and stressing the importance of considering functional pathways to understand the evolutionary history of populations. PMID:26017457

  14. Polymorphisms in the Non-Muscle Myosin Heavy Chain Gene (MYH9) Are Associated with Lower Glomerular Filtration Rate in Mixed Ancestry Diabetic Subjects from South Africa

    PubMed Central

    Matsha, Tandi Edith; Masconi, Katya; Yako, Yandiswa Yolanda; Hassan, Mogamat Shafick; Macharia, Muiriri; Erasmus, Rajiv Timothy; Kengne, Andre Pascal

    2012-01-01

    Objective Though single nucleotide polymorphisms (SNPs) in the non-muscle myosin gene (MYH9) have been reported to explain most of the excess risk of nondiabetic chronic kidney disease (CKD), in African-Americans, some studies have also shown associations with diabetic end-stage renal disease. We investigated the association of MYH9 SNPs with renal traits in a mixed-ancestry South African population prone to diabetes. Research Design and Methods Three SNPs known to be associated with CKD (rs4821480, rs5756152 and rs12107) were genotyped using Taqman assay in 716 adults (198 with diabetes) from the Bellville-South community, Cape Town. Glomerular filtration rate was estimated (eGFR) and urinary albumin/creatinine ratio (ACR) assessed. Multivariable regressions were used to relate the SNPs with renal traits. Results Mean age was 53.6 years, with the expected differences observed in characteristics by diabetic status. Significant associations were found between rs575152 and serum creatinine, and eGFR in the total population, and in diabetic participants (all p≤0.003), but not in non-diabetics (all p≥0.16), with significant interactions by diabetes status (interaction-p≤0.009). The association with ACR was borderline in diabetic participants (p = 0.05) and non-significant in non-diabetics (p = 0.85), with significant interaction (interaction p = 0.02). rs12107 was associated with fasting-, 2-hour glucose and HbA1c in diabetic participants only (interaction-p≤0.003), but not with renal traits. Conclusion MYH9 SNPs were associated with renal traits only in diabetic participants in this population. Our findings and other studies suggest that MYH9 may have a broader genetic risk effect on kidney diseases. PMID:23285077

  15. Proportional Reasoning of Preservice Elementary Education Majors: An Epistemic Model of the Proportional Reasoning Construct.

    ERIC Educational Resources Information Center

    Fleener, M. Jayne

    Current research and learning theory suggest that a hierarchy of proportional reasoning exists that can be tested. Using G. Vergnaud's four complexity variables (structure, content, numerical characteristics, and presentation) and T. E. Kieren's model of rational number knowledge building, an epistemic model of proportional reasoning was…

  16. Proportional reasoning competence among different student populations

    NASA Astrophysics Data System (ADS)

    Wong, King

    2012-10-01

    A collaborative project between Western Washington University, Rutgers University, and New Mexico State University seeks to understand student's competence level on proportional reasoning. We have been collecting and analyzing data from introductory physics and science education courses using a set of assessment tasks. We utilize the notion of constructs to categorize student thinking according to repetitive patterns. Results suggest that, when students confront ratio and proportion problems, they often experience a gap between the mechanics of the mathematical operations and the conscious understanding of what they are doing. In this poster we will share results of our findings from different courses, institutions, and student populations. Supported by NSF grants DUE-1045227, DUE-1045231, DUE-1045250..

  17. Black African Traditional Mathematics

    ERIC Educational Resources Information Center

    Zaslavsky, Claudia

    1970-01-01

    Discusses the traditional number systems and the origin of the number names used by several African peoples living south of the Sahara. Also included are limitations in African mathematical development, and possible topics for research. (RP)

  18. The Proportion of Stars with Planets

    NASA Astrophysics Data System (ADS)

    Woolfson, M. M.

    2016-04-01

    Estimates of the proportion of Sun-like stars with accompanying planets vary widely; the best present estimate is that it is about 0.34. The capture theory of planet formation involves an interaction between a condensed star and either a diffuse protostar or a high-density region in a dense embedded cluster. The protostar, or dense region, is tidally stretched into a filament that is gravitationally unstable and breaks up into a string of protoplanetary blobs, which subsequently collapse to form planets, some of which are captured by the star. A computational model, in which the passage of collapsing protostars, with initial radii 1000, 1500 and 2000 au, through a dense embedded cluster are followed, is used to estimate the proportion of protostars that would be disrupted to give planets, in environments with star number-densities in the range 5000-25,000 pc-3. It is concluded from the results that the capture theory might explain the presently-estimated proportion of stars with exoplanet companions, although other possible ways of producing exoplanets are not excluded.

  19. NASA CONNECT: Proportionality: Modeling the Future

    NASA Technical Reports Server (NTRS)

    2000-01-01

    'Proportionality: Modeling the Future' is the sixth of seven programs in the 1999-2000 NASA CONNECT series. Produced by NASA Langley Research Center's Office of Education, NASA CONNECT is an award-winning series of instructional programs designed to enhance the teaching of math, science and technology concepts in grades 5-8. NASA CONNECT establishes the 'connection' between the mathematics, science, and technology concepts taught in the classroom and NASA research. Each program in the series supports the national mathematics, science, and technology standards; includes a resource-rich teacher guide; and uses a classroom experiment and web-based activity to complement and enhance the math, science, and technology concepts presented in the program. NASA CONNECT is FREE and the programs in the series are in the public domain. Visit our web site and register. http://connect.larc.nasa.gov 'Proportionality: Modeling the Future', students will examine how patterns, measurement, ratios, and proportions are used in the research, development, and production of airplanes.

  20. The use of polycarbonate in proportional counters

    SciTech Connect

    Trow, M.; Smith, A. )

    1992-01-01

    Proportional counters are relatively sensitive to contamination through outgassing and the range of electrical insulators suitable for use in their manufacture is quite limited. Although small amounts of plastics such as polychlorotrifluoroethylene have been used as feedthroughs, ceramics are most commonly used when sealed counters with long lives are required. Ceramics have poor and widely scattered mechanical properties and the use of a more robust material is often highly desirable. Of particular interest is the use of polymers and this work examines polycarbonate in particular. To investigate its suitability in terms of outgassing a simple cylindrical, single anode proportional counter containing a large sample of polycarbonate was baked at {similar to}100 {degree}C and filled with a CO{sub 2}/Ar/Xe mixture (5:47.5:47.5 by pressure, respectively). Subsequent measurements of the counter indicated an increase in gain, which, after a second similar filling, was identified to be associated with a preferential loss of CO{sub 2} to the polycarbonate. The consequences of this result and the circumstances under which polycarbonate could be used on a large scale in the construction of proportional counters are discussed.

  1. Evaluation of facial beauty using anthropometric proportions.

    PubMed

    Milutinovic, Jovana; Zelic, Ksenija; Nedeljkovic, Nenad

    2014-01-01

    The improvement of a patient's facial appearance is one of the main goals of contemporary orthodontic treatment. The aim of this investigation was to evaluate the difference in facial proportions between attractive and anonymous females in order to establish objective facial features which are widely considered as beautiful. The study included two groups: first group consisted of 83 Caucasian female subjects between 22 and 28 years of age who were selected from the population of students at the University of Belgrade, and the second group included 24 attractive celebrity Caucasian females. The en face facial photographs were taken in natural head position (NHP). Numerous parameters were recorded on these photographs, in order to establish facial symmetry and correlation with the ideal set of proportions. This study showed significant difference between anonymous and attractive females. Attractive females showed smaller face in general and uniformity of the facial thirds and fifths, and most of the facial parameters meet the criteria of the ideal proportions. PMID:24701166

  2. Evaluation of Facial Beauty Using Anthropometric Proportions

    PubMed Central

    Milutinovic, Jovana

    2014-01-01

    The improvement of a patient's facial appearance is one of the main goals of contemporary orthodontic treatment. The aim of this investigation was to evaluate the difference in facial proportions between attractive and anonymous females in order to establish objective facial features which are widely considered as beautiful. The study included two groups: first group consisted of 83 Caucasian female subjects between 22 and 28 years of age who were selected from the population of students at the University of Belgrade, and the second group included 24 attractive celebrity Caucasian females. The en face facial photographs were taken in natural head position (NHP). Numerous parameters were recorded on these photographs, in order to establish facial symmetry and correlation with the ideal set of proportions. This study showed significant difference between anonymous and attractive females. Attractive females showed smaller face in general and uniformity of the facial thirds and fifths, and most of the facial parameters meet the criteria of the ideal proportions. PMID:24701166

  3. The African Connection

    ERIC Educational Resources Information Center

    Oguntoyinbo, Lekan

    2012-01-01

    From student and faculty exchanges to joint research projects, U.S. universities maintain a broad spectrum of collaborative relationships with African universities. It's unclear how many U.S. colleges and universities have partnerships with African universities. The African Studies Association, an organization of scholars, doesn't keep that kind…

  4. Genetic Ancestry, Social Classification, and Racial Inequalities in Blood Pressure in Southeastern Puerto Rico

    PubMed Central

    Gravlee, Clarence C.; Non, Amy L.; Mulligan, Connie J.

    2009-01-01

    Background The role of race in human genetics and biomedical research is among the most contested issues in science. Much debate centers on the relative importance of genetic versus sociocultural factors in explaining racial inequalities in health. However, few studies integrate genetic and sociocultural data to test competing explanations directly. Methodology/Principal Findings We draw on ethnographic, epidemiologic, and genetic data collected in southeastern Puerto Rico to isolate two distinct variables for which race is often used as a proxy: genetic ancestry versus social classification. We show that color, an aspect of social classification based on the culturally defined meaning of race in Puerto Rico, better predicts blood pressure than does a genetic-based estimate of continental ancestry. We also find that incorporating sociocultural variables reveals a new and significant association between a candidate gene polymorphism for hypertension (α2C adrenergic receptor deletion) and blood pressure. Conclusions/Significance This study addresses the recognized need to measure both genetic and sociocultural factors in research on racial inequalities in health. Our preliminary results provide the most direct evidence to date that previously reported associations between genetic ancestry and health may be attributable to sociocultural factors related to race and racism, rather than to functional genetic differences between racially defined groups. Our results also imply that including sociocultural variables in future research may improve our ability to detect significant allele-phenotype associations. Thus, measuring sociocultural factors related to race may both empower future genetic association studies and help to clarify the biological consequences of social inequalities. PMID:19742303

  5. The Missing Link of Jewish European Ancestry: Contrasting the Rhineland and the Khazarian Hypotheses

    PubMed Central

    Elhaik, Eran

    2013-01-01

    The question of Jewish ancestry has been the subject of controversy for over two centuries and has yet to be resolved. The “Rhineland hypothesis” depicts Eastern European Jews as a “population isolate” that emerged from a small group of German Jews who migrated eastward and expanded rapidly. Alternatively, the “Khazarian hypothesis” suggests that Eastern European Jews descended from the Khazars, an amalgam of Turkic clans that settled the Caucasus in the early centuries CE and converted to Judaism in the 8th century. Mesopotamian and Greco–Roman Jews continuously reinforced the Judaized empire until the 13th century. Following the collapse of their empire, the Judeo–Khazars fled to Eastern Europe. The rise of European Jewry is therefore explained by the contribution of the Judeo–Khazars. Thus far, however, the Khazars’ contribution has been estimated only empirically, as the absence of genome-wide data from Caucasus populations precluded testing the Khazarian hypothesis. Recent sequencing of modern Caucasus populations prompted us to revisit the Khazarian hypothesis and compare it with the Rhineland hypothesis. We applied a wide range of population genetic analyses to compare these two hypotheses. Our findings support the Khazarian hypothesis and portray the European Jewish genome as a mosaic of Near Eastern-Caucasus, European, and Semitic ancestries, thereby consolidating previous contradictory reports of Jewish ancestry. We further describe a major difference among Caucasus populations explained by the early presence of Judeans in the Southern and Central Caucasus. Our results have important implications for the demographic forces that shaped the genetic diversity in the Caucasus and for medical studies. PMID:23241444

  6. The Matrilineal Ancestry of Ashkenazi Jewry: Portrait of a Recent Founder Event

    PubMed Central

    Behar, Doron M.; Metspalu, Ene; Kivisild, Toomas; Achilli, Alessandro; Hadid, Yarin; Tzur, Shay; Pereira, Luisa; Amorim, Antonio; Quintana-Murci, Lluís; Majamaa, Kari; Herrnstadt, Corinna; Howell, Neil; Balanovsky, Oleg; Kutuev, Ildus; Pshenichnov, Andrey; Gurwitz, David; Bonne-Tamir, Batsheva; Torroni, Antonio; Villems, Richard; Skorecki, Karl

    2006-01-01

    Both the extent and location of the maternal ancestral deme from which the Ashkenazi Jewry arose remain obscure. Here, using complete sequences of the maternally inherited mitochondrial DNA (mtDNA), we show that close to one-half of Ashkenazi Jews, estimated at 8,000,000 people, can be traced back to only 4 women carrying distinct mtDNAs that are virtually absent in other populations, with the important exception of low frequencies among non-Ashkenazi Jews. We conclude that four founding mtDNAs, likely of Near Eastern ancestry, underwent major expansion(s) in Europe within the past millennium. PMID:16404693

  7. Two ancient human genomes reveal Polynesian ancestry among the indigenous Botocudos of Brazil.

    PubMed

    Malaspinas, Anna-Sapfo; Lao, Oscar; Schroeder, Hannes; Rasmussen, Morten; Raghavan, Maanasa; Moltke, Ida; Campos, Paula F; Sagredo, Francisca Santana; Rasmussen, Simon; Gonçalves, Vanessa F; Albrechtsen, Anders; Allentoft, Morten E; Johnson, Philip L F; Li, Mingkun; Reis, Silvia; Bernardo, Danilo V; DeGiorgio, Michael; Duggan, Ana T; Bastos, Murilo; Wang, Yong; Stenderup, Jesper; Moreno-Mayar, J Victor; Brunak, Søren; Sicheritz-Ponten, Thomas; Hodges, Emily; Hannon, Gregory J; Orlando, Ludovic; Price, T Douglas; Jensen, Jeffrey D; Nielsen, Rasmus; Heinemeier, Jan; Olsen, Jesper; Rodrigues-Carvalho, Claudia; Lahr, Marta Mirazón; Neves, Walter A; Kayser, Manfred; Higham, Thomas; Stoneking, Mark; Pena, Sergio D J; Willerslev, Eske

    2014-11-01

    Understanding the peopling of the Americas remains an important and challenging question. Here, we present (14)C dates, and morphological, isotopic and genomic sequence data from two human skulls from the state of Minas Gerais, Brazil, part of one of the indigenous groups known as 'Botocudos'. We find that their genomic ancestry is Polynesian, with no detectable Native American component. Radiocarbon analysis of the skulls shows that the individuals had died prior to the beginning of the 19th century. Our findings could either represent genomic evidence of Polynesians reaching South America during their Pacific expansion, or European-mediated transport. PMID:25455029

  8. Optimizing care for African-American HIV-positive patients.

    PubMed

    Smith, Kimberly Y; Brutus, Andre; Cathcart, Ronald; Gathe, Joseph; Johnson, William; Jordan, Wilbert; Kwakwa, Helena A; Nkwanyou, Joseph; Page, Carlos; Scott, Robert; Vaughn, Anita C; Virgil, Luther A; Williamson, Diana

    2003-10-01

    The African-American community has been disproportionately affected HIV/AIDS, as noted by higher reported rates of HIV infection, higher proportion of AIDS cases, and more deaths caused by complications of AIDS than whites and other ethnic groups. In addition, epidemiologic trends suggest that African Americans with HIV infection are more often diagnosed later in the course of HIV disease than whites. Numerous reasons account for this disparity, including the lack of perception of risk and knowledge about HIV transmission as well as a delays in HIV testing and diagnosis in the African-American community. Understanding the important considerations in the management of HIV infection in the African-American patient may create awareness among health care professionals and broaden the knowledge of HIV-infected patients within the African-American community. PMID:14588093

  9. Tissue equivalent proportional counter neutron monitor

    SciTech Connect

    Smith, R.C.; Strode, J.N.

    1980-06-01

    The Tissue Equivalent Proportional Counter (TEPC) is a sensitive area monitoring instrument that can be used either in place at fixed locations or as a portable neutron exposure measuring device. The system monitors low levels of neutron radiation exposure and has the capability of accurately measuring neutron exposure rates as low as 0.1 mrem/hr. The computerized analysis system calculates the quality factor which is important for situations where the neutron to gamma ratio may vary significantly and irregularly such as in fuel fabrication or handling facilities.

  10. Cosmic muon detector using proportional chambers

    NASA Astrophysics Data System (ADS)

    Varga, Dezső; Gál, Zoltán; Hamar, Gergő; Sára Molnár, Janka; Oláh, Éva; Pázmándi, Péter

    2015-11-01

    A set of classical multi-wire proportional chambers was designed and constructed with the main purpose of efficient cosmic muon detection. These detectors are relatively simple to construct, and at the same time are low cost, making them ideal for educational purposes. The detector layers have efficiencies above 99% for minimum ionizing cosmic muons, and their position resolution is about 1 cm, that is, particle trajectories are clearly observable. Visualization of straight tracks is possible using an LED array, with the discriminated and latched signal driving the display. Due to the exceptional operating stability of the chambers, the design can also be used for cosmic muon telescopes.

  11. Sensing circuits for multiwire proportional chambers

    NASA Technical Reports Server (NTRS)

    Peterson, H. T.; Worley, E. R.

    1977-01-01

    Integrated sensing circuits were designed, fabricated, and packaged for use in determining the direction and fluence of ionizing radiation passing through a multiwire proportional chamber. CMOS on sapphire was selected because of its high speed and low power capabilities. The design of the proposed circuits is described and the results of computer simulations are presented. The fabrication processes for the CMOS on sapphire sensing circuits and hybrid substrates are outlined. Several design options are described and the cost implications of each discussed. To be most effective, each chip should handle not more than 32 inputs, and should be mounted on its own hybrid substrate.

  12. Neutron spectrometry with He-3 proportional counters

    SciTech Connect

    Manolopoulou, M.; Fragopoulou, M.; Stoulos, S.; Vagena, E.; Westmeier, W.; Zamani, M.

    2011-07-01

    Helium filled proportional counters are widely used in the field of neutron detection and spectrometry. In this work the response of a commercially available He-3 counter is studied experimentally and calculated with Monte Carlo for the neutron energy range from 230 keV up to about 7 MeV. The calculated response of the system is used to determine neutron yield energy distribution emitted from an extended {sup nat}U/Pb assembly irradiated with 1.6 GeV deuterons. The results are in acceptable agreement with the calculated neutron distribution with DCM-DEM code. (authors)

  13. ProPortal: A Database for Prochlorococcus

    DOE Data Explorer

    Huang, Katherine [Chisholm lab, MIT

    Prochlorococcus is a marine cyanobacterium that numerically dominates the mid-latitude oceans, and is the smallest known oxygenic phototroph. All isolates described thus far can be assigned to either a tightly clustered high-light (HL) adapted clade, or a more divergent low-light (LL) adapted group. They are closely related to, but distinct from, marine Synechococcus. The genomes of 12 strains have been sequenced and they range in size from 1.6 to 2.6 Mbp. They represent diverse lineages, spanning the rRNA diversity (97 to 99.93% similarity) of cultured representatives of this group. Our analyses of these genomes inform our understanding of how adaptation occurs in the oceans along gradients of light, nutrients, and other environmental factors, providing essential context for interpreting rapidly expanding metagenomic datasets. [Copied from http://proportal.mit.edu/project/prochlorococcus/] ProPortal allows users to browse and search genome date for not only Prochlorococcus, but Cyanophage and Synechococcus. Microarray data, environmental cell concentration data, and metagenome information are also available.

  14. Body size and proportions in early hominids.

    PubMed

    McHenry, H M

    1992-04-01

    The discovery of several associated body parts of early hominids whose taxonomic identity is known inspires this study of body size and proportions in early hominids. The approach consists of finding the relationship between various measures of skeletal size and body mass in modern ape and human specimens of known body weight. This effort leads to 78 equations which predict body weight from 95 fossil specimens ranging in geological age between 4 and 1.4 mya. Predicted weights range from 10 kg to over 160 kg, but the partial associated skeletons provide the essential clues as to which predictions are most reliable. Measures of hindlimb joint size are the best and probably those equations based on the human samples are better than those based on all Hominoidea. Using hindlimb joint size of specimens of relatively certain taxonomy and assuming these measures were more like those of modern humans than of apes, the male and female averages are as follows: Australopithecus afarensis, 45 and 29 kg; A. africanus, 41 and 30 kg; A. robustus, 40 and 32 kg; A. boisei, 49 and 34 kg; H. habilis, 52 and 32 kg. These values appear to be consistent with the range of size variation seen in the entire postcranial samples that can be assigned to species. If hominoid (i.e., ape and human combined) proportions are assumed, the males would be 10 to 23 kg larger and the females 4 to 10 kg larger. PMID:1580350

  15. Kalman-predictive-proportional-integral-derivative (KPPID)

    SciTech Connect

    Fluerasu, A.; Sutton, M.

    2004-12-17

    With third generation synchrotron X-ray sources, it is possible to acquire detailed structural information about the system under study with time resolution orders of magnitude faster than was possible a few years ago. These advances have generated many new challenges for changing and controlling the state of the system on very short time scales, in a uniform and controlled manner. For our particular X-ray experiments on crystallization or order-disorder phase transitions in metallic alloys, we need to change the sample temperature by hundreds of degrees as fast as possible while avoiding over or under shooting. To achieve this, we designed and implemented a computer-controlled temperature tracking system which combines standard Proportional-Integral-Derivative (PID) feedback, thermal modeling and finite difference thermal calculations (feedforward), and Kalman filtering of the temperature readings in order to reduce the noise. The resulting Kalman-Predictive-Proportional-Integral-Derivative (KPPID) algorithm allows us to obtain accurate control, to minimize the response time and to avoid over/under shooting, even in systems with inherently noisy temperature readings and time delays. The KPPID temperature controller was successfully implemented at the Advanced Photon Source at Argonne National Laboratories and was used to perform coherent and time-resolved X-ray diffraction experiments.

  16. Energy Proportionality for Disk Storage Using Replication

    SciTech Connect

    Kim, Jinoh; Rotem, Doron

    2010-09-09

    Energy saving has become a crucial concern in datacenters as several reports predict that the anticipated energy costs over a three year period will exceed hardware acquisition. In particular, saving energy for storage is of major importance as storage devices (and cooling them off) may contribute over 25 percent of the total energy consumed in a datacenter. Recent work introduced the concept of energy proportionality and argued that it is a more relevant metric than just energy saving as it takes into account the tradeoff between energy consumption and performance. In this paper, we present a novel approach, called FREP (Fractional Replication for Energy Proportionality), for energy management in large datacenters. FREP includes areplication strategy and basic functions to enable flexible energy management. Specifically, our method provides performance guarantees by adaptively controlling the power states of a group of disks based on observed and predicted workloads. Our experiments, using a set of real and synthetic traces, show that FREP dramatically reduces energy requirements with a minimal response time penalty.

  17. Promoting Students' Proportional Reasoning Using Invention Tasks

    NASA Astrophysics Data System (ADS)

    Boudreaux, Andrew

    2012-10-01

    To many students, introductory physics may seem a fast-moving parade of abstract, mysterious quantities. Most such quantities are rooted in proportional reasoning. Using ratio, physicists construct the force experienced by a unit charge and characterize motion with the change in velocity for a unit time. While physicists reason about these ratios without conscious effort, students may resort to memorized algorithms and struggle to match the appropriate algorithm to the situation encountered. Dan Schwartz and colleagues at Stanford University have developed invention instruction as a means to prepare students for future learning. Invention tasks present open-ended situations in which students must invent a procedure or quantity in order to make meaningful comparisons. Through creative thinking and struggle, students are primed to make sense of the accepted scientific solution. A collaboration between Western Washington University, Rutgers, and New Mexico State has developed sequences of invention tasks to promote proportional reasoning. Central to our work is the development of assessments to gauge student learning. This talk presents an overview of the coordinated research and curriculum development project together with selected examples.

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

    PubMed Central

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

    2013-01-01

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

  19. Hyperinsulinemia and acanthosis nigricans in African Americans.

    PubMed Central

    Stuart, C. A.; Gilkison, C. R.; Keenan, B. S.; Nagamani, M.

    1997-01-01

    Compared with the US white, non-Hispanic population, the African-American population has a nearly two-fold higher prevalence of noninsulin-dependent diabetes mellitus (NIDDM). Obesity, which usually precedes NIDDM, is associated with the skin lesion acanthosis nigricans in African Americans. This study was undertaken to determine what the relationship of acanthosis nigricans was to hyperinsulinemia, a major risk factor for NIDDM. Eighty-nine African-American subjects with acanthosis nigricans and 25 others without the skin lesion were evaluated using oral glucose tolerance testing and responsiveness to insulin. Noninsulin-dependent diabetes mellitus was present in 19 of the subjects with acanthosis nigricans. The prevalence of NIDDM in this group increased with increasing age, reaching 50% among those in their 40s. Fasting plasma insulin concentration was in direct proportion to the severity of the acanthosis nigricans involvement of the neck. These data suggest that among African Americans, this skin lesion is a marker for hyperinsulinemia and insulin resistance. Furthermore, the presence of acanthosis nigricans identifies a subset with a much higher prevalence of NIDDM than is present in African Americans in the general population. PMID:9264219

  20. Genetic analysis of Thai cattle reveals a Southeast Asian indicine ancestry

    PubMed Central

    Wangkumhang, Pongsakorn; Wilantho, Alisa; Shaw, Philip J.; Flori, Laurence; Moazami-Goudarzi, Katayoun; Gautier, Mathieu; Duangjinda, Monchai; Assawamakin, Anunchai

    2015-01-01

    Cattle commonly raised in Thailand have characteristics of Bos indicus (zebu). We do not know when or how cattle domestication in Thailand occurred, and so questions remain regarding their origins and relationships to other breeds. We obtained genome-wide SNP genotypic data of 28 bovine individuals sampled from four regions: North (Kho-Khaolampoon), Northeast (Kho-Isaan), Central (Kho-Lan) and South (Kho-Chon) Thailand. These regional varieties have distinctive traits suggestive of breed-like genetic variations. From these data, we confirmed that all four Thai varieties are Bos indicus and that they are distinct from other indicine breeds. Among these Thai cattle, a distinctive ancestry pattern is apparent, which is the purest within Kho-Chon individuals. This ancestral component is only present outside of Thailand among other indicine breeds in Southeast Asia. From this pattern, we conclude that a unique Bos indicus ancestor originated in Southeast Asia, and native Kho-Chon Thai cattle retain the signal of this ancestry with limited admixture of other bovine ancestors. PMID:26528405

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

    PubMed

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

    2016-09-01

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

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

    PubMed Central

    2010-01-01

    Background In general, sugar porters function by proton-coupled symport or facilitative transport modes. Symporters, coupled to electrochemical energy, transport nutrients against a substrate gradient. Facilitative carriers transport sugars along a concentration gradient, thus transport is dependent upon extracellular nutrient levels. Across bacteria, fungi, unicellular non-vertebrates and plants, proton-coupled hexose symport is a crucial process supplying energy under conditions of nutrient flux. In mammals it has been assumed that evolution of whole body regulatory mechanisms would eliminate this need. To determine whether any isoforms bearing this function might be conserved in mammals, we investigated the relationship between the transporters of animals and the proton-coupled hexose symporters found in other species. Results We took a comparative genomic approach and have performed the first comprehensive and statistically supported phylogenetic analysis of all mammalian glucose transporter (GLUT) isoforms. Our data reveals the mammalian GLUT proteins segregate into five distinct classes. This evolutionary ancestry gives insight to structure, function and transport mechanisms within the groups. Combined with biological assays, we present novel evidence that, in response to changing nutrient availability and environmental pH, proton-coupled, active glucose symport function is maintained in mammalian cells. Conclusions The analyses show the ancestry, evolutionary conservation and biological importance of the GLUT classes. These findings significantly extend our understanding of the evolution of mammalian glucose transport systems. They also reveal that mammals may have conserved an adaptive response to nutrient demand that would have important physiological implications to cell survival and growth. PMID:20487568

  3. Ancestry informative markers for distinguishing between Thai populations based on genome-wide association datasets.

    PubMed

    Vongpaisarnsin, Kornkiat; Listman, Jennifer Beth; Malison, Robert T; Gelernter, Joel

    2015-07-01

    The main purpose of this work was to identify a set of AIMs that stratify the genetic structure and diversity of the Thai population from a high-throughput autosomal genome-wide association study. In this study, more than one million SNPs from the international HapMap database and the Thai depression genome-wide association study have been examined to identify ancestry informative markers (AIMs) that distinguish between Thai populations. An efficient strategy is proposed to identify and characterize such SNPs and to test high-resolution SNP data from international HapMap populations. The best AIMs are identified to stratify the population and to infer genetic ancestry structure. A total of 124 AIMs were clearly clustered geographically across the continent, whereas only 89 AIMs stratified the Thai population from East Asian populations. Finally, a set of 273 AIMs was able to distinguish northern from southern Thai subpopulations. These markers will be of particular value in identifying the ethnic origins in regions where matching by self-reports is unavailable or unreliable, which usually occurs in real forensic cases. PMID:25759192

  4. Effects of Sample Selection Bias on the Accuracy of Population Structure and Ancestry Inference

    PubMed Central

    Shringarpure, Suyash; Xing, Eric P.

    2014-01-01

    Population stratification is an important task in genetic analyses. It provides information about the ancestry of individuals and can be an important confounder in genome-wide association studies. Public genotyping projects have made a large number of datasets available for study. However, practical constraints dictate that of a geographical/ethnic population, only a small number of individuals are genotyped. The resulting data are a sample from the entire population. If the distribution of sample sizes is not representative of the populations being sampled, the accuracy of population stratification analyses of the data could be affected. We attempt to understand the effect of biased sampling on the accuracy of population structure analysis and individual ancestry recovery. We examined two commonly used methods for analyses of such datasets, ADMIXTURE and EIGENSOFT, and found that the accuracy of recovery of population structure is affected to a large extent by the sample used for analysis and how representative it is of the underlying populations. Using simulated data and real genotype data from cattle, we show that sample selection bias can affect the results of population structure analyses. We develop a mathematical framework for sample selection bias in models for population structure and also proposed a correction for sample selection bias using auxiliary information about the sample. We demonstrate that such a correction is effective in practice using simulated and real data. PMID:24637351

  5. Common Ancestry Is a Poor Predictor of Competitive Traits in Freshwater Green Algae.

    PubMed

    Narwani, Anita; Alexandrou, Markos A; Herrin, James; Vouaux, Alaina; Zhou, Charles; Oakley, Todd H; Cardinale, Bradley J

    2015-01-01

    Phytoplankton species traits have been used to successfully predict the outcome of competition, but these traits are notoriously laborious to measure. If these traits display a phylogenetic signal, phylogenetic distance (PD) can be used as a proxy for trait variation. We provide the first investigation of the degree of phylogenetic signal in traits related to competition in freshwater green phytoplankton. We measured 17 traits related to competition and tested whether they displayed a phylogenetic signal across a molecular phylogeny of 59 species of green algae. We also assessed the fit of five models of trait evolution to trait variation across the phylogeny. There was no significant phylogenetic signal for 13 out of 17 ecological traits. For 7 traits, a non-phylogenetic model provided the best fit. For another 7 traits, a phylogenetic model was selected, but parameter values indicated that trait variation evolved recently, diminishing the importance of common ancestry. This study suggests that traits related to competition in freshwater green algae are not generally well-predicted by patterns of common ancestry. We discuss the mechanisms by which the link between phylogenetic distance and phenotypic differentiation may be broken. PMID:26348482

  6. Reconstructing Past Admixture Processes from Local Genomic Ancestry Using Wavelet Transformation

    PubMed Central

    Sanderson, Jean; Sudoyo, Herawati; Karafet, Tatiana M.; Hammer, Michael F.; Cox, Murray P.

    2015-01-01

    Admixture between long-separated populations is a defining feature of the genomes of many species. The mosaic block structure of admixed genomes can provide information about past contact events, including the time and extent of admixture. Here, we describe an improved wavelet-based technique that better characterizes ancestry block structure from observed genomic patterns. principal components analysis is first applied to genomic data to identify the primary population structure, followed by wavelet decomposition to develop a new characterization of local ancestry information along the chromosomes. For testing purposes, this method is applied to human genome-wide genotype data from Indonesia, as well as virtual genetic data generated using genome-scale sequential coalescent simulations under a wide range of admixture scenarios. Time of admixture is inferred using an approximate Bayesian computation framework, providing robust estimates of both admixture times and their associated levels of uncertainty. Crucially, we demonstrate that this revised wavelet approach, which we have released as the R package adwave, provides improved statistical power over existing wavelet-based techniques and can be used to address a broad range of admixture questions. PMID:25852078

  7. Reconstructing Past Admixture Processes from Local Genomic Ancestry Using Wavelet Transformation.

    PubMed

    Sanderson, Jean; Sudoyo, Herawati; Karafet, Tatiana M; Hammer, Michael F; Cox, Murray P

    2015-06-01

    Admixture between long-separated populations is a defining feature of the genomes of many species. The mosaic block structure of admixed genomes can provide information about past contact events, including the time and extent of admixture. Here, we describe an improved wavelet-based technique that better characterizes ancestry block structure from observed genomic patterns. principal components analysis is first applied to genomic data to identify the primary population structure, followed by wavelet decomposition to develop a new characterization of local ancestry information along the chromosomes. For testing purposes, this method is applied to human genome-wide genotype data from Indonesia, as well as virtual genetic data generated using genome-scale sequential coalescent simulations under a wide range of admixture scenarios. Time of admixture is inferred using an approximate Bayesian computation framework, providing robust estimates of both admixture times and their associated levels of uncertainty. Crucially, we demonstrate that this revised wavelet approach, which we have released as the R package adwave, provides improved statistical power over existing wavelet-based techniques and can be used to address a broad range of admixture questions. PMID:25852078

  8. Common Ancestry Is a Poor Predictor of Competitive Traits in Freshwater Green Algae

    PubMed Central

    Narwani, Anita; Alexandrou, Markos A.; Herrin, James; Vouaux, Alaina; Zhou, Charles; Oakley, Todd H.; Cardinale, Bradley J.

    2015-01-01

    Phytoplankton species traits have been used to successfully predict the outcome of competition, but these traits are notoriously laborious to measure. If these traits display a phylogenetic signal, phylogenetic distance (PD) can be used as a proxy for trait variation. We provide the first investigation of the degree of phylogenetic signal in traits related to competition in freshwater green phytoplankton. We measured 17 traits related to competition and tested whether they displayed a phylogenetic signal across a molecular phylogeny of 59 species of green algae. We also assessed the fit of five models of trait evolution to trait variation across the phylogeny. There was no significant phylogenetic signal for 13 out of 17 ecological traits. For 7 traits, a non-phylogenetic model provided the best fit. For another 7 traits, a phylogenetic model was selected, but parameter values indicated that trait variation evolved recently, diminishing the importance of common ancestry. This study suggests that traits related to competition in freshwater green algae are not generally well-predicted by patterns of common ancestry. We discuss the mechanisms by which the link between phylogenetic distance and phenotypic differentiation may be broken. PMID:26348482

  9. Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men

    PubMed Central

    Freedman, Matthew L.; Haiman, Christopher A.; Patterson, Nick; McDonald, Gavin J.; Tandon, Arti; Waliszewska, Alicja; Penney, Kathryn; Steen, Robert G.; Ardlie, Kristin; John, Esther M.; Oakley-Girvan, Ingrid; Whittemore, Alice S.; Cooney, Kathleen A.; Ingles, Sue A.; Altshuler, David; Henderson, Brian E.; Reich, David

    2006-01-01

    A whole-genome admixture scan in 1,597 African Americans identified a 3.8 Mb interval on chromosome 8q24 as significantly associated with susceptibility to prostate cancer [logarithm of odds (LOD) = 7.1]. The increased risk because of inheriting African ancestry is greater in men diagnosed before 72 years of age (P < 0.00032) and may contribute to the epidemiological observation that the higher risk for prostate cancer in African Americans is greatest in younger men (and attenuates with older age). The same region was recently identified through linkage analysis of prostate cancer, followed by fine-mapping. We strongly replicated this association (P < 4.2 × 10−9) but find that the previously described alleles do not explain more than a fraction of the admixture signal. Thus, admixture mapping indicates a major, still-unidentified risk gene for prostate cancer at 8q24, motivating intense work to find it. PMID:16945910

  10. TRIAC/SCR proportional control circuit

    DOEpatents

    Hughes, Wallace J.

    1999-01-01

    A power controller device which uses a voltage-to-frequency converter in conjunction with a zero crossing detector to linearly and proportionally control AC power being supplied to a load. The output of the voltage-to frequency converter controls the "reset" input of a R-S flip flop, while an "0" crossing detector controls the "set" input. The output of the flip flop triggers a monostable multivibrator controlling the SCR or TRIAC firing circuit connected to the load. Logic gates prevent the direct triggering of the multivibrator in the rare instance where the "reset" and "set" inputs of the flip flop are in coincidence. The control circuit can be supplemented with a control loop, providing compensation for line voltage variations.

  11. TRIAC/SCR proportional control circuit

    DOEpatents

    Hughes, W.J.

    1999-04-06

    A power controller device is disclosed which uses a voltage-to-frequency converter in conjunction with a zero crossing detector to linearly and proportionally control AC power being supplied to a load. The output of the voltage-to frequency converter controls the ``reset`` input of a R-S flip flop, while an ``0`` crossing detector controls the ``set`` input. The output of the flip flop triggers a monostable multivibrator controlling the SCR or TRIAC firing circuit connected to the load. Logic gates prevent the direct triggering of the multivibrator in the rare instance where the ``reset`` and ``set`` inputs of the flip flop are in coincidence. The control circuit can be supplemented with a control loop, providing compensation for line voltage variations. 9 figs.

  12. Absolute calibration of TFTR helium proportional counters

    SciTech Connect

    Strachan, J.D.; Diesso, M.; Jassby, D.; Johnson, L.; McCauley, S.; Munsat, T.; Roquemore, A.L.; Barnes, C.W. |; Loughlin, M. |

    1995-06-01

    The TFTR helium proportional counters are located in the central five (5) channels of the TFTR multichannel neutron collimator. These detectors were absolutely calibrated using a 14 MeV neutron generator positioned at the horizontal midplane of the TFTR vacuum vessel. The neutron generator position was scanned in centimeter steps to determine the collimator aperture width to 14 MeV neutrons and the absolute sensitivity of each channel. Neutron profiles were measured for TFTR plasmas with time resolution between 5 msec and 50 msec depending upon count rates. The He detectors were used to measure the burnup of 1 MeV tritons in deuterium plasmas, the transport of tritium in trace tritium experiments, and the residual tritium levels in plasmas following 50:50 DT experiments.

  13. Boron-10 Lined Proportional Counter Model Validation

    SciTech Connect

    Lintereur, Azaree T.; Siciliano, Edward R.; Kouzes, Richard T.

    2012-06-30

    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 the development of an alternative neutron coincidence counter. The goal of this project is to design, build and demonstrate a boron-lined proportional tube-based alternative system in the configuration of a coincidence counter. This report discusses the validation studies performed to establish the degree of accuracy of the computer modeling methods current used to simulate the response of boron-lined tubes. This is the precursor to developing models for the uranium neutron coincidence collar under Task 2 of this project.

  14. A proportional temperature controller with automatic shutoff

    NASA Astrophysics Data System (ADS)

    Lucich, G. M.; Holland, P. W.

    1980-08-01

    A sensitive, proportional temperature controller useful in the temperature range from 40 to 400 C with an accuracy of plus or minus 0.1 C is described. It is potentially useful for regulating temperatures in air chambers, liquid baths, furnaces and reaction vessels and for other applications. This instrument was developed to control the duration and temperature of the heating cycle of a charcoal filled adsorber that is part of a special helium analyzer. The controller was made from commercially available parts and can be easily modified to provide continuous temperature control. The circuit is solid state and employs no electromechanical devices. Over a 2 year period of use as a component of the special helium analyzer, this temperature controller performed successfully and required no maintenance.

  15. Effects of Varying Proportions of Glass on Reflectance Spectra of HED Polymict Breccias

    NASA Technical Reports Server (NTRS)

    Buchanan, P. C.; Reddy, V; LeCorre, L.; Cloutis, E. A.; Mann, P.; Le, L.

    2014-01-01

    Some meteorites contain significant amounts of glass, which, in most cases, probably results from impact processes on parent bodies.. Yamato 82202 is an example of one of the unequilibrated eucrites that contains significant proportions of impact glass distributed as veins throughout the meteorite. In other cases, fragments of glass are distributed throughout polymict breccias. For example, the polymict eucrite EET 87509 contains rare angular fragments of devitrified glass. Proportions of glass in most of these meteorites and in lithic clasts within these meteorites may vary locally from small amounts (less than one percent) to much larger amounts (subequal proportions of glass and mineral material). For example, some fragments within the South African polymict eucrite Macibini contain approximately 50% glass. The presence of these variable proportions of meteorite glass confirm the increased recognition that impact processes played an important role in the histories of asteroidal bodies. This study attempts to quantify the effects of a glass component on reflectance spectra by analyzing in the laboratory mixtures of varying proportions of a well-characterized HED polymict breccia and glass derived by melting a bulk sample of that breccia.

  16. Recent African origin of modern humans revealed by complete sequences of hominoid mitochondrial DNAs.

    PubMed Central

    Horai, S; Hayasaka, K; Kondo, R; Tsugane, K; Takahata, N

    1995-01-01

    We analyzed the complete mitochondrial DNA (mtDNA) sequences of three humans (African, European, and Japanese), three African apes (common and pygmy chimpanzees, and gorilla), and one orangutan in an attempt to estimate most accurately the substitution rates and divergence times of hominoid mtDNAs. Nonsynonymous substitutions and substitutions in RNA genes have accumulated with an approximately clock-like regularity. From these substitutions and under the assumption that the orangutan and African apes diverged 13 million years ago, we obtained a divergence time for humans and chimpanzees of 4.9 million years. This divergence time permitted calibration of the synonymous substitution rate (3.89 x 10(-8)/site per year). To obtain the substitution rate in the displacement (D)-loop region, we compared the three human mtDNAs and measured the relative abundance of substitutions in the D-loop region and at synonymous sites. The estimated substitution rate in the D-loop region was 7.00 x 10(-8)/site per year. Using both synonymous and D-loop substitutions, we inferred the age of the last common ancestor of the human mtDNAs as 143,000 +/- 18,000 years. The shallow ancestry of human mtDNAs, together with the observation that the African sequence is the most diverged among humans, strongly supports the recent African origin of modern humans, Homo sapiens sapiens. PMID:7530363

  17. Genetic Evidence of African Slavery at the Beginning of the Trans-Atlantic Slave Trade

    PubMed Central

    Martiniano, Rui; Coelho, Catarina; Ferreira, Maria Teresa; Neves, Maria João; Pinhasi, Ron; Bradley, Daniel G.

    2014-01-01

    An archaeological excavation in Valle da Gafaria (Lagos, Portugal), revealed two contiguous burial places outside the medieval city walls, dating from the 15th–17th centuries AD: one was interpreted as a Leprosarium cemetery and the second as an urban discard deposit, where signs of violent, unceremonious burials suggested that these remains may belong to slaves captured in Africa by the Portuguese. We obtained random short autosomal sequence reads from seven individuals: two from the latter site and five from the Leprosarium and used these to call SNP identities and estimate ancestral affinities with modern reference data. The Leprosarium site samples were less preserved but gave some probability of both African and European ancestry. The two discard deposit burials each gave African affinity signals, which were further refined toward modern West African or Bantu genotyped samples. These data from distressed burials illustrate an African contribution to a low status stratum of Lagos society at a time when this port became a hub of the European trade in African slaves which formed a precursor to the transatlantic transfer of millions. PMID:25104065

  18. Genetic evidence of African slavery at the beginning of the trans-Atlantic slave trade.

    PubMed

    Martiniano, Rui; Coelho, Catarina; Ferreira, Maria Teresa; Neves, Maria João; Pinhasi, Ron; Bradley, Daniel G

    2014-01-01

    An archaeological excavation in Valle da Gafaria (Lagos, Portugal), revealed two contiguous burial places outside the medieval city walls, dating from the 15(th)-17(th) centuries AD: one was interpreted as a Leprosarium cemetery and the second as an urban discard deposit, where signs of violent, unceremonious burials suggested that these remains may belong to slaves captured in Africa by the Portuguese. We obtained random short autosomal sequence reads from seven individuals: two from the latter site and five from the Leprosarium and used these to call SNP identities and estimate ancestral affinities with modern reference data. The Leprosarium site samples were less preserved but gave some probability of both African and European ancestry. The two discard deposit burials each gave African affinity signals, which were further refined toward modern West African or Bantu genotyped samples. These data from distressed burials illustrate an African contribution to a low status stratum of Lagos society at a time when this port became a hub of the European trade in African slaves which formed a precursor to the transatlantic transfer of millions. PMID:25104065

  19. Forensic STR loci reveal common genetic ancestry of the Thai-Malay Muslims and Thai Buddhists in the deep Southern region of Thailand.

    PubMed

    Kutanan, Wibhu; Kitpipit, Thitika; Phetpeng, Sukanya; Thanakiatkrai, Phuvadol

    2014-12-01

    Among the people living in the five deep Southern Thai provinces, Thai-Malay Muslims (MUS) constitute the majority, while the remaining are Thai Buddhists (BUD). Cultural, linguistic and religious differences between these two populations have been previously reported. However, their biological relationship has never been investigated. In this study, we aimed to reveal the genetic structure and genetic affinity between MUS and BUD by analyzing 15 autosomal short tandem repeats. Both distance and model-based clustering methods showed significant genetic homogeneity between these two populations, suggesting a common biological ancestry. After Islamization in this region during the fourteenth century AD, gradual albeit nonstatistically significant genetic changes occurred within these two populations. Cultural barriers possibly influenced these genetic changes. MUS have closer admixture to Malaysian-Malay Muslims than BUD countrywide. Admixture proportions also support certain degree of genetic dissimilarity between the two studied populations, as shown by the unequal genetic contribution from Malaysian-Malay Muslims. Cultural transformation and recent minor genetic admixture are the likely processes that shaped the genetic structure of both MUS and BUD. PMID:25339232

  20. Calibration of proportional counters in microdosimetry

    SciTech Connect

    Varma, M.N.

    1982-01-01

    Many microdosimetric spectra for low LET as well as high LET radiations are measured using commercially available (similar to EG and G) Rossi proportional counters. This paper discusses the corrections to be applied to data when calibration of the counter is made using one type of radiation, and then the counter is used in a different radiation field. The principal correction factor is due to differences in W-value of the radiation used for calibration and the radiation for which microdosimetric measurements are made. Both propane and methane base tissue-equivalent (TE) gases are used in these counters. When calibrating the detectors, it is important to use the correct stopping power value for that gas. Deviations in y-bar/sub F/ and y-bar/sub D/ are calculated for /sup 60/Co using different extrapolation procedures from 0.15 keV/..mu..m to zero event size. These deviations can be as large as 30%. Advantages of reporting microdosimetric parameters such as y-bar/sub F/ and y-bar/sub D/ above a certain minimum cut-off are discussed.

  1. Proportional mortality of 50 years and above

    PubMed Central

    Swaroop, S.; Uemura, K.

    1957-01-01

    In 1954 the United Nations Committee of Experts on International Definition and Measurement of Standards and Levels of Living suggested that for the measurement of levels of living quantifiable or potentially quantifiable components should be considered separately. An attempt is made in the present paper to evolve a single, comprehensive numerical indicator to quantify the component “health, including demographic conditions”. The use of an objective statistical technique as a guide in the selection of such an indicator is suggested. From the application of this technique, it is concluded that the percentage of deaths at the ages 50 years and over to total deaths (proportional mortality) affords a fairly suitable yardstick by which broad inter-country comparisons may be made. This indicator has the advantages of simplicity of calculation, comprehensiveness, availability of data, possibility of international comparability despite the varying quality of basic statistical information, sensitivity for the purpose of inter-country comparisons, and validity for studying levels and trends. PMID:13500159

  2. The African superswell

    NASA Technical Reports Server (NTRS)

    Nyblade, Andrew A.; Robinson, Scott W.

    1994-01-01

    Maps of residual bathymetry in the ocean basins around the African continent reveal a broad bathymetric swell in the southeastern Atlantic Ocean with an amplitude of about 500 m. We propose that this region of anomalously shallow bathymetry, together with the contiguous eastern and southern African plateaus, form a superswell which we refer to as the African superswell. The origin of the African superswell is uncertain. However, rifting and volcanism in eastern Africa, as well as heat flow measurements in southern Africa and the southeastern Atlantic Ocean, suggest that the superswell may be attributed, at least in part, to heating of the lithosphere.

  3. Multiple Origins and Regional Dispersal of Resistant dhps in African Plasmodium falciparum Malaria

    PubMed Central

    Pearce, Richard J.; Pota, Hirva; Evehe, Marie-Solange B.; Bâ, El-Hadj; Mombo-Ngoma, Ghyslain; Malisa, Allen L.; Ord, Rosalynn; Inojosa, Walter; Matondo, Alexandre; Diallo, Diadier A.; Mbacham, Wilfred; van den Broek, Ingrid V.; Swarthout, Todd D.; Getachew, Asefaw; Dejene, Seyoum; Grobusch, Martin P.; Njie, Fanta; Kweku, Margaret; Owusu-Agyei, Seth; Chandramohan, Daniel; Bonnet, Maryline; Guthmann, Jean-Paul; Clarke, Sian; Barnes, Karen I.; Streat, Elizabeth; Katokele, Stark T.; Uusiku, Petrina; Agboghoroma, Chris O.; Elegba, Olufunmilayo Y.; Cissé, Badara; A-Elbasit, Ishraga E.; Giha, Hayder A.; Kachur, S. Patrick; Lynch, Caroline; Rwakimari, John B.; Chanda, Pascalina; Hawela, Moonga; Naidoo, Inbarani; Roper, Cally

    2009-01-01

    Background Although the molecular basis of resistance to a number of common antimalarial drugs is well known, a geographic description of the emergence and dispersal of resistance mutations across Africa has not been attempted. To that end we have characterised the evolutionary origins of antifolate resistance mutations in the dihydropteroate synthase (dhps) gene and mapped their contemporary distribution. Methods and Findings We used microsatellite polymorphism flanking the dhps gene to determine which resistance alleles shared common ancestry and found five major lineages each of which had a unique geographical distribution. The extent to which allelic lineages were shared among 20 African Plasmodium falciparum populations revealed five major geographical groupings. Resistance lineages were common to all sites within these regions. The most marked differentiation was between east and west African P. falciparum, in which resistance alleles were not only of different ancestry but also carried different resistance mutations. Conclusions Resistant dhps has emerged independently in multiple sites in Africa during the past 10–20 years. Our data show the molecular basis of resistance differs between east and west Africa, which is likely to translate into differing antifolate sensitivity. We have also demonstrated that the dispersal patterns of resistance lineages give unique insights into recent parasite migration patterns. PMID:19365539

  4. Explaining the visible and the invisible: Public knowledge of genetics, ancestry, physical appearance and race in Colombia

    PubMed Central

    Schwartz-Marín, Ernesto; Wade, Peter

    2015-01-01

    Using data from focus groups conducted in Colombia, we explore how educated lay audiences faced with scenarios about ancestry and genetics draw on widespread and dominant notions of nation, race and belonging in Colombia to ascribe ancestry to collectivities and to themselves as individuals. People from a life sciences background tend to deploy idioms of race and genetics more readily than people from a humanities and race-critical background. When they considered individuals, people tempered or domesticated the more mechanistic explanations about racialized physical appearance, ancestry and genetics that were apparent at the collective level. Ideas of the latency and manifestation of invisible traits were an aspect of this domestication. People ceded ultimate authority to genetic science, but deployed it to work alongside what they already knew. Notions of genetic essentialism co-exist with the strategic use of genetic ancestry in ways that both fix and unfix race. Our data indicate the importance of attending to the different epistemological stances through which people define authoritative knowledge and to the importance of distinguishing the scale of resolution at which the question of diversity is being posed. PMID:27480001

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

    PubMed

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

    2014-03-01

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

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

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2013-03-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2014-11-01

    Understanding the fundamental mechanisms behind the complex landscape of corporate mergers and acquisitions is of crucial importance to economies across the world. Adapting ideas from the fields of complexity and evolutionary dynamics to analyse business ecosystems, we show here that ancestry, i.e. the cumulative sum of historical mergers across all ancestors, is the key characteristic to company mergers and acquisitions. We verify this by comparing an agent-based model to an extensive range of business data, covering the period from