Genetic aspects of athletic performance: the African runners phenomenon.

PubMed

Vancini, Rodrigo Luiz; Pesquero, João Bosco; Fachina, Rafael Júlio; Andrade, Marília Dos Santos; Borin, João Paulo; Montagner, Paulo César; de Lira, Claudio Andre Barbosa

2014-01-01

The current dominance of African runners in long-distance running is an intriguing phenomenon that highlights the close relationship between genetics and physical performance. Many factors in the interesting interaction between genotype and phenotype (eg, high cardiorespiratory fitness, higher hemoglobin concentration, good metabolic efficiency, muscle fiber composition, enzyme profile, diet, altitude training, and psychological aspects) have been proposed in the attempt to explain the extraordinary success of these runners. Increasing evidence shows that genetics may be a determining factor in physical and athletic performance. But, could this also be true for African long-distance runners? Based on this question, this brief review proposed the role of genetic factors (mitochondrial deoxyribonucleic acid, the Y chromosome, and the angiotensin-converting enzyme and the alpha-actinin-3 genes) in the amazing athletic performance observed in African runners, especially the Kenyans and Ethiopians, despite their environmental constraints.

Understanding participation by African Americans in cancer genetics research.

PubMed

McDonald, Jasmine A; Barg, Frances K; Weathers, Benita; Guerra, Carmen E; Troxel, Andrea B; Domchek, Susan; Bowen, Deborah; Shea, Judy A; Halbert, Chanita Hughes

2012-01-01

Understanding genetic factors that contribute to racial differences in cancer outcomes may reduce racial disparities in cancer morbidity and mortality. Achieving this goal will be limited by low rates of African American participation in cancer genetics research. We conducted a qualitative study with African American adults (n = 91) to understand attitudes about participating in cancer genetics research and to identify factors that are considered when making a decision about participating in this type of research. Participants would consider the potential benefits to themselves, family members, and their community when making a decision to participate in cancer genetics research. However, concerns about exploitation, distrust of researchers, and investigators' motives were also important to participation decisions. Individuals would also consider who has access to their personal information and what would happen to these data. Side effects, logistical issues, and the potential to gain knowledge about health issues were also described as important factors in decision making. African Americans may consider a number of ethical, legal, and social issues when making a decision to participate in cancer genetics research. These issues should be addressed as part of recruitment efforts.

Genetic analysis shows low levels of hybridization between African wildcats (Felis silvestris lybica) and domestic cats (F. s. catus) in South Africa.

PubMed

Le Roux, Johannes J; Foxcroft, Llewellyn C; Herbst, Marna; MacFadyen, Sandra

2015-01-01

Hybridization between domestic and wild animals is a major concern for biodiversity conservation, and as habitats become increasingly fragmented, conserving biodiversity at all levels, including genetic, becomes increasingly important. Except for tropical forests and true deserts, African wildcats occur across the African continent; however, almost no work has been carried out to assess its genetic status and extent of hybridization with domestic cats. For example, in South Africa it has been argued that the long-term viability of maintaining pure wildcat populations lies in large protected areas only, isolated from human populations. Two of the largest protected areas in Africa, the Kgalagadi Transfrontier and Kruger National Parks, as well as the size of South Africa and range of landscape uses, provide a model situation to assess how habitat fragmentation and heterogeneity influences the genetic purity of African wildcats. Using population genetic and home range data, we examined the genetic purity of African wildcats and their suspected hybrids across South Africa, including areas within and outside of protected areas. Overall, we found African wildcat populations to be genetically relatively pure, but instances of hybridization and a significant relationship between the genetic distinctiveness (purity) of wildcats and human population pressure were evident. The genetically purest African wildcats were found in the Kgalagadi Transfrontier Park, while samples from around Kruger National Park showed cause for concern, especially combined with the substantial human population density along the park's boundary. While African wildcat populations in South Africa generally appear to be genetically pure, with low levels of hybridization, our genetic data do suggest that protected areas may play an important role in maintaining genetic purity by reducing the likelihood of contact with domestic cats. We suggest that approaches such as corridors between protected areas

[Gene geography of Chile: regional distribution of American, European and African genetic contributions].

PubMed

Fuentes, Macarena; Pulgar, Iván; Gallo, Carla; Bortolini, María-Cátira; Canizales-Quinteros, Samuel; Bedoya, Gabriel; González-José, Rolando; Ruiz-Linares, Andrés; Rothhammer, Francisco

2014-03-01

The geographical distribution of genes plays a key role in genetic epidemiology. The Chilean population has three major stem groups (Native American, European and African). To estimate the regional rate of American, European and African admixture of the Chilean population. Forty single nucleotide polymorphisms (SNP´s) which exhibit substantially different frequencies between Amerindian populations (ancestry-informative markers or AIM´s), were genotyped in a sample of 923 Chilean participants to estimate individual genetic ancestry. The American, European and African individual average admixture estimates for the 15 Chilean Regions were relatively homogeneous and not statistically different. However, higher American components were found in northern and southern Chile and higher European components were found in central Chile. A negative correlation between African admixture and latitude was observed. On the average, American and European genetic contributions were similar and significantly higher than the African contribution. Weighted mean American, European and African genetic contributions of 44.34% ± 3 9%, 51.85% ± 5.44% and 3.81% ± 0.45%, were estimated. Fifty two percent of subjects harbor African genes. Individuals with Aymara and Mapuche surnames have an American admixture of 58.64% and 68.33%, respectively. Half of the Chilean population harbors African genes. Participants with Aymara and Mapuche surnames had a higher American genetic contribution than the general Chilean population. These results confirm the usefulness of surnames as a first approximation to determine genetic ancestry.

Education, genetic ancestry, and blood pressure in African Americans and Whites.

PubMed

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

2012-08-01

We assessed the relative roles of education and genetic ancestry in predicting blood pressure (BP) within African Americans and explored the association between education and BP across racial groups. We used t tests and linear regressions to examine the associations of genetic ancestry, estimated from a genomewide set of autosomal markers, and education with BP variation among African Americans in the Family Blood Pressure Program. We also performed linear regressions in self-identified African Americans and Whites to explore the association of education with BP across racial groups. Education, but not genetic ancestry, significantly predicted BP variation in the African American subsample (b=-0.51 mm Hg per year additional education; P=.001). Although education was inversely associated with BP in the total population, within-group analyses showed that education remained a significant predictor of BP only among the African Americans. We found a significant interaction (b=3.20; P=.006) between education and self-identified race in predicting BP. Racial disparities in BP may be better explained by differences in education than by genetic ancestry. Future studies of ancestry and disease should include measures of the social environment.

Analysis of pharmacogenetic traits in two distinct South African populations

PubMed Central

2011-01-01

Our knowledge of pharmacogenetic variability in diverse populations is scarce, especially in sub-Saharan Africa. To bridge this gap in knowledge, we characterised population frequencies of clinically relevant pharmacogenetic traits in two distinct South African population groups. We genotyped 211 tagging single nucleotide polymorphisms (tagSNPs) in 12 genes that influence antiretroviral drug disposition, in 176 South African individuals belonging to two distinct population groups residing in the Western Cape: the Xhosa (n = 109) and Cape Mixed Ancestry (CMA) (n = 67) groups. The minor allele frequencies (MAFs) of eight tagSNPs in six genes (those encoding the ATP binding cassette sub-family B, member 1 [ABCB1], four members of the cytochrome P450 family [CYP2A7P1, CYP2C18, CYP3A4, CYP3A5] and UDP-glucuronosyltransferase 1 [UGT1A1]) were significantly different between the Xhosa and CMA populations (Bonferroni p < 0.05). Twenty-seven haplotypes were inferred in four genes (CYP2C18, CYP3A4, the gene encoding solute carrier family 22 member 6 [SLC22A6] and UGT1A1) between the two South African populations. Characterising the Xhosa and CMA population frequencies of variant alleles important for drug transport and metabolism can help to establish the clinical relevance of pharmacogenetic testing in these populations. PMID:21712189

Genetic structure of drone congregation areas of Africanized honeybees in southern Brazil

PubMed Central

2009-01-01

As yet, certain aspects of the Africanization process are not well understood, for example, the reproductive behavior of African and European honeybees and how the first Africanized swarms were formed and spread. Drone congregation areas (DCAs) are the ideal place to study honeybee reproduction under natural conditions since hundreds of drones from various colonies gather together in the same geographical area for mating. In the present study, we assessed the genetic structure of seven drone congregations and four commercial European-derived and Africanized apiaries in southern Brazil, employing seven microsatellite loci for this purpose. We also estimated the number of mother-colonies that drones of a specific DCA originated from. Pairwise comparison failed to reveal any population sub-structuring among the DCAs, thus indicating low mutual genetic differentiation. We also observed high genetic similarity between colonies of commercial apiaries and DCAs, besides a slight contribution from a European-derived apiary to a DCA formed nearby. Africanized DCAs seem to have a somewhat different genetic structure when compared to the European. PMID:21637465

Genetic structure of drone congregation areas of Africanized honeybees in southern Brazil.

PubMed

Collet, Thais; Cristino, Alexandre Santos; Quiroga, Carlos Fernando Prada; Soares, Ademilson Espencer Egea; Del Lama, Marco Antônio

2009-10-01

As yet, certain aspects of the Africanization process are not well understood, for example, the reproductive behavior of African and European honeybees and how the first Africanized swarms were formed and spread. Drone congregation areas (DCAs) are the ideal place to study honeybee reproduction under natural conditions since hundreds of drones from various colonies gather together in the same geographical area for mating. In the present study, we assessed the genetic structure of seven drone congregations and four commercial European-derived and Africanized apiaries in southern Brazil, employing seven microsatellite loci for this purpose. We also estimated the number of mother-colonies that drones of a specific DCA originated from. Pairwise comparison failed to reveal any population sub-structuring among the DCAs, thus indicating low mutual genetic differentiation. We also observed high genetic similarity between colonies of commercial apiaries and DCAs, besides a slight contribution from a European-derived apiary to a DCA formed nearby. Africanized DCAs seem to have a somewhat different genetic structure when compared to the European.

Education, Genetic Ancestry, and Blood Pressure in African Americans and Whites

PubMed Central

Gravlee, Clarence C.; Mulligan, Connie J.

2012-01-01

Objectives. We assessed the relative roles of education and genetic ancestry in predicting blood pressure (BP) within African Americans and explored the association between education and BP across racial groups. Methods. We used t tests and linear regressions to examine the associations of genetic ancestry, estimated from a genomewide set of autosomal markers, and education with BP variation among African Americans in the Family Blood Pressure Program. We also performed linear regressions in self-identified African Americans and Whites to explore the association of education with BP across racial groups. Results. Education, but not genetic ancestry, significantly predicted BP variation in the African American subsample (b = −0.51 mm Hg per year additional education; P = .001). Although education was inversely associated with BP in the total population, within-group analyses showed that education remained a significant predictor of BP only among the African Americans. We found a significant interaction (b = 3.20; P = .006) between education and self-identified race in predicting BP. Conclusions. Racial disparities in BP may be better explained by differences in education than by genetic ancestry. Future studies of ancestry and disease should include measures of the social environment. PMID:22698014

Genetically Distinct Subsets within ANCA-Associated Vasculitis

PubMed Central

Lyons, Paul A.; Rayner, Tim F.; Trivedi, Sapna; Holle, Julia U.; Watts, Richard A.; Jayne, David R.W.; Baslund, Bo; Brenchley, Paul; Bruchfeld, Annette; Chaudhry, Afzal N.; Tervaert, Jan Willem Cohen; Deloukas, Panos; Feighery, Conleth; Gross, Wolfgang L.; Guillevin, Loic; Gunnarsson, Iva; P, Lorraine Harper M.R.C; Hrušková, Zdenka; Little, Mark A.; Martorana, Davide; Neumann, Thomas; Ohlsson, Sophie; Padmanabhan, Sandosh; Pusey, Charles D.; Salama, Alan D.; Sanders, Jan-Stephan F.; Savage, Caroline O.; Segelmark, Mårten; Stegeman, Coen A.; Tesař, Vladimir; Vaglio, Augusto; Wieczorek, Stefan; Wilde, Benjamin; Zwerina, Jochen; Rees, Andrew J.; Clayton, David G.; Smith, Kenneth G.C.

2013-01-01

BACKGROUND Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis. METHODS A genomewide association study was performed in a discovery cohort of 1233 U.K. patients with ANCA-associated vasculitis and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria. RESULTS We found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti–proteinase 3 ANCA was associated with HLA-DP and the genes encoding α1-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P = 6.2×10−89, P = 5.6×10−12, and P = 2.6×10−7, respectively). Anti–myeloperoxidase ANCA was associated with HLA-DQ (P = 2.1×10−8). CONCLUSIONS This study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA–associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA–associated vasculitis and myeloperoxidase ANCA–associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.) PMID

Genetic analysis shows low levels of hybridization between African wildcats (Felis silvestris lybica) and domestic cats (F. s. catus) in South Africa

PubMed Central

Le Roux, Johannes J; Foxcroft, Llewellyn C; Herbst, Marna; MacFadyen, Sandra

2015-01-01

Hybridization between domestic and wild animals is a major concern for biodiversity conservation, and as habitats become increasingly fragmented, conserving biodiversity at all levels, including genetic, becomes increasingly important. Except for tropical forests and true deserts, African wildcats occur across the African continent; however, almost no work has been carried out to assess its genetic status and extent of hybridization with domestic cats. For example, in South Africa it has been argued that the long-term viability of maintaining pure wildcat populations lies in large protected areas only, isolated from human populations. Two of the largest protected areas in Africa, the Kgalagadi Transfrontier and Kruger National Parks, as well as the size of South Africa and range of landscape uses, provide a model situation to assess how habitat fragmentation and heterogeneity influences the genetic purity of African wildcats. Using population genetic and home range data, we examined the genetic purity of African wildcats and their suspected hybrids across South Africa, including areas within and outside of protected areas. Overall, we found African wildcat populations to be genetically relatively pure, but instances of hybridization and a significant relationship between the genetic distinctiveness (purity) of wildcats and human population pressure were evident. The genetically purest African wildcats were found in the Kgalagadi Transfrontier Park, while samples from around Kruger National Park showed cause for concern, especially combined with the substantial human population density along the park's boundary. While African wildcat populations in South Africa generally appear to be genetically pure, with low levels of hybridization, our genetic data do suggest that protected areas may play an important role in maintaining genetic purity by reducing the likelihood of contact with domestic cats. We suggest that approaches such as corridors between protected areas

Genetic basis of systemic lupus erythematosus: a review of the unique genetic contributions in African Americans.

PubMed

Harley, John B; Kelly, Jennifer A

2002-08-01

Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving critical genetic and environmental risk factors. SLE is a relatively common disease among African American women, affecting as many as one in 250. A collection of more than 250 African American and European American pedigrees multiplex for SLE have been collected in Oklahoma over the past decade for the purpose of identifying the genetic risk factors involved in the pathogenesis of SLE. A genome scan has been performed, and interestingly, the linkage results usually dominate in families from one or the other of these ethnicities. For example, the linkage effect at 1q21-22 near FcgammaRIIA is much stronger in the African American pedigrees than in the European American pedigrees. On the other hand, a gene near the top of chromosome4 (at 4p l6-15) contributes to SLE in the European American pedigrees, but not in the African American pedigrees. The racially-specific results lead to the tentative conclusion of genetic differences associated with SLE in African Americans and European Americans. The identification of the genes responsible for the observed linkage effects will provide fundamental knowledge concerning SLE and may even provide new targets for therapy and strategies to defeat this enigmatic and difficult disease.

Characterization of the genetic variation present in CYP3A4 in three South African populations.

PubMed

Drögemöller, Britt; Plummer, Marieth; Korkie, Lundi; Agenbag, Gloudi; Dunaiski, Anke; Niehaus, Dana; Koen, Liezl; Gebhardt, Stefan; Schneider, Nicol; Olckers, Antonel; Wright, Galen; Warnich, Louise

2013-01-01

The CYP3A4 enzyme is the most abundant human cytochrome P450 (CYP) and is regarded as the most important enzyme involved in drug metabolism. Inter-individual and inter-population variability in gene expression and enzyme activity are thought to be influenced, in part, by genetic variation. Although Southern African individuals have been shown to exhibit the highest levels of genetic diversity, they have been under-represented in pharmacogenetic research to date. Therefore, the aim of this study was to identify genetic variation within CYP3A4 in three South African population groups comprising of 29 Khoisan, 65 Xhosa and 65 Mixed Ancestry (MA) individuals. To identify known and novel CYP3A4 variants, 15 individuals were randomly selected from each of the population groups for bi-directional Sanger sequencing of ~600 bp of the 5'-upstream region and all thirteen exons including flanking intronic regions. Genetic variants detected were genotyped in the rest of the cohort. In total, 24 SNPs were detected, including CYP3A4(*)12, CYP3A4(*)15, and the reportedly functional CYP3A4(*)1B promoter polymorphism, as well as two novel non-synonymous variants. These putatively functional variants, p.R162W and p.Q200H, were present in two of the three populations and all three populations, respectively, and in silico analysis predicted that the former would damage the protein product. Furthermore, the three populations were shown to exhibit distinct genetic profiles. These results confirm that South African populations show unique patterns of variation in the genes encoding xenobiotic metabolizing enzymes. This research suggests that population-specific genetic profiles for CYP3A4 and other drug metabolizing genes would be essential to make full use of pharmacogenetics in Southern Africa. Further investigation is needed to determine if the identified genetic variants influence CYP3A4 metabolism phenotype in these populations.

Complex Ancient Genetic Structure and Cultural Transitions in Southern African Populations.

PubMed

Montinaro, Francesco; Busby, George B J; Gonzalez-Santos, Miguel; Oosthuitzen, Ockie; Oosthuitzen, Erika; Anagnostou, Paolo; Destro-Bisol, Giovanni; Pascali, Vincenzo L; Capelli, Cristian

2017-01-01

The characterization of the structure of southern African populations has been the subject of numerous genetic, medical, linguistic, archaeological, and anthropological investigations. Current diversity in the subcontinent is the result of complex events of genetic admixture and cultural contact between early inhabitants and migrants that arrived in the region over the last 2000 years. Here, we analyze 1856 individuals from 91 populations, comprising novel and published genotype data, to characterize the genetic ancestry profiles of 631 individuals from 51 southern African populations. Combining both local ancestry and allele frequency based analyses, we identify a tripartite, ancient, Khoesan-related genetic structure. This structure correlates neither with linguistic affiliation nor subsistence strategy, but with geography, revealing the importance of isolation-by-distance dynamics in the area. Fine-mapping of these components in southern African populations reveals admixture and cultural reversion involving several Khoesan groups, and highlights that Bantu speakers and Coloured individuals have different mixtures of these ancient ancestries. Copyright © 2017 Montinaro et al.

AFRICAN GENETIC DIVERSITY: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping

PubMed Central

Campbell, Michael C.; Tishkoff, Sarah A.

2010-01-01

Comparative studies of ethnically diverse human populations, particularly in Africa, are important for reconstructing human evolutionary history and for understanding the genetic basis of phenotypic adaptation and complex disease. African populations are characterized by greater levels of genetic diversity, extensive population substructure, and less linkage disequilibrium (LD) among loci compared to non-African populations. Africans also possess a number of genetic adaptations that have evolved in response to diverse climates and diets, as well as exposure to infectious disease. This review summarizes patterns and the evolutionary origins of genetic diversity present in African populations, as well as their implications for the mapping of complex traits, including disease susceptibility. PMID:18593304

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

PubMed

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

2011-01-06

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

Genetic African Ancestry and Markers of Mineral Metabolism in CKD

PubMed Central

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

2016-01-01

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

Genetic African Ancestry and Markers of Mineral Metabolism in CKD.

PubMed

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

2016-04-07

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

African Indigenous Cattle: Unique Genetic Resources in a Rapidly Changing World

PubMed Central

Mwai, Okeyo; Hanotte, Olivier; Kwon, Young-Jun; Cho, Seoae

2015-01-01

At least 150 indigenous African cattle breeds have been named, but the majority of African cattle populations remain largely uncharacterized. As cattle breeds and populations in Africa adapted to various local environmental conditions, they acquired unique features. We know now that the history of African cattle was particularly complex and while several of its episodes remain debated, there is no doubt that African cattle population evolved dramatically over time. Today, we find a mosaic of genetically diverse population from the purest Bos taurus to the nearly pure Bos indicus. African cattle are now found all across the continent, with the exception of the Sahara and the river Congo basin. They are found on the rift valley highlands as well as below sea level in the Afar depression. These unique livestock genetic resources are in danger to disappear rapidly following uncontrolled crossbreeding and breed replacements with exotic breeds. Breeding improvement programs of African indigenous livestock remain too few while paradoxically the demand of livestock products is continually increasing. Many African indigenous breeds are endangered now, and their unique adaptive traits may be lost forever. This paper reviews the unique known characteristics of indigenous African cattle populations while describing the opportunities, the necessity and urgency to understand and utilize these resources to respond to the needs of the people of the continent and to the benefit of African farmers. PMID:26104394

Genetic diversity and population structure of African village dogs based on microsatellite and immunity-related molecular markers.

PubMed

Vychodilova, Leona; Necesankova, Michaela; Albrechtova, Katerina; Hlavac, Jan; Modry, David; Janova, Eva; Vyskocil, Mirko; Mihalca, Andrei D; Kennedy, Lorna J; Horin, Petr

2018-01-01

The village and street dogs represent a unique model of canine populations. In the absence of selective breeding and veterinary care, they are subject mostly to natural selection. Their analyses contribute to understanding general mechanisms governing the genetic diversity, evolution and adaptation. In this study, we analyzed the genetic diversity and population structure of African village dogs living in villages in three different geographical areas in Northern Kenya. Data obtained for neutral microsatellite molecular markers were compared with those computed for potentially non-neutral markers of candidate immunity-related genes. The neutral genetic diversity was similar to other comparable village dog populations studied so far. The overall genetic diversity in microsatellites was higher than the diversity of European pure breeds, but it was similar to the range of diversity observed in a group composed of many European breeds, indicating that the African population has maintained a large proportion of the genetic diversity of the canine species as a whole. Microsatellite marker diversity indicated that the entire population is subdivided into three genetically distinct, although closely related subpopulations. This genetical partitioning corresponded to their geographical separation and the observed gene flow well correlated with the communication patterns among the three localities. In contrast to neutral microsatellites, the genetic diversity in immunity-related candidate SNP markers was similar across all three subpopulations and to the European group. It seems that the genetic structure of this particular population of Kenyan village dogs is mostly determined by geographical and anthropogenic factors influencing the gene flow between various subpopulations rather than by biological factors, such as genetic contribution of original migrating populations and/or the pathogen-mediated selection. On the other hand, the study of oldest surviving dogs suggested a

Strengthening human genetics research in Africa: report of the 9th meeting of the African Society of Human Genetics in Dakar in May 2016.

PubMed

Ndiaye Diallo, R; Gadji, M; Hennig, B J; Guèye, M V; Gaye, A; Diop, J P D; Sylla Niang, M; Lopez Sall, P; Guèye, P M; Dem, A; Faye, O; Dieye, A; Cisse, A; Sembene, M; Ka, S; Diop, N; Williams, S M; Matovu, E; Ramesar, R S; Wonkam, A; Newport, M; Rotimi, C; Ramsay, M

2017-01-01

The 9th meeting of the African Society of Human Genetics, in partnership with the Senegalese Cancer Research and Study Group and the Human Heredity and Health in Africa (H3Africa) Consortium, was held in Dakar, Senegal. The theme was Strengthening Human Genetics Research in Africa. The 210 delegates came from 21 African countries and from France, Switzerland, UK, UAE, Canada and the USA. The goal was to highlight genetic and genomic science across the African continent with the ultimate goal of improving the health of Africans and those across the globe, and to promote the careers of young African scientists in the field. A session on the sustainability of genomic research in Africa brought to light innovative and practical approaches to supporting research in resource-limited settings and the importance of promoting genetics in academic, research funding, governmental and private sectors. This meeting led to the formation of the Senegalese Society for Human Genetics.

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

PubMed Central

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

2012-01-01

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

African genetic diversity provides novel insights into evolutionary history and local adaptations.

PubMed

Choudhury, Ananyo; Aron, Shaun; Sengupta, Dhriti; Hazelhurst, Scott; Ramsay, Michèle

2018-05-08

Genetic variation and susceptibility to disease are shaped by human demographic history. We can now study the genomes of extant Africans and uncover traces of population migration, admixture, assimilation and selection by applying sophisticated computational algorithms. There are four major ethnolinguistic divisions among present day Africans: Hunter-gatherer populations in southern and central Africa; Nilo-Saharan speakers from north and northeast Africa; Afro-Asiatic speakers from east Africa; and Niger-Congo speakers who are the predominant ethnolinguistic group spread across most of sub-Saharan Africa. The enormous ethnolinguistic diversity in sub-Saharan African populations is largely paralleled by extensive genetic diversity and until a decade ago, little was known about the origins and divergence of these groups. Results from large-scale population genetic studies, and more recently whole genome sequence data, are unraveling the critical role of events like migration and admixture and environment factors including diet, infectious diseases and climatic conditions in shaping current population diversity. It is now possible to start providing quantitative estimates of divergence times, population size and dynamic processes that have affected populations and their genetic risk for disease. Finally, the availability of ancient genomes from Africa is providing historical insights of unprecedented depth. In this review, we highlight some key interpretations that have emerged from recent African genome studies.

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

PubMed Central

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

2011-01-01

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

Complex population structure in African village dogs and its implications for inferring dog domestication history

PubMed Central

Boyko, Adam R.; Boyko, Ryan H.; Boyko, Corin M.; Parker, Heidi G.; Castelhano, Marta; Corey, Liz; Degenhardt, Jeremiah D.; Auton, Adam; Hedimbi, Marius; Kityo, Robert; Ostrander, Elaine A.; Schoenebeck, Jeffrey; Todhunter, Rory J.; Jones, Paul; Bustamante, Carlos D.

2009-01-01

High genetic diversity of East Asian village dogs has recently been used to argue for an East Asian origin of the domestic dog. However, global village dog genetic diversity and the extent to which semiferal village dogs represent distinct, indigenous populations instead of admixtures of various dog breeds has not been quantified. Understanding these issues is critical to properly reconstructing the timing, number, and locations of dog domestication. To address these questions, we sampled 318 village dogs from 7 regions in Egypt, Uganda, and Namibia, measuring genetic diversity >680 bp of the mitochondrial D-loop, 300 SNPs, and 89 microsatellite markers. We also analyzed breed dogs, including putatively African breeds (Afghan hounds, Basenjis, Pharaoh hounds, Rhodesian ridgebacks, and Salukis), Puerto Rican street dogs, and mixed breed dogs from the United States. Village dogs from most African regions appear genetically distinct from non-native breed and mixed-breed dogs, although some individuals cluster genetically with Puerto Rican dogs or United States breed mixes instead of with neighboring village dogs. Thus, African village dogs are a mosaic of indigenous dogs descended from early migrants to Africa, and non-native, breed-admixed individuals. Among putatively African breeds, Pharaoh hounds, and Rhodesian ridgebacks clustered with non-native rather than indigenous African dogs, suggesting they have predominantly non-African origins. Surprisingly, we find similar mtDNA haplotype diversity in African and East Asian village dogs, potentially calling into question the hypothesis of an East Asian origin for dog domestication. PMID:19666600

Complex population structure in African village dogs and its implications for inferring dog domestication history.

PubMed

Boyko, Adam R; Boyko, Ryan H; Boyko, Corin M; Parker, Heidi G; Castelhano, Marta; Corey, Liz; Degenhardt, Jeremiah D; Auton, Adam; Hedimbi, Marius; Kityo, Robert; Ostrander, Elaine A; Schoenebeck, Jeffrey; Todhunter, Rory J; Jones, Paul; Bustamante, Carlos D

2009-08-18

High genetic diversity of East Asian village dogs has recently been used to argue for an East Asian origin of the domestic dog. However, global village dog genetic diversity and the extent to which semiferal village dogs represent distinct, indigenous populations instead of admixtures of various dog breeds has not been quantified. Understanding these issues is critical to properly reconstructing the timing, number, and locations of dog domestication. To address these questions, we sampled 318 village dogs from 7 regions in Egypt, Uganda, and Namibia, measuring genetic diversity >680 bp of the mitochondrial D-loop, 300 SNPs, and 89 microsatellite markers. We also analyzed breed dogs, including putatively African breeds (Afghan hounds, Basenjis, Pharaoh hounds, Rhodesian ridgebacks, and Salukis), Puerto Rican street dogs, and mixed breed dogs from the United States. Village dogs from most African regions appear genetically distinct from non-native breed and mixed-breed dogs, although some individuals cluster genetically with Puerto Rican dogs or United States breed mixes instead of with neighboring village dogs. Thus, African village dogs are a mosaic of indigenous dogs descended from early migrants to Africa, and non-native, breed-admixed individuals. Among putatively African breeds, Pharaoh hounds, and Rhodesian ridgebacks clustered with non-native rather than indigenous African dogs, suggesting they have predominantly non-African origins. Surprisingly, we find similar mtDNA haplotype diversity in African and East Asian village dogs, potentially calling into question the hypothesis of an East Asian origin for dog domestication.

Genetic Determinism and the Innate-Acquired Distinction in Medicine

PubMed Central

2009-01-01

This article illustrates in which sense genetic determinism is still part of the contemporary interactionist consensus in medicine. Three dimensions of this consensus are discussed: kinds of causes, a continuum of traits ranging from monogenetic diseases to car accidents, and different kinds of determination due to different norms of reaction. On this basis, this article explicates in which sense the interactionist consensus presupposes the innate–acquired distinction. After a descriptive Part 1, Part 2 reviews why the innate–acquired distinction is under attack in contemporary philosophy of biology. Three arguments are then presented to provide a limited and pragmatic defense of the distinction: an epistemic, a conceptual, and a historical argument. If interpreted in a certain manner, and if the pragmatic goals of prevention and treatment (ideally specifying what medicine and health care is all about) are taken into account, then the innate–acquired distinction can be a useful epistemic tool. It can help, first, to understand that genetic determination does not mean fatalism, and, second, to maintain a system of checks and balances in the continuing nature–nurture debates. PMID:20234831

Reasoning across Ontologically Distinct Levels: Students' Understandings of Molecular Genetics

ERIC Educational Resources Information Center

Duncan, Ravit Golan; Reiser, Brian J.

2007-01-01

In this article we apply a novel analytical framework to explore students' difficulties in understanding molecular genetics--a domain that is particularly challenging to learn. Our analytical framework posits that reasoning in molecular genetics entails mapping across ontologically distinct levels--an information level containing the genetic…

Puerto Rico and Florida manatees represent genetically distinct groups

USGS Publications Warehouse

Hunter, Margaret E.; Mignucci-Giannoni, Antonio A.; Tucker, Kimberly Pause; King, Timothy L.; Bonde, Robert K.; Gray, Brian A.; McGuire, Peter M.

2012-01-01

The West Indian manatee (Trichechus manatus) populations in Florida (T. m. latirostris) and Puerto Rico (T. m. manatus) are considered distinct subspecies and are listed together as endangered under the United States Endangered Species Act. Sustained management and conservation efforts for the Florida subspecies have led to the suggested reclassification of the species to a threatened or delisted status. However, the two populations are geographically distant, morphologically distinct, and habitat degradation and boat strikes continue to threaten the Puerto Rico population. Here, 15 microsatellite markers and mitochondrial control region sequences were used to determine the relatedness of the two populations and investigate the genetic diversity and phylogeographic organization of the Puerto Rico population. Highly divergent allele frequencies were identified between Florida and Puerto Rico using microsatellite (F ST = 0.16; R ST = 0.12 (P ST = 0.66; Φ ST = 0.50 (P E = 0.45; NA = 3.9), were similar, but lower than those previously identified in Florida (HE = 0.48, NA = 4.8). Within Puerto Rico, the mitochondrial genetic diversity values (π = 0.001; h = 0.49) were slightly lower than those previously reported (π = 0.002; h = 0.54) and strong phylogeographic structure was identified (F ST global = 0.82; Φ ST global = 0.78 (P < 0.001)). The genetic division with Florida, low diversity, small population size (N = 250), and distinct threats and habitat emphasize the need for separate protections in Puerto Rico. Conservation efforts including threat mitigation, migration corridors, and protection of subpopulations could lead to improved genetic variation in the endangered Puerto Rico manatee population.

Beliefs about Genetically Targeted Care in African Americans

PubMed Central

Halbert, Chanita Hughes; McDonald, Jasmine A.; Magwood, Gayenell; Jefferson, Melanie

2018-01-01

We examined beliefs about genetically targeted care (GTC) among African American men and women in a hospital-based sample and identified sociodemographic, cultural, and clinical factors having significant independent associations with these beliefs. Specifically, beliefs about GTC were evaluated after respondents were randomly primed with a racial or non-racial cue about race and genetics. Despite priming with a racial or non-racial cue, many respondents had positive beliefs about GTC. But, 49% believed that GTC would limit access to medical treatment, 46% believed that people will not trust GTC, and 20% believed that people like them would not benefit from GTC. Racial and non-racial priming did not have significant associations with negative beliefs about GTC. However, cultural beliefs related to temporal orientation were associated significantly with believing that genetically targeted care will limit access to medical treatment. Greater levels of future temporal orientation were associated with a reduced likelihood of endorsing this belief (OR = 0.70, 95% CI = 0.49, 1.01, p = 0.05). Respondents who had a chronic medical condition had an almost three-fold greater likelihood of believing that they would not benefit from GTC (OR = 2.90, 95% CI = 1.00, 8.37, p = 0.05). Greater exposure to information about genetic testing for chronic conditions was also associated with a reduced likelihood of believing that they would not benefit from GTC (OR = 0.40, 95% CI = 0.64, 0.91, p = 0.02). African Americans have diverse beliefs about GTC that should be considered as genetic and genomic services are offered. PMID:28599763

Genetically distinct genogroup IV norovirus strains identified in wastewater.

PubMed

Kitajima, Masaaki; Rachmadi, Andri T; Iker, Brandon C; Haramoto, Eiji; Gerba, Charles P

2016-12-01

We investigated the prevalence and genetic diversity of genogroup IV norovirus (GIV NoV) strains in wastewater in Arizona, United States, over a 13-month period. Among 50 wastewater samples tested, GIV NoVs were identified in 13 (26 %) of the samples. A total of 47 different GIV NoV strains were identified, which were classified into two genetically distinct clusters: the GIV.1 human cluster and a unique genetic cluster closely related to strains previously identified in Japanese wastewater. The results provide additional evidence of the considerable genetic diversity among GIV NoV strains through the analysis of wastewater containing virus strains shed from all populations.

Genetic Alterations in Prostate Cancers among African American Men and Comparisons with Cancers from European and Asian Patients

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-14-1-0303 TITLE: Genetic Alterations in Prostate Cancers among African-American Men and Comparisons with Cancers from...COVERED 29 Sep 2015 – 28 Sep 2016 4. TITLE AND SUBTITLE Genetic Alterations in Prostate Cancers among African- American Men and Comparisons with Cancers...identification of patients with aggressive PCa in African Americans. 15. SUBJECT TERMS Prostate cancer; genetics 16. SECURITY CLASSIFICATION OF

Distinct developmental genetic mechanisms underlie convergently evolved tooth gain in sticklebacks

PubMed Central

Ellis, Nicholas A.; Glazer, Andrew M.; Donde, Nikunj N.; Cleves, Phillip A.; Agoglia, Rachel M.; Miller, Craig T.

2015-01-01

Teeth are a classic model system of organogenesis, as repeated and reciprocal epithelial and mesenchymal interactions pattern placode formation and outgrowth. Less is known about the developmental and genetic bases of tooth formation and replacement in polyphyodonts, which are vertebrates with continual tooth replacement. Here, we leverage natural variation in the threespine stickleback fish Gasterosteus aculeatus to investigate the genetic basis of tooth development and replacement. We find that two derived freshwater stickleback populations have both convergently evolved more ventral pharyngeal teeth through heritable genetic changes. In both populations, evolved tooth gain manifests late in development. Using pulse-chase vital dye labeling to mark newly forming teeth in adult fish, we find that both high-toothed freshwater populations have accelerated tooth replacement rates relative to low-toothed ancestral marine fish. Despite the similar evolved phenotype of more teeth and an accelerated adult replacement rate, the timing of tooth number divergence and the spatial patterns of newly formed adult teeth are different in the two populations, suggesting distinct developmental mechanisms. Using genome-wide linkage mapping in marine-freshwater F2 genetic crosses, we find that the genetic basis of evolved tooth gain in the two freshwater populations is largely distinct. Together, our results support a model whereby increased tooth number and an accelerated tooth replacement rate have evolved convergently in two independently derived freshwater stickleback populations using largely distinct developmental and genetic mechanisms. PMID:26062935

Genetic Counseling for Breast Cancer Susceptibility in African American Women

DTIC Science & Technology

2006-09-01

support following breast cancer diagnosis among African American women;33 the availability of spousal and/or partner support following test results... Nanda R, Schumm LP, Cummings S, Fackenthal JD, et al. Genetic testing in an ethnically diverse cohort of high-risk women: a comparative analysis of... diagnosis and treatment on intrusion in African American breast cancer survivors at an increased risk of hereditary disease. Studies are also needed to

High Genetic Diversity and Distinctiveness of Rear-Edge Climate Relicts Maintained by Ancient Tetraploidisation for Alnus glutinosa

PubMed Central

Lepais, Olivier; Muller, Serge D.; Ben Saad-Limam, Samia; Benslama, Mohamed; Rhazi, Laila; Belouahem-Abed, Djamila; Daoud-Bouattour, Amina; Gammar, Amor Mokhtar; Ghrabi-Gammar, Zeineb; Bacles, Cécile Fanny Emilie

2013-01-01

Populations located at the rear-edge of a species’ distribution may have disproportionate ecological and evolutionary importance for biodiversity conservation in a changing global environment. Yet genetic studies of such populations remain rare. This study investigates the evolutionary history of North-African low latitude marginal populations of Alnus glutinosa Gaertn., a European tree species that plays a significant ecological role as a keystone of riparian ecosystems. We genotyped 551 adults from 19 populations located across North Africa at 12 microsatellite loci and applied a coalescent-based simulation approach to reconstruct the demographic and evolutionary history of these populations. Surprisingly, Moroccan trees were tetraploids demonstrating a strong distinctiveness of these populations within a species otherwise known as diploid. Best-fitting models of demographic reconstruction revealed the relict nature of Moroccan populations that were found to have withstood past climate change events and to be much older than Algerian and Tunisian populations. This study highlights the complex demographic history that can be encountered in rear-edge distribution margins that here consist of both old stable climate relict and more recent populations, distinctively diverse genetically both quantitatively and qualitatively. We emphasize the high evolutionary and conservation value of marginal rear-edge populations of a keystone riparian species in the context of on-going climate change in the Mediterranean region. PMID:24098677

Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry.

PubMed

Feng, Ye; Rhie, Suhn Kyong; Huo, Dezheng; Ruiz-Narvaez, Edward A; Haddad, Stephen A; Ambrosone, Christine B; John, Esther M; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah; Bandera, Elisa V; Ingles, Sue A; Press, Michael F; Deming, Sandra L; Rodriguez-Gil, Jorge L; Zheng, Yonglan; Yao, Song; Han, Yoo-Jeong; Ogundiran, Temidayo O; Rebbeck, Timothy R; Adebamowo, Clement; Ojengbede, Oladosu; Falusi, Adeyinka G; Hennis, Anselm; Nemesure, Barbara; Ambs, Stefan; Blot, William; Cai, Qiuyin; Signorello, Lisa; Nathanson, Katherine L; Lunetta, Kathryn L; Sucheston-Campbell, Lara E; Bensen, Jeannette T; Chanock, Stephen J; Marchand, Loic Le; Olshan, Andrew F; Kolonel, Laurence N; Conti, David V; Coetzee, Gerhard A; Stram, Daniel O; Olopade, Olufunmilayo I; Palmer, Julie R; Haiman, Christopher A

2017-07-01

Background: Genome-wide association studies have identified approximately 100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Because of different patterns of linkage disequilibrium, many of these genetic markers may not represent signals in populations of African ancestry. Methods: We tested 74 breast cancer risk variants and conducted fine-mapping of these susceptibility regions in 6,522 breast cancer cases and 7,643 controls of African ancestry from three genetic consortia (AABC, AMBER, and ROOT). Results: Fifty-four of the 74 variants (73%) were found to have ORs that were directionally consistent with those previously reported, of which 12 were nominally statistically significant ( P < 0.05). Through fine-mapping, in six regions ( 3p24, 12p11, 14q13, 16q12/FTO, 16q23, 19p13 ), we observed seven markers that better represent the underlying risk variant for overall breast cancer or breast cancer subtypes, whereas in another two regions ( 11q13, 16q12/TOX3 ), we identified suggestive evidence of signals that are independent of the reported index variant. Overlapping chromatin features and regulatory elements suggest that many of the risk alleles lie in regions with biological functionality. Conclusions: Through fine-mapping of known susceptibility regions, we have revealed alleles that better characterize breast cancer risk in women of African ancestry. Impact: The risk alleles identified represent genetic markers for modeling and stratifying breast cancer risk in women of African ancestry. Cancer Epidemiol Biomarkers Prev; 26(7); 1016-26. ©2017 AACR . ©2017 American Association for Cancer Research.

Heritability of Nociception IV: Neuropathic pain assays are genetically distinct across methods of peripheral nerve injury

PubMed Central

Young, Erin E.; Costigan, Michael; Herbert, Teri A.; Lariviere, William R.

2013-01-01

Prior genetic correlation analysis of 22 heritable behavioral measures of nociception and hypersensitivity in the mouse identified five genetically distinct pain types. In the present study, we reanalyzed that dataset and included the results of an additional nine assays of nociception and hypersensitivity to: 1) replicate the previously identified five pain types; 2) test whether any of the newly added pain assays represent novel genetically distinct pain types; 3) test the level of genetic relatedness among nine commonly employed neuropathic pain assays. Multivariate analysis of pairwise correlations between assays shows that the newly added zymosan-induced heat hypersensitivity assay does not conform to the two previously identified groups of heat hypersensitivity assays and cyclophosphamide-induced cystitis, the first organ-specific visceral pain model examined, is genetically distinct from other inflammatory assays. The four included mechanical hypersensitivity assays are genetically distinct, and do not comprise a single pain type as previously reported. Among the nine neuropathic pain assays including autotomy, chemotherapy, nerve ligation and spared nerve injury assays, at least four genetically distinct types of neuropathic sensory abnormalities were identified, corresponding to differences in nerve injury method. In addition, two itch assays and Comt genotype were compared to the expanded set of nociception and hypersensitivity assays. Comt genotype was strongly related only to spontaneous inflammatory nociception assays. These results indicate the priority for continued investigation of genetic mechanisms in several assays newly identified to represent genetically distinct pain types. PMID:24071598

Community leaders' perspectives on engaging African Americans in biobanks and other human genetics initiatives.

PubMed

Buseh, Aaron G; Stevens, Patricia E; Millon-Underwood, Sandra; Townsend, Leolia; Kelber, Sheryl T

2013-10-01

There is limited information about what African Americans think about biobanks and the ethical questions surrounding them. Likewise, there is a gap in capacity to successfully enroll African Americans as biobank donors. The purposes of this community-based participatory study were to: (a) explore African Americans' perspectives on genetics/genomic research, (b) understand facilitators and barriers to participation in such studies, and (c) enlist their ideas about how to attract and sustain engagement of African Americans in genetics initiatives. As the first phase in a mixed methods study, we conducted four focus groups with 21 African American community leaders in one US Midwest city. The sample consisted of executive directors of community organizations and prominent community activists. Data were analyzed thematically. Skepticism about biomedical research and lack of trust characterized discussions about biomedical research and biobanks. The Tuskegee Untreated Syphilis Study and the Henrietta Lacks case influenced their desire to protect their community from harm and exploitation. Connections between genetics and family history made genetics/genomics research personal, pitting intrusion into private affairs against solutions. Participants also expressed concerns about ethical issues involved in genomics research, calling attention to how research had previously been conducted in their community. Participants hoped personalized medicine might bring health benefits to their people and proposed African American communities have a "seat at the table." They called for basic respect, authentic collaboration, bidirectional education, transparency and prerogative, and meaningful benefits and remuneration. Key to building trust and overcoming African Americans' trepidation and resistance to participation in biobanks are early and persistent engagement with the community, partnerships with community stakeholders to map research priorities, ethical conduct of research, and

Genetic structure of the gentle Africanized honey bee population (gAHB) in Puerto Rico.

PubMed

Galindo-Cardona, Alberto; Acevedo-Gonzalez, Jenny P; Rivera-Marchand, Bert; Giray, Tugrul

2013-08-06

The Africanized honey bee is one of the most spectacular invasions in the Americas. African bees escaped from apiaries in Brazil in 1956, spread over Americas and by 1994 they were reported in Puerto Rico. In contrast to other places, the oceanic island conditions in Puerto Rico may mean a single introduction and different dynamics of the resident European and new-coming Africanized bees.To examine the genetic variation of honey bee feral populations and colonies from different locations in Puerto Rico, we used eight known polymorphic microsatellite loci. In Puerto Rico, gAHB population does not show any genetic structure (Fst = 0.0783), and is best described as one honey bee population, product of hybridization of AHB and EHB. The genetic variability in this Africanized population was similar to that reported in studies from Texas. We observed that European private allele frequencies are high in all but one locus. This contrasts with mainland Africanized populations, where European allele frequencies are diminished. Two loci with European private alleles, one on Linkage Group 7, known to carry two known defensiveness Quantitative Trait Loci (QTLs), and the other on Linkage Group 1, known to carry three functionally studied genes and 11 candidate genes associated with Varroa resistance mechanisms were respectively, significantly greater or lower in European allele frequency than the other loci with European private alleles. Genetic structure of Puerto Rico gAHB differs from mainland AHB populations, probably representing evolutionary processes on the island.

Full-Genome Characterization and Genetic Evolution of West African Isolates of Bagaza Virus

PubMed Central

Faye, Oumar; Diagne, Moussa Moise; Fall, Gamou; Sembene, Mbacke; Sall, Amadou Alpha; Faye, Ousmane

2018-01-01

Bagaza virus is a mosquito-borne flavivirus, first isolated in 1966 in Central African Republic. It has currently been identified in mosquito pools collected in the field in West and Central Africa. Emergence in wild birds in Europe and serological evidence in encephalitis patients in India raise questions on its genetic evolution and the diversity of isolates circulating in Africa. To better understand genetic diversity and evolution of Bagaza virus, we describe the full-genome characterization of 11 West African isolates, sampled from 1988 to 2014. Parameters such as genetic distances, N-glycosylation patterns, recombination events, selective pressures, and its codon adaptation to human genes are assessed. Our study is noteworthy for the observation of N-glycosylation and recombination in Bagaza virus and provides insight into its Indian origin from the 13th century. Interestingly, evidence of Bagaza virus codon adaptation to human house-keeping genes is also observed to be higher than those of other flaviviruses well known in human infections. Genetic variations on genome of West African Bagaza virus could play an important role in generating diversity and may promote Bagaza virus adaptation to other vertebrates and become an important threat in human health. PMID:29652824

Full-Genome Characterization and Genetic Evolution of West African Isolates of Bagaza Virus.

PubMed

Faye, Martin; Faye, Oumar; Diagne, Moussa Moise; Fall, Gamou; Weidmann, Manfred; Sembene, Mbacke; Sall, Amadou Alpha; Faye, Ousmane

2018-04-13

Bagaza virus is a mosquito-borne flavivirus, first isolated in 1966 in Central African Republic. It has currently been identified in mosquito pools collected in the field in West and Central Africa. Emergence in wild birds in Europe and serological evidence in encephalitis patients in India raise questions on its genetic evolution and the diversity of isolates circulating in Africa. To better understand genetic diversity and evolution of Bagaza virus, we describe the full-genome characterization of 11 West African isolates, sampled from 1988 to 2014. Parameters such as genetic distances, N-glycosylation patterns, recombination events, selective pressures, and its codon adaptation to human genes are assessed. Our study is noteworthy for the observation of N-glycosylation and recombination in Bagaza virus and provides insight into its Indian origin from the 13th century. Interestingly, evidence of Bagaza virus codon adaptation to human house-keeping genes is also observed to be higher than those of other flaviviruses well known in human infections. Genetic variations on genome of West African Bagaza virus could play an important role in generating diversity and may promote Bagaza virus adaptation to other vertebrates and become an important threat in human health.

Perceptions of genetics research as harmful to society: differences among samples of African-Americans and European-Americans.

PubMed

Furr, L Allen

2002-01-01

Genetics has the potential not only to find cures for diseases, but to possess the mechanisms to change the bio-social make-up of populations. A specific question that has arisen on this issue is how developments in genetic technology may intersect with existing race and ethnic relations. Evidence of the racialization of some genetic disorders has been demonstrated elsewhere. The purpose of this study is to compare and contrast African-American and European-American attitudes on the benefits of genetics research for society. Findings show that African-Americans were more likely to say genetics research is harmful for society. This relationship remained statistically significant after controls were introduced in a regression model. Demographic characteristics and self-rated knowledge of genetics had no effect on attitudes among African-Americans. A willingness to use genetic services correlated with favorable attitudes. Differences in social position may lead some groups to opposing interpretations and symbolic meanings of genetics. This may be true in the context of this study because the social meanings of genetics may be tainted by racialization, historical attempts at eugenics, and the potential abuse of genetics targeting groups partially defined by superficial genetic characteristics.

Genetic structure of the gentle Africanized honey bee population (gAHB) in Puerto Rico

PubMed Central

2013-01-01

Background The Africanized honey bee is one of the most spectacular invasions in the Americas. African bees escaped from apiaries in Brazil in 1956, spread over Americas and by 1994 they were reported in Puerto Rico. In contrast to other places, the oceanic island conditions in Puerto Rico may mean a single introduction and different dynamics of the resident European and new-coming Africanized bees. To examine the genetic variation of honey bee feral populations and colonies from different locations in Puerto Rico, we used eight known polymorphic microsatellite loci. Results In Puerto Rico, gAHB population does not show any genetic structure (Fst = 0.0783), and is best described as one honey bee population, product of hybridization of AHB and EHB. The genetic variability in this Africanized population was similar to that reported in studies from Texas. We observed that European private allele frequencies are high in all but one locus. This contrasts with mainland Africanized populations, where European allele frequencies are diminished. Two loci with European private alleles, one on Linkage Group 7, known to carry two known defensiveness Quantitative Trait Loci (QTLs), and the other on Linkage Group 1, known to carry three functionally studied genes and 11 candidate genes associated with Varroa resistance mechanisms were respectively, significantly greater or lower in European allele frequency than the other loci with European private alleles. Conclusions Genetic structure of Puerto Rico gAHB differs from mainland AHB populations, probably representing evolutionary processes on the island. PMID:23915100

Mitochondrial DNA (mtDNA) haplotypes reveal maternal population genetic affinities of Sea Island Gullah-speaking African Americans.

PubMed

McLean, David C; Spruill, Ida; Argyropoulos, George; Page, Grier P; Shriver, Mark D; Garvey, W Timothy

2005-08-01

To better understand the population substructure of African Americans living in coastal South Carolina, we used restriction site polymorphisms and an insertion/deletion in mitochondrial DNA (mtDNA) to construct seven-position haplotypes across 1,395 individuals from Sierra Leone, Africa, from U.S. European Americans, and from the New World African-derived populations of Jamaica, Gullah-speaking African Americans of the South Carolina Sea Islands (Gullahs), African Americans living in Charleston, South Carolina, and West Coast African Americans. Analyses showed a high degree of similarity within the New World African-derived populations, where haplotype frequencies and diversities were similar. Phi-statistics indicated that very little genetic differentiation has occurred within New World African-derived populations, but that there has been significant differentiation of these populations from Sierra Leoneans. Genetic distance estimates indicated a close relationship of Gullahs and Jamaicans with Sierra Leoneans, while African Americans living in Charleston and the West Coast were progressively more distantly related to the Sierra Leoneans. We observed low maternal European American admixture in the Jamaican and Gullah samples (m = 0.020 and 0.064, respectively) that increased sharply in a clinal pattern from Charleston African Americans to West Coast African Americans (m = 0.099 and 0.205, respectively). The appreciably reduced maternal European American admixture noted in the Gullah indicates that the Gullah may be uniquely situated to allow genetic epidemiology studies of complex diseases in African Americans with low European American admixture. (c) 2004 Wiley-Liss, Inc.

Knowledge, group-based medical mistrust, future expectations, and perceived disadvantages of medical genetic testing: perspectives of Black African immigrants/refugees.

PubMed

Buseh, A; Kelber, S; Millon-Underwood, S; Stevens, P; Townsend, L

2014-01-01

Reasons for low participation of ethnic minorities in genetic studies are multifactorial and often poorly understood. Based on published literature, participation in genetic testing is low among Black African immigrants/refugees although they are purported to bear disproportionate disease burden. Thus, research involving Black African immigrant/refugee populations that examine their perspectives on participating in genetic studies is needed. This report examines and describes the knowledge of medical genetics, group-based medical mistrust, and future expectations of genetic research and the influence of these measures on the perceived disadvantages of genetic testing among Black African immigrants/refugees. Using a cross-sectional survey design, a nonprobability sample (n = 212) of Black African immigrants/refugees was administered a questionnaire. Participants ranged in age from 18 to 61 years (mean = 38.91, SD = 9.78). The questionnaire consisted of 5 instruments: (a) sociodemographic characteristics, (b) Knowledge of Medical Genetics scale, (c) Group-Based Medical Mistrust Scale, (d) Future Expectations/Anticipated Consequences of Genetics Research scale, and (e) Perceived Disadvantages of Genetic Testing scale. Participants were concerned that genetic research may result in scientists 'playing God,' interfering with the natural order of life. In multivariate analyses, the perceived disadvantages of genetic testing increased as medical mistrust and anticipated negative impacts of genetic testing increased. Increase in genetic knowledge contributed to a decrease in perceived disadvantages. Our findings suggest that recruitment of Black African immigrants/refugees in genetic studies should address potential low knowledge of genetics, concerns about medical mistrust, the expectations/anticipated consequences of genetic research, and the perceived disadvantages of genetic testing.

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

Known genetic susceptibility factors for chronic pancreatitis in patients of European ancestry are rare in patients of African ancestry.

PubMed

Phillips, Anna Evans; LaRusch, Jessica; Greer, Phil; Abberbock, Judah; Alkaade, Samer; Amann, Stephen T; Anderson, Michelle A; Baillie, John; Banks, Peter A; Brand, Randall E; Conwell, Darwin; Coté, Gregory A; Forsmark, Christopher E; Gardner, Timothy B; Gelrud, Andres; Guda, Nalini; Lewis, Michele; Money, Mary E; Muniraj, Thiruvengadam; Sandhu, Bimaljit S; Sherman, Stuart; Singh, Vikesh K; Slivka, Adam; Tang, Gong; Wilcox, C Mel; Whitcomb, David C; Yadav, Dhiraj

2018-05-19

Multiple pathogenic genetic variants are associated with pancreatitis in patients of European (EA) and Asian ancestries, but studies on patients of African ancestry (AA) are lacking. We evaluated the prevalence of known genetic variations in African-American subjects in the US. We studied prospectively enrolled controls (n = 238) and patients with chronic (CP) (n = 232) or recurrent acute pancreatitis (RAP) (n = 45) in the NAPS2 studies from 2000-2014 of self-identified AA. Demographic and phenotypic information was obtained from structured questionnaires. Ancestry and admixture were evaluated by principal component analysis (PCA). Genotyping was performed for pathogenic genetic variants in PRSS1, SPINK1, CFTR and CTRC. Prevalence of disease-associated variants in NAPS2 subjects of AA and EA was compared. When compared with CP subjects of EA (n = 862), prevalence of established pathogenic genetic variants was infrequent in AA patients with CP, overall (29 vs. 8.19%, OR 4.60, 95% CI 2.74-7.74, p < 0.001), and after stratification by alcohol etiology (p < 0.001). On PCA, AA cases were more heterogeneous but distinct from EA subjects; no difference was observed between AA subjects with and without CP-associated variants. Of 19 A A patients with CP who had pathogenic genetic variants, 2 had variants in PRSS1 (R122H, R122C), 4 in SPINK1 (all N34S heterozygotes), 12 in CFTR (2 CFTR sev , 9 CFTR BD , 1 compound heterozygote with CFTR sev and CFTR BD ), and 1 in CTRC (R254W). Pathogenic genetic variants reported in EA patients are significantly less common in AA patients. Further studies are needed to determine the complex risk factors for AA subjects with pancreatitis. Copyright © 2018. Published by Elsevier B.V.

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

PubMed

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

2012-12-01

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

Novel genetic risk factors for asthma in African American children: Precision Medicine and the SAGE II Study.

PubMed

White, Marquitta J; Risse-Adams, O; Goddard, P; Contreras, M G; Adams, J; Hu, D; Eng, C; Oh, S S; Davis, A; Meade, K; Brigino-Buenaventura, E; LeNoir, M A; Bibbins-Domingo, K; Pino-Yanes, M; Burchard, E G

2016-07-01

Asthma, an inflammatory disorder of the airways, is the most common chronic disease of children worldwide. There are significant racial/ethnic disparities in asthma prevalence, morbidity, and mortality among US children. This trend is mirrored in obesity, which may share genetic and environmental risk factors with asthma. The majority of asthma biomedical research has been performed in populations of European decent. We sought to identify genetic risk factors for asthma in African American children. We also assessed the generalizability of genetic variants associated with asthma in European and Asian populations to African American children. Our study population consisted of 1227 (812 asthma cases, 415 controls) African American children with genome-wide single nucleotide polymorphism (SNP) data. Logistic regression was used to identify associations between SNP genotype and asthma status. We identified a novel variant in the PTCHD3 gene that is significantly associated with asthma (rs660498, p = 2.2 × 10(-7)) independent of obesity status. Approximately 5 % of previously reported asthma genetic associations identified in European populations replicated in African Americans. Our identification of novel variants associated with asthma in African American children, coupled with our inability to replicate the majority of findings reported in European Americans, underscores the necessity for including diverse populations in biomedical studies of asthma.

Biology and ecology of Neosho Smallmouth Bass and the genetically distinct Ouachita lineage

USGS Publications Warehouse

Brewer, Shannon K.; Long, James M.; Tringali, Michael D.; Long, James M.; Birdsong, Timothy W.; Allen, Michael S.

2015-01-01

We reviewed the published and gray literature associated with Neosho Smallmouth Bass and the genetically-distinct Ouachita lineage. Substantial inter-stream variation appears to occur among these populations, particularly related to age. The Neosho subspecies is more abundant, grows faster, and lives longer than the genetically-distinct Ouachita lineage. Recruitment is highly variable among streams for both populations and appears to be related to some undescribed aspects of hydrology but also likely reflect bias due to sampling gear. Information on annual and seasonal trends is lacking for the Neosho subspecies and the Ouachita lineages, particularly as related to the spawning period. Conservation efforts for these lineages might benefit from agencies partnering to achieve goals that extend beyond a particular agencies responsibilities and state boundaries. Recognition of spatial and temporal considerations, combined with a better understanding of the population dynamics as related to abundance, growth, mortality and reproduction would benefit the creation of more effective conservation and management strategies for genetically-distinct populations of Smallmouth Bass.

Distinct subspecies or phenotypic plasticity? Genetic and morphological differentiation of mountain honey bees in East Africa.

PubMed

Gruber, Karl; Schöning, Caspar; Otte, Marianne; Kinuthia, Wanja; Hasselmann, Martin

2013-09-01

Identifying the forces shaping intraspecific phenotypic and genotypic divergence are of key importance in evolutionary biology. Phenotypic divergence may result from local adaptation or, especially in species with strong gene flow, from pronounced phenotypic plasticity. Here, we examine morphological and genetic divergence among populations of the western honey bee Apis mellifera in the topographically heterogeneous East African region. The currently accepted "mountain refugia hypothesis" states that populations living in disjunct montane forests belong to a different lineage than those in savanna habitats surrounding these forests. We obtained microsatellite data, mitochondrial sequences, and morphometric data from worker honey bees collected from feral colonies in three montane forests and corresponding neighboring savanna regions in Kenya. Honey bee colonies from montane forests showed distinct worker morphology compared with colonies in savanna areas. Mitochondrial sequence data did not support the existence of the two currently accepted subspecies. Furthermore, analyses of the microsatellite data with a Bayesian clustering method did not support the existence of two source populations as it would be expected under the mountain refugia scenario. Our findings suggest that phenotypic plasticity rather than distinct ancestry is the leading cause behind the phenotypic divergence observed between montane forest and savanna honey bees. Our study thus corroborates the idea that high gene flow may select for increased plasticity.

African and Non-African Admixture Components in African Americans and An African Caribbean Population

PubMed Central

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.

2013-01-01

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 (r2 = 0.992, r2 = 0.912, respectively). To investigate other African contributions to African American and Barbadian admixture, we performed PCA on ~14,000 (14k) genome-wide SNPs in AAs, ACs, Yorubans, Luhya and Maasai African groups, and estimated genetic distances (FST). We found AAs and ACs were closest genetically (FST = 0.008), and both were closer to the Yorubans than the other East African populations. In our sample of individuals of African descent, ~400 well-defined AIMs were just as good for detecting substructure as ~14,000 random SNPs drawn from a genome-wide panel of markers. PMID:20717976

Genetic characterization and phylogenetic position of Echinococcus felidis (Cestoda: Taeniidae) from the African lion.

PubMed

Hüttner, Marion; Nakao, Minoru; Wassermann, Torsten; Siefert, Ludwig; Boomker, Joop D F; Dinkel, Anke; Sako, Yasuhito; Mackenstedt, Ute; Romig, Thomas; Ito, Akira

2008-06-01

Echinococcus felidis had been described in 1937 from African lions, but was later included in Echinococcus granulosus as a subspecies or a strain. In the absence of any genetic characterization, most previous records of this taxon from a variety of large African mammals remained unconfirmed due to the lack of diagnostic criteria and the possible confusion with the sympatric E. granulosus sensu stricto, Echinococcus ortleppi and Echinococcus canadensis. In this study, we obtained taeniid eggs from lion feces in Uganda and amplified DNA from individual eggs. Mitochondrial and nuclear DNA sequences showed similarities with those of other Echinococcus spp., but high values of percentage divergence of mitochondrial genes indicated the presence of a distinct species. In a second step, we compared this material with the preserved specimens of adult E. granulosus felidis, which had been identified morphologically approximately 40 years ago in South Africa. All DNA fragments (<200 bp) that could be amplified from the adults showed 100% similarity with the Ugandan material. In the phylogenetic tree of Echinococcus which was constructed from the mitochondrial genes, E. felidis is positioned as a sister taxon of E. granulosus sensu stricto. The data obtained will facilitate the development of diagnostic tools necessary to study the epidemiology of this enigmatic parasite.

Relationship between Distinct African Cholera Epidemics Revealed via MLVA Haplotyping of 337 Vibrio cholerae Isolates.

PubMed

Moore, Sandra; Miwanda, Berthe; Sadji, Adodo Yao; Thefenne, Hélène; Jeddi, Fakhri; Rebaudet, Stanislas; de Boeck, Hilde; Bidjada, Bawimodom; Depina, Jean-Jacques; Bompangue, Didier; Abedi, Aaron Aruna; Koivogui, Lamine; Keita, Sakoba; Garnotel, Eric; Plisnier, Pierre-Denis; Ruimy, Raymond; Thomson, Nicholas; Muyembe, Jean-Jacques; Piarroux, Renaud

2015-01-01

Since cholera appeared in Africa during the 1970s, cases have been reported on the continent every year. In Sub-Saharan Africa, cholera outbreaks primarily cluster at certain hotspots including the African Great Lakes Region and West Africa. In this study, we applied MLVA (Multi-Locus Variable Number Tandem Repeat Analysis) typing of 337 Vibrio cholerae isolates from recent cholera epidemics in the Democratic Republic of the Congo (DRC), Zambia, Guinea and Togo. We aimed to assess the relationship between outbreaks. Applying this method, we identified 89 unique MLVA haplotypes across our isolate collection. MLVA typing revealed the short-term divergence and microevolution of these Vibrio cholerae populations to provide insight into the dynamics of cholera outbreaks in each country. Our analyses also revealed strong geographical clustering. Isolates from the African Great Lakes Region (DRC and Zambia) formed a closely related group, while West African isolates (Togo and Guinea) constituted a separate cluster. At a country-level scale our analyses revealed several distinct MLVA groups, most notably DRC 2011/2012, DRC 2009, Zambia 2012 and Guinea 2012. We also found that certain MLVA types collected in the DRC persisted in the country for several years, occasionally giving rise to expansive epidemics. Finally, we found that the six environmental isolates in our panel were unrelated to the epidemic isolates. To effectively combat the disease, it is critical to understand the mechanisms of cholera emergence and diffusion in a region-specific manner. Overall, these findings demonstrate the relationship between distinct epidemics in West Africa and the African Great Lakes Region. This study also highlights the importance of monitoring and analyzing Vibrio cholerae isolates.

Genetics and southern African prehistory: an archaeological view.

PubMed

Mitchell, Peter

2010-01-01

Southern African populations speaking languages that are often - but inaccurately - grouped together under the label 'Khoisan' are an important focus of molecular genetic research, not least in tracking the early stages of human genetic diversification. This paper reviews these studies from an archaeological standpoint, concentrating on modern human origins, the introduction of pastoralism to southern Africa and admixture between the region's indigenous foragers and incoming Bantu-speaking farmers. To minimise confusion and facilitate correlation with anthropological, linguistic and archaeological data it emphasises the need to use ethnolinguistic labels accurately and with due regard for the particular histories of individual groups. It also stresses the geographically and culturally biased nature of the genetic studies undertaken to date, which employ data from only a few 'Khoisan' groups. Specific topics for which the combined deployment of genetic and archaeological methods would be particularly useful include the early history of Ju-Hoan- and Tuu-speaking hunter-gatherers, the expansion of Khoe-speaking populations, the chronology of genetic exchange between hunter-gatherers and farmers, and the origins of the Sotho/Tswana- and Nguni-speaking populations that dominate much of southern Africa today.

Effects of Genetic Counseling for Hypertension on Changes in Lifestyle Behaviors among African-American Women

PubMed Central

Taylor, Jacquelyn Y.; Wu, Chun Yi

2010-01-01

Genetic counseling research has been used for diseases such as breast and other cancers, but genetic counseling for hypertension has been understudied. African-American women have the highest prevalence of hypertension and cardiovascular disease of any group in the United States. Because hypertension and related cardiovascular sequela have a profound impact on the health and well being of African-American women, providing genetic counseling for hypertension is important in order to determine risk and to provide early interventions. The purpose of this study is to examine lifestyle changes among urban African-American women following genetic counseling for hypertension as compared to baseline. Specific lifestyle factors include the impact of changes in physical activity, of sodium intake, and of body mass index on systolic and diastolic blood pressure and pulse pressure. Results of this study indicated that systolic and diastolic blood pressure readings and pulse pressure readings decreased six months after genetic counseling, although the findings were not statistically significant. Body mass index remained relatively unchanged after genetic counseling, but minutes of increased physical activity was reported, although this was not significant. However, a statistically significant decrease in sodium intake (p = .033) was noted from baseline to 6-month follow-up after genetic counseling. With the exception of sodium, changes in lifestyle behaviors, blood pressure, and pulse pressure readings did not differ significantly from baseline. However, changes in lifestyle behaviors in a positive direction are important and worth noting. Further studies on genetic counseling for hypertension with longer follow-up periods are needed to determine the effectiveness of genetic counseling on changes in lifestyle behaviors and blood pressure readings. PMID:19691178

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

Increased genetic diversity of ADME genes in African Americans compared with their putative ancestral source populations and implications for Pharmacogenomics

PubMed Central

2014-01-01

Background African Americans have been treated as a representative population for African ancestry for many purposes, including pharmacogenomic studies. However, the contribution of European ancestry is expected to result in considerable differences in the genetic architecture of African American individuals compared with an African genome. In particular, the genetic admixture influences the genomic diversity of drug metabolism-related genes, and may cause high heterogeneity of drug responses in admixed populations such as African Americans. Results The genomic ancestry information of African-American (ASW) samples was obtained from data of the 1000 Genomes Project, and local ancestral components were also extracted for 32 core genes and 252 extended genes, which are associated with drug absorption, distribution, metabolism, and excretion (ADME) genes. As expected, the global genetic diversity pattern in ASW was determined by the contributions of its putative ancestral source populations, and the whole profiles of ADME genes in ASW are much closer to those in YRI than in CEU. However, we observed much higher diversity in some functionally important ADME genes in ASW than either CEU or YRI, which could be a result of either genetic drift or natural selection, and we identified some signatures of the latter. We analyzed the clinically relevant polymorphic alleles and haplotypes, and found that 28 functional mutations (including 3 missense, 3 splice, and 22 regulator sites) exhibited significantly higher differentiation between the three populations. Conclusions Analysis of the genetic diversity of ADME genes showed differentiation between admixed population and its ancestral source populations. In particular, the different genetic diversity between ASW and YRI indicated that the ethnic differences in pharmacogenomic studies are broadly existed despite that African ancestry is dominant in Africans Americans. This study should advance our understanding of the genetic

Challenges in recruiting African-American women for a breast cancer genetics study.

PubMed

Compadre, Amanda J; Simonson, Melinda E; Gray, Katy; Runnells, Gail; Kadlubar, Susan; Zorn, Kristin K

2018-01-01

African-American women, especially in the southern United States, are underrepresented in cancer genetics research. A study was designed to address this issue by investigating the germline mutation rate in African-American women in Arkansas with a personal and/or family history of breast cancer. Women were tested for these mutations using a large panel of breast cancer susceptibility genes. In this analysis, we discuss the challenges encountered in recruiting African-American women from an existing biorepository to participate in this study. We attempted to contact 965 African-American women with a personal and/or family history of breast cancer who participated in Spit for the Cure (SFTC) between 2007 and 2013 and provided consent to be recontacted. The SFTC participants were invited by telephone and email to participate in the genetic study. Enrollment required completion of a phone interview to obtain a family and medical history and return of a signed consent form. Among eligible SFTC participants, 39.6% (382/965) were able to be contacted with the phone numbers and email addresses they provided. Of these, 174 (45.5%) completed a phone interview and returned a signed consent form. Others were not able to be contacted ( n  = 583), declined to participate ( n  = 57), did not keep phone interview appointments ( n  = 82), completed the phone interview but never returned a signed consent ( n  = 54), were deceased ( n  = 13), or were too confused to consent to participate ( n  = 2). Recruiting African-American women into our breast cancer genetics study proved challenging primarily due to difficulty establishing contact with potential participants. Given their prior participation in breast cancer research, we anticipated that this would be a highly motivated population. Indeed, when we were able to contact SFTC participants, only 14.9% declined to participate in our study. Innovative communication, retention, and recruitment strategies are

African Ancestry and Genetic Risk for Uterine Leiomyomata

PubMed Central

Wise, Lauren A.; Ruiz-Narvaez, Edward A.; Palmer, Julie R.; Cozier, Yvette C.; Tandon, Arti; Patterson, Nick; Radin, Rose G.; Rosenberg, Lynn; Reich, David

2012-01-01

Rates of uterine leiomyomata (UL) are 2–3 times higher in African Americans than in European Americans. It is unclear whether inherited factors explain the ethnic disparity. To investigate the presence of risk alleles for UL that are highly differentiated in frequency between African Americans and European Americans, the authors conducted an admixture-based genome-wide scan of 2,453 UL cases confirmed by ultrasound or surgery in the Black Women's Health Study (1997–2009), a national prospective cohort study. Controls (n = 2,102) were women who did not report a UL diagnosis through 2009. Mean percentage of European ancestry was significantly lower among cases (20.00%) than among controls (21.63%; age-adjusted mean difference = −1.76%, 95% confidence interval: −2.40, −1.12; P < 0.0001), and the association was stronger in younger cases. Admixture analyses showed suggestive evidence of association at chromosomes 2, 4, and 10. The authors also genotyped a dense set of tag single nucleotide polymorphisms at different loci associated with UL in Japanese women but failed to replicate the associations. This suggests that genetic variation for UL differs in populations with and without African ancestry. The admixture findings further indicate that no single highly differentiated locus is responsible for the ethnic disparity in UL, raising the possibility that multiple variants jointly contribute to the higher incidence of UL in African Americans. PMID:23161897

Alpha-thalassemia genetic testing: an important anemia diagnostic tool in patients of African heritage.

PubMed

Dasanu, Constantin A

2010-01-01

Inherited alpha-thalassemia genotypes have been shown to have a rather high prevalence in some patient populations of African heritage. These genotypes lead to mild anemia with microcytic indices and a normal hemoglobin electrophoresis. In our outpatient department, we analyzed 54 consecutive patients of African descent with longstanding microcytic anemia, but no evidence of iron deficiency. We detected alpha-thalassemia gene deletions in 94 percent of these patients. Alpha-thalassemia genetic testing appears cost-effective in an otherwise unexplained, longstanding microcytic anemia in patients of African origin.

Distinct subspecies or phenotypic plasticity? Genetic and morphological differentiation of mountain honey bees in East Africa

PubMed Central

Gruber, Karl; Schöning, Caspar; Otte, Marianne; Kinuthia, Wanja; Hasselmann, Martin

2013-01-01

Identifying the forces shaping intraspecific phenotypic and genotypic divergence are of key importance in evolutionary biology. Phenotypic divergence may result from local adaptation or, especially in species with strong gene flow, from pronounced phenotypic plasticity. Here, we examine morphological and genetic divergence among populations of the western honey bee Apis mellifera in the topographically heterogeneous East African region. The currently accepted “mountain refugia hypothesis” states that populations living in disjunct montane forests belong to a different lineage than those in savanna habitats surrounding these forests. We obtained microsatellite data, mitochondrial sequences, and morphometric data from worker honey bees collected from feral colonies in three montane forests and corresponding neighboring savanna regions in Kenya. Honey bee colonies from montane forests showed distinct worker morphology compared with colonies in savanna areas. Mitochondrial sequence data did not support the existence of the two currently accepted subspecies. Furthermore, analyses of the microsatellite data with a Bayesian clustering method did not support the existence of two source populations as it would be expected under the mountain refugia scenario. Our findings suggest that phenotypic plasticity rather than distinct ancestry is the leading cause behind the phenotypic divergence observed between montane forest and savanna honey bees. Our study thus corroborates the idea that high gene flow may select for increased plasticity. PMID:24223262

A recombinant vesicular stomatitis virus-based Lassa fever vaccine protects guinea pigs and macaques against challenge with geographically and genetically distinct Lassa viruses.

PubMed

Safronetz, David; Mire, Chad; Rosenke, Kyle; Feldmann, Friederike; Haddock, Elaine; Geisbert, Thomas; Feldmann, Heinz

2015-04-01

Lassa virus (LASV) is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a "universal" LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models. Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV) expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection / disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever. Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever.

Genetic susceptibility loci for subtypes of breast cancer in an African American population

PubMed Central

Palmer, Julie R.; Ruiz-Narvaez, Edward A.; Rotimi, Charles N.; Cupples, L. Adrienne; Cozier, Yvette C.; Adams-Campbell, Lucile L.; Rosenberg, Lynn

2012-01-01

Background Most genome-wide association scans (GWAS) have been carried out in European ancestry populations; no risk variants for breast cancer have been identified solely from African ancestry GWAS data. Few GWAS hits have replicated in African ancestry populations. Methods In a nested case-control study of breast cancer in the Black Women’s Health Study (1,199 cases/1,948 controls), we evaluated index SNPs in 21 loci from GWAS of European or Asian ancestry populations, overall, in subtypes defined by estrogen (ER) and progesterone (PR) receptor status (ER+/PR+, n=336; ER−/PR−, n=229), and in triple-negative breast cancer (TNBC, N=81). To evaluate the contribution of genetic factors to population differences in breast cancer subtype, we also examined global percent African ancestry. Results Index SNPs in five loci were replicated, including three associated with ER−/PR− breast cancer (TERT rs10069690 in 5p15.33, rs704010 in 10q22.3, and rs8170 in 19p13.11): per allele odds ratios were 1.29 (95% confidence interval (CI) 1.04–1.59), p=0.02, 1.52 (95% CI 1.12–2.08), p=0.01, and 1.30 (95% CI 1.01–1.68), p=0.04, respectively. Stronger associations were observed for TNBC. Furthermore, cases in the highest quintile of percent African ancestry were three times more likely to have TNBC than ER+/PR+ cancer. Conclusions These findings provide the first confirmation of the TNBC SNP rs8170 in an African ancestry population, and independent confirmation of the TERT ER− SNP. Further, the risk of developing ER− breast cancer, particularly TNBC, increased with increasing proportion of global African ancestry. Impact The findings demonstrate the importance of genetic factors in the disproportionately high occurrence of TNBC in African American women. PMID:23136140

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.

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

Genetic studies of African populations: an overview on disease susceptibility and response to vaccines and therapeutics.

PubMed

Sirugo, Giorgio; Hennig, Branwen J; Adeyemo, Adebowale A; Matimba, Alice; Newport, Melanie J; Ibrahim, Muntaser E; Ryckman, Kelli K; Tacconelli, Alessandra; Mariani-Costantini, Renato; Novelli, Giuseppe; Soodyall, Himla; Rotimi, Charles N; Ramesar, Raj S; Tishkoff, Sarah A; Williams, Scott M

2008-07-01

Africa is the ultimate source of modern humans and as such harbors more genetic variation than any other continent. For this reason, studies of the patterns of genetic variation in African populations are crucial to understanding how genes affect phenotypic variation, including disease predisposition. In addition, the patterns of extant genetic variation in Africa are important for understanding how genetic variation affects infectious diseases that are a major problem in Africa, such as malaria, tuberculosis, schistosomiasis, and HIV/AIDS. Therefore, elucidating the role that genetic susceptibility to infectious diseases plays is critical to improving the health of people in Africa. It is also of note that recent and ongoing social and cultural changes in sub-Saharan Africa have increased the prevalence of non-communicable diseases that will also require genetic analyses to improve disease prevention and treatment. In this review we give special attention to many of the past and ongoing studies, emphasizing those in Sub-Saharan Africans that address the role of genetic variation in human disease.

African ancestry, lung function and the effect of genetics

PubMed Central

Wehrmeister, Fernando C.; Hartwig, Fernando P.; Perez-Padilla, Rogelio; Gigante, Denise P.; Barros, Fernando C.; Oliveira, Isabel O.; Ferreira, Gustavo D.; Horta, Bernardo L.

2015-01-01

African-Americans have smaller lung function compared with European-Americans. The aim of this study was to disentangle the contribution of genetics from other variables on lung function. A cohort was followed from birth to 30 years of age in Brazil. Several variables were collected: genomic analysis based on DNA; forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) obtained by spirometry; height measured by anthropometrists; and thorax circumference evaluated by photonic scanner. Crude and adjusted linear regression models were calculated according to African ancestry. The sample comprised 2869 participants out of 3701 members of the cohort. Males with higher African ancestry by DNA analysis had a smaller FEV1 (−0.13 L, 95% CI −0.23– −0.03 L) and FVC (−0.21 L, 95% CI −0.32– −0.09 L) compared with those with less African ancestry, having accounted for height, sitting to standing height ratio and other confounders. Similar effects were seen in females. After adjustment, ancestry remained significantly associated with lung function, but the large effect of adjustment for confounding among males (but not females) does not allow us to exclude the possibility that residual confounding may still account for these findings. PMID:25700383

Grandmothers as gems of genetic wisdom: exploring South African traditional beliefs about the causes of childhood genetic disorders.

PubMed

Penn, Claire; Watermeyer, Jennifer; MacDonald, Carol; Moabelo, Colleen

2010-02-01

With its diverse cultural and linguistic profile, South Africa provides a unique context to explore contextual influences on the process of genetic counseling. Prior research suggests intergenerational differences regarding models of causation which influence treatment-seeking paths. This pilot study therefore aimed to explore South African traditional beliefs regarding common childhood genetic disorders. Three focus groups were conducted with fifteen grandmothers from different cultural backgrounds in an urban community. Questions pertained to the role of the grandmother, traditional beliefs regarding causes of genetic disorders, explanations of heredity, and prevention and management of genetic disorders. Results indicate a variety of cultural explanations for causes of childhood genetic disorders. These causes can be classified into categories related to lifestyle, behavior, social issues, culture, religion, genetic, and familial causes. Prevention and treatment issues are also highlighted. These findings have implications for genetic counseling practice, which needs to include a greater focus on cultural issues.

Systematic review on the conservation genetics of African savannah elephants.

PubMed

Zacarias, Daniel; Bini, Luis Mauricio; Loyola, Rafael

2016-01-01

In this paper we review the conservation genetics of African savannah elephants, aiming to understand the spatio-temporal research trends and their underlying factors. As such, we explore three questions associated to the conservation genetics and molecular ecology of these elephants: (1) what are the research trends concerning the conservation genetics of Loxodonta africana ? (2) Do richer countries conduct more research on the genetics of African elephants? (3) Which attributes influence where scholars conduct their research? We examined available peer-reviewed publications from 1993 to 2014 in complementary online databases, including the ISI/Web of Science (WoS), Scopus and Google Scholar (GS), and searched for publications in scientific journals as well as in the reference section of these publications. We analyzed the annual trend of publications in this field of research, including the number of authors, levels of collaboration among authors, year of publication, publishing journal and the countries from where genetic samples were collected. Additionally, we identified main research clusters, authors, and institutional collaborations, based on co-citation and co-occurrence networks. We found that during the study period there was a positive trend in the number of publications and a reduction in the number of authors per paper. Twenty-five countries contributed, with the majority of publications authored by researchers in the USA, Kenya and South Africa. The majority of samples were collected in Kenya, Tanzania and South Africa. Research outputs are associated with the existence of long-term conservation/research projects and research potential as measured by the literacy rate and the number of higher education institutions in a country. Five research clusters were identified, focusing on the origin and evolution of the species, methodological issues and the relatedness among elephant species. Research in this field should be expanded to additional countries

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

PubMed Central

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

2012-01-01

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

The African baobab (Adansonia digitata, Malvaceae): genetic resources in neglected populations of the Nuba Mountains, Sudan.

PubMed

Wiehle, Martin; Prinz, Kathleen; Kehlenbeck, Katja; Goenster, Sven; Mohamed, Seifeldin Ali; Finkeldey, Reiner; Buerkert, Andreas; Gebauer, Jens

2014-09-01

• Adansonia digitata L. is one of the most important indigenous fruit trees of mainland Africa. Despite its significance for subsistence and income generation of local communities, little is known about the genetic and morphological variability of East African populations of A. digitata, including those of Sudan. The aim of the current study, therefore, was to analyze genetic and morphological variability of different baobab populations in Kordofan, Sudan and to estimate the effect of human intervention on genetic differentiation and diversity.• A total of 306 trees were randomly sampled from seven spatially separated locations in the Nuba Mountains, Sudan, to cover a wide range of differing environmental gradients and management regimes ('homesteads' and 'wild'). Genetic analyses were conducted using nine microsatellite markers. Because of the tetraploid nature of A. digitata, different approaches were applied to estimate patterns of genetic diversity. Investigations were completed by measurements of dendrometric and fruit morphological characters.• Genetic diversity was balanced and did not differ between locations or management regimes, although tendencies of higher diversity in 'homesteads' were observed. A Bayesian cluster approach detected two distinct gene pools in the sample set, mainly caused by one highly diverse population close to a main road. The variability of tree characters and fruit morphometries was high, and significantly different between locations.• Results indicated a rather positive effect with human intervention. The observed populations provide a promising gene pool and likely comprise ecotypes well-adapted to environmental conditions at the northern distribution range of the species, which should be considered in conservation and management programs. © 2014 Botanical Society of America, Inc.

Evaluation of the genetic distinctiveness of Greater Sage-grouse in the Bi-State Planning Area

USGS Publications Warehouse

Oyler-McCance, Sara J.; Casazza, Michael L.

2011-01-01

The purpose of this study was to further characterize a distinct population of Greater Sage-grouse: the population located along the border between Nevada and California (Bi-State Planning Area) and centered around the Mono Basin. This population was previously determined to be genetically distinct from other Greater Sage-grouse populations across their range. Previous genetic work focused on characterizing genetic variation across the species' range and thereby used a coarse sampling approach for species characterization. The goal of this study was to investigate this population further by obtaining samples from breeding locations within the population and analyzing those samples with the same mitochondrial and microsatellite loci used in previous studies. Blood samples were collected in six locations within the Bi-State Planning Area. Genetic data from subpopulations were then compared with each other and also with two populations outside of the Bi-State Planning Area. Particular attention was paid to subpopulation boundaries and internal dynamics by drawing comparisons among particular regions within the Bi-State Planning Area and regions proximal to it. All newly sampled subpopulations contained mitochondrial haplotypes and allele frequencies that were consistent with the genetically unique Bi-State (Mono Basin) Greater Sage-grouse described previously. This reinforces the fact that this group of Greater Sage-grouse is genetically unique and warrants special attention. Maintaining the genetic integrity of this population could protect the evolutionary potential of this population of Greater Sage-grouse. Additionally, the White Mountains subpopulation was found to be significantly distinct from all other Bi-State subpopulations.

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

PubMed

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

2014-10-01

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

Genetic Variability of Smoking Persistence in African Americans

PubMed Central

Hamidovic, A; Kasberger, J; Young, T; Goodloe, R; Redline, S; Buxbaum, S; Benowitz, N; Bergen, A; Butler, K; Franceschini, N; Gharib, S; Hitsman, B; Levy, D; Meng, Y; Papanicolaou, G; Preiss, S; Spring, B; Styn, M; Tong, E; White, W; Wiggins, K; Jorgenson, E

2011-01-01

To date, most genetic association analyses of smoking behaviors have been conducted in populations of European ancestry and many of these studies focused on the phenotype that measures smoking quantity, i.e. cigarettes per day. Additional association studies in diverse populations with different linkage disequilibrium (LD) patterns and an alternate phenotype, such as total tobacco exposure which accounts for intermittent periods of smoking cessation within a larger smoking period as measured in large cardiovascular risk studies, can aid the search for variants relevant to smoking behavior. For these reasons, we undertook an association analysis using a genotyping array that includes 2100 genes to analyze smoking persistence in unrelated African-American participants from The Atherosclerosis Risk in Communities (ARIC) study. A locus located ~ 4 Kb downstream from the 3’ UTR of the Brain-Derived Neurotrophic Factor (BDNF) significantly influenced smoking persistence. In addition, independent variants rs12915366 and rs12914385 in the cluster of genes encoding nicotinic acetylcholine receptor subunits (CHRNA5-CHRNA3-CHRNB4) on 15q25.1 were also associated with the phenotype in this sample of African American subjects. To our knowledge, this is the first study to more extensively evaluate the genome in the African American population as a limited number of previous studies of smoking behavior in this population included evaluations of only single genomic regions. PMID:21436384

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

A Recombinant Vesicular Stomatitis Virus-Based Lassa Fever Vaccine Protects Guinea Pigs and Macaques against Challenge with Geographically and Genetically Distinct Lassa Viruses

PubMed Central

Safronetz, David; Mire, Chad; Rosenke, Kyle; Feldmann, Friederike; Haddock, Elaine; Geisbert, Thomas; Feldmann, Heinz

2015-01-01

Background Lassa virus (LASV) is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a “universal” LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models. Methodologies/principle findings Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV) expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection / disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever. Conclusions/significance Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever. PMID:25884628

The African Lupus Genetics Network (ALUGEN) registry: standardized, prospective follow-up studies in African patients with systemic lupus erythematosus.

PubMed

Hodkinson, B; Mapiye, D; Jayne, D; Kalla, A; Tiffin, N; Okpechi, I

2016-03-01

The prevalence and severity of systemic lupus erythematosus (SLE) differs between ethnic groups and geographical regions. Although initially reported as rare, there is growing evidence that SLE is prevalent and runs a severe course in Africa. There is a paucity of prospective studies on African SLE patients. The African Lupus Genetics Network (ALUGEN) is a multicentred framework seeking to prospectively assess outcomes in SLE patients in Africa. Outcomes measured will be death, hospital admission, disease activity flares, and SLE-related damage. We will explore predictors for these outcomes including clinical, serological, socio-demographic, therapeutic and genetic factors. Further, we will investigate comorbidities and health-related quality of life amongst these patients. Data of patients recently (≤ 5 yrs) diagnosed with SLE will be collected at baseline and annual follow-up visits, and captured electronically. The ALUGEN project will facilitate standardized data capture for SLE cases in Africa, allowing participating centres to develop their own SLE registries, and enabling collaboration to enrich our understanding of inter-ethnic and regional variations in disease expression. Comprehensive, high-quality multi-ethnic data on African SLE patients will expand knowledge of the disease and inform clinical practice, in addition to augmenting research capacity and networking links and providing a platform for future biomarker and interventional studies. © The Author(s) 2015.

Are life satisfaction and self-esteem distinct constructs? A black South African perspective.

PubMed

Westaway, Margaret S; Maluka, Constance S

2005-10-01

As part of a longitudinal project on Quality of Life, a study was undertaken to extend the applicability of the 5-item Satisfaction With Life Scale, developed in the USA, in South Africa. Data on basic sociodemographic characteristics, the scale, and the 10-item Rosenberg Self-esteem scale were available for 360 Black South Africans (151 men and 209 women), ages 21 to 83 years (M = 38.6 yr., SD = 10.3). Factor analysis applied to scale scores gave two factors, accounting for 71% of the variance. Factor I was loaded by 10 Self-esteem items and Factor II by four of the five Life Satisfaction items. Coefficient alpha was .77 for the Satisfaction With Life Scale and .97 for the Rosenberg Self-esteem Scale. Life Satisfaction was related to Self-esteem (r = .17, p < .01). It was concluded that Life Satisfaction and Self-esteem appear to be distinct, unitary constructs, but responses to Item 5 on the Satisfaction With Life Scale require cautious interpretation and may contribute to the weak r, although so may the collectivist culture of Black South Africans.

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

PubMed Central

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

2017-01-01

Abstract Objectives. To evaluate whether genetic and environmental factors associated with RA in European and Asian ancestry populations are also associated with RA in African ancestry individuals. Methods. A case–control study was undertaken in 197 RA cases and 868 controls of African ancestry (Black African, Black Caribbean or Black British ethnicity) from South London. Smoking and alcohol consumption data at RA diagnosis was captured. Genotyping was undertaken (Multi-Ethnic Genotyping Array) and human leukocyte antigen (HLA) alleles imputed. The following European/Asian RA susceptibility factors were tested: 99 genome-wide loci combined into a genetic risk score; HLA region [20 haplotypes; shared epitope (SE)]; smoking; and alcohol consumption. The SE was tested for its association with radiological erosions. Logistic regression models were used, including ancestry-informative principal components, to control for admixture. Results. European/Asian susceptibility loci were associated with RA in African ancestry individuals. The genetic risk score provided an odds ratio (OR) for RA of 1.53 (95% CI: 1.31, 1.79; P = 1.3 × 10 −7). HLA haplotype ORs in European and African ancestry individuals were highly correlated (r = 0.83, 95% CI: 0.56, 0.94; P = 1.1 × 10 −4). Ever-smoking increased (OR = 2.36, 95% CI: 1.46, 3.82; P = 4.6 × 10 −4) and drinking alcohol reduced (OR = 0.34, 95% CI: 0.20, 0.56; P = 2.7 × 10 −5) RA risk in African ancestry individuals. The SE was associated with erosions (OR = 2.61, 95% CI: 1.36, 5.01; P = 3.9 × 10 −3). Conclusion. Gene–environment RA risk factors identified in European/Asian ancestry populations are relevant in African ancestry individuals. As modern statistical methods facilitate analysing ancestrally diverse populations, future genetic studies should incorporate African ancestry individuals to ensure their implications for precision medicine are universally applicable. PMID:28407095

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

PubMed

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

2017-08-01

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

Novel genetic predictors of venous thromboembolism risk in African Americans

PubMed Central

Hernandez, Wenndy; Gamazon, Eric R.; Smithberger, Erin; O’Brien, Travis J.; Harralson, Arthur F.; Tuck, Matthew; Barbour, April; Kittles, Rick A.; Cavallari, Larisa H.

2016-01-01

Venous thromboembolism (VTE) is the third most common life-threatening cardiovascular condition in the United States, with African Americans (AAs) having a 30% to 60% higher incidence compared with other ethnicities. The mechanisms underlying population differences in the risk of VTE are poorly understood. We conducted the first genome-wide association study in AAs, comprising 578 subjects, followed by replication of highly significant findings in an independent cohort of 159 AA subjects. Logistic regression was used to estimate the association between genetic variants and VTE risk. Through bioinformatics analysis of the top signals, we identified expression quantitative trait loci (eQTLs) in whole blood and investigated the messenger RNA expression differences in VTE cases and controls. We identified and replicated single-nucleotide polymorphisms on chromosome 20 (rs2144940, rs2567617, and rs1998081) that increased risk of VTE by 2.3-fold (P < 6 × 10−7). These risk variants were found in higher frequency among populations of African descent (>20%) compared with other ethnic groups (<10%). We demonstrate that SNPs on chromosome 20 are cis-eQTLs for thrombomodulin (THBD), and the expression of THBD is lower among VTE cases compared with controls (P = 9.87 × 10−6). We have identified novel polymorphisms associated with increased risk of VTE in AAs. These polymorphisms are predominantly found among populations of African descent and are associated with THBD gene expression. Our findings provide new molecular insight into a mechanism regulating VTE susceptibility and identify common genetic variants that increase the risk of VTE in AAs, a population disproportionately affected by this disease. PMID:26888256

Bio science: genetic genealogy testing and the pursuit of African ancestry.

PubMed

Nelson, Alondra

2008-10-01

This paper considers the extent to which the geneticization of 'race' and ethnicity is the prevailing outcome of genetic testing for genealogical purposes. The decoding of the human genome precipitated a change of paradigms in genetics research, from an emphasis on genetic similarity to a focus on molecular-level differences among individuals and groups. This shift from lumping to splitting spurred ongoing disagreements among scholars about the significance of 'race' and ethnicity in the genetics era. I characterize these divergent perspectives as 'pragmatism' and 'naturalism'. Drawing upon ethnographic fieldwork and interviews, I argue that neither position fully accounts for how understandings of 'race' and ethnicity are being transformed with genetic genealogy testing. While there is some acquiescence to genetic thinking about ancestry, and by implication, 'race', among African-American and black British consumers of genetic genealogy testing, test-takers also adjudicate between sources of genealogical information and from these construct meaningful biographical narratives. Consumers engage in highly situated 'objective' and 'affiliative' self-fashioning, interpreting genetic test results in the context of their 'genealogical aspirations'. I conclude that issues of site, scale, and subjectification must be attended to if scholars are to understand whether and to what extent social identities are being transformed by recent developments in genetic science.

An initial investigation of associations between dopamine-linked genetic variation and smoking motives in African Americans.

PubMed

Bidwell, L C; McGeary, J E; Gray, J C; Palmer, R H C; Knopik, V S; MacKillop, J

2015-11-01

Nicotine dependence (ND) is a heterogeneous phenotype with complex genetic influences that may vary across ethnicities. The use of intermediate phenotypes may clarify genetic influences and reveal specific etiological pathways. Prior work in European Americans has found that the four Primary Dependence Motives (PDM) subscales (Automaticity, Craving, Loss of Control, and Tolerance) of the Wisconsin Inventory of Smoking Motives represent core features of nicotine dependence and are promising intermediate phenotypes for understanding genetic pathways to ND. However, no studies have examined PDM as an intermediate phenotype in African American smokers, an ethnic population that displays unique patterns of smoking and genetic variation. In the current study, 268 African American daily smokers completed a phenotypic assessment and provided a sample of DNA. Associations among haplotypes in the NCAM1-TTC12-ANKK1-DRD2 gene cluster, a dopamine-related gene region associated with ND, PDM intermediate phenotypes, and ND were examined. Dopamine-related genetic variation in the DBH and COMT genes was also considered on an exploratory basis. Mediational analysis was used to test the indirect pathway from genetic variation to smoking motives to nicotine dependence. NCAM1-TTC12-ANKK1-DRD2 region variation was significantly associated with the Automaticity subscale and, further, Automaticity significantly mediated associations among NCAM1-TTC12-ANKK1-DRD2 cluster variants and ND. DBH was also significantly associated with Automaticity, Craving, and Tolerance; Automaticity and Tolerance also served as mediators of the DBH-ND relationship. These results suggest that PDM, Automaticity in particular, may be a viable intermediate phenotype for understanding dopamine-related genetic influences on ND in African American smokers. Findings support a model in which putatively dopaminergic variants exert influence on ND through an effect on patterns of automatic routinized smoking. Copyright �

Chad Genetic Diversity Reveals an African History Marked by Multiple Holocene Eurasian Migrations.

PubMed

Haber, Marc; Mezzavilla, Massimo; Bergström, Anders; Prado-Martinez, Javier; Hallast, Pille; Saif-Ali, Riyadh; Al-Habori, Molham; Dedoussis, George; Zeggini, Eleftheria; Blue-Smith, Jason; Wells, R Spencer; Xue, Yali; Zalloua, Pierre A; Tyler-Smith, Chris

2016-12-01

Understanding human genetic diversity in Africa is important for interpreting the evolution of all humans, yet vast regions in Africa, such as Chad, remain genetically poorly investigated. Here, we use genotype data from 480 samples from Chad, the Near East, and southern Europe, as well as whole-genome sequencing from 19 of them, to show that many populations today derive their genomes from ancient African-Eurasian admixtures. We found evidence of early Eurasian backflow to Africa in people speaking the unclassified isolate Laal language in southern Chad and estimate from linkage-disequilibrium decay that this occurred 4,750-7,200 years ago. It brought to Africa a Y chromosome lineage (R1b-V88) whose closest relatives are widespread in present-day Eurasia; we estimate from sequence data that the Chad R1b-V88 Y chromosomes coalesced 5,700-7,300 years ago. This migration could thus have originated among Near Eastern farmers during the African Humid Period. We also found that the previously documented Eurasian backflow into Africa, which occurred ∼3,000 years ago and was thought to be mostly limited to East Africa, had a more westward impact affecting populations in northern Chad, such as the Toubou, who have 20%-30% Eurasian ancestry today. We observed a decline in heterozygosity in admixed Africans and found that the Eurasian admixture can bias inferences on their coalescent history and confound genetic signals from adaptation and archaic introgression. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Genetic diversity of lactase persistence in East African populations.

PubMed

Hassan, Hisham Y; van Erp, Anke; Jaeger, Martin; Tahir, Hanan; Oosting, Marije; Joosten, Leo A B; Netea, Mihai G

2016-01-04

The expression of lactase which digests lactose from milk in humans is generally lost after weaning, but selected mutations influencing the promoter of the lactase gene have spread into the human populations. This is considered a classical example of gene-culture co-evolution, and several studies suggested that the lactase gene has been under strong directional evolutionary selective pressure in the past 5000 to 10,000 years. In the present study we investigated the distribution of three gene variants leading to lactase persistence in 12 different East African populations as well as one European population. Our results show that with the exception of Copts and Nilotic populations who are fully lactose non-persistent, the majority of populations of East Africa show at least partly lactose persistence, with both ethnic and socio-economic aspects playing an important role in the distribution of genetic variants. In this study, the variants C/G-13907 and T/G-13915, which are the major variants among the nomadic Arabs in the Arabia and Beja of East Africa, showed remarkable frequencies in Sudanese populations, especially those of pastoralists, in line with the historical links and bidirectional migration of nomadic populations between Arabia and East Africa. The C/T-13910 variant, generally associated with European populations is uniquely present among the Fulani. These data indicate that a combination of socio-economic, ethnic and evolutionary factors converged to shape the genetic structure of lactase persistence in East African populations.

Genetic Distinctiveness of Rye In situ Accessions from Portugal Unveils a New Hotspot of Unexplored Genetic Resources

PubMed Central

Monteiro, Filipa; Vidigal, Patrícia; Barros, André B.; Monteiro, Ana; Oliveira, Hugo R.; Viegas, Wanda

2016-01-01

Rye (Secale cereale L.) is a cereal crop of major importance in many parts of Europe and rye breeders are presently very concerned with the restrict pool of rye genetic resources available. Such narrowing of rye genetic diversity results from the presence of “Petkus” pool in most modern rye varieties as well as “Petkus” × “Carsten” heterotic pool in hybrid rye breeding programs. Previous studies on rye's genetic diversity revealed moreover a common genetic background on landraces (ex situ) and cultivars, regardless of breeding level or geographical origin. Thus evaluation of in situ populations is of utmost importance to unveil “on farm” diversity, which is largely undervalued. Here, we perform the first comprehensive assessment of rye's genetic diversity and population structuring using cultivars, ex situ landraces along a comprehensive sampling of in situ accessions from Portugal, through a molecular-directed analysis using SSRs markers. Rye genetic diversity and population structure analysis does not present any geographical trend but disclosed marked differences between genetic backgrounds of in situ accessions and those of cultivars/ex situ collections. Such genetic distinctiveness of in situ accessions highlights their unexplored potential as new genetic resources, which can be used to boost rye breeding strategies and the production of new varieties. Overall, our study successfully demonstrates the high prospective impact of comparing genetic diversity and structure of cultivars, ex situ, and in situ samples in ascertaining the status of plant genetic resources (PGR). PMID:27630658

Genetic diversity and population structure of South African smallholder farmer sheep breeds determined using the OvineSNP50 beadchip.

PubMed

Molotsi, Annelin H; Taylor, Jeremy F; Cloete, Schalk W P; Muchadeyi, Farai; Decker, Jared E; Whitacre, Lynsey K; Sandenbergh, Lise; Dzama, Kennedy

2017-12-01

A population structure study was performed in South African ovine populations using the OvineSNP50 beadchip. Blood samples were obtained from 295 sheep of which 172 had been identified as smallholder Dorpers, 4 smallholder White Dorpers, 46 purebred Dorpers, 26 purebred South African Mutton Merinos and 47 purebred Namaqua Afrikaners. Blood from the latter three breeds were obtained from a resource flock maintained on the Nortier research farm. Genetic diversity was estimated using allelic richness (A r ), observed heterozygosity (H o ), expected heterozygosity (H e ) and inbreeding coefficient (F). Population structure analysis was performed using fastSTRUCTURE to determine the breed composition of each genotyped individual. The Namaqua Afrikaner had the lowest H e of 0.280 ± 0.18 while the H e of smallholder Dorper, Dorper and South African Mutton Merino did not differ and were 0.364 ± 0.13, 0.332 ± 0.16 and 0.329 ± 0.17, respectively. The average inbreeding coefficient was highest for the pure breeds, Namaqua Afrikaner, Dorper and South African Mutton Merino compared to the average inbreeding coefficient for the smallholder Dorper population. The smallholder Dorper were introgressed with Namaqua Afrikaner, South African Mutton Merino and White Dorpers. Similarly, the smallholder Dorper population was more genetically diverse than the purebred Dorper, South African Mutton Merino and Namaqua Afrikaner from the research farm. The higher genetic diversity among the smallholder sheep may be advantageous for their fitness and can be used to facilitate selective breeding.

Characterizing Genetic Risk at Known Prostate Cancer Susceptibility Loci in African Americans

PubMed Central

Haiman, Christopher A.; Chen, Gary K.; Blot, William J.; Strom, Sara S.; Berndt, Sonja I.; Kittles, Rick A.; Rybicki, Benjamin A.; Isaacs, William B.; Ingles, Sue A.; Stanford, Janet L.; Diver, W. Ryan; Witte, John S.; Chanock, Stephen J.; Kolb, Suzanne; Signorello, Lisa B.; Yamamura, Yuko; Neslund-Dudas, Christine; Thun, Michael J.; Murphy, Adam; Casey, Graham; Sheng, Xin; Wan, Peggy; Pooler, Loreall C.; Monroe, Kristine R.; Waters, Kevin M.; Le Marchand, Loic; Kolonel, Laurence N.; Stram, Daniel O.; Henderson, Brian E.

2011-01-01

GWAS of prostate cancer have been remarkably successful in revealing common genetic variants and novel biological pathways that are linked with its etiology. A more complete understanding of inherited susceptibility to prostate cancer in the general population will come from continuing such discovery efforts and from testing known risk alleles in diverse racial and ethnic groups. In this large study of prostate cancer in African American men (3,425 prostate cancer cases and 3,290 controls), we tested 49 risk variants located in 28 genomic regions identified through GWAS in men of European and Asian descent, and we replicated associations (at p≤0.05) with roughly half of these markers. Through fine-mapping, we identified nearby markers in many regions that better define associations in African Americans. At 8q24, we found 9 variants (p≤6×10−4) that best capture risk of prostate cancer in African Americans, many of which are more common in men of African than European descent. The markers found to be associated with risk at each locus improved risk modeling in African Americans (per allele OR = 1.17) over the alleles reported in the original GWAS (OR = 1.08). In summary, in this detailed analysis of the prostate cancer risk loci reported from GWAS, we have validated and improved upon markers of risk in some regions that better define the association with prostate cancer in African Americans. Our findings with variants at 8q24 also reinforce the importance of this region as a major risk locus for prostate cancer in men of African ancestry. PMID:21637779

Race and Beta-Blocker Survival Benefit in Patients With Heart Failure: An Investigation of Self-Reported Race and Proportion of African Genetic Ancestry.

PubMed

Luzum, Jasmine A; Peterson, Edward; Li, Jia; She, Ruicong; Gui, Hongsheng; Liu, Bin; Spertus, John A; Pinto, Yigal M; Williams, L Keoki; Sabbah, Hani N; Lanfear, David E

2018-05-08

It remains unclear whether beta-blockade is similarly effective in black patients with heart failure and reduced ejection fraction as in white patients, but self-reported race is a complex social construct with both biological and environmental components. The objective of this study was to compare the reduction in mortality associated with beta-blocker exposure in heart failure and reduced ejection fraction patients by both self-reported race and by proportion African genetic ancestry. Insured patients with heart failure and reduced ejection fraction (n=1122) were included in a prospective registry at Henry Ford Health System. This included 575 self-reported blacks (129 deaths, 22%) and 547 self-reported whites (126 deaths, 23%) followed for a median 3.0 years. Beta-blocker exposure (BBexp) was calculated from pharmacy claims, and the proportion of African genetic ancestry was determined from genome-wide array data. Time-dependent Cox proportional hazards regression was used to separately test the association of BBexp with all-cause mortality by self-reported race or by proportion of African genetic ancestry. Both sets of models were evaluated unadjusted and then adjusted for baseline risk factors and beta-blocker propensity score. BBexp effect estimates were protective and of similar magnitude both by self-reported race and by African genetic ancestry (adjusted hazard ratio=0.56 in blacks and adjusted hazard ratio=0.48 in whites). The tests for interactions with BBexp for both self-reported race and for African genetic ancestry were not statistically significant in any model ( P >0.1 for all). Among black and white patients with heart failure and reduced ejection fraction, reduction in all-cause mortality associated with BBexp was similar, regardless of self-reported race or proportion African genetic ancestry. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

The episode of genetic drift defining the migration of humans out of Africa is derived from a large east African population size.

PubMed

Elhassan, Nuha; Gebremeskel, Eyoab Iyasu; Elnour, Mohamed Ali; Isabirye, Dan; Okello, John; Hussien, Ayman; Kwiatksowski, Dominic; Hirbo, Jibril; Tishkoff, Sara; Ibrahim, Muntaser E

2014-01-01

Human genetic variation particularly in Africa is still poorly understood. This is despite a consensus on the large African effective population size compared to populations from other continents. Based on sequencing of the mitochondrial Cytochrome C Oxidase subunit II (MT-CO2), and genome wide microsatellite data we observe evidence suggesting the effective size (Ne) of humans to be larger than the current estimates, with a foci of increased genetic diversity in east Africa, and a population size of east Africans being at least 2-6 fold larger than other populations. Both phylogenetic and network analysis indicate that east Africans possess more ancestral lineages in comparison to various continental populations placing them at the root of the human evolutionary tree. Our results also affirm east Africa as the likely spot from which migration towards Asia has taken place. The study reflects the spectacular level of sequence variation within east Africans in comparison to the global sample, and appeals for further studies that may contribute towards filling the existing gaps in the database. The implication of these data to current genomic research, as well as the need to carry out defined studies of human genetic variation that includes more African populations; particularly east Africans is paramount.

Tick-Borne Transmission of Two Genetically Distinct Anaplasma marginale Strains following Superinfection of the Mammalian Reservoir Host

USDA-ARS?s Scientific Manuscript database

Strain superinfection affects the dynamics of epidemiological spread of pathogens through a host population. Superinfection has recently been shown to occur for genetically distinct strains of the tick-borne pathogen Anaplasma marginale that encode distinctly different surface protein variants. Supe...

Hunter-gatherer genomic diversity suggests a southern African origin for modern humans

PubMed Central

Henn, Brenna M.; Gignoux, Christopher R.; Jobin, Matthew; Granka, Julie M.; Macpherson, J. M.; Kidd, Jeffrey M.; Rodríguez-Botigué, Laura; Ramachandran, Sohini; Hon, Lawrence; Brisbin, Abra; Lin, Alice A.; Underhill, Peter A.; Comas, David; Kidd, Kenneth K.; Norman, Paul J.; Parham, Peter; Bustamante, Carlos D.; Mountain, Joanna L.; Feldman, Marcus W.

2011-01-01

Africa is inferred to be the continent of origin for all modern human populations, but the details of human prehistory and evolution in Africa remain largely obscure owing to the complex histories of hundreds of distinct populations. We present data for more than 580,000 SNPs for several hunter-gatherer populations: the Hadza and Sandawe of Tanzania, and the ≠Khomani Bushmen of South Africa, including speakers of the nearly extinct N|u language. We find that African hunter-gatherer populations today remain highly differentiated, encompassing major components of variation that are not found in other African populations. Hunter-gatherer populations also tend to have the lowest levels of genome-wide linkage disequilibrium among 27 African populations. We analyzed geographic patterns of linkage disequilibrium and population differentiation, as measured by FST, in Africa. The observed patterns are consistent with an origin of modern humans in southern Africa rather than eastern Africa, as is generally assumed. Additionally, genetic variation in African hunter-gatherer populations has been significantly affected by interaction with farmers and herders over the past 5,000 y, through both severe population bottlenecks and sex-biased migration. However, African hunter-gatherer populations continue to maintain the highest levels of genetic diversity in the world. PMID:21383195

Cattle genome-wide analysis reveals genetic signatures in trypanotolerant N'Dama.

PubMed

Kim, Soo-Jin; Ka, Sojeong; Ha, Jung-Woo; Kim, Jaemin; Yoo, DongAhn; Kim, Kwondo; Lee, Hak-Kyo; Lim, Dajeong; Cho, Seoae; Hanotte, Olivier; Mwai, Okeyo Ally; Dessie, Tadelle; Kemp, Stephen; Oh, Sung Jong; Kim, Heebal

2017-05-12

Indigenous cattle in Africa have adapted to various local environments to acquire superior phenotypes that enhance their survival under harsh conditions. While many studies investigated the adaptation of overall African cattle, genetic characteristics of each breed have been poorly studied. We performed the comparative genome-wide analysis to assess evidence for subspeciation within species at the genetic level in trypanotolerant N'Dama cattle. We analysed genetic variation patterns in N'Dama from the genomes of 101 cattle breeds including 48 samples of five indigenous African cattle breeds and 53 samples of various commercial breeds. Analysis of SNP variances between cattle breeds using wMI, XP-CLR, and XP-EHH detected genes containing N'Dama-specific genetic variants and their potential associations. Functional annotation analysis revealed that these genes are associated with ossification, neurological and immune system. Particularly, the genes involved in bone formation indicate that local adaptation of N'Dama may engage in skeletal growth as well as immune systems. Our results imply that N'Dama might have acquired distinct genotypes associated with growth and regulation of regional diseases including trypanosomiasis. Moreover, this study offers significant insights into identifying genetic signatures for natural and artificial selection of diverse African cattle breeds.

Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas

PubMed Central

Mikhail, Jane; Kato, Ikuko; Suzuki, Rumiko; Yamaoka, Yoshio; Sheppard, Samuel K.; Falush, Daniel

2017-01-01

For the last 500 years, the Americas have been a melting pot both for genetically diverse humans and for the pathogenic and commensal organisms associated with them. One such organism is the stomach-dwelling bacterium Helicobacter pylori, which is highly prevalent in Latin America where it is a major current public health challenge because of its strong association with gastric cancer. By analyzing the genome sequence of H. pylori isolated in North, Central and South America, we found evidence for admixture between H. pylori of European and African origin throughout the Americas, without substantial input from pre-Columbian (hspAmerind) bacteria. In the US, strains of African and European origin have remained genetically distinct, while in Colombia and Nicaragua, bottlenecks and rampant genetic exchange amongst isolates have led to the formation of national gene pools. We found three outer membrane proteins with atypical levels of Asian ancestry in American strains, as well as alleles that were nearly fixed specifically in South American isolates, suggesting a role for the ethnic makeup of hosts in the colonization of incoming strains. Our results show that new H. pylori subpopulations can rapidly arise, spread and adapt during times of demographic flux, and suggest that differences in transmission ecology between high and low prevalence areas may substantially affect the composition of bacterial populations. PMID:28231283

Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas.

PubMed

Thorell, Kaisa; Yahara, Koji; Berthenet, Elvire; Lawson, Daniel J; Mikhail, Jane; Kato, Ikuko; Mendez, Alfonso; Rizzato, Cosmeri; Bravo, María Mercedes; Suzuki, Rumiko; Yamaoka, Yoshio; Torres, Javier; Sheppard, Samuel K; Falush, Daniel

2017-02-01

For the last 500 years, the Americas have been a melting pot both for genetically diverse humans and for the pathogenic and commensal organisms associated with them. One such organism is the stomach-dwelling bacterium Helicobacter pylori, which is highly prevalent in Latin America where it is a major current public health challenge because of its strong association with gastric cancer. By analyzing the genome sequence of H. pylori isolated in North, Central and South America, we found evidence for admixture between H. pylori of European and African origin throughout the Americas, without substantial input from pre-Columbian (hspAmerind) bacteria. In the US, strains of African and European origin have remained genetically distinct, while in Colombia and Nicaragua, bottlenecks and rampant genetic exchange amongst isolates have led to the formation of national gene pools. We found three outer membrane proteins with atypical levels of Asian ancestry in American strains, as well as alleles that were nearly fixed specifically in South American isolates, suggesting a role for the ethnic makeup of hosts in the colonization of incoming strains. Our results show that new H. pylori subpopulations can rapidly arise, spread and adapt during times of demographic flux, and suggest that differences in transmission ecology between high and low prevalence areas may substantially affect the composition of bacterial populations.

Patterns of population subdivision, gene flow and genetic variability in the African wild dog (Lycaon pictus).

PubMed

Girman, D J; Vilà, C; Geffen, E; Creel, S; Mills, M G; McNutt, J W; Ginsberg, J; Kat, P W; Mamiya, K H; Wayne, R K

2001-07-01

African wild dogs are large, highly mobile carnivores that are known to disperse over considerable distances and are rare throughout much of their geographical range. Consequently, genetic variation within and differentiation between geographically separated populations is predicted to be minimal. We determined the genetic diversity of mitochondrial DNA (mtDNA) control region sequences and microsatellite loci in seven populations of African wild dogs. Analysis of mtDNA nucleotide diversity suggests that, historically, wild dog populations have been small relative to other large carnivores. However, population declines due to recent habitat loss have not caused a dramatic reduction in genetic diversity. We found one historical and eight recent mtDNA genotypes in 280 individuals that defined two highly divergent clades. In contrast to a previous, more limited, mtDNA analysis, sequences from these clades are not geographically restricted to eastern or southern African populations. Rather, we found a large admixture zone spanning populations from Botswana, Zimbabwe and south-eastern Tanzania. Mitochondrial and microsatellite differentiation between populations was significant and unique mtDNA genotypes and alleles characterized the populations. However, gene flow estimates (Nm) based on microsatellite data were generally greater than one migrant per generation. In contrast, gene flow estimates based on the mtDNA control region were lower than expected given differences in the mode of inheritance of mitochondrial and nuclear markers which suggests a male bias in long-distance dispersal.

Global genetic diversity of Aedes aegypti.

PubMed

Gloria-Soria, Andrea; Ayala, Diego; Bheecarry, Ambicadutt; Calderon-Arguedas, Olger; Chadee, Dave D; Chiappero, Marina; Coetzee, Maureen; Elahee, Khouaildi Bin; Fernandez-Salas, Ildefonso; Kamal, Hany A; Kamgang, Basile; Khater, Emad I M; Kramer, Laura D; Kramer, Vicki; Lopez-Solis, Alma; Lutomiah, Joel; Martins, Ademir; Micieli, Maria Victoria; Paupy, Christophe; Ponlawat, Alongkot; Rahola, Nil; Rasheed, Syed Basit; Richardson, Joshua B; Saleh, Amag A; Sanchez-Casas, Rosa Maria; Seixas, Gonçalo; Sousa, Carla A; Tabachnick, Walter J; Troyo, Adriana; Powell, Jeffrey R

2016-11-01

Mosquitoes, especially Aedes aegypti, are becoming important models for studying invasion biology. We characterized genetic variation at 12 microsatellite loci in 79 populations of Ae. aegypti from 30 countries in six continents, and used them to infer historical and modern patterns of invasion. Our results support the two subspecies Ae. aegypti formosus and Ae. aegypti aegypti as genetically distinct units. Ae. aegypti aegypti populations outside Africa are derived from ancestral African populations and are monophyletic. The two subspecies co-occur in both East Africa (Kenya) and West Africa (Senegal). In rural/forest settings (Rabai District of Kenya), the two subspecies remain genetically distinct, whereas in urban settings, they introgress freely. Populations outside Africa are highly genetically structured likely due to a combination of recent founder effects, discrete discontinuous habitats and low migration rates. Ancestral populations in sub-Saharan Africa are less genetically structured, as are the populations in Asia. Introduction of Ae. aegypti to the New World coinciding with trans-Atlantic shipping in the 16th to 18th centuries was followed by its introduction to Asia in the late 19th century from the New World or from now extinct populations in the Mediterranean Basin. Aedes mascarensis is a genetically distinct sister species to Ae. aegypti s.l. This study provides a reference database of genetic diversity that can be used to determine the likely origin of new introductions that occur regularly for this invasive species. The genetic uniqueness of many populations and regions has important implications for attempts to control Ae. aegypti, especially for the methods using genetic modification of populations. © 2016 John Wiley & Sons Ltd.

Global Genetic Diversity of Aedes aegypti

PubMed Central

Gloria-Soria, Andrea; Ayala, Diego; Bheecarry, Ambicadutt; Calderon-Arguedas, Olger; Chadee, Dave D.; Chiappero, Marina; Coetzee, Maureen; Elahee, Khouaildi bin; Fernandez-Salas, Ildefonso; Kamal, Hany A.; Kamgang, Basile; Khater, Emad I. M.; Kramer, Laura D.; Kramer, Vicki; Lopez-Solis, Alma; Lutomiah, Joel; Martins, Ademir; Micieli, Maria Victoria; Paupy, Christophe; Ponlawat, Alongkot; Rahola, Nil; Rasheed, Syed Basit; Richardson, Joshua B.; Saleh, Amag A.; Sanchez-Casas, Rosa Maria; Seixas, Gonçalo; Sousa, Carla A.; Tabachnick, Walter J.; Troyo, Adriana; Powell, Jeffrey R.

2016-01-01

Mosquitoes, especially Aedes aegypti, are becoming important models for studying invasion biology. We characterized genetic variation at 12 microsatellite loci in 79 populations of Ae. aegypti, from 30 countries in six continents and used them to infer historical and modern patterns of invasion. Our results support the two subspecies Ae. aegypti formosus and Ae. aegypti aegypti as genetically distinct units. Ae. aegypti aegypti populations outside Africa are derived from ancestral African populations and are monophyletic. The two subspecies co-occur in both East Africa (Kenya) and West Africa (Senegal). In rural/forest settings (Rabai District of Kenya) the two subspecies remain genetically distinct whereas in urban settings they introgress freely. Populations outside Africa are highly genetically structured likely due to a combination of recent founder effects, discrete discontinuous habitats, and low migration rates. Ancestral populations in sub-Saharan Africa are less genetically structured, as are the populations in Asia. Introduction of Ae. aegypti to the New World coinciding with trans-Atlantic shipping in the 16th to 18th Centuries was followed by its introduction to Asia in the late 19th Century from the New World or from now extinct populations in the Mediterranean Basin. Aedes mascarensis is a genetically distinct sister species to Ae. aegypti s.l.. This study provides a reference database of genetic diversity that can be used to determine the likely origin of new introductions that occur regularly for this invasive species. The genetic uniqueness of many populations and regions has important implications for attempts to control Ae. aegypti, especially for methods using genetic modification of populations. PMID:27671732

Autosomal and mtDNA Markers Affirm the Distinctiveness of Lions in West and Central Africa.

PubMed

Bertola, Laura D; Tensen, Laura; van Hooft, Pim; White, Paula A; Driscoll, Carlos A; Henschel, Philipp; Caragiulo, Anthony; Dias-Freedman, Isabela; Sogbohossou, Etotépé A; Tumenta, Pricelia N; Jirmo, Tuqa H; de Snoo, Geert R; de Iongh, Hans H; Vrieling, Klaas

2015-01-01

The evolutionary history of a species is key for understanding the taxonomy and for the design of effective management strategies for species conservation. The knowledge about the phylogenetic position of the lion (Panthera leo) in West/Central Africa is largely based on mitochondrial markers. Previous studies using mtDNA only have shown this region to hold a distinct evolutionary lineage. In addition, anthropogenic factors have led to a strong decline in West/Central African lion numbers, thus, the conservation value of these populations is particularly high. Here, we investigate whether autosomal markers are concordant with previously described phylogeographic patterns, and confirm the unique position of the West/Central African lion. Analysis of 20 microsatellites and 1,454 bp of the mitochondrial DNA in 16 lion populations representing the entire geographic range of the species found congruence in both types of markers, identifying four clusters: 1) West/Central Africa, 2) East Africa, 3) Southern Africa and 4) India. This is not in line with the current taxonomy, as defined by the IUCN, which only recognizes an African and an Asiatic subspecies. There are no indications that genetic diversity in West/Central Africa lions is lower than in either East or Southern Africa, however, given this genetic distinction and the recent declines of lion numbers in this region, we strongly recommend prioritization of conservation projects in West/Central Africa. As the current taxonomic nomenclature does not reflect the evolutionary history of the lion, we suggest that a taxonomic revision of the lion is warranted.

Autosomal and mtDNA Markers Affirm the Distinctiveness of Lions in West and Central Africa

PubMed Central

Bertola, Laura D.; Tensen, Laura; van Hooft, Pim; White, Paula A.; Driscoll, Carlos A.; Henschel, Philipp; Caragiulo, Anthony; Dias-Freedman, Isabela; Sogbohossou, Etotépé A.; Tumenta, Pricelia N.; Jirmo, Tuqa H.; de Snoo, Geert R.

2015-01-01

The evolutionary history of a species is key for understanding the taxonomy and for the design of effective management strategies for species conservation. The knowledge about the phylogenetic position of the lion (Panthera leo) in West/Central Africa is largely based on mitochondrial markers. Previous studies using mtDNA only have shown this region to hold a distinct evolutionary lineage. In addition, anthropogenic factors have led to a strong decline in West/Central African lion numbers, thus, the conservation value of these populations is particularly high. Here, we investigate whether autosomal markers are concordant with previously described phylogeographic patterns, and confirm the unique position of the West/Central African lion. Analysis of 20 microsatellites and 1,454 bp of the mitochondrial DNA in 16 lion populations representing the entire geographic range of the species found congruence in both types of markers, identifying four clusters: 1) West/Central Africa, 2) East Africa, 3) Southern Africa and 4) India. This is not in line with the current taxonomy, as defined by the IUCN, which only recognizes an African and an Asiatic subspecies. There are no indications that genetic diversity in West/Central Africa lions is lower than in either East or Southern Africa, however, given this genetic distinction and the recent declines of lion numbers in this region, we strongly recommend prioritization of conservation projects in West/Central Africa. As the current taxonomic nomenclature does not reflect the evolutionary history of the lion, we suggest that a taxonomic revision of the lion is warranted. PMID:26466139

Variant Discovery and Fine Mapping of Genetic Loci Associated with Blood Pressure Traits in Hispanics and African Americans.

PubMed

Franceschini, Nora; Carty, Cara L; Lu, Yingchang; Tao, Ran; Sung, Yun Ju; Manichaikul, Ani; Haessler, Jeff; Fornage, Myriam; Schwander, Karen; Zubair, Niha; Bien, Stephanie; Hindorff, Lucia A; Guo, Xiuqing; Bielinski, Suzette J; Ehret, Georg; Kaufman, Joel D; Rich, Stephen S; Carlson, Christopher S; Bottinger, Erwin P; North, Kari E; Rao, D C; Chakravarti, Aravinda; Barrett, Paula Q; Loos, Ruth J F; Buyske, Steven; Kooperberg, Charles

2016-01-01

Despite the substantial burden of hypertension in US minority populations, few genetic studies of blood pressure have been conducted in Hispanics and African Americans, and it is unclear whether many of the established loci identified in European-descent populations contribute to blood pressure variation in non-European descent populations. Using the Metabochip array, we sought to characterize the genetic architecture of previously identified blood pressure loci, and identify novel cardiometabolic variants related to systolic and diastolic blood pressure in a multi-ethnic US population including Hispanics (n = 19,706) and African Americans (n = 18,744). Several known blood pressure loci replicated in African Americans and Hispanics. Fourteen variants in three loci (KCNK3, FGF5, ATXN2-SH2B3) were significantly associated with blood pressure in Hispanics. The most significant diastolic blood pressure variant identified in our analysis, rs2586886/KCNK3 (P = 5.2 x 10-9), also replicated in independent Hispanic and European-descent samples. African American and trans-ethnic meta-analysis data identified novel variants in the FGF5, ULK4 and HOXA-EVX1 loci, which have not been previously associated with blood pressure traits. Our identification and independent replication of variants in KCNK3, a gene implicated in primary hyperaldosteronism, as well as a variant in HOTTIP (HOXA-EVX1) suggest that further work to clarify the roles of these genes may be warranted. Overall, our findings suggest that loci identified in European descent populations also contribute to blood pressure variation in diverse populations including Hispanics and African Americans-populations that are understudied for hypertension genetic risk factors.

Meta-analysis of genome-wide association studies identifies genetic risk factors for stroke in African-Americans

PubMed Central

Carty, Cara L.; Keene, Keith L.; Cheng, Yu-Ching; Meschia, James F.; Chen, Wei-Min; Nalls, Mike; Bis, Joshua C.; Kittner, Steven J.; Rich, Stephen S.; Tajuddin, Salman; Zonderman, Alan B.; Evans, Michele K.; Langefeld, Carl D.; Gottesman, Rebecca; Mosley, Thomas H.; Shahar, Eyal; Woo, Daniel; Yaffe, Kristine; Liu, YongMei; Sale, Michèle M.; Dichgans, Martin; Malik, Rainer; Longstreth, WT; Mitchell, Braxton D.; Psaty, Bruce M.; Kooperberg, Charles; Reiner, Alexander; Worrall, Bradford B.; Fornage, Myriam

2015-01-01

Background and Purpose The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African-Americans despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population genome-wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. Methods Using METAL, we conducted meta-analyses of GWAS in 14,746 African-Americans (1,365 ischemic and 1,592 total stroke cases) from COMPASS, and tested SNPs with P<10−6 for validation in METASTROKE, a consortium of ischemic stroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. Results The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613, P=3.9×10−8) in African-Americans. Nominal associations (P<10−6) for total or ischemic stroke were observed for 18 variants in or near genes implicated in cell cycle/ mRNA pre-splicing (PTPRG, CDC5L), platelet function (HPS4), blood-brain barrier permeability (CLDN17), immune response (ELTD1, WDFY4, IL1F10-IL1RN), and histone modification (HDAC9). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 (P=0.03), and 1p31.1 (P=0.018). Four of 7 previously reported ischemic stroke loci (PITX2, HDAC9, CDKN2A/CDKN2B and ZFHX3) were nominally associated (P<0.05) with stroke in COMPASS. Conclusions We identified a novel SNP associated with total stroke in African-Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African-Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations. PMID:26089329

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

PubMed

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

2015-06-01

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). 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. 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. 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.

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

Genetic Heterogeneity in Colorectal Cancer Associations in Americans of African vs. European Descent

PubMed Central

Kupfer, Sonia S.; Anderson, Jeffrey R.; Hooker, Stanley; Skol, Andrew; Kittles, Rick A.; Keku, Temitope O.; Sandler, Robert S.; Ellis, Nathan A.

2013-01-01

Background & Aims Genome-wide association studies of colorectal cancer (CRC) have identified risk variants in 10 genomic regions. None of these studies included African Americans, who have the highest incidence and mortality from CRC in the US. For the 10 genomic regions, we performed an association study of Americans of African and European descent. Methods We genotyped 22 single nucleotide polymorphisms (SNPs) in DNA samples from 1194 patients with CRC (795 African Americans and 399 European Americans) and 1352 controls (985 African Americans and 367 European Americans). At chromosome 8q24.21 region 3, we analyzed 6 SNPs from 1000 African American cases and 1393 controls. Association testing was done using multivariate logistic regression controlling for ancestry, age, and sex. Results Sizes and directions of association for all SNPs tested in European Americans were consistent with previously published studies, but for 9 of 22 SNPs tested in African Americans, they were of an opposite direction. Among African Americans, the SNP rs6983267 at 8q24.21 was not associated with CRC (odds ratio [OR]=1.18; P=0.12); instead, the 8q24.21 SNP rs7014346 (OR=1.15; p=0.03) was associated with CRC in this population. At 15q13.3, rs10318 was associated with CRC in both populations. At 10p14, the opposite allele of rs10795668 was associated with CRC in African Americans (OR=1.35; P=0.04). At 11q23.1, rs3802842 was significantly associated with rectal cancer risk only among African Americans (OR 1.34; P=0.01); this observation was made in previous studies. Among European Americans, SNPs at 8q24.21, 11q23.1, and 16q22.1 were associated with CRC, in agreement with previous reports. Conclusion There is genetic heterogeneity in CRC associations in Americans of African vs. European descent. PMID:20659471

Molecular investigation of genetic assimilation during the rapid adaptive radiations of East African cichlid fishes.

PubMed

Gunter, Helen M; Schneider, Ralf F; Karner, Immanuel; Sturmbauer, Christian; Meyer, Axel

2017-12-01

Adaptive radiations are characterized by adaptive diversification intertwined with rapid speciation within a lineage resulting in many ecologically specialized, phenotypically diverse species. It has been proposed that adaptive radiations can originate from ancestral lineages with pronounced phenotypic plasticity in adaptive traits, facilitating ecologically driven phenotypic diversification that is ultimately fixed through genetic assimilation of gene regulatory regions. This study aimed to investigate how phenotypic plasticity is reflected in gene expression patterns in the trophic apparatus of several lineages of East African cichlid fishes, and whether the observed patterns support genetic assimilation. This investigation used a split brood experimental design to compare adaptive plasticity in species from within and outside of adaptive radiations. The plastic response was induced in the crushing pharyngeal jaws through feeding individuals either a hard or soft diet. We find that nonradiating, basal lineages show higher levels of adaptive morphological plasticity than the derived, radiated lineages, suggesting that these differences have become partially genetically fixed during the formation of the adaptive radiations. Two candidate genes that may have undergone genetic assimilation, gif and alas1, were identified, in addition to alterations in the wiring of LPJ patterning networks. Taken together, our results suggest that genetic assimilation may have dampened the inducibility of plasticity related genes during the adaptive radiations of East African cichlids, flattening the reaction norms and canalizing their feeding phenotypes, driving adaptation to progressively more narrow ecological niches. © 2017 John Wiley & Sons Ltd.

Reconciling Apparent Conflicts between Mitochondrial and Nuclear Phylogenies in African Elephants

PubMed Central

Georgiadis, Nicholas J.; David, Victor A.; Zhao, Kai; Stephens, Robert M.; Kolokotronis, Sergios-Orestis; Roca, Alfred L.

2011-01-01

Conservation strategies for African elephants would be advanced by resolution of conflicting claims that they comprise one, two, three or four taxonomic groups, and by development of genetic markers that establish more incisively the provenance of confiscated ivory. We addressed these related issues by genotyping 555 elephants from across Africa with microsatellite markers, developing a method to identify those loci most effective at geographic assignment of elephants (or their ivory), and conducting novel analyses of continent-wide datasets of mitochondrial DNA. Results showed that nuclear genetic diversity was partitioned into two clusters, corresponding to African forest elephants (99.5% Cluster-1) and African savanna elephants (99.4% Cluster-2). Hybrid individuals were rare. In a comparison of basal forest “F” and savanna “S” mtDNA clade distributions to nuclear DNA partitions, forest elephant nuclear genotypes occurred only in populations in which S clade mtDNA was absent, suggesting that nuclear partitioning corresponds to the presence or absence of S clade mtDNA. We reanalyzed African elephant mtDNA sequences from 81 locales spanning the continent and discovered that S clade mtDNA was completely absent among elephants at all 30 sampled tropical forest locales. The distribution of savanna nuclear DNA and S clade mtDNA corresponded closely to range boundaries traditionally ascribed to the savanna elephant species based on habitat and morphology. Further, a reanalysis of nuclear genetic assignment results suggested that West African elephants do not comprise a distinct third species. Finally, we show that some DNA markers will be more useful than others for determining the geographic origins of illegal ivory. These findings resolve the apparent incongruence between mtDNA and nuclear genetic patterns that has confounded the taxonomy of African elephants, affirm the limitations of using mtDNA patterns to infer elephant systematics or population structure

The head and body lice of humans are genetically distinct (Insecta: Phthiraptera, Pediculidae): evidence from double infestations.

PubMed

Leo, N P; Hughes, J M; Yang, X; Poudel, S K S; Brogdon, W G; Barker, S C

2005-07-01

Little is known about the population genetics of the louse infestations of humans. We used microsatellite DNA to study 11 double infestations, that is, hosts infested with head lice and body lice simultaneously. We tested for population structure on a host, and for population structure among seven hosts that shared sleeping quarters. We also sought evidence of migration among louse populations. Our results showed that: (i) the head and body lice on these individual hosts were two genetically distinct populations; (ii) each host had their own populations of head and body lice that were genetically distinct to those on other hosts; and (iii) lice had migrated from head to head, and from body to body, but not between heads and bodies. Our results indicate that head and body lice are separate species.

Insight into the genetic composition of South African Sanga cattle using SNP data from cattle breeds worldwide.

PubMed

Makina, Sithembile O; Whitacre, Lindsey K; Decker, Jared E; Taylor, Jeremy F; MacNeil, Michael D; Scholtz, Michiel M; van Marle-Köster, Este; Muchadeyi, Farai C; Makgahlela, Mahlako L; Maiwashe, Azwihangwisi

2016-11-15

Understanding the history of cattle breeds is important because it provides the basis for developing appropriate selection and breed improvement programs. In this study, patterns of ancestry and admixture in Afrikaner, Nguni, Drakensberger and Bonsmara cattle of South Africa were investigated. We used 50 K single nucleotide polymorphism genotypes that were previously generated for the Afrikaner (n = 36), Nguni (n = 50), Drakensberger (n = 47) and Bonsmara (n = 44) breeds, and for 394 reference animals representing European taurine, African taurine, African zebu and Bos indicus. Our findings support previous conclusions that Sanga cattle breeds are composites between African taurine and Bos indicus. Among these breeds, the Afrikaner breed has significantly diverged from its ancestral forebears, probably due to genetic drift and selection to meet breeding objectives of the breed society that enable registration. The Nguni, Drakensberger and Bonsmara breeds are admixed, perhaps unintentionally in the case of Nguni and Drakensberger, but certainly by design in the case of Bonsmara, which was developed through crossbreeding between the Afrikaner, Hereford and Shorthorn breeds. We established patterns of admixture and ancestry for South African Sanga cattle breeds, which provide a basis for developing appropriate strategies for their genetic improvement.

Genetic factors influencing bone mineral content in a black South African population.

PubMed

May, Andrew; Pettifor, John M; Norris, Shane A; Ramsay, Michèle; Lombard, Zané

2013-11-01

Bone mass differs according to ethnic classification, with individuals of African ancestry attaining the highest measurements across numerous skeletal sites. Elevated bone mass is even maintained in those individuals exposed to adverse environmental factors, suggesting a prominent genetic effect that may have clinical or therapeutic value. Using a candidate gene approach, we investigated associations of six candidate genes (ESR1, TNFRSF11A, TNFRSF11B, TNFSF11, SOST and SPP1) with bone mass at the hip and lumbar spine amongst pre-pubertal black South African children (mean age 10.6 years) who formed part of the longitudinal Birth to Twenty cohort. 151 black children were genotyped at 366 polymorphic loci, including 112 previously associated and 254 tagging single nucleotide polymorphisms (SNPs). Linear regression was used to highlight significant associations whilst adjusting for height, weight, sex and bone area. Twenty-seven markers (8 previously associated and 19 tag SNPs; P < 0.05) were found to be associated with either femoral neck (18) or lumbar spine (9) bone mineral content. These signals were derived from three genes, namely ESR1 (17), TNFRSF11B (9) and SPP1 (1). One marker (rs2485209) maintained its association with the femoral neck after correction for multiple testing (P = 0.038). When compared to results amongst Caucasian adults, we detected differences with respect to associated skeletal sites. Allele frequencies and linkage disequilibrium patterns were also significantly different between populations. Hence, our results support the existence of a strong genetic effect acting at the femoral neck in black South African children, whilst simultaneously highlighting possible causes that account for inter-ethnic bone mass diversity.

Distinct Age and Self-Rated Health Crossover Mortality Effects for African Americans: Evidence from a National Cohort Study

PubMed Central

Roth, David L.; Skarupski, Kimberly A.; Crews, Deidra C.; Howard, Virginia J.; Locher, Julie L.

2016-01-01

The predictive effects of age and self-rated health (SRH) on all-cause mortality are known to differ across race and ethnic groups. African American adults have higher mortality rates than Whites at younger ages, but this mortality disparity diminishes with advancing age and may “crossover” at about 75 to 80 years of age, when African Americans may show lower mortality rates. This pattern of findings reflects a lower overall association between age and mortality for African Americans than for Whites, and health-related mechanisms are typically cited as the reason for this age-based crossover mortality effect. However, a lower association between poor SRH and mortality has also been found for African Americans than for Whites, and it is not known if the reduced age and SRH associations with mortality for African Americans reflect independent or overlapping mechanisms. This study examined these two mortality predictors simultaneously in a large epidemiological study of 12,181 African Americans and 17,436 Whites. Participants were 45 or more years of age when they enrolled in the national REasons for Geographic and Racial Differences in Stroke (REGARDS) study between 2003 and 2007. Consistent with previous studies, African Americans had poorer SRH than Whites even after adjusting for demographic and health history covariates. Survival analysis models indicated statistically significant and independent race*age, race*SRH, and age*SRH interaction effects on all-cause mortality over an average 9-year follow-up period. Advanced age and poorer SRH were both weaker mortality risk factors for African Americans than for Whites. These two effects were distinct and presumably tapped different causal mechanisms. This calls into question the health-related explanation for the age-based mortality crossover effect and suggests that other mechanisms, including behavioral, social, and cultural factors, should be considered in efforts to better understand the age-based mortality

Distinct age and self-rated health crossover mortality effects for African Americans: Evidence from a national cohort study.

PubMed

Roth, David L; Skarupski, Kimberly A; Crews, Deidra C; Howard, Virginia J; Locher, Julie L

2016-05-01

The predictive effects of age and self-rated health (SRH) on all-cause mortality are known to differ across race and ethnic groups. African American adults have higher mortality rates than Whites at younger ages, but this mortality disparity diminishes with advancing age and may "crossover" at about 75-80 years of age, when African Americans may show lower mortality rates. This pattern of findings reflects a lower overall association between age and mortality for African Americans than for Whites, and health-related mechanisms are typically cited as the reason for this age-based crossover mortality effect. However, a lower association between poor SRH and mortality has also been found for African Americans than for Whites, and it is not known if the reduced age and SRH associations with mortality for African Americans reflect independent or overlapping mechanisms. This study examined these two mortality predictors simultaneously in a large epidemiological study of 12,181 African Americans and 17,436 Whites. Participants were 45 or more years of age when they enrolled in the national REasons for Geographic and Racial Differences in Stroke (REGARDS) study between 2003 and 2007. Consistent with previous studies, African Americans had poorer SRH than Whites even after adjusting for demographic and health history covariates. Survival analysis models indicated statistically significant and independent race*age, race*SRH, and age*SRH interaction effects on all-cause mortality over an average 9-year follow-up period. Advanced age and poorer SRH were both weaker mortality risk factors for African Americans than for Whites. These two effects were distinct and presumably tapped different causal mechanisms. This calls into question the health-related explanation for the age-based mortality crossover effect and suggests that other mechanisms, including behavioral, social, and cultural factors, should be considered in efforts to better understand the age-based mortality

Genetic diversity and connectivity in the East African giant mud crab Scylla serrata: Implications for fisheries management.

PubMed

Rumisha, Cyrus; Huyghe, Filip; Rapanoel, Diary; Mascaux, Nemo; Kochzius, Marc

2017-01-01

The giant mud crab Scylla serrata provides an important source of income and food to coastal communities in East Africa. However, increasing demand and exploitation due to the growing coastal population, export trade, and tourism industry are threatening the sustainability of the wild stock of this species. Because effective management requires a clear understanding of the connectivity among populations, this study was conducted to assess the genetic diversity and connectivity in the East African mangrove crab S. serrata. A section of 535 base pairs of the cytochrome oxidase subunit I (COI) gene and eight microsatellite loci were analysed from 230 tissue samples of giant mud crabs collected from Kenya, Tanzania, Mozambique, Madagascar, and South Africa. Microsatellite genetic diversity (He) ranged between 0.56 and 0.6. The COI sequences showed 57 different haplotypes associated with low nucleotide diversity (current nucleotide diversity = 0.29%). In addition, the current nucleotide diversity was lower than the historical nucleotide diversity, indicating overexploitation or historical bottlenecks in the recent history of the studied population. Considering that the coastal population is growing rapidly, East African countries should promote sustainable fishing practices and sustainable use of mangrove resources to protect mud crabs and other marine fauna from the increasing pressure of exploitation. While microsatellite loci did not show significant genetic differentiation (p > 0.05), COI sequences revealed significant genetic divergence between sites on the East coast of Madagascar (ECM) and sites on the West coast of Madagascar, mainland East Africa, as well as the Seychelles. Since East African countries agreed to achieve the Convention on Biological Diversity (CBD) target to protect over 10% of their marine areas by 2020, the observed pattern of connectivity and the measured genetic diversity can serve to provide useful information for designing networks of

Bight of Benin: a Maternal Perspective of Four Beninese Populations and their Genetic Implications on the American Populations of African Ancestry.

PubMed

Primativo, Giuseppina; Ottoni, Claudio; Biondi, Gianfranco; Serafino, Sara; Martínez-Labarga, Cristina; Larmuseau, Maarten H D; Scardi, Michele; Decorte, Ronny; Rickards, Olga

2017-03-01

The understanding of the first movements of the ancestral populations within the African continent is still unclear, particularly in West Africa, due to several factors that have shaped the African genetic pool across time. To improve the genetic representativeness of the Beninese population and to better understand the patterns of human settlement inside West Africa and the dynamics of peopling of the Democratic Republic of Benin, we analyzed the maternal genetic variation of 193 Beninese individuals belonging to Bariba, Berba, Dendi, and Fon populations. Results support the oral traditions indicating that the western neighbouring populations have been the ancestors of the first Beninese populations, and the extant genetic structure of the Beninese populations is most likely the result of admixture between populations from neighbouring countries and native people. The present findings highlight how the Beninese populations contributed to the gene pool of the extant populations of some American populations of African ancestry. This strengthens the hypothesis that the Bight of Benin was not only an assembly point for the slave trade during the Trans-Atlantic Slave Trade but also an important slave trapping area. © 2017 John Wiley & Sons Ltd/University College London.

Genetic structure of South African Nguni (Zulu) sheep populations reveals admixture with exotic breeds

PubMed Central

Kunene, Nokuthula Winfred

2018-01-01

The population of Zulu sheep is reported to have declined by 7.4% between 2007 and 2011 due to crossbreeding. There is insufficient information on the genetic diversity of the Zulu sheep populations in the different area of KwaZulu Natal where they are reared. The study investigated genetic variation and genetic structure within and among eight Zulu sheep populations using 26 microsatellite markers. In addition, Damara, Dorper and South African Merino breeds were included to assess the genetic relationship between these breeds and the Zulu sheep. The results showed that there is considerable genetic diversity among the Zulu sheep populations (expected heterozygosity ranging from 0.57 to 0.69) and the level of inbreeding was not remarkable. The structure analysis results revealed that Makhathini Research Station and UNIZULU research station share common genetic structure, while three populations (Nongoma, Ulundi and Nquthu) had some admixture with the exotic Dorper breed. Thus, there is a need for sustainable breeding and conservation programmes to control the gene flow, in order to stop possible genetic dilution of the Zulu sheep. PMID:29698497

Genetic structure of South African Nguni (Zulu) sheep populations reveals admixture with exotic breeds.

PubMed

Selepe, Mokhethi Matthews; Ceccobelli, Simone; Lasagna, Emiliano; Kunene, Nokuthula Winfred

2018-01-01

The population of Zulu sheep is reported to have declined by 7.4% between 2007 and 2011 due to crossbreeding. There is insufficient information on the genetic diversity of the Zulu sheep populations in the different area of KwaZulu Natal where they are reared. The study investigated genetic variation and genetic structure within and among eight Zulu sheep populations using 26 microsatellite markers. In addition, Damara, Dorper and South African Merino breeds were included to assess the genetic relationship between these breeds and the Zulu sheep. The results showed that there is considerable genetic diversity among the Zulu sheep populations (expected heterozygosity ranging from 0.57 to 0.69) and the level of inbreeding was not remarkable. The structure analysis results revealed that Makhathini Research Station and UNIZULU research station share common genetic structure, while three populations (Nongoma, Ulundi and Nquthu) had some admixture with the exotic Dorper breed. Thus, there is a need for sustainable breeding and conservation programmes to control the gene flow, in order to stop possible genetic dilution of the Zulu sheep.

Racial disparity in pathophysiologic pathways of preterm birth based on genetic variants

PubMed Central

Menon, Ramkumar; Pearce, Brad; Velez, Digna R; Merialdi, Mario; Williams, Scott M; Fortunato, Stephen J; Thorsen, Poul

2009-01-01

Objective To study pathophysiologic pathways in spontaneous preterm birth and possibly the racial disparity associating with maternal and fetal genetic variations, using bioinformatics tools. Methods A large scale candidate gene association study was performed on 1442 SNPs in 130 genes in a case (preterm birth < 36 weeks) control study (term birth > 37 weeks). Both maternal and fetal DNA from Caucasians (172 cases and 198 controls) and 279 African-Americans (82 cases and 197 controls) were used. A single locus association (genotypic) analysis followed by hierarchical clustering was performed, where clustering was based on p values for significant associations within each race. Using Ingenuity Pathway Analysis (IPA) software, known pathophysiologic pathways in both races were determined. Results From all SNPs entered into the analysis, the IPA mapped genes to specific disease functions. Gene variants in Caucasians were implicated in disease functions shared with other known disorders; specifically, dermatopathy, inflammation, and hematological disorders. This may reflect abnormal cervical ripening and decidual hemorrhage. In African-Americans inflammatory pathways were the most prevalent. In Caucasians, maternal gene variants showed the most prominent role in disease functions, whereas in African Americans it was fetal variants. The IPA software was used to generate molecular interaction maps that differed between races and also between maternal and fetal genetic variants. Conclusion Differences at the genetic level revealed distinct disease functions and operational pathways in African Americans and Caucasians in spontaneous preterm birth. Differences in maternal and fetal contributions in pregnancy outcome are also different between African Americans and Caucasians. These results present a set of explicit testable hypotheses regarding genetic associations with preterm birth in African Americans and Caucasians PMID:19527514

Y-Chromosome and mtDNA Genetics Reveal Significant Contrasts in Affinities of Modern Middle Eastern Populations with European and African Populations

PubMed Central

Badro, Danielle A.; Youhanna, Sonia C.; Salloum, Angélique; Ghassibe-Sabbagh, Michella; Johnsrud, Brian; Khazen, Georges; Matisoo-Smith, Elizabeth; Soria-Hernanz, David F.; Wells, R. Spencer; Tyler-Smith, Chris; Platt, Daniel E.; Zalloua, Pierre A.

2013-01-01

The Middle East was a funnel of human expansion out of Africa, a staging area for the Neolithic Agricultural Revolution, and the home to some of the earliest world empires. Post LGM expansions into the region and subsequent population movements created a striking genetic mosaic with distinct sex-based genetic differentiation. While prior studies have examined the mtDNA and Y-chromosome contrast in focal populations in the Middle East, none have undertaken a broad-spectrum survey including North and sub-Saharan Africa, Europe, and Middle Eastern populations. In this study 5,174 mtDNA and 4,658 Y-chromosome samples were investigated using PCA, MDS, mean-linkage clustering, AMOVA, and Fisher exact tests of FST's, RST's, and haplogroup frequencies. Geographic differentiation in affinities of Middle Eastern populations with Africa and Europe showed distinct contrasts between mtDNA and Y-chromosome data. Specifically, Lebanon's mtDNA shows a very strong association to Europe, while Yemen shows very strong affinity with Egypt and North and East Africa. Previous Y-chromosome results showed a Levantine coastal-inland contrast marked by J1 and J2, and a very strong North African component was evident throughout the Middle East. Neither of these patterns were observed in the mtDNA. While J2 has penetrated into Europe, the pattern of Y-chromosome diversity in Lebanon does not show the widespread affinities with Europe indicated by the mtDNA data. Lastly, while each population shows evidence of connections with expansions that now define the Middle East, Africa, and Europe, many of the populations in the Middle East show distinctive mtDNA and Y-haplogroup characteristics that indicate long standing settlement with relatively little impact from and movement into other populations. PMID:23382925

Y-chromosome and mtDNA genetics reveal significant contrasts in affinities of modern Middle Eastern populations with European and African populations.

PubMed

Badro, Danielle A; Douaihy, Bouchra; Haber, Marc; Youhanna, Sonia C; Salloum, Angélique; Ghassibe-Sabbagh, Michella; Johnsrud, Brian; Khazen, Georges; Matisoo-Smith, Elizabeth; Soria-Hernanz, David F; Wells, R Spencer; Tyler-Smith, Chris; Platt, Daniel E; Zalloua, Pierre A

2013-01-01

The Middle East was a funnel of human expansion out of Africa, a staging area for the Neolithic Agricultural Revolution, and the home to some of the earliest world empires. Post LGM expansions into the region and subsequent population movements created a striking genetic mosaic with distinct sex-based genetic differentiation. While prior studies have examined the mtDNA and Y-chromosome contrast in focal populations in the Middle East, none have undertaken a broad-spectrum survey including North and sub-Saharan Africa, Europe, and Middle Eastern populations. In this study 5,174 mtDNA and 4,658 Y-chromosome samples were investigated using PCA, MDS, mean-linkage clustering, AMOVA, and Fisher exact tests of F(ST)'s, R(ST)'s, and haplogroup frequencies. Geographic differentiation in affinities of Middle Eastern populations with Africa and Europe showed distinct contrasts between mtDNA and Y-chromosome data. Specifically, Lebanon's mtDNA shows a very strong association to Europe, while Yemen shows very strong affinity with Egypt and North and East Africa. Previous Y-chromosome results showed a Levantine coastal-inland contrast marked by J1 and J2, and a very strong North African component was evident throughout the Middle East. Neither of these patterns were observed in the mtDNA. While J2 has penetrated into Europe, the pattern of Y-chromosome diversity in Lebanon does not show the widespread affinities with Europe indicated by the mtDNA data. Lastly, while each population shows evidence of connections with expansions that now define the Middle East, Africa, and Europe, many of the populations in the Middle East show distinctive mtDNA and Y-haplogroup characteristics that indicate long standing settlement with relatively little impact from and movement into other populations.

Genetic Variation in TLR Genes in Ugandan and South African Populations and Comparison with HapMap Data

PubMed Central

Randhawa, April Kaur; Horne, David J.; Adams, Mark D.; Shey, Muki; Barnholtz-Sloan, Jill; Mayanja-Kizza, Harriet; Kaplan, Gilla; Hanekom, Willem A.; Boom, W. Henry; Hawn, Thomas R.; Stein, Catherine M.

2012-01-01

Genetic epidemiological studies of complex diseases often rely on data from the International HapMap Consortium for identification of single nucleotide polymorphisms (SNPs), particularly those that tag haplotypes. However, little is known about the relevance of the African populations used to collect HapMap data for study populations conducted elsewhere in Africa. Toll-like receptor (TLR) genes play a key role in susceptibility to various infectious diseases, including tuberculosis. We conducted full-exon sequencing in samples obtained from Uganda (n = 48) and South Africa (n = 48), in four genes in the TLR pathway: TLR2, TLR4, TLR6, and TIRAP. We identified one novel TIRAP SNP (with minor allele frequency [MAF] 3.2%) and a novel TLR6 SNP (MAF 8%) in the Ugandan population, and a TLR6 SNP that is unique to the South African population (MAF 14%). These SNPs were also not present in the 1000 Genomes data. Genotype and haplotype frequencies and linkage disequilibrium patterns in Uganda and South Africa were similar to African populations in the HapMap datasets. Multidimensional scaling analysis of polymorphisms in all four genes suggested broad overlap of all of the examined African populations. Based on these data, we propose that there is enough similarity among African populations represented in the HapMap database to justify initial SNP selection for genetic epidemiological studies in Uganda and South Africa. We also discovered three novel polymorphisms that appear to be population-specific and would only be detected by sequencing efforts. PMID:23112821

Genetic and environmental determinants of volumetric and areal BMD in multi-generational families of African ancestry: the Tobago Family Health Study.

PubMed

Wang, Xiaojing; Kammerer, Candace M; Wheeler, Victor W; Patrick, Alan L; Bunker, Clareann H; Zmuda, Joseph M

2007-04-01

BMD is higher and fracture risk is lower among individuals of African versus European descent, but little is known about the genetic architecture of BMD in the former group. Heritabilities of areal and volumetric BMD were moderate in our large families of African descent but differed for trabecular and cortical BMD. Populations of African ancestry have lower osteoporotic fracture risk and higher BMD than other ethnic groups. However, there is a paucity of information regarding the genetic and environmental influences on bone health among populations of African heritage. We dissected the genetic architecture of areal BMD measured by DXA at the proximal femur, lumbar spine, and whole body and volumetric BMD measured by pQCT at the distal and proximal radius and tibia in 283 women and 188 men > or =18 years of age (mean, 43 years) from eight multigenerational Afro-Caribbean families (mean family size > 50). Using quantitative genetic methods, we estimated the residual heritability and the effects of anthropometric, demographic, lifestyle, and medical variables on areal and volumetric BMD. Compared with U.S. non-Hispanic blacks and whites, areal BMD at the femoral neck was highest in the Afro-Caribbean men and women at all ages. Trabecular volumetric BMD decreased linearly with increasing age, whereas cortical volumetric BMD did not decrease until age 40-49, especially in women. Anthropometric, lifestyle, and medical factors accounted for 12-32% of the variation in areal and volumetric BMD, and residual heritabilities (range, 0.23-0.52) were similar to those reported in other ethnic groups. Heritability of cortical BMD was substantially lower than that of areal or trabecular volumetric BMD, although the measured covariates accounted for a similar proportion of the total phenotypic variation. Our study is the first comprehensive genetic epidemiologic analysis of volumetric BMD measured by QCT and the first analysis of these traits in extended families of African descent

Phylogeographic Evidence for 2 Genetically Distinct Zoonotic Plasmodium knowlesi Parasites, Malaysia.

PubMed

Yusof, Ruhani; Ahmed, Md Atique; Jelip, Jenarun; Ngian, Hie Ung; Mustakim, Sahlawati; Hussin, Hani Mat; Fong, Mun Yik; Mahmud, Rohela; Sitam, Frankie Anak Thomas; Japning, J Rovie-Ryan; Snounou, Georges; Escalante, Ananias A; Lau, Yee Ling

2016-08-01

Infections of humans with the zoonotic simian malaria parasite Plasmodium knowlesi occur throughout Southeast Asia, although most cases have occurred in Malaysia, where P. knowlesi is now the dominant malaria species. This apparently skewed distribution prompted an investigation of the phylogeography of this parasite in 2 geographically separated regions of Malaysia, Peninsular Malaysia and Malaysian Borneo. We investigated samples collected from humans and macaques in these regions. Haplotype network analyses of sequences from 2 P. knowlesi genes, type A small subunit ribosomal 18S RNA and cytochrome c oxidase subunit I, showed 2 genetically distinct divergent clusters, 1 from each of the 2 regions of Malaysia. We propose that these parasites represent 2 distinct P. knowlesi types that independently became zoonotic. These types would have evolved after the sea-level rise at the end of the last ice age, which separated Malaysian Borneo from Peninsular Malaysia.

Phylogeographic Evidence for 2 Genetically Distinct Zoonotic Plasmodium knowlesi Parasites, Malaysia

PubMed Central

Yusof, Ruhani; Ahmed, Md Atique; Jelip, Jenarun; Ngian, Hie Ung; Mustakim, Sahlawati; Hussin, Hani Mat; Fong, Mun Yik; Mahmud, Rohela; Sitam, Frankie Anak Thomas; Japning, J. Rovie-Ryan; Snounou, Georges; Escalante, Ananias A.

2016-01-01

Infections of humans with the zoonotic simian malaria parasite Plasmodium knowlesi occur throughout Southeast Asia, although most cases have occurred in Malaysia, where P. knowlesi is now the dominant malaria species. This apparently skewed distribution prompted an investigation of the phylogeography of this parasite in 2 geographically separated regions of Malaysia, Peninsular Malaysia and Malaysian Borneo. We investigated samples collected from humans and macaques in these regions. Haplotype network analyses of sequences from 2 P. knowlesi genes, type A small subunit ribosomal 18S RNA and cytochrome c oxidase subunit I, showed 2 genetically distinct divergent clusters, 1 from each of the 2 regions of Malaysia. We propose that these parasites represent 2 distinct P. knowlesi types that independently became zoonotic. These types would have evolved after the sea-level rise at the end of the last ice age, which separated Malaysian Borneo from Peninsular Malaysia. PMID:27433965

Genetic ancestry is associated with subclinical cardiovascular disease in African Americans and Hispanics from the Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Wassel, Christina L.; Pankow, James S.; Peralta, Carmen A.; Choudhry, Shweta; Seldin, Michael F.; Arnett, Donna K.

2009-01-01

Background Differences in cardiovascular disease (CVD) burden exist among racial/ethnic groups in the United States, with African Americans having the highest prevalence. Subclinical CVD measures have also been shown to differ by race/ethnicity. In the United States, there has been significant intermixing among racial/ethnic groups creating admixed populations. Very little research exists on the relationship of genetic ancestry and subclinical CVD measures. Methods and Results These associations were investigated in 712 African-American and 705 Hispanic participants from the MESA candidate gene sub-study. Individual ancestry was estimated from 199 genetic markers using STRUCTURE. Associations of ancestry and coronary artery calcium (CAC) and common and internal carotid intima media thickness (cIMT) were evaluated using log-binomial and linear regression models. Splines indicated linear associations of ancestry with subclinical CVD measures in African-Americans, but presence of threshold effects in Hispanics. Among African Americans, each standard deviation (SD) increase in European ancestry was associated with an 8% (95% CI (1.02, 1.15), p=0.01) greater CAC prevalence. Each SD increase in European ancestry was also associated with a 2% (95% CI (−3.4%, −0.5%), p=0.008) lower common cIMT in African Americans. Among Hispanics, the highest tertile of European ancestry was associated with a 34% greater CAC prevalence, p=0.02 as compared to lowest tertile. Conclusions The linear association of ancestry and subclinical CVD suggests that genetic effects may be important in determining CAC and cIMT among African-Americans. Our results also suggest that CAC and common cIMT may be important phenotypes for further study with admixture mapping. PMID:20031644

Spatial and temporal patterns of neutral and adaptive genetic variation in the endangered African wild dog (Lycaon pictus).

PubMed

Marsden, Clare D; Woodroffe, Rosie; Mills, Michael G L; McNutt, J Weldon; Creel, Scott; Groom, Rosemary; Emmanuel, Masenga; Cleaveland, Sarah; Kat, Pieter; Rasmussen, Gregory S A; Ginsberg, Joshua; Lines, Robin; André, Jean-Marc; Begg, Colleen; Wayne, Robert K; Mable, Barbara K

2012-03-01

Deciphering patterns of genetic variation within a species is essential for understanding population structure, local adaptation and differences in diversity between populations. Whilst neutrally evolving genetic markers can be used to elucidate demographic processes and genetic structure, they are not subject to selection and therefore are not informative about patterns of adaptive variation. As such, assessments of pertinent adaptive loci, such as the immunity genes of the major histocompatibility complex (MHC), are increasingly being incorporated into genetic studies. In this study, we combined neutral (microsatellite, mtDNA) and adaptive (MHC class II DLA-DRB1 locus) markers to elucidate the factors influencing patterns of genetic variation in the African wild dog (Lycaon pictus); an endangered canid that has suffered extensive declines in distribution and abundance. Our genetic analyses found all extant wild dog populations to be relatively small (N(e)  < 30). Furthermore, through coalescent modelling, we detected a genetic signature of a recent and substantial demographic decline, which correlates with human expansion, but contrasts with findings in some other African mammals. We found strong structuring of wild dog populations, indicating the negative influence of extensive habitat fragmentation and loss of gene flow between habitat patches. Across populations, we found that the spatial and temporal structure of microsatellite diversity and MHC diversity were correlated and strongly influenced by demographic stability and population size, indicating the effects of genetic drift in these small populations. Despite this correlation, we detected signatures of selection at the MHC, implying that selection has not been completely overwhelmed by genetic drift. © 2012 Blackwell Publishing Ltd.

Development and characterization of microsatellite markers in the African forest elephant (Loxodonta cyclotis).

PubMed

Gugala, Natalie A; Ishida, Yasuko; Georgiadis, Nicholas J; Roca, Alfred L

2016-07-26

African elephants comprise two species, the savanna elephant (Loxodonta africana) and the forest elephant (L. cyclotis), which are distinct morphologically and genetically. Forest elephants are seriously threatened by poaching for meat and ivory, and by habitat destruction. However, microsatellite markers have thus far been developed only in African savanna elephants and Asian elephants, Elephas maximus. The application of microsatellite markers across deeply divergent lineages may produce irregular patterns such as large indels or null alleles. Thus we developed novel microsatellite markers using DNA from two African forest elephants. One hundred microsatellite loci were identified in next generation shotgun sequences from two African forest elephants, of which 53 were considered suitable for testing. Twenty-three microsatellite markers successfully amplified elephant DNA without amplifying human DNA; these were further characterized in 15 individuals from Lope National Park, Gabon. Three of the markers were monomorphic and four of them carried only two alleles. The remaining sixteen polymorphic loci carried from 3 to 8 alleles, with observed heterozygosity ranging from 0.27 to 0.87, expected heterozygosity from 0.40 to 0.86, and the Shannon diversity index from 0.73 to 1.86. Linkage disequilibrium was not detected between loci, and no locus deviated from Hardy-Weinberg equilibrium. The markers developed in this study will be useful for genetic analyses of the African forest elephant and contribute to their conservation and management.

Distinct Genetic Architectures for Male and Female Inflorescence Traits of Maize

PubMed Central

Brown, Patrick J.; Upadyayula, Narasimham; Mahone, Gregory S.; Tian, Feng; Bradbury, Peter J.; Myles, Sean; Holland, James B.; Flint-Garcia, Sherry; McMullen, Michael D.; Buckler, Edward S.; Rocheford, Torbert R.

2011-01-01

We compared the genetic architecture of thirteen maize morphological traits in a large population of recombinant inbred lines. Four traits from the male inflorescence (tassel) and three traits from the female inflorescence (ear) were measured and studied using linkage and genome-wide association analyses and compared to three flowering and three leaf traits previously studied in the same population. Inflorescence loci have larger effects than flowering and leaf loci, and ear effects are larger than tassel effects. Ear trait models also have lower predictive ability than tassel, flowering, or leaf trait models. Pleiotropic loci were identified that control elongation of ear and tassel, consistent with their common developmental origin. For these pleiotropic loci, the ear effects are larger than tassel effects even though the same causal polymorphisms are likely involved. This implies that the observed differences in genetic architecture are not due to distinct features of the underlying polymorphisms. Our results support the hypothesis that genetic architecture is a function of trait stability over evolutionary time, since the traits that changed most during the relatively recent domestication of maize have the largest effects. PMID:22125498

Genetic relatedness and disrupted social structure in a poached population of African elephants.

PubMed

Gobush, Kathleen; Kerr, Ben; Wasser, Samuel

2009-02-01

We use genetic measures of relatedness and observations of female bonding to examine the demographic signature of historically heavy poaching of a population of free-ranging African elephants. We collected dung samples to obtain DNA and observed behaviour from 102 elephant families over a 25-month period in 2003-2005 in Mikumi National Park, Tanzania. Poaching reduced the population by 75% in the decade prior to the 1989 ivory trade ban; park records indicate that poaching dropped significantly in Mikumi following the ban. Using 10 microsatellite loci, DNA was genotyped in 203 elephants and pair-wise relatedness was calculated among adult females within and between groups. The Mikumi population is characterized by small group size, considerable variation in group relatedness, females with no first-order adult relatives and females that form only weak social bonds. We used gene-drop analysis and a model of a genetically intact pedigree to compare our observed Mikumi group relatedness to a simulated genetically intact unpoached expectation. The majority of groups in Mikumi contain 2 to 3 adults; of these, 45% were classified as genetically disrupted. Bonding, quantified with a pair-wise association index, was significantly correlated with relatedness; however only half of the females formed strong bonds with other females, and relatedness was substantially lower for a given bond strength as compared to an unpoached population. Female African elephants without kin demonstrated considerable behavioural plasticity in this disturbed environment, grouping with other females lacking kin, with established groups, or remaining alone, unable to form any stable adult female-bonds. We interpret these findings as the remaining effect of poaching disturbance in Mikumi, despite a drop in the level of poaching since the commercial trade in ivory was banned 15 years ago.

Selfish genetic elements favor the evolution of a distinction between soma and germline.

PubMed

Johnson, Louise J

2008-08-01

Many multicellular organisms have evolved a dedicated germline. This can benefit the whole organism, but its advantages to genetic parasites have not been explored. Here I model the evolutionary success of a selfish element, such as a transposable element or endosymbiont, which is capable of creating or strengthening a germline-soma distinction in a primitively multicellular host, and find that it will always benefit the element to do so. Genes causing germline sequestration can therefore spread in a population even if germline sequestration is maladaptive for the host organism. Costly selfish elements are expected to survive only in sexual populations, so sexual species may experience an additional push toward germline-soma distinction, and hence toward cell differentiation and multicellularity.

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.

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

Comparative phylogeography and population genetics within Buteo lineatus reveals evidence of distinct evolutionary lineages

USGS Publications Warehouse

Hull, J.M.; Strobel, Bradley N.; Boal, C.W.; Hull, A.C.; Dykstra, C.R.; Irish, A.M.; Fish, A.M.; Ernest, H.B.

2008-01-01

Traditional subspecies classifications may suggest phylogenetic relationships that are discordant with evolutionary history and mislead evolutionary inference. To more accurately describe evolutionary relationships and inform conservation efforts, we investigated the genetic relationships and demographic histories of Buteo lineatus subspecies in eastern and western North America using 21 nuclear microsatellite loci and 375-base pairs of mitochondrial control region sequence. Frequency based analyses of mitochondrial sequence data support significant population distinction between eastern (B. l. lineatus/alleni/texanus) and western (B. l. elegans) subspecies of B. lineatus. This distinction was further supported by frequency and Bayesian analyses of the microsatellite data. We found evidence of differing demographic histories between regions; among eastern sites, mitochondrial data suggested that rapid population expansion occurred following the end of the last glacial maximum, with B. l. texanus population expansion preceding that of B. l. lineatus/alleni. No evidence of post-glacial population expansion was detected among western samples (B. l. elegans). Rather, microsatellite data suggest that the western population has experienced a recent bottleneck, presumably associated with extensive anthropogenic habitat loss during the 19th and 20th centuries. Our data indicate that eastern and western populations of B. lineatus are genetically distinct lineages, have experienced very different demographic histories, and suggest management as separate conservation units may be warranted. ?? 2008 Elsevier Inc. All rights reserved.

Genetic architecture of the Delis-Kaplan Executive Function System Trail Making Test: evidence for distinct genetic influences on executive function.

PubMed

Vasilopoulos, Terrie; Franz, Carol E; Panizzon, Matthew S; Xian, Hong; Grant, Michael D; Lyons, Michael J; Toomey, Rosemary; Jacobson, Kristen C; Kremen, William S

2012-03-01

To examine how genes and environments contribute to relationships among Trail Making Test (TMT) conditions and the extent to which these conditions have unique genetic and environmental influences. Participants included 1,237 middle-aged male twins from the Vietnam Era Twin Study of Aging. The Delis-Kaplan Executive Function System TMT included visual searching, number and letter sequencing, and set-shifting components. Phenotypic correlations among TMT conditions ranged from 0.29 to 0.60, and genes accounted for the majority (58-84%) of each correlation. Overall heritability ranged from 0.34 to 0.62 across conditions. Phenotypic factor analysis suggested a single factor. In contrast, genetic models revealed a single common genetic factor but also unique genetic influences separate from the common factor. Genetic variance (i.e., heritability) of number and letter sequencing was completely explained by the common genetic factor while unique genetic influences separate from the common factor accounted for 57% and 21% of the heritabilities of visual search and set shifting, respectively. After accounting for general cognitive ability, unique genetic influences accounted for 64% and 31% of those heritabilities. A common genetic factor, most likely representing a combination of speed and sequencing, accounted for most of the correlation among TMT 1-4. Distinct genetic factors, however, accounted for a portion of variance in visual scanning and set shifting. Thus, although traditional phenotypic shared variance analysis techniques suggest only one general factor underlying different neuropsychological functions in nonpatient populations, examining the genetic underpinnings of cognitive processes with twin analysis can uncover more complex etiological processes.

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

PubMed Central

Mbugi, Erasto V.; Katale, Bugwesa Z.; Streicher, Elizabeth M.; Keyyu, Julius D.; Kendall, Sharon L.; Dockrell, Hazel M.; Michel, Anita L.; Rweyemamu, Mark M.; Warren, Robin M.; Matee, Mecky I.; van Helden, Paul D.; Couvin, David; Rastogi, Nalin

2016-01-01

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA

The contributions of admixture and genetic drift to diversity among post-contact populations in the Americas.

PubMed

Koehl, Anthony J; Long, Jeffrey C

2018-02-01

We present a model that partitions Nei's minimum genetic distance between admixed populations into components of admixture and genetic drift. We applied this model to 17 admixed populations in the Americas to examine how admixture and drift have contributed to the patterns of genetic diversity. We analyzed 618 short tandem repeat loci in 949 individuals from 49 population samples. Thirty-two samples serve as proxies for continental ancestors. Seventeen samples represent admixed populations: (4) African-American and (13) Latin American. We partition genetic distance, and then calculate fixation indices and principal coordinates to interpret our results. A computer simulation confirms that our method correctly estimates drift and admixture components of genetic distance when the assumptions of the model are met. The partition of genetic distance shows that both admixture and genetic drift contribute to patterns of genetic diversity. The admixture component of genetic distance provides evidence for two distinct axes of continental ancestry. However, the genetic distances show that ancestry contributes to only one axis of genetic differentiation. The genetic distances among the 13 Latin American populations in this analysis show contributions from both differences in ancestry and differences in genetic drift. By contrast, the genetic distances among the four African American populations in this analysis owe mostly to genetic drift because these groups have similar fractions of European and African ancestry. The genetic structure of admixed populations in the Americas reflects more than admixture. We show that the history of serial founder effects constrains the impact of admixture on allele frequencies to a single dimension. Genetic drift in the admixed populations imposed a new level of genetic structure onto that created by admixture. © 2017 Wiley Periodicals, Inc.

Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent.

PubMed

Aminkeng, F; Ross, C J D; Rassekh, S R; Brunham, L R; Sistonen, J; Dube, M-P; Ibrahim, M; Nyambo, T B; Omar, S A; Froment, A; Bodo, J-M; Tishkoff, S; Carleton, B C; Hayden, M R

2014-04-01

There is established clinical evidence for differences in drug response, cure rates and survival outcomes between different ethnic populations, but the causes are poorly understood. Differences in frequencies of functional genetic variants in key drug response and metabolism genes may significantly influence drug response differences in different populations. To assess this, we genotyped 1330 individuals of African (n=372) and European (n=958) descent for 4535 single-nucleotide polymorphisms in 350 key drug absorption, distribution, metabolism, elimination and toxicity genes. Important and remarkable differences in the distribution of genetic variants were observed between Africans and Europeans and among the African populations. These could translate into significant differences in drug efficacy and safety profiles, and also in the required dose to achieve the desired therapeutic effect in different populations. Our data points to the need for population-specific genetic variation in personalizing medicine and care.

Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent

PubMed Central

Aminkeng, F; Ross, CJD; Rassekh, SR; Brunham, LR; Sistonen, J; Dube, M-P; Ibrahim, M; Nyambo, TB; Omar, SA; Froment, A; Bodo, J-M; Tishkoff, S; Carleton, BC; Hayden, MR

2015-01-01

There is established clinical evidence for differences in drug response, cure rates and survival outcomes between different ethnic populations, but the causes are poorly understood. Differences in frequencies of functional genetic variants in key drug response and metabolism genes may significantly influence drug response differences in different populations. To assess this, we genotyped 1330 individuals of African (n = 372) and European (n = 958) descent for 4535 single-nucleotide polymorphisms in 350 key drug absorption, distribution, metabolism, elimination and toxicity genes. Important and remarkable differences in the distribution of genetic variants were observed between Africans and Europeans and among the African populations. These could translate into significant differences in drug efficacy and safety profiles, and also in the required dose to achieve the desired therapeutic effect in different populations. Our data points to the need for population-specific genetic variation in personalizing medicine and care. PMID:23588107

Genetic connectivity across marginal habitats: the elephants of the Namib Desert.

PubMed

Ishida, Yasuko; Van Coeverden de Groot, Peter J; Leggett, Keith E A; Putnam, Andrea S; Fox, Virginia E; Lai, Jesse; Boag, Peter T; Georgiadis, Nicholas J; Roca, Alfred L

2016-09-01

Locally isolated populations in marginal habitats may be genetically distinctive and of heightened conservation concern. Elephants inhabiting the Namib Desert have been reported to show distinctive behavioral and phenotypic adaptations in that severely arid environment. The genetic distinctiveness of Namibian desert elephants relative to other African savanna elephant (Loxodonta africana) populations has not been established. To investigate the genetic structure of elephants in Namibia, we determined the mitochondrial (mt) DNA control region sequences and genotyped 17 microsatellite loci in desert elephants (n = 8) from the Hoanib River catchment and the Hoarusib River catchment. We compared these to the genotypes of elephants (n = 77) from other localities in Namibia. The mtDNA haplotype sequences and frequencies among desert elephants were similar to those of elephants in Etosha National Park, the Huab River catchment, the Ugab River catchment, and central Kunene, although the geographically distant Caprivi Strip had different mtDNA haplotypes. Likewise, analysis of the microsatellite genotypes of desert-dwelling elephants revealed that they were not genetically distinctive from Etosha elephants, and there was no evidence for isolation by distance across the Etosha region. These results, and a review of the historical record, suggest that a high learning capacity and long-distance migrations allowed Namibian elephants to regularly shift their ranges to survive in the face of high variability in climate and in hunting pressure.

East African cheetahs: evidence for two population bottlenecks?

PubMed Central

O'Brien, S J; Wildt, D E; Bush, M; Caro, T M; FitzGibbon, C; Aggundey, I; Leakey, R E

1987-01-01

A combined population genetic and reproductive analysis was undertaken to compare free-ranging cheetahs from east Africa (Acinonyx jubatus raineyi) with the genetically impoverished and reproductively impaired south African subspecies (Acinonyx jubatus jubatus). Like that of their south African counterparts, the quality of semen specimens from east African cheetahs was poor, with a low concentration of spermatozoa (25.3 X 10(6) per ejaculate) and a high incidence of morphological abnormalities (79%). From an electrophoretic survey of the products of 49 genetic loci in A. jubatus raineyi, two allozyme polymorphisms were detected; one of these, for a nonspecific esterase, shows an allele that is rare (less than 1% incidence) in south African specimens. Estimates of polymorphism (2-4%) and average heterozygosity (0.0004-0.014) affirm the cheetah as the least genetically variable felid species. The genetic distance between south and east African cheetahs was low (0.004), suggesting that the development of genetic uniformity preceded the recent geographic isolation of the subspecies. We propose that at least two population bottlenecks followed by inbreeding produced the modern cheetah species. The first and most extreme was ancient, possibly late Pleistocene (circa 10,000 years ago); the second was more recent (within the last century) and led to the south African populations. PMID:3467370

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

Genetic Architecture of the Delis-Kaplan Executive Function System Trail Making Test: Evidence for Distinct Genetic Influences on Executive Function

PubMed Central

Vasilopoulos, Terrie; Franz, Carol E.; Panizzon, Matthew S.; Xian, Hong; Grant, Michael D.; Lyons, Michael J; Toomey, Rosemary; Jacobson, Kristen C.; Kremen, William S.

2012-01-01

Objective To examine how genes and environments contribute to relationships among Trail Making test conditions and the extent to which these conditions have unique genetic and environmental influences. Method Participants included 1237 middle-aged male twins from the Vietnam-Era Twin Study of Aging (VESTA). The Delis-Kaplan Executive Function System Trail Making test included visual searching, number and letter sequencing, and set-shifting components. Results Phenotypic correlations among Trails conditions ranged from 0.29 – 0.60, and genes accounted for the majority (58–84%) of each correlation. Overall heritability ranged from 0.34 to 0.62 across conditions. Phenotypic factor analysis suggested a single factor. In contrast, genetic models revealed a single common genetic factor but also unique genetic influences separate from the common factor. Genetic variance (i.e., heritability) of number and letter sequencing was completely explained by the common genetic factor while unique genetic influences separate from the common factor accounted for 57% and 21% of the heritabilities of visual search and set-shifting, respectively. After accounting for general cognitive ability, unique genetic influences accounted for 64% and 31% of those heritabilities. Conclusions A common genetic factor, most likely representing a combination of speed and sequencing accounted for most of the correlation among Trails 1–4. Distinct genetic factors, however, accounted for a portion of variance in visual scanning and set-shifting. Thus, although traditional phenotypic shared variance analysis techniques suggest only one general factor underlying different neuropsychological functions in non-patient populations, examining the genetic underpinnings of cognitive processes with twin analysis can uncover more complex etiological processes. PMID:22201299

Pleistocene North African genomes link Near Eastern and sub-Saharan African human populations.

PubMed

van de Loosdrecht, Marieke; Bouzouggar, Abdeljalil; Humphrey, Louise; Posth, Cosimo; Barton, Nick; Aximu-Petri, Ayinuer; Nickel, Birgit; Nagel, Sarah; Talbi, El Hassan; El Hajraoui, Mohammed Abdeljalil; Amzazi, Saaïd; Hublin, Jean-Jacques; Pääbo, Svante; Schiffels, Stephan; Meyer, Matthias; Haak, Wolfgang; Jeong, Choongwon; Krause, Johannes

2018-05-04

North Africa is a key region for understanding human history, but the genetic history of its people is largely unknown. We present genomic data from seven 15,000-year-old modern humans, attributed to the Iberomaurusian culture, from Morocco. We find a genetic affinity with early Holocene Near Easterners, best represented by Levantine Natufians, suggesting a pre-agricultural connection between Africa and the Near East. We do not find evidence for gene flow from Paleolithic Europeans to Late Pleistocene North Africans. The Taforalt individuals derive one-third of their ancestry from sub-Saharan Africans, best approximated by a mixture of genetic components preserved in present-day West and East Africans. Thus, we provide direct evidence for genetic interactions between modern humans across Africa and Eurasia in the Pleistocene. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Patterns of family health history communication among older African American adults.

PubMed

Hovick, Shelly R; Yamasaki, Jill S; Burton-Chase, Allison M; Peterson, Susan K

2015-01-01

This qualitative study examined patterns of communication regarding family health history among older African American adults. The authors conducted 5 focus groups and 6 semi-structured interviews with African Americans aged 60 years and older (N = 28). The authors identified 4 distinct patterns of family health history communication: noncommunication, open communication, selective communication (communication restricted to certain people or topics), and one-way communication (communication not reciprocated by younger family members). In general, participants favored open family health history communication, often resulting from desires to change patterns of noncommunication in previous generations regarding personal and family health history. Some participants indicated that they were selective about what and with whom they shared health information in order to protect their privacy and not worry others. Others described family health history communication as one-way or unreciprocated by younger family members who appeared uninterested or unwilling to share personal and family health information. The communication patterns that the authors identified are consistent with communication privacy management theory and with findings from studies focused on genetic testing results for hereditary conditions, suggesting that individuals are consistent in their communication of health and genetic risk information. Findings may guide the development of health message strategies for African Americans to increase family health history communication.

Genetic diversity, breed composition and admixture of Kenyan domestic pigs.

PubMed

Mujibi, Fidalis Denis; Okoth, Edward; Cheruiyot, Evans K; Onzere, Cynthia; Bishop, Richard P; Fèvre, Eric M; Thomas, Lian; Masembe, Charles; Plastow, Graham; Rothschild, Max

2018-01-01

The genetic diversity of African pigs, whether domestic or wild has not been widely studied and there is very limited published information available. Available data suggests that African domestic pigs originate from different domestication centers as opposed to international commercial breeds. We evaluated two domestic pig populations in Western Kenya, in order to characterize the genetic diversity, breed composition and admixture of the pigs in an area known to be endemic for African swine fever (ASF). One of the reasons for characterizing these specific populations is the fact that a proportion of indigenous pigs have tested ASF virus (ASFv) positive but do not present with clinical symptoms of disease indicating some form of tolerance to infection. Pigs were genotyped using either the porcine SNP60 or SNP80 chip. Village pigs were sourced from Busia and Homabay counties in Kenya. Because bush pigs (Potamochoerus larvatus) and warthogs (Phacochoerus spp.) are known to be tolerant to ASFv infection (exhibiting no clinical symptoms despite infection), they were included in the study to assess whether domestic pigs have similar genomic signatures. Additionally, samples representing European wild boar and international commercial breeds were included as references, given their potential contribution to the genetic make-up of the target domestic populations. The data indicate that village pigs in Busia are a non-homogenous admixed population with significant introgression of genes from international commercial breeds. Pigs from Homabay by contrast, represent a homogenous population with a "local indigenous' composition that is distinct from the international breeds, and clusters more closely with the European wild boar than African wild pigs. Interestingly, village pigs from Busia that tested negative by PCR for ASFv genotype IX, had significantly higher local ancestry (>54%) compared to those testing positive, which contained more commercial breed gene introgression

Landscape genomics and pathway analysis to understand genetic adaptation of South African indigenous goat populations.

PubMed

Mdladla, K; Dzomba, E F; Muchadeyi, F C

2018-04-01

In Africa, extensively raised livestock populations in most smallholder farming communities are exposed to harsh and heterogeneous climatic conditions and disease pathogens that they adapt to in order to survive. Majority of these livestock species, including goats, are of non-descript and uncharacterized breeds and their response to natural selection presented by heterogeneous environments is still unresolved. This study investigated genetic diversity and its association with environmental and geographic conditions in 194 South African indigenous goats from different geographic locations genotyped on the Illumina goat SNP50K panel. Population structure analysis revealed a homogeneous genetic cluster of the Tankwa goats, restricted to the Northern Cape province. Overall, the Boer, Kalahari Red, and Savanna showed a wide geographic spread of shared genetic components, whereas the village ecotypes revealed a longitudinal distribution. The relative importance of environmental factors on genetic variation of goat populations was assessed using redundancy analysis (RDA). Climatic and geographic variables explained 22% of the total variation while climatic variables alone accounted for 17% of the diversity. Geographic variables solitarily explained 1% of the total variation. The first axis (Model I) of the RDA analysis revealed 329 outlier SNPs. Landscape genomic approaches of spatial analysis method (SAM) identified a total of 843 (1.75%) SNPs, while latent factor mixed models (LFMM) identified 714 (1.48%) SNPs significantly associated with environmental variables. Significant markers were within genes involved in biological functions potentially important for environmental adaptation. Overall, the study suggested environmental factors to have some effect in shaping the genetic variation of South African indigenous goat populations. Loci observed to be significant and under selection may be responsible for the adaption of the goat populations to local production systems.

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

Genetically-Adjusted PSA Values May Prevent Delayed Biopsies in African-American Men

PubMed Central

Donin, Nicholas; Loeb, Stacy; Cooper, Phillip R.; Roehl, Kimberly A.; Baumann, Nikola A.; J.Catalona, William; Helfand, Brian T.

2014-01-01

Purpose Genetic variants called PSA-single nucleotide polymorphisms (PSA-SNPs) have been associated with serum PSA levels. We previously demonstrated that genetic correction of serum PSA in Caucasian men could reduce both potentially unnecessary biopsies by 15% to 20% and potentially delayed biopsies by 3%. Our objective was to evaluate whether genetic correction with the PSA-SNPs could reduce potentially unnecessary and/or delayed biopsies in African-American (AA) men. Materials and Methods We compared the genotypes of 4 PSA-SNPs between 964 Caucasian and 363 AA men without known PC. We adjusted PSA values based upon an individual's PSA-SNP carrier status, and calculated the percentage of men that would meet commonly used PSA thresholds for biopsy (≥2.5 or ≥4.0ng/mL) before and after genetic correction. Potentially unnecessary and delayed biopsies were defined as those men who went below and above the biopsy threshold after genetic correction, respectively. Results Overall, 349 (96.1%) and 354 (97.5%) AA men had measured PSA levels <2.5 and <4.0 ng/mL. Genetic correction in AA men did not avoid any potentially unnecessary biopsies, but resulted in a significant (p<0.001) reduction in potentially delayed biopsies by 2.5% and 3.9% based upon the biopsy threshold cutoff. Conclusions There are significant differences in the influence of the PSA-SNPs between AA and Caucasian men without known PC, as genetic correction resulted in an increased proportion of AA men crossing the threshold for biopsy. These results raise the question whether genetic differences in PSA might contribute to delayed PC diagnosis in AA patients. PMID:24712975

Association of African genetic ancestry with fasting glucose and HbA1c levels in non-diabetic individuals: the Boston Area Community Health (BACH) Prediabetes Study.

PubMed

Meigs, James B; Grant, Richard W; Piccolo, Rebecca; López, Lenny; Florez, Jose C; Porneala, Bianca; Marceau, Lisa; McKinlay, John B

2014-09-01

To test among diabetes-free urban community-dwelling adults the hypothesis that the proportion of African genetic ancestry is positively associated with glycaemia, after accounting for other continental ancestry proportions, BMI and socioeconomic status (SES). The Boston Area Community Health cohort is a multi-stage 1:1:1 stratified random sample of self-identified African-American, Hispanic and white adults from three Boston inner city areas. We measured 62 ancestry informative markers, fasting glucose (FG), HbA1c, BMI and SES (income, education, occupation and insurance status) and analysed 1,387 eligible individuals (379 African-American, 411 Hispanic, 597 white) without clinical or biochemical evidence of diabetes. We used three-heritage multinomial linear regression models to test the association of FG or HbA1c with genetic ancestry proportion adjusted for: (1) age and sex; (2) age, sex and BMI; and (3) age, sex, BMI and SES. Mean age- and sex-adjusted FG levels were 5.73 and 5.54 mmol/l among those with 100% African or European ancestry, respectively. Using per cent European ancestry as the referent, each 1% increase in African ancestry proportion was associated with an age- and sex-adjusted FG increase of 0.0019 mmol/l (p = 0.01). In the BMI- and SES-adjusted model the slope was 0.0019 (p = 0.02). Analysis of HbA1c gave similar results. A greater proportion of African genetic ancestry is independently associated with higher FG levels in a non-diabetic community-based cohort, even accounting for other ancestry proportions, obesity and SES. The results suggest that differences between African-Americans and whites in type 2 diabetes risk may include genetically mediated differences in glucose homeostasis.

Multigene Phylogeography of Bactrocera caudata (Insecta: Tephritidae): Distinct Genetic Lineages in Northern and Southern Hemispheres

PubMed Central

Yong, Hoi-Sen; Lim, Phaik-Eem; Tan, Ji; Song, Sze-Looi; Suana, I Wayan; Eamsobhana, Praphathip

2015-01-01

Bactrocera caudata is a pest of pumpkin flower. Specimens of B. caudata from the northern hemisphere (mainland Asia) and southern hemisphere (Indonesia) were analysed using the partial DNA sequences of the nuclear 28S rRNA and internal transcribed spacer region 2 (ITS-2) genes, and the mitochondrial cytochrome c oxidase subunit I (COI), cytochrome c oxidase subunit II (COII) and 16S rRNA genes. The COI, COII, 16S rDNA and concatenated COI+COII+16S and COI+COII+16S+28S+ITS-2 nucleotide sequences revealed that B. caudata from the northern hemisphere (Peninsular Malaysia, East Malaysia, Thailand) was distinctly different from the southern hemisphere (Indonesia: Java, Bali and Lombok), without common haplotype between them. Phylogenetic analysis revealed two distinct clades (northern and southern hemispheres), indicating distinct genetic lineage. The uncorrected ‘p’ distance for the concatenated COI+COII+16S nucleotide sequences between the taxa from the northern and southern hemispheres (‘p’ = 4.46-4.94%) was several folds higher than the ‘p’ distance for the taxa in the northern hemisphere (‘p’ = 0.00-0.77%) and the southern hemisphere (‘p’ = 0.00%). This distinct difference was also reflected by concatenated COI+COII+16S+28S+ITS-2 nucleotide sequences with an uncorrected 'p' distance of 2.34-2.69% between the taxa of northern and southern hemispheres. In accordance with the type locality the Indonesian taxa belong to the nominal species. Thus the taxa from the northern hemisphere, if they were to constitute a cryptic species of the B. caudata species complex based on molecular data, need to be formally described as a new species. The Thailand and Malaysian B. caudata populations in the northern hemisphere showed distinct genetic structure and phylogeographic pattern. PMID:26090853

If I Could in a Small Way Help”: Motivations for and Beliefs about Sample Donation for Genetic Research

PubMed Central

Michie, Marsha; Henderson, Gail; Garrett, Joanne; Corbie-Smith, Giselle

2012-01-01

Human genome research depends upon participants who donate genetic samples, but few studies have explored in depth the motivations of genetic research donors. This mixed methods study examines telephone interviews with 752 sample donors in a U.S. genetic epidemiology study investigating colorectal cancer. Quantitative and qualitative results indicate that most participants wanted to help society, and that many also wanted information about their own health, even though such information was not promised. Qualitative analysis reveals that donors believed their samples contributed to a scientific “common good”; imagined samples as information rather than tissues; and often blurred distinctions between research and diagnostic testing of samples. Differences between African American and White perspectives were distinct from educational and other possible explanatory factors. PMID:21680977

Diabetes mellitus in two genetically distinct populations in Jordan

PubMed Central

Al-Eitan, Laith N.; Nassar, Ahmad M.; Dajani, Rana B.; Almomani, Basima A.; Saadeh, Nesreen A.

2017-01-01

Objectives: To compare clinical, anthropometric, and laboratory characteristics in diabetes type 2 patients of 2 genetically-distinct ethnicities living in Jordan, Arabs and Circassians/Chechens. Methods: This cross sectional ethnic comparison study was conducted in King Abdullah University Hospital, Irbid and The National Center for Diabetes, Endocrinology, and Genetics, Amman, Jordan between June 2013 and February 2014. A sample of 347 (237 Arab and 110 Circassian/Chechen) people living with diabetes were included in the study. Data were collected through direct interviews with the participants. Clinical data were collected using a questionnaire and anthropometric measurements. Laboratory data were extracted from the patients’ medical records. Results: More Arabs with diabetes had hypertension as a comorbidity than Circassians/Chechens with diabetes. Arabs living with diabetes were generally more obese, whereas Circassians/Chechens living with diabetes had worse lipid control. Arabs with diabetes had higher means of glycated haemoglobin (HbA1c) and fasting blood sugar, and more Arabs with diabetes had unsatisfactory glycemic control (60.6%) than Circassians/Chechens with diabetes (38.2%) (HbA1c ≥7.0%). Most participants (88.8%) had at least one lipid abnormality (dyslipidemia). Conclusion: Multiple discrepancies among the 2 ethnic diabetic populations were found. New diabetes management recommendations and policies should be used when treating people living with diabetes of those ethnicities, particularly in areas of glycemic control, lipid control, and obesity. PMID:28133689

Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes

PubMed Central

Chen, Brian H.; Li, Jiang; Chen, Wei-Min; Guo, Xiuqing; Liu, Jiankang; Bielinski, Suzette J.; Yanek, Lisa R.; Nalls, Michael A.; Comeau, Mary E.; Rasmussen-Torvik, Laura J.; Jensen, Richard A.; Evans, Daniel S.; Sun, Yan V.; An, Ping; Patel, Sanjay R.; Lu, Yingchang; Long, Jirong; Armstrong, Loren L.; Wagenknecht, Lynne; Yang, Lingyao; Snively, Beverly M.; Palmer, Nicholette D.; Mudgal, Poorva; Langefeld, Carl D.; Keene, Keith L.; Freedman, Barry I.; Mychaleckyj, Josyf C.; Nayak, Uma; Raffel, Leslie J.; Goodarzi, Mark O.; Chen, Y-D Ida; Taylor, Herman A.; Correa, Adolfo; Sims, Mario; Couper, David; Pankow, James S.; Boerwinkle, Eric; Adeyemo, Adebowale; Doumatey, Ayo; Chen, Guanjie; Mathias, Rasika A.; Vaidya, Dhananjay; Singleton, Andrew B.; Zonderman, Alan B.; Igo, Robert P.; Sedor, John R.; Kabagambe, Edmond K.; Siscovick, David S.; McKnight, Barbara; Rice, Kenneth; Liu, Yongmei; Hsueh, Wen-Chi; Zhao, Wei; Bielak, Lawrence F.; Kraja, Aldi; Province, Michael A.; Bottinger, Erwin P.; Gottesman, Omri; Cai, Qiuyin; Zheng, Wei; Blot, William J.; Lowe, William L.; Pacheco, Jennifer A.; Crawford, Dana C.; Grundberg, Elin; Rich, Stephen S.; Hayes, M. Geoffrey; Shu, Xiao-Ou; Loos, Ruth J. F.; Borecki, Ingrid B.; Peyser, Patricia A.; Cummings, Steven R.; Psaty, Bruce M.; Fornage, Myriam; Iyengar, Sudha K.; Evans, Michele K.; Becker, Diane M.; Kao, W. H. Linda; Wilson, James G.; Rotter, Jerome I.; Sale, Michèle M.; Liu, Simin; Rotimi, Charles N.; Bowden, Donald W.

2014-01-01

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15×10−94African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies. PMID:25102180

Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.

PubMed

Ng, Maggie C Y; Shriner, Daniel; Chen, Brian H; Li, Jiang; Chen, Wei-Min; Guo, Xiuqing; Liu, Jiankang; Bielinski, Suzette J; Yanek, Lisa R; Nalls, Michael A; Comeau, Mary E; Rasmussen-Torvik, Laura J; Jensen, Richard A; Evans, Daniel S; Sun, Yan V; An, Ping; Patel, Sanjay R; Lu, Yingchang; Long, Jirong; Armstrong, Loren L; Wagenknecht, Lynne; Yang, Lingyao; Snively, Beverly M; Palmer, Nicholette D; Mudgal, Poorva; Langefeld, Carl D; Keene, Keith L; Freedman, Barry I; Mychaleckyj, Josyf C; Nayak, Uma; Raffel, Leslie J; Goodarzi, Mark O; Chen, Y-D Ida; Taylor, Herman A; Correa, Adolfo; Sims, Mario; Couper, David; Pankow, James S; Boerwinkle, Eric; Adeyemo, Adebowale; Doumatey, Ayo; Chen, Guanjie; Mathias, Rasika A; Vaidya, Dhananjay; Singleton, Andrew B; Zonderman, Alan B; Igo, Robert P; Sedor, John R; Kabagambe, Edmond K; Siscovick, David S; McKnight, Barbara; Rice, Kenneth; Liu, Yongmei; Hsueh, Wen-Chi; Zhao, Wei; Bielak, Lawrence F; Kraja, Aldi; Province, Michael A; Bottinger, Erwin P; Gottesman, Omri; Cai, Qiuyin; Zheng, Wei; Blot, William J; Lowe, William L; Pacheco, Jennifer A; Crawford, Dana C; Grundberg, Elin; Rich, Stephen S; Hayes, M Geoffrey; Shu, Xiao-Ou; Loos, Ruth J F; Borecki, Ingrid B; Peyser, Patricia A; Cummings, Steven R; Psaty, Bruce M; Fornage, Myriam; Iyengar, Sudha K; Evans, Michele K; Becker, Diane M; Kao, W H Linda; Wilson, James G; Rotter, Jerome I; Sale, Michèle M; Liu, Simin; Rotimi, Charles N; Bowden, Donald W

2014-08-01

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.

Lack of genetic linkage evidence for a trans-acting factor having a large effect on plasma lipoprotein[a] levels in African Americans.

PubMed

Barkley, Ruth Ann; Brown, Andrew C; Hanis, Craig L; Kardia, Sharon L; Turner, Stephen T; Boerwinkle, Eric

2003-07-01

The distribution of plasma lipoprotein[a] (Lp[a]) concentrations, a risk factor for cardiovascular disease, varies greatly among racial groups, with African Americans having values that are shifted toward higher levels than those of whites. The underlying cause of this heterogeneity is unknown, but a role for "trans-acting" factors has been hypothesized. This study used genetic linkage analysis to localize genetic factors influencing Lp[a] levels in African Americans that were absent in other populations; linkage results were analyzed separately in non-Hispanic whites, Hispanic whites, and African Americans. As expected, all three samples showed highly significant linkage at the approximate location of the lysophosphatidic acid locus. The white populations also independently had regions of significant linkage on chromosome 19 (LOD 3.80) and suggestive linkage on chromosomes 12 (LOD 1.60), 14 (LOD 2.56), and 19 (LOD 2.52). No linkage evidence was found to support the hypothesis of another single gene with large effects specifically segregating in African Americans that may account for their elevated Lp[a] levels.

Genetic and epigenetic associations to obesity-related appetite phenotypes among African-American children.

PubMed

Gardner, K R; Sapienza, C; Fisher, J O

2015-12-01

Genetic and epigenetic variations may be an important contributer to altered eating behaviors in childhood which may lead to weight gain and obesity later in life. This study aimed to evaluate epigenetic as well as genetic associations with appetite in young children. Participants were 32 non-obese and 32 obese African-American children aged 5-6 years. Saliva was collected from each child, and RNA and DNA were extracted for analysis. Individuals were genotyped for eating- and obesity-associated single nucleotide polymorphisms in seven candidate genes (FTO, MAOA, SH2B1, LEPR, DNMT3B, BDNF and CCKAR), and DNA methylation levels were measured in the upstream promoter region of each. Transcript levels of MAOA and FTO were also assessed. The Children's Eating Behavior Questionnaire (CEBQ) was used to assess the aspects of appetite. Child obesity was assessed using measured height and weight, and percent body fat was measured by dual-energy X-ray absorptiometry. Food responsiveness was higher and satiety responsiveness was lower among obese than non-obese female children (P = 0.001 and P = 0.031), but did not differ among male children. Epigenetic analysis of the BDNF promoter revealed associations with altered satiety responsiveness among female children (P < 0.01). The findings provide new evidence of epigenetic associations with altered appetite among young African-American girls. © 2015 World Obesity.

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

PubMed Central

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

2013-01-01

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

Spectrum of genetic variation at the ABCC6 locus in South Africans: Pseudoxanthoma elasticum patients and healthy individuals.

PubMed

Ramsay, Michèle; Greenberg, Tarryn; Lombard, Zane; Labrum, Robyn; Lubbe, Steven; Aron, Shaun; Marais, Anna-Susan; Terry, Sharon; Bercovitch, Lionel; Viljoen, Denis

2009-06-01

Pseudoxanthoma elasticum (PXE) is an autosomal recessive metabolic disorder with ectopic mineralization in the skin, eyes and cardiovascular system. PXE is caused by mutations in ABCC6. To examine 54 unrelated South African PXE patients for ABCC6 PXE causing mutations. Patients were screened for mutations in ABCC6 using two strategies. The first involved a comprehensive screening of all the ABCC6 exons and flanking regions by dHPLC or sequencing whereas the second involved screening patients only for the common PXE mutations. The ABCC6 gene was screened in ten white and ten black healthy unrelated South Africans in order to examine the level of common non-PXE associated variation. The Afrikaner founder mutation, R1339C, was present in 0.41 of white ABCC6 PXE alleles, confirming the founder effect and its presence in both Afrikaans- (34/63 PXE alleles) and English-speakers (4/28). Eleven mutations were detected in the white patients (of European origin), including two nonsense mutations, 6 missense mutations, two frameshift mutations and a large deletion mutation. The five "Coloured" patients (of mixed Khoisan, Malay, European and African origin) included three compound heterozygotes with R1339C as one of the mutations. The three black patients (sub-Saharan African origin) were all apparent homozygotes for the R1314W mutation. Blacks showed a trend towards a higher degree of neurtral variation (18 variants) when compared to whites (12 variants). Delineation of the ABCC6 mutation profile in South African PXE patients will be used as a guide for molecular genetic testing in a clinical setting and for genetic counselling.

Genetic variation in IL-16 miRNA target site and time to prostate cancer diagnosis in African American men

PubMed Central

Hughes, Lucinda; Ruth, Karen; Rebbeck, Timothy R.; Giri, Veda N.

2013-01-01

Background Men with a family history of prostate cancer and African American men are at high risk for prostate cancer and in need of personalized risk estimates to inform screening decisions. This study evaluated genetic variants in genes encoding microRNA (miRNA) binding sites for informing of time to prostate cancer diagnosis among ethnically-diverse, high-risk men undergoing prostate cancer screening. Methods The Prostate Cancer Risk Assessment Program (PRAP) is a longitudinal screening program for high-risk men. Eligibility includes men ages 35-69 with a family history of prostate cancer or African descent. Participants with ≥ 1 follow-up visit were included in the analyses (n=477). Genetic variants in regions encoding miRNA binding sites in four target genes (ALOX15, IL-16, IL-18, and RAF1) previously implicated in prostate cancer development were evaluated. Genotyping methods included Taqman® SNP Genotyping Assay (Applied Biosystems) or pyrosequencing. Cox models were used to assess time to prostate cancer diagnosis by risk genotype. Results Among 256 African Americans with ≥ one follow-up visit, the TT genotype at rs1131445 in IL-16 was significantly associated with earlier time to prostate cancer diagnosis vs. the CC/CT genotypes (p=0.013), with a suggestive association after correction for false-discovery (p=0.065). Hazard ratio after controlling for age and PSA for TT vs. CC/CT among African Americans was 3.0 (95% CI 1.26-7.12). No association to time to diagnosis was detected among Caucasians by IL-16 genotype. No association to time to prostate cancer diagnosis was found for the other miRNA target genotypes. Conclusions Genetic variation in IL-16 encoding miRNA target site may be informative of time to prostate cancer diagnosis among African American men enrolled in prostate cancer risk assessment, which may inform individualized prostate cancer screening strategies in the future. PMID:24061634

Genome sequence, population history, and pelage genetics of the endangered African wild dog (Lycaon pictus).

PubMed

Campana, Michael G; Parker, Lillian D; Hawkins, Melissa T R; Young, Hillary S; Helgen, Kristofer M; Szykman Gunther, Micaela; Woodroffe, Rosie; Maldonado, Jesús E; Fleischer, Robert C

2016-12-09

The African wild dog (Lycaon pictus) is an endangered African canid threatened by severe habitat fragmentation, human-wildlife conflict, and infectious disease. A highly specialized carnivore, it is distinguished by its social structure, dental morphology, absence of dewclaws, and colorful pelage. We sequenced the genomes of two individuals from populations representing two distinct ecological histories (Laikipia County, Kenya and KwaZulu-Natal Province, South Africa). We reconstructed population demographic histories for the two individuals and scanned the genomes for evidence of selection. We show that the African wild dog has undergone at least two effective population size reductions in the last 1,000,000 years. We found evidence of Lycaon individual-specific regions of low diversity, suggestive of inbreeding or population-specific selection. Further research is needed to clarify whether these population reductions and low diversity regions are characteristic of the species as a whole. We documented positive selection on the Lycaon mitochondrial genome. Finally, we identified several candidate genes (ASIP, MITF, MLPH, PMEL) that may play a role in the characteristic Lycaon pelage.

African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks.

PubMed

Erkizan, Hayriye Verda; Johnson, Kory; Ghimbovschi, Svetlana; Karkera, Deepa; Trachiotis, Gregory; Adib, Houtan; Hoffman, Eric P; Wadleigh, Robert G

2017-06-19

Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), the subtype that shows marked variation in geographic frequency. The molecular architecture of African-American ESCC is still poorly understood. It is unclear why African-American ESCC is more aggressive and the survival rate in these patients is worse than those of other ethnic groups. To begin to define genetic alterations that occur in African-American ESCC we conducted microarray expression profiling in pairs of esophageal squamous cell tumors and matched control tissues. We found significant dysregulation of genes encoding drug-metabolizing enzymes and stress response components of the NRF2- mediated oxidative damage pathway, potentially representing key genes in African-American esophageal squamous carcinogenesis. Loss of activity of drug metabolizing enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence and aggressiveness of ESCC in this ethnic group. To determine whether certain genes are uniquely altered in African-American ESCC we performed a meta-analysis of ESCC expression profiles in our African-American samples and those of several Asian samples. Down-regulation of TP53 pathway components represented the most common feature in ESCC of all ethnic groups. Importantly, this analysis revealed a potential distinctive molecular underpinning of African-American ESCC, that is, a widespread and prominent involvement of the NRF2 pathway. Taken together, these findings highlight the remarkable interplay of genetic and environmental factors in the pathogenesis of African-American ESCC.

African Lineage Brucella melitensis Isolates from Omani Livestock.

PubMed

Foster, Jeffrey T; Walker, Faith M; Rannals, Brandy D; Hussain, M Hammad; Drees, Kevin P; Tiller, Rebekah V; Hoffmaster, Alex R; Al-Rawahi, Abdulmajeed; Keim, Paul; Saqib, Muhammad

2017-01-01

Brucellosis is a common livestock disease in the Middle East and North Africa, but remains poorly described in the region both genetically and epidemiologically. Traditionally found in goats and sheep, Brucella melitensis is increasingly recognized as infecting camels. Most studies of brucellosis in camels to date have focused on serological surveys, providing only limited understanding of the molecular epidemiology of circulating strains. We genotyped B. melitensis isolates from Omani camels using whole genome SNP assays and VNTRs to provide context for regional brucellosis cases. We identified a lineage of B. melitensis circulating in camels as well as in goats, sheep, and cattle in Oman. This lineage is genetically distinct from most genotypes from the Arabian Peninsula and from isolates from much of the rest of the Middle East. We then developed diagnostic assays that rapidly identify strains from this lineage. In analyses of genotypes from throughout the region, Omani isolates were genetically most closely related to strains from brucellosis cases in humans and livestock in North Africa. Our findings suggest an African origin for B. melitensis in Oman that has likely occurred through the trade of infected livestock. Moreover, African lineages of B. melitensis appear to be undersampled and consequently are underrepresented in genetic databases for Brucella . As we begin to more fully understand global genomic diversity of B. melitensis , finding and characterizing these unique but widespread lineages is essential. We predict that increased sampling of humans and livestock in Africa will reveal little known diversity in this important zoonotic pathogen.

Genetic and archaeological perspectives on the initial modern human colonization of southern Asia.

PubMed

Mellars, Paul; Gori, Kevin C; Carr, Martin; Soares, Pedro A; Richards, Martin B

2013-06-25

It has been argued recently that the initial dispersal of anatomically modern humans from Africa to southern Asia occurred before the volcanic "supereruption" of the Mount Toba volcano (Sumatra) at ∼74,000 y before present (B.P.)-possibly as early as 120,000 y B.P. We show here that this "pre-Toba" dispersal model is in serious conflict with both the most recent genetic evidence from both Africa and Asia and the archaeological evidence from South Asian sites. We present an alternative model based on a combination of genetic analyses and recent archaeological evidence from South Asia and Africa. These data support a coastally oriented dispersal of modern humans from eastern Africa to southern Asia ∼60-50 thousand years ago (ka). This was associated with distinctively African microlithic and "backed-segment" technologies analogous to the African "Howiesons Poort" and related technologies, together with a range of distinctively "modern" cultural and symbolic features (highly shaped bone tools, personal ornaments, abstract artistic motifs, microblade technology, etc.), similar to those that accompanied the replacement of "archaic" Neanderthal by anatomically modern human populations in other regions of western Eurasia at a broadly similar date.

Clear genetic distinctiveness between human- and pig-derived Trichuris based on analyses of mitochondrial datasets.

PubMed

Liu, Guo-Hua; Gasser, Robin B; Su, Ang; Nejsum, Peter; Peng, Lifei; Lin, Rui-Qing; Li, Ming-Wei; Xu, Min-Jun; Zhu, Xing-Quan

2012-01-01

The whipworm, Trichuris trichiura, causes trichuriasis in ∼600 million people worldwide, mainly in developing countries. Whipworms also infect other animal hosts, including pigs (T. suis), dogs (T. vulpis) and non-human primates, and cause disease in these hosts, which is similar to trichuriasis of humans. Although Trichuris species are considered to be host specific, there has been considerable controversy, over the years, as to whether T. trichiura and T. suis are the same or distinct species. Here, we characterised the entire mitochondrial genomes of human-derived Trichuris and pig-derived Trichuris, compared them and then tested the hypothesis that the parasites from these two host species are genetically distinct in a phylogenetic analysis of the sequence data. Taken together, the findings support the proposal that T. trichiura and T. suis are separate species, consistent with previous data for nuclear ribosomal DNA. Using molecular analytical tools, employing genetic markers defined herein, future work should conduct large-scale studies to establish whether T. trichiura is found in pigs and T. suis in humans in endemic regions.

Clear Genetic Distinctiveness between Human- and Pig-Derived Trichuris Based on Analyses of Mitochondrial Datasets

PubMed Central

Liu, Guo-Hua; Gasser, Robin B.; Su, Ang; Nejsum, Peter; Peng, Lifei; Lin, Rui-Qing; Li, Ming-Wei; Xu, Min-Jun; Zhu, Xing-Quan

2012-01-01

The whipworm, Trichuris trichiura, causes trichuriasis in ∼600 million people worldwide, mainly in developing countries. Whipworms also infect other animal hosts, including pigs (T. suis), dogs (T. vulpis) and non-human primates, and cause disease in these hosts, which is similar to trichuriasis of humans. Although Trichuris species are considered to be host specific, there has been considerable controversy, over the years, as to whether T. trichiura and T. suis are the same or distinct species. Here, we characterised the entire mitochondrial genomes of human-derived Trichuris and pig-derived Trichuris, compared them and then tested the hypothesis that the parasites from these two host species are genetically distinct in a phylogenetic analysis of the sequence data. Taken together, the findings support the proposal that T. trichiura and T. suis are separate species, consistent with previous data for nuclear ribosomal DNA. Using molecular analytical tools, employing genetic markers defined herein, future work should conduct large-scale studies to establish whether T. trichiura is found in pigs and T. suis in humans in endemic regions. PMID:22363831

Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures

PubMed Central

Koch, Manja; Baurecht, Hansjörg; Ried, Janina S.; Rodriguez, Elke; Schlesinger, Sabrina; Volks, Natalie; Gieger, Christian; Rückert, Ina-Maria; Heinrich, Luise; Willenborg, Christina; Smith, Catherine; Peters, Annette; Thorand, Barbara; Koenig, Wolfgang; Lamina, Claudia; Jansen, Henning; Kronenberg, Florian; Seissler, Jochen; Thiery, Joachim; Rathmann, Wolfgang; Schunkert, Heribert; Erdmann, Jeanette; Barker, Jonathan; Nair, Rajan P; Tsoi, Lam C; Elder, James T; Mrowietz, Ulrich; Weichenthal, Michael; Mucha, Sören; Schreiber, Stefan; Franke, Andre; Schmitt, Jochen; Lieb, Wolfgang; Weidinger, Stephan

2015-01-01

Psoriasis has been linked to cardiometabolic diseases, but epidemiological findings are inconsistent. We investigated the association between psoriasis and cardiometabolic outcomes in a German cross-sectional study (n=4.185) and a prospective cohort of German Health Insurance beneficiaries (n=1.811.098). A potential genetic overlap was explored using genome-wide data from >22.000 coronary artery disease (CAD) and >4.000 psoriasis cases, and with a dense genotyping study of cardiometabolic risk loci on 927 psoriasis cases and 3.717 controls. Controlling for major confounders, in the cross-sectional analysis psoriasis was significantly associated with type 2 diabetes (T2D, adjusted odd’s ratio OR=2.36; 95% confidence interval CI=1.26–4.41) and myocardial infarction (MI, OR=2.26, 95% CI=1.03–4.96). In the longitudinal study, psoriasis slightly increased the risk for incident T2D (adjusted relative risk RR=1.11; 95%CI=1.08–1.14) and MI (RR=1.14; 95%CI=1.06–1.22), with highest risk increments in systemically treated psoriasis, which accounted for 11 and 17 excess cases of T2D and MI per 10,000 person-years. Except for weak signals from within the MHC, there was no evidence for genetic risk loci shared between psoriasis and cardiometabolic traits. Our findings suggest that psoriasis, in particular severe psoriasis, increases risk for T2D and MI, and that the genetic architecture of psoriasis and cardiometabolic traits is largely distinct. PMID:25599394

Genetic Diversity and Population Structure of Ethiopian Sheep Populations Revealed by High-Density SNP Markers

PubMed Central

Edea, Zewdu; Dessie, Tadelle; Dadi, Hailu; Do, Kyoung-Tag; Kim, Kwan-Suk

2017-01-01

Sheep in Ethiopia are adapted to a wide range of environments, including extreme habitats. Elucidating their genetic diversity is critical for improving breeding strategies and mapping quantitative trait loci associated with productivity. To this end, the present study investigated the genetic diversity and population structure of five Ethiopian sheep populations exhibiting distinct phenotypes and sampled from distinct production environments, including arid lowlands and highlands. To investigate the genetic relationships in greater detail and infer population structure of Ethiopian sheep breeds at the continental and global levels, we analyzed genotypic data of selected sheep breeds from the Ovine SNP50K HapMap dataset. All Ethiopian sheep samples were genotyped with Ovine Infinium HD SNP BeadChip (600K). Mean genetic diversity ranged from 0.29 in Arsi-Bale to 0.32 in Menz sheep, while estimates of genetic differentiation among populations ranged from 0.02 to 0.07, indicating low to moderate differentiation. An analysis of molecular variance revealed that 94.62 and 5.38% of the genetic variation was attributable to differences within and among populations, respectively. Our population structure analysis revealed clustering of five Ethiopian sheep populations according to tail phenotype and geographic origin—i.e., short fat-tailed (very cool high-altitude), long fat-tailed (mid to high-altitude), and fat-rumped (arid low-altitude), with clear evidence of admixture between long fat-tailed populations. North African sheep breeds showed higher levels of within-breed diversity, but were less differentiated than breeds from Eastern and Southern Africa. When African breeds were grouped according to geographic origin (North, South, and East), statistically significant differences were detected among groups (regions). A comparison of population structure between Ethiopian and global sheep breeds showed that fat-tailed breeds from Eastern and Southern Africa clustered

Patterns of Ancestry, Signatures of Natural Selection, and Genetic Association with Stature in Western African Pygmies

PubMed Central

Jarvis, Joseph P.; Ferwerda, Bart; Froment, Alain; Bodo, Jean-Marie; Beggs, William; Hoffman, Gabriel; Mezey, Jason; Tishkoff, Sarah A.

2012-01-01

African Pygmy groups show a distinctive pattern of phenotypic variation, including short stature, which is thought to reflect past adaptation to a tropical environment. Here, we analyze Illumina 1M SNP array data in three Western Pygmy populations from Cameroon and three neighboring Bantu-speaking agricultural populations with whom they have admixed. We infer genome-wide ancestry, scan for signals of positive selection, and perform targeted genetic association with measured height variation. We identify multiple regions throughout the genome that may have played a role in adaptive evolution, many of which contain loci with roles in growth hormone, insulin, and insulin-like growth factor signaling pathways, as well as immunity and neuroendocrine signaling involved in reproduction and metabolism. The most striking results are found on chromosome 3, which harbors a cluster of selection and association signals between approximately 45 and 60 Mb. This region also includes the positional candidate genes DOCK3, which is known to be associated with height variation in Europeans, and CISH, a negative regulator of cytokine signaling known to inhibit growth hormone-stimulated STAT5 signaling. Finally, pathway analysis for genes near the strongest signals of association with height indicates enrichment for loci involved in insulin and insulin-like growth factor signaling. PMID:22570615

Differences in salinity tolerance of genetically distinct Phragmites australis clones

PubMed Central

Achenbach, Luciana; Eller, Franziska; Nguyen, Loc Xuan; Brix, Hans

2013-01-01

Different clones of the wetland grass Phragmites australis differ in their morphology and physiology, and hence in their ability to cope with environmental stress. We analysed the responses of 15 P. australis clones with distinct ploidy levels (PLs) (4n, 6n, 8n, 10n, 12n) and geographic origins (Romania, Russia, Japan, Czech Republic, Australia) to step-wise increased salinity (8, 16, 24, 32, 40, 56 and 72 ppt). Shoot elongation rate, photosynthesis and plant part-specific ion accumulation were studied in order to assess if traits associated with salinity tolerance can be related to the genetic background and the geographic origin of the clones. Salt stress affected all clones, but at different rates. The maximum height was reduced from 1860 mm in control plants to 660 mm at 40 ppt salinity. The shoot elongation rate of salt-exposed plants varied significantly between clones until 40 ppt salinity. The light-saturated photosynthesis rate (Pmax) was stimulated by a salinity of 8 ppt, but decreased significantly at higher salinities. The stomatal conductance (gs) and the transpiration rate (E) decreased with increasing salinity. Only three clones survived at 72 ppt salinity, although their rates of photosynthesis were strongly inhibited. The roots and basal leaves of the salt-exposed plants accumulated high concentrations of water-extractable Na+ (1646 and 1004 µmol g−1 dry mass (DM), respectively) and Cl− (1876 and 1400 µmol g−1 DM, respectively). The concentrations of water-extractable Mg2+ and Ca2+ were reduced in salt-exposed plants compared with controls. The variation of all the measured parameters was higher among clones than among PLs. We conclude that the salinity tolerance of distinct P. australis clones varies widely and can be partially attributed to their longitudinal geographic origin, but not to PL. Further investigation will help in improving the understanding of this species' salt tolerance mechanisms and their connection to genetic factors.

ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties.

PubMed

St Pourcain, B; Robinson, E B; Anttila, V; Sullivan, B B; Maller, J; Golding, J; Skuse, D; Ring, S; Evans, D M; Zammit, S; Fisher, S E; Neale, B M; Anney, R J L; Ripke, S; Hollegaard, M V; Werge, T; Ronald, A; Grove, J; Hougaard, D M; Børglum, A D; Mortensen, P B; Daly, M J; Davey Smith, G

2018-02-01

Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether overlap in common genetic influences between these clinical conditions and impairments in social communication depends on the developmental stage of the assessed trait. Social communication difficulties were measured in typically-developing youth (Avon Longitudinal Study of Parents and Children, N⩽5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34 241 cases, 45 604 controls, 1235 trios) were either obtained through the Psychiatric Genomics Consortium (PGC) or the Danish iPSYCH project. Overlap in genetic influences between ASD and social communication difficulties during development decreased with age, both in the PGC-ASD and the iPSYCH-ASD sample. Genetic overlap between schizophrenia and social communication difficulties, by contrast, persisted across age, as observed within two independent PGC-SCZ2 subsamples, and showed an increase in magnitude for traits assessed during later adolescence. ASD- and schizophrenia-related polygenic effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors influencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic influences with impairments in social communication, but reveal distinct developmental profiles in their genetic links, consistent with the onset of clinical symptoms.

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

PubMed

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

2015-10-01

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

Fine-scale genetic structure and cryptic associations reveal evidence of kin-based sociality in the African forest elephant.

PubMed

Schuttler, Stephanie G; Philbrick, Jessica A; Jeffery, Kathryn J; Eggert, Lori S

2014-01-01

Spatial patterns of relatedness within animal populations are important in the evolution of mating and social systems, and have the potential to reveal information on species that are difficult to observe in the wild. This study examines the fine-scale genetic structure and connectivity of groups within African forest elephants, Loxodonta cyclotis, which are often difficult to observe due to forest habitat. We tested the hypothesis that genetic similarity will decline with increasing geographic distance, as we expect kin to be in closer proximity, using spatial autocorrelation analyses and Tau K(r) tests. Associations between individuals were investigated through a non-invasive genetic capture-recapture approach using network models, and were predicted to be more extensive than the small groups found in observational studies, similar to fission-fusion sociality found in African savanna (Loxodonta africana) and Asian (Elephas maximus) species. Dung samples were collected in Lopé National Park, Gabon in 2008 and 2010 and genotyped at 10 microsatellite loci, genetically sexed, and sequenced at the mitochondrial DNA control region. We conducted analyses on samples collected at three different temporal scales: a day, within six-day sampling sessions, and within each year. Spatial autocorrelation and Tau K(r) tests revealed genetic structure, but results were weak and inconsistent between sampling sessions. Positive spatial autocorrelation was found in distance classes of 0-5 km, and was strongest for the single day session. Despite weak genetic structure, individuals within groups were significantly more related to each other than to individuals between groups. Social networks revealed some components to have large, extensive groups of up to 22 individuals, and most groups were composed of individuals of the same matriline. Although fine-scale population genetic structure was weak, forest elephants are typically found in groups consisting of kin and based on matrilines

Genetic analysis of Saccharomyces cerevisiae strains isolated from palm wine in eastern Nigeria. Comparison with other African strains.

PubMed

Ezeronye, O U; Legras, J-L

2009-05-01

To study the yeast diversity of Nigerian palm wines by comparison with other African strains. Twenty-three Saccharomyces cerevisiae strains were obtained from palm wine samples collected at four locations in eastern Nigeria, and characterized using different molecular techniques: internal transcribed spacer restriction fragment length polymorphism and sequence analysis, pulsed field gel electrophoresis, inter delta typing and microsatellite multilocus analysis. These techniques revealed that palm wine yeasts represent a group of closely related strains that includes other West African isolates (CBS400, NCYC110, DVPG6044). Population analysis revealed an excess of homozygote strains and an allelic richness similar to wine suggestive of local domestication. Several other African yeast strains were not connected to this group. Ghana sorghum beer strains and other African strains (DBVPG1853 and MUCL28071) displayed strikingly high relatedness with European bread, beer or wine strains, and the genome of strain MUCL30909 contained African and wine-type alleles, indicating its hybrid origin. Nigerian palm wine yeast represents a local specific yeast flora, whereas a European origin or hybrid was suspected for several other Africa isolates. This study presents the first genetic characterization of an autochthonous African palm wine yeast population and confirms the idea that human intervention has favoured yeast migration.

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

Population genetics of the potentially invasive African fruit fly species, Ceratitis rosa and Ceratitis fasciventris (Diptera: Tephritidae).

PubMed

Baliraine, F N; Bonizzoni, M; Guglielmino, C R; Osir, E O; Lux, S A; Mulaa, F J; Gomulski, L M; Zheng, L; Quilici, S; Gasperi, G; Malacrida, A R

2004-03-01

A set of 10 microsatellite markers was used to survey the levels of genetic variability and to analyse the genetic aspects of the population dynamics of two potentially invasive pest fruit fly species, Ceratitis rosa and C. fasciventris, in Africa. The loci were derived from the closely related species, C. capitata. The degree of microsatellite polymorphism in C. rosa and C. fasciventris was extensive and comparable to that of C. capitata. In C. rosa, the evolution of microsatellite polymorphism in its distribution area reflects the colonization history of this species. The mainland populations are more polymorphic than the island populations. Low levels of differentiation were found within the Africa mainland area, while greater levels of differentiation affect the islands. Ceratitis fasciventris is a central-east African species. The microsatellite data over the Uganda/Kenya spatial scale suggest a recent expansion and possibly continuing gene flow within this area. The microsatellite variability data from C. rosa and C. fasciventris, together with those of C. capitata, support the hypothesis of an east African origin of the Ceratitis spp.

A comparison of nephron number, glomerular volume and kidney weight in Senegalese Africans and African Americans

PubMed Central

McNamara, Bridgette J.; Diouf, Boucar; Douglas-Denton, Rebecca N.; Hughson, Michael D.; Hoy, Wendy E.; Bertram, John F.

2010-01-01

Background. Low nephron number is determined in utero and is a proposed risk for essential hypertension. Glomerular volume is inversely correlated with nephron number, and genetic and environmental factors that determine nephron number are thought to determine glomerular volume. This study compared total glomerular (nephron) number (Nglom), mean glomerular volume (Vglom) and kidney weight in two geographically separated black populations with significant common genetic ancestry. Methods. Unbiased stereology was used to determine Nglom and Vglom in kidneys collected at coronial autopsy in an age- and sex-matched sample of 39 adult Africans from Dakar in Senegal, West Africa and 39 African Americans from Mississippi in the USA. Results. African Americans were taller and heavier than their Senegalese counterparts. Nglom was remarkably similar—with a geometric mean of 937 967 in Senegalese and 904 412 in African Americans (P = 0.62). Vglom was correlated inversely with Nglom and directly with body surface area in both groups, but Vglom was 54% greater in African Americans than in Senegalese Africans [8.30 ± 2.92 (SD) and 5.38 ± 1.25  μm3 × 106, respectively] and remained significantly larger (38%) after adjustment for body size. Vglom increased with age in African Americans, but not in the Senegalese. Kidney weight was larger in African Americans (P < 0.0001), but kidney-to-body weight ratio was not different between groups. Conclusions. Despite similar nephron numbers, a common genetic constitution, and even in relation to current body size, African Americans have larger Vglom than Senegalese subjects. This may mark exposure to environmental stressors or hereditary traits concentrated in the population's relocation to North America. PMID:20154008

A comparison of nephron number, glomerular volume and kidney weight in Senegalese Africans and African Americans.

PubMed

McNamara, Bridgette J; Diouf, Boucar; Douglas-Denton, Rebecca N; Hughson, Michael D; Hoy, Wendy E; Bertram, John F

2010-05-01

Low nephron number is determined in utero and is a proposed risk for essential hypertension. Glomerular volume is inversely correlated with nephron number, and genetic and environmental factors that determine nephron number are thought to determine glomerular volume. This study compared total glomerular (nephron) number (N(glom)), mean glomerular volume (V(glom)) and kidney weight in two geographically separated black populations with significant common genetic ancestry. Unbiased stereology was used to determine N(glom) and V(glom) in kidneys collected at coronial autopsy in an age- and sex-matched sample of 39 adult Africans from Dakar in Senegal, West Africa and 39 African Americans from Mississippi in the USA. African Americans were taller and heavier than their Senegalese counterparts. N(glom) was remarkably similar-with a geometric mean of 937 967 in Senegalese and 904 412 in African Americans (P = 0.62). V(glom) was correlated inversely with N(glom) and directly with body surface area in both groups, but V(glom) was 54% greater in African Americans than in Senegalese Africans [8.30 +/- 2.92 (SD) and 5.38 +/- 1.25 microm(3) x 10(6), respectively] and remained significantly larger (38%) after adjustment for body size. V(glom) increased with age in African Americans, but not in the Senegalese. Kidney weight was larger in African Americans (P < 0.0001), but kidney-to-body weight ratio was not different between groups. Despite similar nephron numbers, a common genetic constitution, and even in relation to current body size, African Americans have larger V(glom) than Senegalese subjects. This may mark exposure to environmental stressors or hereditary traits concentrated in the population's relocation to North America.

Genetic evaluation of the evolutionary distinctness of a federally endangered butterfly, Lange's Metalmark.

PubMed

Proshek, Benjamin; Dupuis, Julian R; Engberg, Anna; Davenport, Ken; Opler, Paul A; Powell, Jerry A; Sperling, Felix A H

2015-04-25

The Mormon Metalmark (Apodemia mormo) species complex occurs as isolated and phenotypically variable colonies in dryland areas across western North America. Lange's Metalmark, A. m. langei, one of the 17 subspecies taxonomically recognized in the complex, is federally listed under the U.S. Endangered Species Act of 1973. Metalmark taxa have traditionally been described based on phenotypic and ecological characteristics, and it is unknown how well this nomenclature reflects their genetic and evolutionary distinctiveness. Genetic variation in six microsatellite loci and mitochondrial cytochrome oxidase subunit I sequence was used to assess the population structure of the A. mormo species complex across 69 localities, and to evaluate A. m. langei's qualifications as an Evolutionarily Significant Unit. We discovered substantial genetic divergence within the species complex, especially across the Continental Divide, with population genetic structure corresponding more closely with geographic proximity and local isolation than with taxonomic divisions originally based on wing color and pattern characters. Lange's Metalmark was as genetically divergent as several other locally isolated populations in California, and even the unique phenotype that warranted subspecific and conservation status is reminiscent of the morphological variation found in some other populations. This study is the first genetic treatment of the A. mormo complex across western North America and potentially provides a foundation for reassessing the taxonomy of the group. Furthermore, these results illustrate the utility of molecular markers to aid in demarcation of biological units below the species level. From a conservation point of view, Apodemia mormo langei's diagnostic taxonomic characteristics may, by themselves, not support its evolutionary significance, which has implications for its formal listing as an Endangered Species.

Altitudinal gradients, biogeographic history and microhabitat adaptation affect fine-scale spatial genetic structure in African and Neotropical populations of an ancient tropical tree species.

PubMed

Torroba-Balmori, Paloma; Budde, Katharina B; Heer, Katrin; González-Martínez, Santiago C; Olsson, Sanna; Scotti-Saintagne, Caroline; Casalis, Maxime; Sonké, Bonaventure; Dick, Christopher W; Heuertz, Myriam

2017-01-01

The analysis of fine-scale spatial genetic structure (FSGS) within populations can provide insights into eco-evolutionary processes. Restricted dispersal and locally occurring genetic drift are the primary causes for FSGS at equilibrium, as described in the isolation by distance (IBD) model. Beyond IBD expectations, spatial, environmental or historical factors can affect FSGS. We examined FSGS in seven African and Neotropical populations of the late-successional rain forest tree Symphonia globulifera L. f. (Clusiaceae) to discriminate the influence of drift-dispersal vs. landscape/ecological features and historical processes on FSGS. We used spatial principal component analysis and Bayesian clustering to assess spatial genetic heterogeneity at SSRs and examined its association with plastid DNA and habitat features. African populations (from Cameroon and São Tomé) displayed a stronger FSGS than Neotropical populations at both marker types (mean Sp = 0.025 vs. Sp = 0.008 at SSRs) and had a stronger spatial genetic heterogeneity. All three African populations occurred in pronounced altitudinal gradients, possibly restricting animal-mediated seed dispersal. Cyto-nuclear disequilibria in Cameroonian populations also suggested a legacy of biogeographic history to explain these genetic patterns. Conversely, Neotropical populations exhibited a weaker FSGS, which may reflect more efficient wide-ranging seed dispersal by Neotropical bats and other dispersers. The population from French Guiana displayed an association of plastid haplotypes with two morphotypes characterized by differential habitat preferences. Our results highlight the importance of the microenvironment for eco-evolutionary processes within persistent tropical tree populations.

Altitudinal gradients, biogeographic history and microhabitat adaptation affect fine-scale spatial genetic structure in African and Neotropical populations of an ancient tropical tree species

PubMed Central

Torroba-Balmori, Paloma; Budde, Katharina B.; Heer, Katrin; González-Martínez, Santiago C.; Olsson, Sanna; Scotti-Saintagne, Caroline; Sonké, Bonaventure; Dick, Christopher W.

2017-01-01

The analysis of fine-scale spatial genetic structure (FSGS) within populations can provide insights into eco-evolutionary processes. Restricted dispersal and locally occurring genetic drift are the primary causes for FSGS at equilibrium, as described in the isolation by distance (IBD) model. Beyond IBD expectations, spatial, environmental or historical factors can affect FSGS. We examined FSGS in seven African and Neotropical populations of the late-successional rain forest tree Symphonia globulifera L. f. (Clusiaceae) to discriminate the influence of drift-dispersal vs. landscape/ecological features and historical processes on FSGS. We used spatial principal component analysis and Bayesian clustering to assess spatial genetic heterogeneity at SSRs and examined its association with plastid DNA and habitat features. African populations (from Cameroon and São Tomé) displayed a stronger FSGS than Neotropical populations at both marker types (mean Sp = 0.025 vs. Sp = 0.008 at SSRs) and had a stronger spatial genetic heterogeneity. All three African populations occurred in pronounced altitudinal gradients, possibly restricting animal-mediated seed dispersal. Cyto-nuclear disequilibria in Cameroonian populations also suggested a legacy of biogeographic history to explain these genetic patterns. Conversely, Neotropical populations exhibited a weaker FSGS, which may reflect more efficient wide-ranging seed dispersal by Neotropical bats and other dispersers. The population from French Guiana displayed an association of plastid haplotypes with two morphotypes characterized by differential habitat preferences. Our results highlight the importance of the microenvironment for eco-evolutionary processes within persistent tropical tree populations. PMID:28771629

Ethnic, racial and cultural identity and perceived benefits and barriers related to genetic testing for breast cancer among at-risk women of African descent in New York City.

PubMed

Sussner, K M; Edwards, T A; Thompson, H S; Jandorf, L; Kwate, N O; Forman, A; Brown, K; Kapil-Pair, N; Bovbjerg, D H; Schwartz, M D; Valdimarsdottir, H B

2011-01-01

Due to disparities in the use of genetic services, there has been growing interest in examining beliefs and attitudes related to genetic testing for breast and/or ovarian cancer risk among women of African descent. However, to date, few studies have addressed critical cultural variations among this minority group and their influence on such beliefs and attitudes. We assessed ethnic, racial and cultural identity and examined their relationships with perceived benefits and barriers related to genetic testing for cancer risk in a sample of 160 women of African descent (49% self-identified African American, 39% Black-West Indian/Caribbean, 12% Black-Other) who met genetic risk criteria and were participating in a larger longitudinal study including the opportunity for free genetic counseling and testing in New York City. All participants completed the following previously validated measures: (a) the multi-group ethnic identity measure (including ethnic search and affirmation subscales) and other-group orientation for ethnic identity, (b) centrality to assess racial identity, and (c) Africentrism to measure cultural identity. Perceived benefits and barriers related to genetic testing included: (1) pros/advantages (including family-related pros), (2) cons/disadvantages (including family-related cons, stigma and confidentiality concerns), and (3) concerns about abuses of genetic testing. In multivariate analyses, several ethnic identity elements showed significant, largely positive relationships to perceived benefits about genetic testing for breast and/or ovarian cancer risk, the exception being ethnic search, which was positively associated with cons/disadvantages, in general, and family-related cons/disadvantages. Racial identity (centrality) showed a significant association with confidentiality concerns. Cultural identity (Africentrism) was not related to perceived benefits and/or barriers. Ethnic and racial identity may influence perceived benefits and barriers

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

PubMed

Sucheston, Lara E; Bensen, Jeannette T; Xu, Zongli; Singh, Prashant K; Preus, Leah; Mohler, James L; Su, L Joseph; Fontham, Elizabeth T H; Ruiz, Bernardo; Smith, Gary J; Taylor, Jack A

2012-01-01

Family history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP. Individual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states. Mean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered "no" to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA. Mean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity

Genetic Ancestry, Self-Reported Race and Ethnicity in African Americans and European Americans in the PCaP Cohort

PubMed Central

Sucheston, Lara E.; Bensen, Jeannette T.; Xu, Zongli; Singh, Prashant K.; Preus, Leah; Mohler, James L.; Su, L. Joseph; Fontham, Elizabeth T. H.; Ruiz, Bernardo; Smith, Gary J.; Taylor, Jack A.

2012-01-01

Background Family history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP. Methods Individual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states. Results Mean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered “no” to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA. Conclusions Mean IA differed by race between states, elucidating a potential contributing factor to these differences

Race, Genetic West African Ancestry, and Prostate Cancer Prediction by PSA in Prospectively Screened High-Risk Men

PubMed Central

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

2008-01-01

Introduction “Race-specific” PSA needs evaluation in men at high-risk for prostate cancer (PCA) for optimizing early detection. Baseline PSA and longitudinal prediction for PCA was examined by self-reported race and genetic West African (WA) ancestry in the Prostate Cancer Risk Assessment Program, a prospective high-risk cohort. Materials and Methods Eligibility criteria are age 35–69 years, FH of PCA, African American (AA) race, or BRCA1/2 mutations. Biopsies have been performed at low PSA values (<4.0 ng/mL). WA ancestry was discerned by genotyping 100 ancestry informative markers. Cox proportional hazards models evaluated baseline PSA, self-reported race, and genetic WA ancestry. Cox models were used for 3-year predictions for PCA. Results 646 men (63% AA) were analyzed. Individual WA ancestry estimates varied widely among self-reported AA men. “Race-specific” differences in baseline PSA were not found by self-reported race or genetic WA ancestry. Among men with ≥ 1 follow-up visit (405 total, 54% AA), three-year prediction for PCA with a PSA of 1.5–4.0 ng/mL was higher in AA men with age in the model (p=0.025) compared to EA men. Hazard ratios of PSA for PCA were also higher by self-reported race (1.59 for AA vs. 1.32 for EA, p=0.04). There was a trend for increasing prediction for PCA with increasing genetic WA ancestry. Conclusions “Race-specific” PSA may need to be redefined as higher prediction for PCA at any given PSA in AA men. Large-scale studies are needed to confirm if genetic WA ancestry explains these findings to make progress in personalizing PCA early detection. PMID:19240249

Genetic and archaeological perspectives on the initial modern human colonization of southern Asia

PubMed Central

Mellars, Paul; Gori, Kevin C.; Carr, Martin; Soares, Pedro A.; Richards, Martin B.

2013-01-01

It has been argued recently that the initial dispersal of anatomically modern humans from Africa to southern Asia occurred before the volcanic “supereruption” of the Mount Toba volcano (Sumatra) at ∼74,000 y before present (B.P.)—possibly as early as 120,000 y B.P. We show here that this “pre-Toba” dispersal model is in serious conflict with both the most recent genetic evidence from both Africa and Asia and the archaeological evidence from South Asian sites. We present an alternative model based on a combination of genetic analyses and recent archaeological evidence from South Asia and Africa. These data support a coastally oriented dispersal of modern humans from eastern Africa to southern Asia ∼60–50 thousand years ago (ka). This was associated with distinctively African microlithic and “backed-segment” technologies analogous to the African “Howiesons Poort” and related technologies, together with a range of distinctively “modern” cultural and symbolic features (highly shaped bone tools, personal ornaments, abstract artistic motifs, microblade technology, etc.), similar to those that accompanied the replacement of “archaic” Neanderthal by anatomically modern human populations in other regions of western Eurasia at a broadly similar date. PMID:23754394

Smoking and Genetic Risk Variation across Populations of European, Asian, and African-American Ancestry - A Meta-analysis of Chromosome 15q25

PubMed Central

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

2012-01-01

Recent meta-analyses of European ancestry subjects show strong evidence for association between smoking quantity and multiple genetic variants on chromosome 15q25. This meta-analysis extends the examination of association between distinct genes in the CHRNA5-CHRNA3-CHRNB4 region and smoking quantity to Asian and African American populations to confirm and refine specific reported associations. Association results for a dichotomized cigarettes smoked per day (CPD) phenotype in 27 datasets (European ancestry (N=14,786), Asian (N=6,889), and African American (N=10,912) for a total of 32,587 smokers) were meta-analyzed by population and results were compared across all three populations. We demonstrate association between smoking quantity and markers in the chromosome 15q25 region across all three populations, and narrow the region of association. Of the variants tested, only rs16969968 is associated with smoking (p < 0.01) in each of these three populations (OR=1.33, 95%C.I.=1.25–1.42, p=1.1×10−17 in meta-analysis across all population samples). Additional variants displayed a consistent signal in both European ancestry and Asian datasets, but not in African Americans. The observed consistent association of rs16969968 with heavy smoking across multiple populations, combined with its known biological significance, suggests rs16969968 is most likely a functional variant that alters risk for heavy smoking. We interpret additional association results that differ across populations as providing evidence for additional functional variants, but we are unable to further localize the source of this association. Using the cross-population study paradigm provides valuable insights to narrow regions of interest and inform future biological experiments. PMID:22539395

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

PubMed

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

2012-05-01

Recent meta-analyses of European ancestry subjects show strong evidence for association between smoking quantity and multiple genetic variants on chromosome 15q25. This meta-analysis extends the examination of association between distinct genes in the CHRNA5-CHRNA3-CHRNB4 region and smoking quantity to Asian and African American populations to confirm and refine specific reported associations. Association results for a dichotomized cigarettes smoked per day phenotype in 27 datasets (European ancestry (N = 14,786), Asian (N = 6,889), and African American (N = 10,912) for a total of 32,587 smokers) were meta-analyzed by population and results were compared across all three populations. We demonstrate association between smoking quantity and markers in the chromosome 15q25 region across all three populations, and narrow the region of association. Of the variants tested, only rs16969968 is associated with smoking (P < 0.01) in each of these three populations (odds ratio [OR] = 1.33, 95% CI = 1.25-1.42, P = 1.1 × 10(-17) in meta-analysis across all population samples). Additional variants displayed a consistent signal in both European ancestry and Asian datasets, but not in African Americans. The observed consistent association of rs16969968 with heavy smoking across multiple populations, combined with its known biological significance, suggests rs16969968 is most likely a functional variant that alters risk for heavy smoking. We interpret additional association results that differ across populations as providing evidence for additional functional variants, but we are unable to further localize the source of this association. Using the cross-population study paradigm provides valuable insights to narrow regions of interest and inform future biological experiments. © 2012 Wiley Periodicals, Inc.

Phylogeographic Patterns in Africa and High Resolution Delineation of Genetic Clades in the Lion (Panthera leo)

NASA Astrophysics Data System (ADS)

Bertola, L. D.; Jongbloed, H.; van der Gaag, K. J.; de Knijff, P.; Yamaguchi, N.; Hooghiemstra, H.; Bauer, H.; Henschel, P.; White, P. A.; Driscoll, C. A.; Tende, T.; Ottosson, U.; Saidu, Y.; Vrieling, K.; de Iongh, H. H.

2016-08-01

Comparative phylogeography of African savannah mammals shows a congruent pattern in which populations in West/Central Africa are distinct from populations in East/Southern Africa. However, for the lion, all African populations are currently classified as a single subspecies (Panthera leo leo), while the only remaining population in Asia is considered to be distinct (Panthera leo persica). This distinction is disputed both by morphological and genetic data. In this study we introduce the lion as a model for African phylogeography. Analyses of mtDNA sequences reveal six supported clades and a strongly supported ancestral dichotomy with northern populations (West Africa, Central Africa, North Africa/Asia) on one branch, and southern populations (North East Africa, East/Southern Africa and South West Africa) on the other. We review taxonomies and phylogenies of other large savannah mammals, illustrating that similar clades are found in other species. The described phylogeographic pattern is considered in relation to large scale environmental changes in Africa over the past 300,000 years, attributable to climate. Refugial areas, predicted by climate envelope models, further confirm the observed pattern. We support the revision of current lion taxonomy, as recognition of a northern and a southern subspecies is more parsimonious with the evolutionary history of the lion.

Phylogeographic Patterns in Africa and High Resolution Delineation of Genetic Clades in the Lion (Panthera leo).

PubMed

Bertola, L D; Jongbloed, H; van der Gaag, K J; de Knijff, P; Yamaguchi, N; Hooghiemstra, H; Bauer, H; Henschel, P; White, P A; Driscoll, C A; Tende, T; Ottosson, U; Saidu, Y; Vrieling, K; de Iongh, H H

2016-08-04

Comparative phylogeography of African savannah mammals shows a congruent pattern in which populations in West/Central Africa are distinct from populations in East/Southern Africa. However, for the lion, all African populations are currently classified as a single subspecies (Panthera leo leo), while the only remaining population in Asia is considered to be distinct (Panthera leo persica). This distinction is disputed both by morphological and genetic data. In this study we introduce the lion as a model for African phylogeography. Analyses of mtDNA sequences reveal six supported clades and a strongly supported ancestral dichotomy with northern populations (West Africa, Central Africa, North Africa/Asia) on one branch, and southern populations (North East Africa, East/Southern Africa and South West Africa) on the other. We review taxonomies and phylogenies of other large savannah mammals, illustrating that similar clades are found in other species. The described phylogeographic pattern is considered in relation to large scale environmental changes in Africa over the past 300,000 years, attributable to climate. Refugial areas, predicted by climate envelope models, further confirm the observed pattern. We support the revision of current lion taxonomy, as recognition of a northern and a southern subspecies is more parsimonious with the evolutionary history of the lion.

Phylogeographic Patterns in Africa and High Resolution Delineation of Genetic Clades in the Lion (Panthera leo)

PubMed Central

Bertola, L. D.; Jongbloed, H.; van der Gaag, K. J.; de Knijff, P.; Yamaguchi, N.; Hooghiemstra, H.; Bauer, H.; Henschel, P.; White, P. A.; Driscoll, C. A.; Tende, T.; Ottosson, U.; Saidu, Y.; Vrieling, K.; de Iongh, H. H.

2016-01-01

Comparative phylogeography of African savannah mammals shows a congruent pattern in which populations in West/Central Africa are distinct from populations in East/Southern Africa. However, for the lion, all African populations are currently classified as a single subspecies (Panthera leo leo), while the only remaining population in Asia is considered to be distinct (Panthera leo persica). This distinction is disputed both by morphological and genetic data. In this study we introduce the lion as a model for African phylogeography. Analyses of mtDNA sequences reveal six supported clades and a strongly supported ancestral dichotomy with northern populations (West Africa, Central Africa, North Africa/Asia) on one branch, and southern populations (North East Africa, East/Southern Africa and South West Africa) on the other. We review taxonomies and phylogenies of other large savannah mammals, illustrating that similar clades are found in other species. The described phylogeographic pattern is considered in relation to large scale environmental changes in Africa over the past 300,000 years, attributable to climate. Refugial areas, predicted by climate envelope models, further confirm the observed pattern. We support the revision of current lion taxonomy, as recognition of a northern and a southern subspecies is more parsimonious with the evolutionary history of the lion. PMID:27488946

Personality assessment and its association with genetic factors in captive Asian and African elephants.

PubMed

Yasui, Saki; Konno, Akitsugu; Tanaka, Masayuki; Idani, Gen'ichi; Ludwig, Arne; Lieckfeldt, Dietmar; Inoue-Murayama, Miho

2013-01-01

Elephants live in a complex society based on matrilineal groups. Management of captive elephants is difficult, partly because each elephant has a unique personality. For a better understanding of elephant well being in captivity, it would be helpful to systematically evaluate elephants' personalities and their underlying biological basis. We sent elephant' personality questionnaires to keepers of 75 elephants. We also used 196 elephant DNA samples to search for genetic polymorphisms in genes expressed in the brain that have been suggested to be related to personality traits. Three genes, androgen receptor (AR), fragile X related mental retardation protein interacting protein (NUFIP2), and acheate-scute homologs 1 (ASH1) contained polymorphic regions. We examined the association of personality with intraspecific genetic variation in 17 Asian and 28 African elephants. The results suggest that the ASH1 genotype was associated with neuroticism in Asian elephants. Subjects with short alleles had lower scores of neuroticism than those with long alleles. This is the first report of an association between a genetic polymorphism and personality in elephants. © 2012 Wiley Periodicals, Inc.

Genetic Ancestry is Associated with Measures of Subclinical Atherosclerosis in African Americans: The Jackson Heart Study

PubMed Central

Gebreab, Samson Y; Riestra, Pia; Khan, Rumana J; Xu, Ruihua; Musani, Solomon K; Tekola-Ayele, Fasil; Correa, Adolfo; Wilson, James G; Rotimi, Charles N; Davis, Sharon K

2015-01-01

Objective To determine whether genetic ancestry was associated with subclinical atherosclerosis measures after adjustment for traditional CVD risk factors, inflammatory marker, socioeconomic status (SES) and psychosocial factors in a large admixed African American population. Approach and Results Participants were drawn from Jackson Heart Study (JHS). Participant’s percent of European Ancestry (PEA) was estimated based on 1747 genetic markers using HAPMIX. Association of PEA with peripheral arterial disease (PAD) and common carotid intima media thickness (cCIMT) were investigated among 2168 participants and with coronary artery calcification (CAC >0) and abdominal aortic calcification (AAC >0) among 1139 participants. The associations were evaluated using multivariable regression models. Our results showed a 1 standard deviation increase in PEA was associated with a lower PAD prevalence after adjusting for age and gender [Prevalence ratio (PR) = 0. 90 (95% CI: 0.82, 0.99); p=0.036]. Adjustments for traditional CVD risk factors, SES, and psychosocial factors attenuated this association [PR=0.91 (0.82, 1.00); p=0.046]. There was also a non-linear association between PEA and CAC and AAC. The lowest PEA was associated with a lower CAC [PR=0.75 (0.58, 0.96); p=0.022] and a lower AAC [PR=0. 80 (0.67, 0.96); p=0.016] compared to the reference group (10th–90th percentile) after adjusting for traditional CVD risk factors, inflammatory marker, SES and psychosocial factors. However, we found no significant association between PEA and cCIMT. Conclusions Overall, our findings indicate that genetic ancestry was associated with subclinical atherosclerosis, suggesting unmeasured risk factors and/or interactions with genetic factors might contribute to the distribution of subclinical atherosclerosis among African Americans. PMID:25745061

Koalas (Phascolarctos cinereus) From Queensland Are Genetically Distinct From 2 Populations in Victoria.

PubMed

Ruiz-Rodriguez, Christina T; Ishida, Yasuko; Murray, Neil D; O'Brien, Stephen J; Graves, Jennifer A M; Greenwood, Alex D; Roca, Alfred L

2016-01-01

The koala (Phascolarctos cinereus) suffered population declines and local extirpation due to hunting in the early 20th century, especially in southern Australia. Koalas were subsequently reintroduced to the Brisbane Ranges (BR) and Stony Rises (SR) by translocating individuals from a population on French Island descended from a small number of founders. To examine genetic diversity and north-south differentiation, we genotyped 13 microsatellite markers in 46 wild koalas from the BR and SR, and 27 Queensland koalas kept at the US zoos. The Queensland koalas displayed much higher heterozygosity (H O = 0.73) than the 2 southern Australian koala populations examined: H O = 0.49 in the BR, whereas H O = 0.41 in the SR. This is consistent with the historical accounts of bottlenecks and founder events affecting the southern populations and contrasts with reports of high genetic diversity in some southern populations. The 2 southern Australian koala populations were genetically similar (F ST = 0.018, P = 0.052). By contrast, northern and southern Australian koalas were highly differentiated (F ST = 0.27, P < 0.001), thereby suggesting that geographic structuring should be considered in the conservation management of koalas. Sequencing of 648bp of the mtDNA control region in Queensland koalas found 8 distinct haplotypes, one of which had not been previously detected among koalas. Queensland koalas displayed high mitochondrial haplotype diversity (H = 0.753) and nucleotide diversity (π = 0.0072), indicating along with the microsatellite data that North American zoos have maintained high levels of genetic diversity among their Queensland koalas. © The American Genetic Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Common polymorphic variation in the genetically diverse African insulin gene and its association with size at birth.

PubMed

Petry, Clive J; Rayco-Solon, Pura; Fulford, Anthony J C; Stead, John D H; Wingate, Dianne L; Ong, Ken K; Sirugo, Giorgio; Prentice, Andrew M; Dunger, David B

2009-09-01

The insulin variable number of tandem repeats (INS VNTR) has been variably associated with size at birth in non-African populations. Small size at birth is a major determinant of neonatal mortality, so the INS VNTR may influence survival. We tested the hypothesis, therefore, that genetic variation around the INS VNTR in a rural Gambian population, who experience seasonal variation in nutrition and subsequently birth weight, may be associated with foetal and early growth. Six polymorphisms flanking the INS VNTR were genotyped in over 2,500 people. Significant associations were detected between the maternally inherited SNP 27 (rs689) allele and birth length [effect size 17.5 (5.2-29.8) mm; P = 0.004; n = 361]. Significant associations were also found between the maternally inherited African-specific SNP 28 (rs5506) allele and post-natal weight gain [effect size 0.19 (0.05-0.32) z score points/year; P = 0.005; n = 728). These results suggest that in the Gambian population studied there are associations between polymorphic variation in the genetically diverse INS gene and foetal and early growth characteristics, which contribute to overall polygenic associations with these traits.

Africanization in the United States: replacement of feral European honeybees (Apis mellifera L.) by an African hybrid swarm.

PubMed

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

2005-08-01

The expansion of Africanized honeybees from South America to the southwestern United States in <50 years is considered one of the most spectacular biological invasions yet documented. In the American tropics, it has been shown that during their expansion Africanized honeybees have low levels of introgressed alleles from resident European populations. In the United States, it has been speculated, but not shown, that Africanized honeybees would hybridize extensively with European honeybees. Here we report a continuous 11-year study investigating temporal changes in the genetic structure of a feral population from the southern United States undergoing Africanization. Our microsatellite data showed that (1) the process of Africanization involved both maternal and paternal bidirectional gene flow between European and Africanized honeybees and (2) the panmitic European population was replaced by panmitic mixtures of A. m. scutellata and European genes within 5 years after Africanization. The post-Africanization gene pool (1998-2001) was composed of a diverse array of recombinant classes with a substantial European genetic contribution (mean 25-37%). Therefore, the resulting feral honeybee population of south Texas was best viewed as a hybrid swarm.

The ties that bind: genetic relatedness predicts the fission and fusion of social groups in wild African elephants.

PubMed

Archie, Elizabeth A; Moss, Cynthia J; Alberts, Susan C

2006-03-07

Many social animals live in stable groups. In contrast, African savannah elephants (Loxodonta africana) live in unusually fluid, fission-fusion societies. That is, 'core' social groups are composed of predictable sets of individuals; however, over the course of hours or days, these groups may temporarily divide and reunite, or they may fuse with other social groups to form much larger social units. Here, we test the hypothesis that genetic relatedness predicts patterns of group fission and fusion among wild, female African elephants. Our study of a single Kenyan population spans 236 individuals in 45 core social groups, genotyped at 11 microsatellite and one mitochondrial DNA (mtDNA) locus. We found that genetic relatedness predicted group fission; adult females remained with their first order maternal relatives when core groups fissioned temporarily. Relatedness also predicted temporary fusion between social groups; core groups were more likely to fuse with each other when the oldest females in each group were genetic relatives. Groups that shared mtDNA haplotypes were also significantly more likely to fuse than groups that did not share mtDNA. Our results suggest that associations between core social groups persist for decades after the original maternal kin have died. We discuss these results in the context of kin selection and its possible role in the evolution of elephant sociality.

Short-range phenotypic divergence among genetically distinct parapatric populations of an Australian funnel-web spider.

PubMed

Wong, Mark K L; Woodman, James D; Rowell, David M

2017-07-01

Speciation involves divergence at genetic and phenotypic levels. Where substantial genetic differentiation exists among populations, examining variation in multiple phenotypic characters may elucidate the mechanisms by which divergence and speciation unfold. Previous work on the Australian funnel-web spider Atrax sutherlandi Gray (2010; Records of the Australian Museum 62 , 285-392; Mygalomorphae: Hexathelidae: Atracinae) has revealed a marked genetic structure along a 110-kilometer transect, with six genetically distinct, parapatric populations attributable to past glacial cycles. In the present study, we explore variation in three classes of phenotypic characters (metabolic rate, water loss, and morphological traits) within the context of this phylogeographic structuring. Variation in metabolic and water loss rates shows no detectable association with genetic structure; the little variation observed in these rates may be due to the spiders' behavioral adaptations (i.e., burrowing), which buffer the effects of climatic gradients across the landscape. However, of 17 morphological traits measured, 10 show significant variation among genetic populations, in a disjunct manner that is clearly not latitudinal. Moreover, patterns of variation observed for morphological traits serving different organismic functions (e.g., prey capture, burrowing, and locomotion) are dissimilar. In contrast, a previous study of an ecologically similar sympatric spider with little genetic structure indicated a strong latitudinal response in 10 traits over the same range. The congruence of morphological variation with deep phylogeographic structure in Tallaganda's A. sutherlandi populations, as well as the inconsistent patterns of variation across separate functional traits, suggest that the spiders are likely in early stages of speciation, with parapatric populations independently responding to local selective forces.

Introducing the Algerian Mitochondrial DNA and Y-Chromosome Profiles into the North African Landscape

PubMed Central

Bekada, Asmahan; Fregel, Rosa; Cabrera, Vicente M.; Larruga, José M.; Pestano, José; Benhamamouch, Soraya; González, Ana M.

2013-01-01

North Africa is considered a distinct geographic and ethnic entity within Africa. Although modern humans originated in this Continent, studies of mitochondrial DNA (mtDNA) and Y-chromosome genealogical markers provide evidence that the North African gene pool has been shaped by the back-migration of several Eurasian lineages in Paleolithic and Neolithic times. More recent influences from sub-Saharan Africa and Mediterranean Europe are also evident. The presence of East-West and North-South haplogroup frequency gradients strongly reinforces the genetic complexity of this region. However, this genetic scenario is beset with a notable gap, which is the lack of consistent information for Algeria, the largest country in the Maghreb. To fill this gap, we analyzed a sample of 240 unrelated subjects from a northwest Algeria cosmopolitan population using mtDNA sequences and Y-chromosome biallelic polymorphisms, focusing on the fine dissection of haplogroups E and R, which are the most prevalent in North Africa and Europe respectively. The Eurasian component in Algeria reached 80% for mtDNA and 90% for Y-chromosome. However, within them, the North African genetic component for mtDNA (U6 and M1; 20%) is significantly smaller than the paternal (E-M81 and E-V65; 70%). The unexpected presence of the European-derived Y-chromosome lineages R-M412, R-S116, R-U152 and R-M529 in Algeria and the rest of the Maghreb could be the counterparts of the mtDNA H1, H3 and V subgroups, pointing to direct maritime contacts between the European and North African sides of the western Mediterranean. Female influx of sub-Saharan Africans into Algeria (20%) is also significantly greater than the male (10%). In spite of these sexual asymmetries, the Algerian uniparental profiles faithfully correlate between each other and with the geography. PMID:23431392

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

PubMed

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

2017-10-05

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

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

PubMed Central

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

2017-01-01

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

Are Africans, Europeans, and Asians different "races"? A guided-inquiry lab for introducing undergraduate students to genetic diversity and preparing them to study natural selection.

PubMed

Kalinowski, Steven T; Andrews, Tessa M; Leonard, Mary J; Snodgrass, Meagan

2012-01-01

Many students do not recognize that individual organisms within populations vary, and this may make it difficult for them to recognize the essential role variation plays in natural selection. Also, many students have weak scientific reasoning skills, and this makes it difficult for them to recognize misconceptions they might have. This paper describes a 2-h laboratory for college students that introduces them to genetic diversity and gives them practice using hypothetico-deductive reasoning. In brief, the lab presents students with DNA sequences from Africans, Europeans, and Asians, and asks students to determine whether people from each continent qualify as distinct "races." Comparison of the DNA sequences shows that people on each continent are not more similar to one another than to people on other continents, and therefore do not qualify as distinct races. Ninety-four percent of our students reported that the laboratory was interesting, and 79% reported that it was a valuable learning experience. We developed and used a survey to measure the extent to which students recognized variation and its significance within populations and showed that the lab increased student awareness of variation. We also showed that the lab improved the ability of students to construct hypothetico-deductive arguments.

The evolution and phylogeography of the African elephant inferred from mitochondrial DNA sequence and nuclear microsatellite markers.

PubMed

Eggert, Lori S; Rasner, Caylor A; Woodruff, David S

2002-10-07

Recent genetic results support the recognition of two African elephant species: Loxodonta africana, the savannah elephant, and Loxodonta cyclotis, the forest elephant. The study, however, did not include the populations of West Africa, where the taxonomic affinities of elephants have been much debated. We examined mitochondrial cytochrome b control region sequences and four microsatellite loci to investigate the genetic differences between the forest and savannah elephants of West and Central Africa. We then combined our data with published control region sequences from across Africa to examine patterns at the continental level. Our analysis reveals several deeply divergent lineages that do not correspond with the currently recognized taxonomy: (i) the forest elephants of Central Africa; the forest and savannah elephants of West Africa; and (iii) the savannah elephants of eastern, southern and Central Africa. We propose that the complex phylogeographic patterns we detect in African elephants result from repeated continental-scale climatic changes over their five-to-six million year evolutionary history. Until there is consensus on the taxonomy, we suggest that the genetic and ecological distinctness of these lineages should be an important factor in conservation management planning.

Report on the 6th African Society of Human Genetics (AfSHG) Meeting, March 12-15, 2009, Yaounde, Cameroon.

PubMed

Sirugo, Giorgio; Williams, Scott M; Royal, Charmaine D M; Newport, Melanie J; Hennig, Branwen J; Mariani-Costantini, Renato; Buonaguro, Franco M; Velez Edwards, Digna R; Ibrahim, Muntaser; Soodyall, Himla; Wonkam, Ambroise; Ramesar, Raj; Rotimi, Charles N

2010-08-01

The African Society of Human Genetics (AfSHG), founded in 2003 with its inaugural meeting in Accra, Ghana,1 has the stated missions of (1) disseminating information about human genetics research in Africa, (2) establishing a mentorship network providing educational resources, including the development of appropriate technology transfer, (3) providing advocacy for human genetic research in Africa, and (4) encouraging collaborative research. Despite its young age, the AfSHG has developed a strong cadre of active researchers, both within and outside of Africa, with more than 400 members (from 16 countries across Africa as well as 8 other countries), and has held six successful meetings, five in Africa and one in the United States.

Phylogeography, genetic structure and population divergence time of cheetahs in Africa and Asia: evidence for long-term geographic isolates.

PubMed

Charruau, P; Fernandes, C; Orozco-Terwengel, P; Peters, J; Hunter, L; Ziaie, H; Jourabchian, A; Jowkar, H; Schaller, G; Ostrowski, S; Vercammen, P; Grange, T; Schlötterer, C; Kotze, A; Geigl, E-M; Walzer, C; Burger, P A

2011-02-01

The cheetah (Acinonyx jubatus) has been described as a species with low levels of genetic variation. This has been suggested to be the consequence of a demographic bottleneck 10 000-12 000 years ago (ya) and also led to the assumption that only small genetic differences exist between the described subspecies. However, analysing mitochondrial DNA and microsatellites in cheetah samples from most of the historic range of the species we found relatively deep phylogeographic breaks between some of the investigated populations, and most of the methods assessed divergence time estimates predating the postulated bottleneck. Mitochondrial DNA monophyly and overall levels of genetic differentiation support the distinctiveness of Northern-East African cheetahs (Acinonyx jubatus soemmeringii). Moreover, combining archaeozoological and contemporary samples, we show that Asiatic cheetahs (Acinonyx jubatus venaticus) are unambiguously separated from African subspecies. Divergence time estimates from mitochondrial and nuclear data place the split between Asiatic and Southern African cheetahs (Acinonyx jubatus jubatus) at 32 000-67 000 ya using an average mammalian microsatellite mutation rate and at 4700-44 000 ya employing human microsatellite mutation rates. Cheetahs are vulnerable to extinction globally and critically endangered in their Asiatic range, where the last 70-110 individuals survive only in Iran. We demonstrate that these extant Iranian cheetahs are an autochthonous monophyletic population and the last representatives of the Asiatic subspecies A. j. venaticus. We advocate that conservation strategies should consider the uncovered independent evolutionary histories of Asiatic and African cheetahs, as well as among some African subspecies. This would facilitate the dual conservation priorities of maintaining locally adapted ecotypes and genetic diversity. © 2011 Blackwell Publishing Ltd.

Phylogeography, genetic structure and population divergence time of cheetahs in Africa and Asia: evidence for long-term geographic isolates

PubMed Central

Charruau, P; Fernandes, C; Orozco-terWengel, P; Peters, J; Hunter, L; Ziaie, H; Jourabchian, A; Jowkar, H; Schaller, G; Ostrowski, S; Vercammen, P; Grange, T; Schlötterer, C; Kotze, A; Geigl, E-M; Walzer, C; Burger, P A

2011-01-01

The cheetah (Acinonyx jubatus) has been described as a species with low levels of genetic variation. This has been suggested to be the consequence of a demographic bottleneck 10 000–12 000 years ago (ya) and also led to the assumption that only small genetic differences exist between the described subspecies. However, analysing mitochondrial DNA and microsatellites in cheetah samples from most of the historic range of the species we found relatively deep phylogeographic breaks between some of the investigated populations, and most of the methods assessed divergence time estimates predating the postulated bottleneck. Mitochondrial DNA monophyly and overall levels of genetic differentiation support the distinctiveness of Northern-East African cheetahs (Acinonyx jubatus soemmeringii). Moreover, combining archaeozoological and contemporary samples, we show that Asiatic cheetahs (Acinonyx jubatus venaticus) are unambiguously separated from African subspecies. Divergence time estimates from mitochondrial and nuclear data place the split between Asiatic and Southern African cheetahs (Acinonyx jubatus jubatus) at 32 000–67 000 ya using an average mammalian microsatellite mutation rate and at 4700–44 000 ya employing human microsatellite mutation rates. Cheetahs are vulnerable to extinction globally and critically endangered in their Asiatic range, where the last 70–110 individuals survive only in Iran. We demonstrate that these extant Iranian cheetahs are an autochthonous monophyletic population and the last representatives of the Asiatic subspecies A. j. venaticus. We advocate that conservation strategies should consider the uncovered independent evolutionary histories of Asiatic and African cheetahs, as well as among some African subspecies. This would facilitate the dual conservation priorities of maintaining locally adapted ecotypes and genetic diversity. PMID:21214655

Genetic and environmental risks for high blood pressure among African American mothers and daughters.

PubMed

Taylor, Jacquelyn Y; Maddox, Rosanna; Wu, Chun Yi

2009-07-01

To determine the relationship between genetic and environmental lifestyle factors (physical activity and sodium) on blood pressure (BP) among African-American women. In this cross-sectional study involving 108 African-American mothers and daughters from a Midwestern area, investigators obtained BP measurements, information on minutes of physical activity, amount of sodium intake, and buccal swab saliva samples. Of the 4 single nucleotide polymorphisms (SNPs) on the sodium bicarbonate cotransporter gene (SLC4A5), rs8179526 had a statistically significant interaction with cytosine/thymine (C/T) genotype by sodium status on systolic BP (SBP; p=.0077). For gene x physical activity interaction, 2 significant interactions (cytosine/adenine [C/A] genotype by physical activity and adenine/adenine [A/A] genotype by physical activity, p=.0107 and p=.0171, respectively) on SBP and 1 on diastolic BP (DBP; A/A genotype by physical activity, p=.0233) were found on rs1017783. Two significant guanine/adenine [G/A] genotype by physical activity interactions were found on rs6731545 for SBP and DBP (p=.0160 and p=.0492, respectively). A gene x environmental interaction with rs8179526 has a protective effect on SBP in African-American women with high sodium intake. Participants with C/T genotype of rs8179526 who consumed greater than 2,300 mg of sodium had lower SBP than those who consumed less than recommended. Women with thymine/thymine (T/T) genotype of rs8179526 who consumed greater than 2,300 mg had lower SBP than those who consumed less. Awareness of both the protective and deleterious properties of rs8179526 in African-American women may one day assist in determining appropriate treatment plans.

Genomic single-nucleotide polymorphisms confirm that Gunnison and Greater sage-grouse are genetically well differentiated and that the Bi-State population is distinct

USGS Publications Warehouse

Oyler-McCance, Sara J.; Cornman, Robert S.; Jones, Kenneth L.; Fike, Jennifer

2015-01-01

Sage-grouse are iconic, declining inhabitants of sagebrush habitats in western North America, and their management depends on an understanding of genetic variation across the landscape. Two distinct species of sage-grouse have been recognized, Greater (Centrocercus urophasianus) and Gunnison sage-grouse (C. minimus), based on morphology, behavior, and variation at neutral genetic markers. A parapatric group of Greater Sage-Grouse along the border of California and Nevada ("Bi-State") is also genetically distinct at the same neutral genetic markers, yet not different in behavior or morphology. Because delineating taxonomic boundaries and defining conservation units is often difficult in recently diverged taxa and can be further complicated by highly skewed mating systems, we took advantage of new genomic methods that improve our ability to characterize genetic variation at a much finer resolution. We identified thousands of single-nucleotide polymorphisms (SNPs) among Gunnison, Greater, and Bi-State sage-grouse and used them to comprehensively examine levels of genetic diversity and differentiation among these groups. The pairwise multilocus fixation index (FST) was high (0.49) between Gunnison and Greater sage-grouse, and both principal coordinates analysis and model-based clustering grouped samples unequivocally by species. Standing genetic variation was lower within the Gunnison Sage-Grouse. The Bi-State population was also significantly differentiated from Greater Sage-Grouse, albeit more weakly (FST = 0.09), and genetic clustering results were consistent with reduced gene flow with Greater Sage-Grouse. No comparable genetic divisions were found within the Greater Sage-Grouse sample, which spanned the southern half of the range. Thus, we provide much stronger genetic evidence supporting the recognition of Gunnison Sage-Grouse as a distinct species with low genetic diversity. Further, our work confirms that the Bi-State population is differentiated from other

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.

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

PubMed Central

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

2014-01-01

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

Improving AFLP analysis of large-scale patterns of genetic variation--a case study with the Central African lianas Haumania spp (Marantaceae) showing interspecific gene flow.

PubMed

Ley, A C; Hardy, O J

2013-04-01

AFLP markers are often used to study patterns of population genetic variation and gene flow because they offer a good coverage of the nuclear genome, but the reliability of AFLP scoring is critical. To assess interspecific gene flow in two African rainforest liana species (Haumania danckelmaniana, H. liebrechtsiana) where previous evidence of chloroplast captures questioned the importance of hybridization and species boundaries, we developed new AFLP markers and a novel approach to select reliable bands from their degree of reproducibility. The latter is based on the estimation of the broad-sense heritability of AFLP phenotypes, an improvement over classical scoring error rates, which showed that the polymorphism of most AFLP bands was affected by a substantial nongenetic component. Therefore, using a quantitative genetics framework, we also modified an existing estimator of pairwise kinship coefficient between individuals correcting for the limited heritability of markers. Bayesian clustering confirms the recognition of the two Haumania species. Nevertheless, the decay of the relatedness between individuals of distinct species with geographic distance demonstrates that hybridization affects the nuclear genome. In conclusion, although we showed that AFLP markers might be substantially affected by nongenetic factors, their analysis using the new methods developed considerably advanced our understanding of the pattern of gene flow in our model species. © 2013 Blackwell Publishing Ltd.

Genetic Variation and Adaptation in Africa: Implications for Human Evolution and Disease

PubMed Central

Gomez, Felicia; Hirbo, Jibril; Tishkoff, Sarah A.

2014-01-01

Because modern humans originated in Africa and have adapted to diverse environments, African populations have high levels of genetic and phenotypic diversity. Thus, genomic studies of diverse African ethnic groups are essential for understanding human evolutionary history and how this leads to differential disease risk in all humans. Comparative studies of genetic diversity within and between African ethnic groups creates an opportunity to reconstruct some of the earliest events in human population history and are useful for identifying patterns of genetic variation that have been influenced by recent natural selection. Here we describe what is currently known about genetic variation and evolutionary history of diverse African ethnic groups. We also describe examples of recent natural selection in African genomes and how these data are informative for understanding the frequency of many genetic traits, including those that cause disease susceptibility in African populations and populations of recent African descent. PMID:24984772

Extensive population genetic structure in the giraffe.

PubMed

Brown, David M; Brenneman, Rick A; Koepfli, Klaus-Peter; Pollinger, John P; Milá, Borja; Georgiadis, Nicholas J; Louis, Edward E; Grether, Gregory F; Jacobs, David K; Wayne, Robert K

2007-12-21

A central question in the evolutionary diversification of large, widespread, mobile mammals is how substantial differentiation can arise, particularly in the absence of topographic or habitat barriers to dispersal. All extant giraffes (Giraffa camelopardalis) are currently considered to represent a single species classified into multiple subspecies. However, geographic variation in traits such as pelage pattern is clearly evident across the range in sub-Saharan Africa and abrupt transition zones between different pelage types are typically not associated with extrinsic barriers to gene flow, suggesting reproductive isolation. By analyzing mitochondrial DNA sequences and nuclear microsatellite loci, we show that there are at least six genealogically distinct lineages of giraffe in Africa, with little evidence of interbreeding between them. Some of these lineages appear to be maintained in the absence of contemporary barriers to gene flow, possibly by differences in reproductive timing or pelage-based assortative mating, suggesting that populations usually recognized as subspecies have a long history of reproductive isolation. Further, five of the six putative lineages also contain genetically discrete populations, yielding at least 11 genetically distinct populations. Such extreme genetic subdivision within a large vertebrate with high dispersal capabilities is unprecedented and exceeds that of any other large African mammal. Our results have significant implications for giraffe conservation, and imply separate in situ and ex situ management, not only of pelage morphs, but also of local populations.

Genetic Ancestry for Sleep Research: Leveraging Health Inequalities to Identify Causal Genetic Variants.

PubMed

Prasad, Bharati; Saxena, Richa; Goel, Namni; Patel, Sanjay R

2018-06-01

Recent evidence has highlighted the health inequalities in sleep behaviors and sleep disorders that adversely affect outcomes in select populations, including African-American and Hispanic-American subjects. Race-related sleep health inequalities are ascribed to differences in multilevel and interlinked health determinants, such as sociodemographic factors, health behaviors, and biology. African-American and Hispanic-American subjects are admixed populations whose genetic inheritance combines two or more ancestral populations originating from different continents. Racial inequalities in admixed populations can be parsed into relevant groups of mediating factors (environmental vs genetic) with the use of measures of genetic ancestry, including the proportion of an individual's genetic makeup that comes from each of the major ancestral continental populations. This review describes sleep health inequalities in African-American and Hispanic-American subjects and considers the potential utility of ancestry studies to exploit these differences to gain insight into the genetic underpinnings of these phenotypes. The inclusion of genetic approaches in future studies of admixed populations will allow greater understanding of the potential biological basis of race-related sleep health inequalities. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Full-length genome analysis of two genetically distinct variants of porcine epidemic diarrhea virus in Thailand.

PubMed

Cheun-Arom, Thaniwan; Temeeyasen, Gun; Tripipat, Thitima; Kaewprommal, Pavita; Piriyapongsa, Jittima; Sukrong, Suchada; Chongcharoen, Wanchai; Tantituvanont, Angkana; Nilubol, Dachrit

2016-10-01

Porcine epidemic diarrhea virus (PEDV) has continued to cause sporadic outbreaks in Thailand since 2007 and a pandemic variant containing an insertion and deletion in the spike gene was responsible for outbreaks. In 2014, there were further outbreaks of the disease occurring within four months of each other. In this study, the full-length genome sequences of two genetically distinct PEDV isolates from the outbreaks were characterized. The two PEDV isolates, CBR1/2014 and EAS1/2014, were 28,039 and 28,033 nucleotides in length and showed 96.2% and 93.6% similarities at nucleotide and amino acid levels respectively. In total, we have observed 1048 nucleotide substitutions throughout the genome. Compared to EAS1/2014, CBR1/2014 has 2 insertions of 4 ((56)GENQ(59)) and 1 ((140)N) amino acid positions 56-59 and 140, and 2 deletions of 2 ((160)DG(161)) and 1 ((1199)Y) amino acid positions 160-161 and 1199. The phylogenetic analysis based on full-length genome of CBR1/2014 isolate has grouped the virus with the pandemic variants. In contrast, EAS1/2014 isolate was grouped with CV777, LZC and SM98, a classical variant. Our findings demonstrated the emergence of EAS1/2014, a classical variant which is novel to Thailand and genetically distinct from the currently circulating endemic variants. This study warrants further investigations into molecular epidemiology and genetic evolution of the PEDV in Thailand. Copyright © 2016 Elsevier B.V. All rights reserved.

Population Genomics of Sub-Saharan Drosophila melanogaster: African Diversity and Non-African Admixture

PubMed Central

Pool, John E.; Corbett-Detig, Russell B.; Sugino, Ryuichi P.; Stevens, Kristian A.; Cardeno, Charis M.; Crepeau, Marc W.; Duchen, Pablo; Emerson, J. J.; Saelao, Perot; Begun, David J.; Langley, Charles H.

2012-01-01

Drosophila melanogaster has played a pivotal role in the development of modern population genetics. However, many basic questions regarding the demographic and adaptive history of this species remain unresolved. We report the genome sequencing of 139 wild-derived strains of D. melanogaster, representing 22 population samples from the sub-Saharan ancestral range of this species, along with one European population. Most genomes were sequenced above 25X depth from haploid embryos. Results indicated a pervasive influence of non-African admixture in many African populations, motivating the development and application of a novel admixture detection method. Admixture proportions varied among populations, with greater admixture in urban locations. Admixture levels also varied across the genome, with localized peaks and valleys suggestive of a non-neutral introgression process. Genomes from the same location differed starkly in ancestry, suggesting that isolation mechanisms may exist within African populations. After removing putatively admixed genomic segments, the greatest genetic diversity was observed in southern Africa (e.g. Zambia), while diversity in other populations was largely consistent with a geographic expansion from this potentially ancestral region. The European population showed different levels of diversity reduction on each chromosome arm, and some African populations displayed chromosome arm-specific diversity reductions. Inversions in the European sample were associated with strong elevations in diversity across chromosome arms. Genomic scans were conducted to identify loci that may represent targets of positive selection within an African population, between African populations, and between European and African populations. A disproportionate number of candidate selective sweep regions were located near genes with varied roles in gene regulation. Outliers for Europe-Africa FST were found to be enriched in genomic regions of locally elevated cosmopolitan

Socioeconomic Status and Lung Cancer: Unraveling the Contribution of Genetic Admixture

PubMed Central

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

2013-01-01

Objectives. We examined the relationship between genetic ancestry, socioeconomic status (SES), and lung cancer among African Americans and Latinos. Methods. We evaluated SES and genetic ancestry in a Northern California lung cancer case–control study (1998–2003) of African Americans and Latinos. Lung cancer case and control participants were frequency matched on age, gender, and race/ethnicity. We assessed case–control differences in individual admixture proportions using the 2-sample t test and analysis of covariance. Logistic regression models examined associations among genetic ancestry, socioeconomic characteristics, and lung cancer. Results. Decreased Amerindian ancestry was associated with higher education among Latino control participants and greater African ancestry was associated with decreased education among African lung cancer case participants. Education was associated with lung cancer among both Latinos and African Americans, independent of smoking, ancestry, age, and gender. Genetic ancestry was not associated with lung cancer among African Americans. Conclusions. Findings suggest that socioeconomic factors may have a greater impact than genetic ancestry on lung cancer among African Americans. The genetic heterogeneity and recent dynamic migration and acculturation of Latinos complicate recruitment; thus, epidemiological analyses and findings should be interpreted cautiously. PMID:23948011

Distinct Mechanisms of Nuclease-Directed DNA-Structure-Induced Genetic Instability in Cancer Genomes.

PubMed

Zhao, Junhua; Wang, Guliang; Del Mundo, Imee M; McKinney, Jennifer A; Lu, Xiuli; Bacolla, Albino; Boulware, Stephen B; Zhang, Changsheng; Zhang, Haihua; Ren, Pengyu; Freudenreich, Catherine H; Vasquez, Karen M

2018-01-30

Sequences with the capacity to adopt alternative DNA structures have been implicated in cancer etiology; however, the mechanisms are unclear. For example, H-DNA-forming sequences within oncogenes have been shown to stimulate genetic instability in mammals. Here, we report that H-DNA-forming sequences are enriched at translocation breakpoints in human cancer genomes, further implicating them in cancer etiology. H-DNA-induced mutations were suppressed in human cells deficient in the nucleotide excision repair nucleases, ERCC1-XPF and XPG, but were stimulated in cells deficient in FEN1, a replication-related endonuclease. Further, we found that these nucleases cleaved H-DNA conformations, and the interactions of modeled H-DNA with ERCC1-XPF, XPG, and FEN1 proteins were explored at the sub-molecular level. The results suggest mechanisms of genetic instability triggered by H-DNA through distinct structure-specific, cleavage-based replication-independent and replication-dependent pathways, providing critical evidence for a role of the DNA structure itself in the etiology of cancer and other human diseases. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus.

PubMed

Horton, Daniel L; Banyard, Ashley C; Marston, Denise A; Wise, Emma; Selden, David; Nunez, Alejandro; Hicks, Daniel; Lembo, Tiziana; Cleaveland, Sarah; Peel, Alison J; Kuzmin, Ivan V; Rupprecht, Charles E; Fooks, Anthony R

2014-05-01

In 2009, a novel lyssavirus (subsequently named Ikoma lyssavirus, IKOV) was detected in the brain of an African civet (Civettictis civetta) with clinical rabies in the Serengeti National Park of Tanzania. The degree of nucleotide divergence between the genome of IKOV and those of other lyssaviruses predicted antigenic distinction from, and lack of protection provided by, available rabies vaccines. In addition, the index case was considered likely to be an incidental spillover event, and therefore the true reservoir of IKOV remained to be identified. The advent of sensitive molecular techniques has led to a rapid increase in the discovery of novel viruses. Detecting viral sequence alone, however, only allows for prediction of phenotypic characteristics and not their measurement. In the present study we describe the in vitro and in vivo characterization of IKOV, demonstrating that it is (1) pathogenic by peripheral inoculation in an animal model, (2) antigenically distinct from current rabies vaccine strains and (3) poorly neutralized by sera from humans and animals immunized against rabies. In a laboratory mouse model, no protection was elicited by a licensed rabies vaccine. We also investigated the role of bats as reservoirs of IKOV. We found no evidence for infection among 483 individuals of at least 13 bat species sampled across sites in the Serengeti and Southern Kenya.

Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus

PubMed Central

Horton, Daniel L.; Banyard, Ashley C.; Marston, Denise A.; Wise, Emma; Selden, David; Nunez, Alejandro; Hicks, Daniel; Lembo, Tiziana; Cleaveland, Sarah; Peel, Alison J.; Kuzmin, Ivan V.; Rupprecht, Charles E.

2014-01-01

In 2009, a novel lyssavirus (subsequently named Ikoma lyssavirus, IKOV) was detected in the brain of an African civet (Civettictis civetta) with clinical rabies in the Serengeti National Park of Tanzania. The degree of nucleotide divergence between the genome of IKOV and those of other lyssaviruses predicted antigenic distinction from, and lack of protection provided by, available rabies vaccines. In addition, the index case was considered likely to be an incidental spillover event, and therefore the true reservoir of IKOV remained to be identified. The advent of sensitive molecular techniques has led to a rapid increase in the discovery of novel viruses. Detecting viral sequence alone, however, only allows for prediction of phenotypic characteristics and not their measurement. In the present study we describe the in vitro and in vivo characterization of IKOV, demonstrating that it is (1) pathogenic by peripheral inoculation in an animal model, (2) antigenically distinct from current rabies vaccine strains and (3) poorly neutralized by sera from humans and animals immunized against rabies. In a laboratory mouse model, no protection was elicited by a licensed rabies vaccine. We also investigated the role of bats as reservoirs of IKOV. We found no evidence for infection among 483 individuals of at least 13 bat species sampled across sites in the Serengeti and Southern Kenya. PMID:24496827

The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans

PubMed Central

2011-01-01

Background Arachidonic acid (AA) is a long-chain omega-6 polyunsaturated fatty acid (PUFA) synthesized from the precursor dihomo-gamma-linolenic acid (DGLA) that plays a vital role in immunity and inflammation. Variants in the Fatty Acid Desaturase (FADS) family of genes on chromosome 11q have been shown to play a role in PUFA metabolism in populations of European and Asian ancestry; no work has been done in populations of African ancestry to date. Results In this study, we report that African Americans have significantly higher circulating levels of plasma AA (p = 1.35 × 10-48) and lower DGLA levels (p = 9.80 × 10-11) than European Americans. Tests for association in N = 329 individuals across 80 nucleotide polymorphisms (SNPs) in the Fatty Acid Desaturase (FADS) locus revealed significant association with AA, DGLA and the AA/DGLA ratio, a measure of enzymatic efficiency, in both racial groups (peak signal p = 2.85 × 10-16 in African Americans, 2.68 × 10-23 in European Americans). Ancestry-related differences were observed at an upstream marker previously associated with AA levels (rs174537), wherein, 79-82% of African Americans carry two copies of the G allele compared to only 42-45% of European Americans. Importantly, the allelic effect of the G allele, which is associated with enhanced conversion of DGLA to AA, on enzymatic efficiency was similar in both groups. Conclusions We conclude that the impact of FADS genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to the larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA. PMID:21599946

Genetic Tracing of Jatropha curcas L. from Its Mesoamerican Origin to the World

PubMed Central

Li, Haiyan; Tsuchimoto, Suguru; Harada, Kyuya; Yamasaki, Masanori; Sakai, Hiroe; Wada, Naoki; Alipour, Atefeh; Sasai, Tomohiro; Tsunekawa, Atsushi; Tsujimoto, Hisashi; Ando, Takayuki; Tomemori, Hisashi; Sato, Shusei; Hirakawa, Hideki; Quintero, Victor P.; Zamarripa, Alfredo; Santos, Primitivo; Hegazy, Adel; Ali, Abdalla M.; Fukui, Kiichi

2017-01-01

Jatropha curcas L. (Jatropha), a shrub species of the family Euphorbiaceae, has been recognized as a promising biofuel plant for reducing greenhouse gas emissions. However, recent attempts at commercial cultivation in Africa and Asia have failed because of low productivity. It is important to elucidate genetic diversity and relationship in worldwide Jatropha genetic resources for breeding of better commercial cultivars. Here, genetic diversity was analyzed by using 246 accessions from Mesoamerica, Africa and Asia, based on 59 simple sequence repeat markers and eight retrotransposon-based insertion polymorphism markers. We found that central Chiapas of Mexico possesses the most diverse genetic resources, and the Chiapas Central Depression could be the center of origin. We identified three genetic groups in Mesoamerica, whose distribution revealed a distinct geographic cline. One of them consists mainly of accessions from central Chiapas. This suggests that it represents the original genetic group. We found two Veracruz accessions in another group, whose ancestors might be shipped from Port of Veracruz to the Old World, to be the source of all African and Asian Jatropha. Our results suggest the human selection that caused low productivity in Africa and Asia, and also breeding strategies to improve African and Asian Jatropha. Cultivars improved in the productivity will contribute to expand mass commercial cultivation of Jatropha in Africa and Asia to increase biofuel production, and finally will support in the battle against the climate change. PMID:28936216

Are Africans, Europeans, and Asians Different “Races”? A Guided-Inquiry Lab for Introducing Undergraduate Students to Genetic Diversity and Preparing Them to Study Natural Selection

PubMed Central

Kalinowski, Steven T.; Andrews, Tessa M.; Leonard, Mary J.; Snodgrass, Meagan

2012-01-01

Many students do not recognize that individual organisms within populations vary, and this may make it difficult for them to recognize the essential role variation plays in natural selection. Also, many students have weak scientific reasoning skills, and this makes it difficult for them to recognize misconceptions they might have. This paper describes a 2-h laboratory for college students that introduces them to genetic diversity and gives them practice using hypothetico-deductive reasoning. In brief, the lab presents students with DNA sequences from Africans, Europeans, and Asians, and asks students to determine whether people from each continent qualify as distinct “races.” Comparison of the DNA sequences shows that people on each continent are not more similar to one another than to people on other continents, and therefore do not qualify as distinct races. Ninety-four percent of our students reported that the laboratory was interesting, and 79% reported that it was a valuable learning experience. We developed and used a survey to measure the extent to which students recognized variation and its significance within populations and showed that the lab increased student awareness of variation. We also showed that the lab improved the ability of students to construct hypothetico-deductive arguments. PMID:22665587

The genome landscape of indigenous African cattle.

PubMed

Kim, Jaemin; Hanotte, Olivier; Mwai, Okeyo Ally; Dessie, Tadelle; Bashir, Salim; Diallo, Boubacar; Agaba, Morris; Kim, Kwondo; Kwak, Woori; Sung, Samsun; Seo, Minseok; Jeong, Hyeonsoo; Kwon, Taehyung; Taye, Mengistie; Song, Ki-Duk; Lim, Dajeong; Cho, Seoae; Lee, Hyun-Jeong; Yoon, Duhak; Oh, Sung Jong; Kemp, Stephen; Lee, Hak-Kyo; Kim, Heebal

2017-02-20

The history of African indigenous cattle and their adaptation to environmental and human selection pressure is at the root of their remarkable diversity. Characterization of this diversity is an essential step towards understanding the genomic basis of productivity and adaptation to survival under African farming systems. We analyze patterns of African cattle genetic variation by sequencing 48 genomes from five indigenous populations and comparing them to the genomes of 53 commercial taurine breeds. We find the highest genetic diversity among African zebu and sanga cattle. Our search for genomic regions under selection reveals signatures of selection for environmental adaptive traits. In particular, we identify signatures of selection including genes and/or pathways controlling anemia and feeding behavior in the trypanotolerant N'Dama, coat color and horn development in Ankole, and heat tolerance and tick resistance across African cattle especially in zebu breeds. Our findings unravel at the genome-wide level, the unique adaptive diversity of African cattle while emphasizing the opportunities for sustainable improvement of livestock productivity on the continent.

If We Would Only Ask: How Henrietta Lacks Continues to Teach Us About Perceptions of Research and Genetic Research Among African Americans Today.

PubMed

Jones, Bridgette L; Vyhlidal, Carrie A; Bradley-Ewing, Andrea; Sherman, Ashley; Goggin, Kathy

2017-08-01

African Americans are under-represented in research, and there are perceptions of unwillingness among African Americans to participate in research. We explored barriers to African American research participation. We conducted a cross-sectional survey to explore knowledge and beliefs regarding medical and genetic research among adults (n = 169) at urban community events. Descriptive data were summarized by frequencies for survey responses. Only 13 % of respondents had ever been approached for research; 93 % of those who had been approached for research had participated. Eighty-six percent of those who had previous research experience indicated willingness to participate again vs. only 30 % among those with no research experience. Seventy-four percent had altruistic views of research; 28 % were concerned about truthfulness of researchers; 52 % feared incidental discoveries. African Americans have favorable views of research; however, few are being engaged in studies. Effective interventions to address identified barriers may improve participation and lead to better health outcomes among African Americans.

Genetically distinct isolates of Spirocerca sp. from a naturally infected red fox (Vulpes vulpes) from Denmark.

PubMed

Al-Sabi, Mohammad Nafi Solaiman; Hansen, Mette Sif; Chriél, Mariann; Holm, Elisabeth; Larsen, Gitte; Enemark, Heidi Larsen

2014-09-15

Spirocerca lupi causes formation of nodules that may transform into sarcoma in the walls of aorta, esophagus and stomach of infected canids. In February 2013, post mortem examination of a red fox (Vulpes vulpes) hunted in Denmark revealed the presence of several nodules containing adult worms of Spirocerca sp. in the stomach and the omentum. The nodules largely consisted of fibrous tissue with infiltration of mononuclear cells, neutrophilic granulocytes and macrophages with hemosiderin deposition. Parasitological examination by three copromicroscopic methods, sedimentation, flotation with saturated sugar-salt solution, and sieving failed to detect eggs of Spirocerca sp. in feces collected from the colon. This is the first report of spirocercosis in Denmark, and may have been caused by a recent introduction by migrating paratenic or definitive host. Analysis of two overlapping partial sequences of the cox1 gene, from individual worms, revealed distinct genetic variation (7-9%) between the Danish worms and isolates of S. lupi from Europe, Asia and Africa. This was confirmed by phylogenetic analysis that clearly separated the Danish worms from other isolates of S. lupi. The distinct genetic differences of the current worms compared to other isolates of S. lupi may suggest the presence of a cryptic species within Spirocerca. Copyright © 2014 Elsevier B.V. All rights reserved.

African diversity from the HLA point of view: influence of genetic drift, geography, linguistics, and natural selection.

PubMed

Sanchez-Mazas, A

2001-09-01

This study investigates the influence of different evolutionary factors on the patterns of human leukocyte antigen (HLA) genetic diversity within sub-Saharan Africa, and between Africa, Europe, and East Asia. This is done by comparing the significance of several statistics computed on equivalent population data sets tested for two HLA class II loci, DRB1 and DPB1, which strongly differ from each other by the shape of their allelic distributions. Similar results are found for the two loci concerning highly significant correlations between geographic and genetic distances at the world scale, high levels of genetic diversity within sub-Saharan Africa and East Asia, and low within Europe, and low genetic differentiations among the three broad continental areas, with no special divergence of Africa. On the other hand, DPB1 behaves as a neutral polymorphism, although a significant excess of heterozygotes is often observed for DRB1. Whereas the pattern observed for DPB1 is explained by geographic differentiations and genetic drift in isolated populations, balancing selection is likely to have prevented genetic differentiations among populations at the DRB1 locus. However, this selective effect did not disrupt the high correlation found between DRB1 and geography at the world scale, nor between DRB1 and linguistic differentiations at the African level.

A genetically distinct hybrid zone occurs for two globally invasive mosquito fish species with striking phenotypic resemblance.

PubMed

Wilk, Rebecca J; Horth, Lisa

2016-12-01

Hybrid zones allow for the investigation of incipient speciation and related evolutionary processes of selection, gene flow, and migration. Interspecific dynamics, like competition, can impact the size, shape, and directional movement of species in hybrid zones. Hybrid zones contribute to a paradox for the biological species concept because interbreeding between species occurs while parental forms remain distinct. A long-standing zone of intergradation or introgression exists for eastern and western mosquito fish ( Gambusia holbrooki and G. affinis ) around Mobile Bay, AL. The region has been studied episodically, over decades, making it perfect for addressing temporal dynamics and for providing a deeper understanding of the genetics of these periodically reclassified fishes (as species or subspecies). We used six microsatellite markers to assess the current population structure and gene flow patterns across 19 populations of mosquito fish and then compared our results with historical data. Genetic evidence demonstrates that the current hybrid zone is located in a similar geographic region as the historical one, even after three decades. Hybrid fish, however, demonstrate relatively low heterozygosity and are genetically distinct from western and eastern mosquito fish populations. Fin ray counts, sometimes used to distinguish the two species from one another, demonstrate more eastern ( G. holbrooki) phenotype fish within the molecular genetic hybrid zone today. Mosquito fish are globally invasive, often found on the leading edge of flooded waters that they colonize, so the impact of hurricanes in the wake of climate change was also evaluated. An increase in the frequency and intensity of hurricanes in the hybrid region has occurred, and this point warrants further attention since hurricanes are known to move these aggressive, invasive species into novel territory. This work contributes to our classical understanding of hybrid zone temporal dynamics, refines our

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

PubMed

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

2017-04-01

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

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

PubMed Central

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

2017-01-01

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

Genetic Diversity of HIV-1 in Tunisia.

PubMed

El Moussi, Awatef; Thomson, Michael M; Delgado, Elena; Cuevas, María Teresa; Nasr, Majda; Abid, Salma; Ben Hadj Kacem, Mohamed Ali; Benaissa Tiouiri, Hanene; Letaief, Amel; Chakroun, Mohamed; Ben Jemaa, Mounir; Hamdouni, Hayet; Tej Dellagi, Rafla; Kheireddine, Khaled; Boutiba, Ilhem; Pérez-Álvarez, Lucía; Slim, Amine

2017-01-01

In this study, the genetic diversity of HIV-1 in Tunisia was analyzed. For this, 193 samples were collected in different regions of Tunisia between 2012 and 2015. A protease and reverse transcriptase fragment were amplified and sequenced. Phylogenetic analyses were performed through maximum likelihood and recombination was analyzed by bootscanning. Six HIV-1 subtypes (B, A1, G, D, C, and F2), 5 circulating recombinant forms (CRF02_AG, CRF25_cpx, CRF43_02G, CRF06_cpx, and CRF19_cpx), and 11 unique recombinant forms were identified. Subtype B (46.4%) and CRF02_AG (39.4%) were the predominant genetic forms. A group of 44 CRF02_AG sequences formed a distinct Tunisian cluster, which also included four viruses from western Europe. Nine viruses were closely related to isolates collected in other African or in European countries. In conclusion, a high HIV-1 genetic diversity is observed in Tunisia and the local spread of CRF02_AG is first documented in this country.

Race, genetics, and human reproductive strategies.

PubMed

Rushton, J P

1996-02-01

The international literature on racial differences is reviewed, novel data are reported, and a distinct pattern is found. People of east Asian ancestry and people of African ancestry average at opposite ends of a continuum, with people of European ancestry averaging intermediately, albeit with much variability within each major race. The racial matrix emerges from measures taken of reproductive behavior, sex hormones, twinning rate, speed of physical maturation, personality, family stability, brain size, intelligence, law abidingness, and social organization. An evolutionary theory of human reproduction is proposed, familiar to biologists as the r-K scale of reproductive strategies. At one end of this scale are r-strategies, which emphasize high reproductive rates; at the other end are K-strategies, which emphasize high levels of parental investment. This scale is generally used to compare the life histories of widely disparate species, but here it is used to describe the immensely smaller variations among human races. It is hypothesized that, again on average, Mongoloid people are more K-selected than Caucasoids, who are more K-selected than Negroids. The r-K scale of reproductive strategies is also mapped on to human evolution. Genetic distances indicate that Africans emerged from the ancestral hominid line about 200,000 years ago, with an African/non-African split about 110,000 years ago, and a Caucasoid/Mongoloid split about 41,000 years ago. Such an ordering fits with and explains how and why the variables cluster.

Unequal contribution of native South African phylogeographic lineages to the invasion of the African clawed frog, Xenopus laevis, in Europe

PubMed Central

Courant, Julien; Herrel, Anthony; Rebelo, Rui; Rödder, Dennis; Measey, G. John; Backeljau, Thierry

2016-01-01

Due to both deliberate and accidental introductions, invasive African Clawed Frog (Xenopus laevis) populations have become established worldwide. In this study, we investigate the geographic origins of invasive X. laevis populations in France and Portugal using the phylogeographic structure of X. laevis in its native South African range. In total, 80 individuals from the whole area known to be invaded in France and Portugal were analysed for two mitochondrial and three nuclear genes, allowing a comparison with 185 specimens from the native range. Our results show that native phylogeographic lineages have contributed differently to invasive European X. laevis populations. In Portugal, genetic and historical data suggest a single colonization event involving a small number of individuals from the south-western Cape region in South Africa. In contrast, French invasive X. laevis encompass two distinct native phylogeographic lineages, i.e., one from the south-western Cape region and one from the northern regions of South Africa. The French X. laevis population is the first example of a X. laevis invasion involving multiple lineages. Moreover, the lack of population structure based on nuclear DNA suggests a potential role for admixture within the invasive French population. PMID:26855879

Biological and phylogenetic characteristics of West African lineages of West Nile virus.

PubMed

Fall, Gamou; Di Paola, Nicholas; Faye, Martin; Dia, Moussa; Freire, Caio César de Melo; Loucoubar, Cheikh; Zanotto, Paolo Marinho de Andrade; Faye, Ousmane; Sall, Amadou Alpha

2017-11-01

The West Nile virus (WNV), isolated in 1937, is an arbovirus (arthropod-borne virus) that infects thousands of people each year. Despite its burden on global health, little is known about the virus' biological and evolutionary dynamics. As several lineages are endemic in West Africa, we obtained the complete polyprotein sequence from three isolates from the early 1990s, each representing a different lineage. We then investigated differences in growth behavior and pathogenicity for four distinct West African lineages in arthropod (Ap61) and primate (Vero) cell lines, and in mice. We found that genetic differences, as well as viral-host interactions, could play a role in the biological properties in different WNV isolates in vitro, such as: (i) genome replication, (ii) protein translation, (iii) particle release, and (iv) virulence. Our findings demonstrate the endemic diversity of West African WNV strains and support future investigations into (i) the nature of WNV emergence, (ii) neurological tropism, and (iii) host adaptation.

Biological and phylogenetic characteristics of West African lineages of West Nile virus

PubMed Central

Faye, Martin; Dia, Moussa; Freire, Caio César de Melo; Loucoubar, Cheikh; Zanotto, Paolo Marinho de Andrade; Faye, Ousmane; Sall, Amadou Alpha

2017-01-01

The West Nile virus (WNV), isolated in 1937, is an arbovirus (arthropod-borne virus) that infects thousands of people each year. Despite its burden on global health, little is known about the virus’ biological and evolutionary dynamics. As several lineages are endemic in West Africa, we obtained the complete polyprotein sequence from three isolates from the early 1990s, each representing a different lineage. We then investigated differences in growth behavior and pathogenicity for four distinct West African lineages in arthropod (Ap61) and primate (Vero) cell lines, and in mice. We found that genetic differences, as well as viral-host interactions, could play a role in the biological properties in different WNV isolates in vitro, such as: (i) genome replication, (ii) protein translation, (iii) particle release, and (iv) virulence. Our findings demonstrate the endemic diversity of West African WNV strains and support future investigations into (i) the nature of WNV emergence, (ii) neurological tropism, and (iii) host adaptation. PMID:29117195

Division of Giardia isolates from humans into two genetically distinct assemblages by electrophoretic analysis of enzymes encoded at 27 loci and comparison with Giardia muris.

PubMed

Mayrhofer, G; Andrews, R H; Ey, P L; Chilton, N B

1995-07-01

Giardia that infect humans are known to be heterogeneous but they are assigned currently to a single species, Giardia intestinalis (syn. G. lamblia). The genetic differences that exist within G. intestinalis have not yet been assessed quantitatively and neither have they been compared in magnitude with those that exist between G. intestinalis and species that are morphologically similar (G. duodenalis) or morphologically distinct (e.g. G. muris). In this study, 60 Australian isolates of G. intestinalis were analysed electrophoretically at 27 enzyme loci and compared with G. muris and a feline isolate of G. duodenalis. Isolates of G. intestinalis were distinct genetically from both G. muris (approximately 80% fixed allelic differences) and the feline G. duodenalis isolate (approximately 75% fixed allelic differences). The G. intestinalis isolates were extremely heterogeneous but they fell into 2 major genetic assemblages, separated by fixed allelic differences at approximately 60% of loci examined. The magnitude of the genetic differences between the G. intestinalis assemblages approached the level that distinguished the G. duodenalis isolate from the morphologically distinct G. muris. This raises important questions about the evolutionary relationships of the assemblages with Homo sapiens, the possibility of ancient or contemporary transmission from animal hosts to humans and the biogeographical origins of the two clusters.

Genome-Wide Association Study of White Blood Cell Count in 16,388 African Americans: the Continental Origins and Genetic Epidemiology Network (COGENT)

PubMed Central

Arepalli, Sampath; Britton, Angela; Chen, Zhao; Couper, David; Curb, J. David; Eaton, Charles B.; Fornage, Myriam; Grant, Struan F. A.; Harris, Tamara B.; Hernandez, Dena; Kamatini, Naoyuki; Keating, Brendan J.; Kubo, Michiaki; LaCroix, Andrea; Lange, Leslie A.; Liu, Simin; Lohman, Kurt; Meng, Yan; Mohler, Emile R.; Musani, Solomon; Nakamura, Yusuke; O'Donnell, Christopher J.; Okada, Yukinori; Palmer, Cameron D.; Papanicolaou, George J.; Patel, Kushang V.; Singleton, Andrew B.; Takahashi, Atsushi; Tang, Hua; Taylor, Herman A.; Taylor, Kent; Thomson, Cynthia; Yanek, Lisa R.; Yang, Lingyao; Ziv, Elad; Zonderman, Alan B.; Folsom, Aaron R.; Evans, Michele K.; Liu, Yongmei; Becker, Diane M.; Snively, Beverly M.; Wilson, James G.

2011-01-01

Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived “null” variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wide association study (GWAS) of total WBC and cell subtype counts in 16,388 African-American participants from 7 population-based cohorts available in the Continental Origins and Genetic Epidemiology Network. In addition to the DARC locus on chromosome 1q23, we identified two other regions (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P<2.5×10−8). The lead SNP (rs9131) on chromosome 4q13 is located in the CXCL2 gene, which encodes a chemotactic cytokine for polymorphonuclear leukocytes. Independent evidence of the novel CXCL2 association with WBC was present in 3,551 Hispanic Americans, 14,767 Japanese, and 19,509 European Americans. The index SNP (rs12149261) on chromosome 16q22 associated with WBC count is located in a large inter-chromosomal segmental duplication encompassing part of the hydrocephalus inducing homolog (HYDIN) gene. We demonstrate that the chromosome 16q22 association finding is most likely due to a genotyping artifact as a consequence of sequence similarity between duplicated regions on chromosomes 16q22 and 1q21. Among the WBC loci recently identified in European or Japanese populations, replication was observed in our African-American meta-analysis for rs445 of CDK6 on chromosome 7q21 and rs4065321 of PSMD3-CSF3 region on chromosome 17q21. In summary, the CXCL2, CDK6, and PSMD3-CSF3 regions are associated with WBC count in African American and other populations. We also demonstrate that large inter-chromosomal duplications

Genetic divergence between two phenotypically distinct bottlenose dolphin ecotypes suggests separate evolutionary trajectories.

PubMed

Fruet, Pedro F; Secchi, Eduardo R; Di Tullio, Juliana C; Simões-Lopes, Paulo César; Daura-Jorge, Fábio; Costa, Ana P B; Vermeulen, Els; Flores, Paulo A C; Genoves, Rodrigo Cezar; Laporta, Paula; Beheregaray, Luciano B; Möller, Luciana M

2017-11-01

Due to their worldwide distribution and occupancy of different types of environments, bottlenose dolphins display considerable morphological variation. Despite limited understanding about the taxonomic identity of such forms and connectivity among them at global scale, coastal (or inshore) and offshore (or oceanic) ecotypes have been widely recognized in several ocean regions. In the Southwest Atlantic Ocean (SWA), however, there are scarce records of bottlenose dolphins differing in external morphology according to habitat preferences that resemble the coastal-offshore pattern observed elsewhere. The main aim of this study was to analyze the genetic variability, and test for population structure between coastal ( n  = 127) and offshore ( n  = 45) bottlenose dolphins sampled in the SWA to assess whether their external morphological distinction is consistent with genetic differentiation. We used a combination of mtDNA control region sequences and microsatellite genotypes to infer population structure and levels of genetic diversity. Our results from both molecular marker types were congruent and revealed strong levels of structuring (microsatellites F ST  = 0.385, p  < .001; mtDNA F ST  =  0.183, p  < .001; Φ ST  = 0.385, p  < .001) and much lower genetic diversity in the coastal than the offshore ecotype, supporting patterns found in previous studies elsewhere. Despite the opportunity for gene flow in potential "contact zones", we found minimal current and historical connectivity between ecotypes, suggesting they are following discrete evolutionary trajectories. Based on our molecular findings, which seem to be consistent with morphological differentiations recently described for bottlenose dolphins in our study area, we recommend recognizing the offshore bottlenose dolphin ecotype as an additional Evolutionarily Significant Unit (ESU) in the SWA. Implications of these results for the conservation of bottlenose dolphins in SWA are also discussed.

High genetic connectivity among estuarine populations of the riverbream Acanthopagrus vagus along the southern African coast

NASA Astrophysics Data System (ADS)

Oosthuizen, Carel J.; Cowley, Paul D.; Kyle, Scotty R.; Bloomer, Paulette

2016-12-01

Physical and/or physiological constraints are assumed to isolate fish populations confined to or dependent on estuarine habitats. Strong isolation by distance is thus expected to affect connectivity. Such structuring has important implications for sustainable utilisation and replenishment of estuarine stocks that are heavily exploited. Here we present a preliminary investigation of the phylogenetic relationships of the riverbream (Acanthopagrus species) along the southern African coast and the geographic genetic structure of what appears to be a locally endemic species or lineage. Mitochondrial DNA (mtDNA) cytochrome b sequences support the notion that the species occurring along the southern African coast is A. vagus and not A. berda as previously thought. Yet, the taxonomy of this widespread Indo-West Pacific species or species-complex requires more in-depth investigation. No genetic differentiation was detected among estuarine populations of A. vagus based on the analyses of mtDNA ND2 gene sequences and 10 polymorphic nuclear microsatellite markers. The star-like genealogy and statistical analyses are consistent with a recent population expansion event. Spatial analyses of microsatellite genotypes fail to reject the null hypothesis of panmixia, indicative of a recent population expansion or ongoing gene flow between different estuaries. The northern localities were identified as containing most of the observed variation. This study not only provides insight into the phylogenetic relationship of A. vagus relative to other Acanthopagrus species but also sheds light on the demographic history and contemporary gene flow of the species.

Extensive population genetic structure in the giraffe

PubMed Central

Brown, David M; Brenneman, Rick A; Koepfli, Klaus-Peter; Pollinger, John P; Milá, Borja; Georgiadis, Nicholas J; Louis, Edward E; Grether, Gregory F; Jacobs, David K; Wayne, Robert K

2007-01-01

Background A central question in the evolutionary diversification of large, widespread, mobile mammals is how substantial differentiation can arise, particularly in the absence of topographic or habitat barriers to dispersal. All extant giraffes (Giraffa camelopardalis) are currently considered to represent a single species classified into multiple subspecies. However, geographic variation in traits such as pelage pattern is clearly evident across the range in sub-Saharan Africa and abrupt transition zones between different pelage types are typically not associated with extrinsic barriers to gene flow, suggesting reproductive isolation. Results By analyzing mitochondrial DNA sequences and nuclear microsatellite loci, we show that there are at least six genealogically distinct lineages of giraffe in Africa, with little evidence of interbreeding between them. Some of these lineages appear to be maintained in the absence of contemporary barriers to gene flow, possibly by differences in reproductive timing or pelage-based assortative mating, suggesting that populations usually recognized as subspecies have a long history of reproductive isolation. Further, five of the six putative lineages also contain genetically discrete populations, yielding at least 11 genetically distinct populations. Conclusion Such extreme genetic subdivision within a large vertebrate with high dispersal capabilities is unprecedented and exceeds that of any other large African mammal. Our results have significant implications for giraffe conservation, and imply separate in situ and ex situ management, not only of pelage morphs, but also of local populations. PMID:18154651

Reconstructing the Population Genetic History of the Caribbean

PubMed Central

Moreno-Estrada, Andrés; Gravel, Simon; Zakharia, Fouad; McCauley, Jacob L.; Byrnes, Jake K.; Gignoux, Christopher R.; Ortiz-Tello, Patricia A.; Martínez, Ricardo J.; Hedges, Dale J.; Morris, Richard W.; Eng, Celeste; Sandoval, Karla; Acevedo-Acevedo, Suehelay; Norman, Paul J.; Layrisse, Zulay; Parham, Peter; Martínez-Cruzado, Juan Carlos; Burchard, Esteban González; Cuccaro, Michael L.; Martin, Eden R.; Bustamante, Carlos D.

2013-01-01

The Caribbean basin is home to some of the most complex interactions in recent history among previously diverged human populations. Here, we investigate the population genetic history of this region by characterizing patterns of genome-wide variation among 330 individuals from three of the Greater Antilles (Cuba, Puerto Rico, Hispaniola), two mainland (Honduras, Colombia), and three Native South American (Yukpa, Bari, and Warao) populations. We combine these data with a unique database of genomic variation in over 3,000 individuals from diverse European, African, and Native American populations. We use local ancestry inference and tract length distributions to test different demographic scenarios for the pre- and post-colonial history of the region. We develop a novel ancestry-specific PCA (ASPCA) method to reconstruct the sub-continental origin of Native American, European, and African haplotypes from admixed genomes. We find that the most likely source of the indigenous ancestry in Caribbean islanders is a Native South American component shared among inland Amazonian tribes, Central America, and the Yucatan peninsula, suggesting extensive gene flow across the Caribbean in pre-Columbian times. We find evidence of two pulses of African migration. The first pulse—which today is reflected by shorter, older ancestry tracts—consists of a genetic component more similar to coastal West African regions involved in early stages of the trans-Atlantic slave trade. The second pulse—reflected by longer, younger tracts—is more similar to present-day West-Central African populations, supporting historical records of later transatlantic deportation. Surprisingly, we also identify a Latino-specific European component that has significantly diverged from its parental Iberian source populations, presumably as a result of small European founder population size. We demonstrate that the ancestral components in admixed genomes can be traced back to distinct sub

Hierarchical spatial genetic structure in a distinct population segment of greater sage-grouse

USGS Publications Warehouse

Oyler-McCance, Sara J.; Casazza, Michael L.; Fike, Jennifer A.; Coates, Peter S.

2014-01-01

Greater sage-grouse (Centrocercus urophasianus) within the Bi-State Management Zone (area along the border between Nevada and California) are geographically isolated on the southwestern edge of the species’ range. Previous research demonstrated that this population is genetically unique, with a high proportion of unique mitochondrial DNA (mtDNA) haplotypes and with significant differences in microsatellite allele frequencies compared to populations across the species’ range. As a result, this population was considered a distinct population segment (DPS) and was recently proposed for listing as threatened under the U.S. Endangered Species Act. A more comprehensive understanding of the boundaries of this genetically unique population (where the Bi-State population begins) and an examination of genetic structure within the Bi-State is needed to help guide effective management decisions. We collected DNA from eight sampling locales within the Bi-State (N = 181) and compared those samples to previously collected DNA from the two most proximal populations outside of the Bi-State DPS, generating mtDNA sequence data and amplifying 15 nuclear microsatellites. Both mtDNA and microsatellite analyses support the idea that the Bi-State DPS represents a genetically unique population, which has likely been separated for thousands of years. Seven mtDNA haplotypes were found exclusively in the Bi-State population and represented 73 % of individuals, while three haplotypes were shared with neighboring populations. In the microsatellite analyses both STRUCTURE and FCA separate the Bi-State from the neighboring populations. We also found genetic structure within the Bi-State as both types of data revealed differences between the northern and southern part of the Bi-State and there was evidence of isolation-by-distance. STRUCTURE revealed three subpopulations within the Bi-State consisting of the northern Pine Nut Mountains (PNa), mid Bi-State, and White Mountains (WM) following a

Genome-wide genetic diversity, population structure and admixture analysis in African and Asian cattle breeds.

PubMed

Edea, Z; Bhuiyan, M S A; Dessie, T; Rothschild, M F; Dadi, H; Kim, K S

2015-02-01

Knowledge about genetic diversity and population structure is useful for designing effective strategies to improve the production, management and conservation of farm animal genetic resources. Here, we present a comprehensive genome-wide analysis of genetic diversity, population structure and admixture based on 244 animals sampled from 10 cattle populations in Asia and Africa and genotyped for 69,903 autosomal single-nucleotide polymorphisms (SNPs) mainly derived from the indicine breed. Principal component analysis, STRUCTURE and distance analysis from high-density SNP data clearly revealed that the largest genetic difference occurred between the two domestic lineages (taurine and indicine), whereas Ethiopian cattle populations represent a mosaic of the humped zebu and taurine. Estimation of the genetic influence of zebu and taurine revealed that Ethiopian cattle were characterized by considerable levels of introgression from South Asian zebu, whereas Bangladeshi populations shared very low taurine ancestry. The relationships among Ethiopian cattle populations reflect their history of origin and admixture rather than phenotype-based distinctions. The high within-individual genetic variability observed in Ethiopian cattle represents an untapped opportunity for adaptation to changing environments and for implementation of within-breed genetic improvement schemes. Our results provide a basis for future applications of genome-wide SNP data to exploit the unique genetic makeup of indigenous cattle breeds and to facilitate their improvement and conservation.

How does mother-to-child transmission of HIV differ among African populations? Lessons from MBL2 genetic variation in Zimbabweans.

PubMed

Mhandire, Kudakwashe; Pharo, Gavin; Kandawasvika, Gwendolene Q; Duri, Kerina; Swart, Marelize; Stray-Pedersen, Babill; Dandara, Collet

2014-07-01

Mannose binding lectin (MBL) is a pathogen pattern recognition protein involved in antimicrobial activities. Variation in MBL2 gene has been extensively implicated in differential outcomes of infectious diseases in studies conducted outside Africa, but virtually very little is known on the role of this candidate gene in the African continent. We investigated human genetic variations in MBL2 in a Zimbabwean pediatric population and their putative associations with HIV infection in perinatally exposed children. One hundred and four children aged 7 to 9 years comprising 68 perinatally exposed to HIV (32 who were born infected and 36 who were uninfected) and 36 unexposed controls were recruited. DNA samples were genotyped for MBL2 polymorphisms using PCR-RFLP and sequencing. HIV infected children had markedly variable and significantly lower mean height (p=0.03) and weight (p=0.005) when compared to the uninfected children. Using all samples, frequencies for MBL2 genetic variants for the Zimbabwean population were calculated. Twelve single nucleotide polymorphisms were observed and minor alleles occurred with the following frequencies: -550C>G (G: 0.02), -435G>A (A: 0.08), -428A>C (C: 0.39), -394A>G (A: 0.39), -328AGAGAA ins/del (AGAGAA ins: 0.44), -245G>A (A: 0.05), -221C>G (C: 0.12), -111A>T (T: 0.10), -70C>T (C: 0.46), +4C>T (C: 0.45), novel -595G>A (A: 0.02), and 170G>A (0.24). We found that the MBL2 +4T variant displayed a trend for association with reduced risk of HIV transmission from mother-to-child but the remaining vast majority of the genetic markers did not show a significant association. We conclude (1) the MBL2 gene is highly polymorphic in the Zimbabwean population, and (2) MBL2 genetic variation does not appear to play a major role in influencing the risk of mother-to-child HIV transmission in our study sample. These observations contest the hitherto significant role of this candidate gene for HIV transmission from mother-to-child in non-African

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

PubMed Central

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

2014-01-01

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

Erlotinib in African Americans with Advanced Non-Small Cell Lung Cancer: A Prospective Randomized Study with Genetic and Pharmacokinetic Analysis

PubMed Central

Phelps, Mitch A.; Stinchcombe, Thomas E.; Blachly, James S.; Zhao, Weiqiang; Schaaf, Larry J.; Starrett, Sherri L.; Wei, Lai; Poi, Ming; Wang, Danxin; Papp, Audrey; Aimiuwu, Josephine; Gao, Yue; Li, Junan; Otterson, Gregory A.; Hicks, William J.; Socinski, Mark A.; Villalona-Calero, Miguel A.

2014-01-01

Prospective studies focusing on EGFR inhibitors in African Americans with NSCLC have not been previously performed. In this phase II randomized study, 55 African Americans with NSCLC received erlotinib 150mg/day or a body weight adjusted dose with subsequent escalations to the maximum allowable, 200mg/day, to achieve rash. Erlotinib and OSI-420 exposures were lower compared to previous reports, consistent with CYP3A pharmacogenetics implying higher metabolic activity. Tumor genetics revealed only two EGFR mutations, EGFR amplification in 17/47 samples, 8 KRAS mutations and 5 EML4-ALK translocations. Although absence of rash was associated with shorter time to progression (TTP), disease control rate, TTP, and 1-year survival were not different between the two dose groups, indicating the dose-to-rash strategy failed to increase clinical benefit. Observed low incidence of toxicity and low erlotinib exposure suggest standardized and maximum allowable dosing may be suboptimal in African Americans. PMID:24781527

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

PubMed Central

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

2016-01-01

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

Genetic diversity and population structure of Plasmodium falciparum over space and time in an African archipelago.

PubMed

Salgueiro, Patrícia; Vicente, José Luís; Figueiredo, Rita Carrilho; Pinto, João

2016-09-01

The archipelago of São Tomé and Principe (STP), West Africa, has suffered the heavy burden of malaria since the 16th century. Until the last decade, when after a successful control program STP has become a low transmission country and one of the few nations with decreases of more than 90% in malaria admission and death rates. We carried out a longitudinal study to determine the genetic structure of STP parasite populations over time and space. Twelve microsatellite loci were genotyped in Plasmodium falciparum samples from two islands collected in 1997, 2000 and 2004. Analysis was performed on proportions of mixed genotype infections, allelic diversity, population differentiation, effective population size and bottleneck effects. We have found high levels of genetic diversity and minimal inter-population genetic differentiation typical of African continental regions with intense and stable malaria transmission. We detected significant differences between the years, with special emphasis for 1997 that showed the highest proportion of samples infected with P. falciparum and the highest mean number of haplotypes per isolate. This study establishes a comprehensive genetic data baseline of a pre-intervention scenario for future studies; taking into account the most recent and successful control intervention on the territory. Copyright © 2016 Elsevier B.V. All rights reserved.

Reviving the African wolf Canis lupus lupaster in North and West Africa: a mitochondrial lineage ranging more than 6,000 km wide.

PubMed

Gaubert, Philippe; Bloch, Cécile; Benyacoub, Slim; Abdelhamid, Adnan; Pagani, Paolo; Djagoun, Chabi Adéyèmi Marc Sylvestre; Couloux, Arnaud; Dufour, Sylvain

2012-01-01

The recent discovery of a lineage of gray wolf in North-East Africa suggests the presence of a cryptic canid on the continent, the African wolf Canis lupus lupaster. We analyzed the mtDNA diversity (cytochrome b and control region) of a series of African Canis including wolf-like animals from North and West Africa. Our objectives were to assess the actual range of C. l. lupaster, to further estimate the genetic characteristics and demographic history of its lineage, and to question its taxonomic delineation from the golden jackal C. aureus, with which it has been considered synonymous. We confirmed the existence of four distinct lineages within the gray wolf, including C. lupus/familiaris (Holarctic wolves and dogs), C. l. pallipes, C. l. chanco and C. l. lupaster. Taxonomic assignment procedures identified wolf-like individuals from Algeria, Mali and Senegal, as belonging to C. l. lupaster, expanding its known distribution c. 6,000 km to the west. We estimated that the African wolf lineage (i) had the highest level of genetic diversity within C. lupus, (ii) coalesced during the Late Pleistocene, contemporaneously with Holarctic wolves and dogs, and (iii) had an effective population size of c. 80,000 females. Our results suggest that the African wolf is a relatively ancient gray wolf lineage with a fairly large, past effective population size, as also suggested by the Pleistocene fossil record. Unique field observations in Senegal allowed us to provide a morphological and behavioral diagnosis of the African wolf that clearly distinguished it from the sympatric golden jackal. However, the detection of C. l. lupaster mtDNA haplotypes in C. aureus from Senegal brings the delineation between the African wolf and the golden jackal into question. In terms of conservation, it appears urgent to further characterize the status of the African wolf with regard to the African golden jackal.

Reviving the African Wolf Canis lupus lupaster in North and West Africa: A Mitochondrial Lineage Ranging More than 6,000 km Wide

PubMed Central

Gaubert, Philippe; Bloch, Cécile; Benyacoub, Slim; Abdelhamid, Adnan; Pagani, Paolo; Djagoun, Chabi Adéyèmi Marc Sylvestre; Couloux, Arnaud; Dufour, Sylvain

2012-01-01

The recent discovery of a lineage of gray wolf in North-East Africa suggests the presence of a cryptic canid on the continent, the African wolf Canis lupus lupaster. We analyzed the mtDNA diversity (cytochrome b and control region) of a series of African Canis including wolf-like animals from North and West Africa. Our objectives were to assess the actual range of C. l. lupaster, to further estimate the genetic characteristics and demographic history of its lineage, and to question its taxonomic delineation from the golden jackal C. aureus, with which it has been considered synonymous. We confirmed the existence of four distinct lineages within the gray wolf, including C. lupus/familiaris (Holarctic wolves and dogs), C. l. pallipes, C. l. chanco and C. l. lupaster. Taxonomic assignment procedures identified wolf-like individuals from Algeria, Mali and Senegal, as belonging to C. l. lupaster, expanding its known distribution c. 6,000 km to the west. We estimated that the African wolf lineage (i) had the highest level of genetic diversity within C. lupus, (ii) coalesced during the Late Pleistocene, contemporaneously with Holarctic wolves and dogs, and (iii) had an effective population size of c. 80,000 females. Our results suggest that the African wolf is a relatively ancient gray wolf lineage with a fairly large, past effective population size, as also suggested by the Pleistocene fossil record. Unique field observations in Senegal allowed us to provide a morphological and behavioral diagnosis of the African wolf that clearly distinguished it from the sympatric golden jackal. However, the detection of C. l. lupaster mtDNA haplotypes in C. aureus from Senegal brings the delineation between the African wolf and the golden jackal into question. In terms of conservation, it appears urgent to further characterize the status of the African wolf with regard to the African golden jackal. PMID:22900047

Glioblastoma with an oligodendroglioma component: distinct clinical behavior, genetic alterations, and outcome.

PubMed

Wang, Yongzhi; Li, Shouwei; Chen, Lingchao; You, Gan; Bao, Zhaoshi; Yan, Wei; Shi, Zhendong; Chen, Yin; Yao, Kun; Zhang, Wei; Kang, Chunsheng; Jiang, Tao

2012-04-01

Glioblastomas (GBMs) containing foci that resemble oligodendroglioma are defined as GBM with oligodendroglioma component (GBMO). However, whether GBMO is a distinct clinicopathological variant of GBM or merely represents a divergent pattern of differentiation remains controversial. We investigated 219 consecutive primary GBMs, of which 40 (18.3%) were confirmed as GBMOs. The clinical features and genetic profiles of the GBMOs were analyzed and compared with the conventional GBMs. The GBMO group showed more frequent tumor-related seizures (P= .027), higher frequency of IDH1 mutation (31% vs. <5%, P= .015), lower MGMT expression (P= .016), and longer survival (19.0 vs. 13.2 months; P= .022). In multivariate Cox regression analyses, presence of an oligodendroglioma component was predictive of longer survival (P= .001), but the extent of the oligodendroglial component appeared not to be linked to prognosis (P= .664). The codeletions of 1p/19q, somewhat surprisingly, were infrequent (<5%) in both GBMO and conventional GBM. In addition, the response to aggressive therapy differed: the GBMO group had no survival advantage associated with aggressive treatment protocols, whereas a clear treatment effect was observed in the conventional GBM group. Collectively, the clinical behavior and genetic alterations of GBMO thus differs from those of conventional GBM. Presence of an oligodendroglial component may therefore be a useful classification and stratification variable in therapeutic trials of GBMs.

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

PubMed Central

Fox, Ervin R.; Young, J. Hunter; Li, Yali; Dreisbach, Albert W.; Keating, Brendan J.; Musani, Solomon K.; Liu, Kiang; Morrison, Alanna C.; Ganesh, Santhi; Kutlar, Abdullah; Ramachandran, Vasan S.; Polak, Josef F.; Fabsitz, Richard R.; Dries, Daniel L.; Farlow, Deborah N.; Redline, Susan; Adeyemo, Adebowale; Hirschorn, Joel N.; Sun, Yan V.; Wyatt, Sharon B.; Penman, Alan D.; Palmas, Walter; Rotter, Jerome I.; Townsend, Raymond R.; Doumatey, Ayo P.; Tayo, Bamidele O.; Mosley, Thomas H.; Lyon, Helen N.; Kang, Sun J.; Rotimi, Charles N.; Cooper, Richard S.; Franceschini, Nora; Curb, J. David; Martin, Lisa W.; Eaton, Charles B.; Kardia, Sharon L.R.; Taylor, Herman A.; Caulfield, Mark J.; Ehret, Georg B.; Johnson, Toby; Chakravarti, Aravinda; Zhu, Xiaofeng; Levy, Daniel; Munroe, Patricia B.; Rice, Kenneth M.; Bochud, Murielle; Johnson, Andrew D.; Chasman, Daniel I.; Smith, Albert V.; Tobin, Martin D.; Verwoert, Germaine C.; Hwang, Shih-Jen; Pihur, Vasyl; Vollenweider, Peter; O'Reilly, Paul F.; Amin, Najaf; Bragg-Gresham, Jennifer L.; Teumer, Alexander; Glazer, Nicole L.; Launer, Lenore; Zhao, Jing Hua; Aulchenko, Yurii; Heath, Simon; Sõber, Siim; Parsa, Afshin; Luan, Jian'an; Arora, Pankaj; Dehghan, Abbas; Zhang, Feng; Lucas, Gavin; Hicks, Andrew A.; Jackson, Anne U.; Peden, John F.; Tanaka, Toshiko; Wild, Sarah H.; Rudan, Igor; Igl, Wilmar; Milaneschi, Yuri; Parker, Alex N.; Fava, Cristiano; Chambers, John C.; Kumari, Meena; JinGo, Min; van der Harst, Pim; Kao, Wen Hong Linda; Sjögren, Marketa; Vinay, D.G.; Alexander, Myriam; Tabara, Yasuharu; Shaw-Hawkins, Sue; Whincup, Peter H.; Liu, Yongmei; Shi, Gang; Kuusisto, Johanna; Seielstad, Mark; Sim, Xueling; Nguyen, Khanh-Dung Hoang; Lehtimäki, Terho; Matullo, Giuseppe; Wu, Ying; Gaunt, Tom R.; Charlotte Onland-Moret, N.; Cooper, Matthew N.; Platou, Carl G.P.; Org, Elin; Hardy, Rebecca; Dahgam, Santosh; Palmen, Jutta; Vitart, Veronique; Braund, Peter S.; Kuznetsova, Tatiana; Uiterwaal, Cuno S.P.M.; Campbell, Harry; Ludwig, Barbara; Tomaszewski, Maciej; Tzoulaki, Ioanna; Palmer, Nicholette D.; Aspelund, Thor; Garcia, Melissa; Chang, Yen-Pei C.; O'Connell, Jeffrey R.; Steinle, Nanette I.; Grobbee, Diederick E.; Arking, Dan E.; Hernandez, Dena; Najjar, Samer; McArdle, Wendy L.; Hadley, David; Brown, Morris J.; Connell, John M.; Hingorani, Aroon D.; Day, Ian N.M.; Lawlor, Debbie A.; Beilby, John P.; Lawrence, Robert W.; Clarke, Robert; Collins, Rory; Hopewell, Jemma C.; Ongen, Halit; Bis, Joshua C.; Kähönen, Mika; Viikari, Jorma; Adair, Linda S.; Lee, Nanette R.; Chen, Ming-Huei; Olden, Matthias; Pattaro, Cristian; Hoffman Bolton, Judith A.; Köttgen, Anna; Bergmann, Sven; Mooser, Vincent; Chaturvedi, Nish; Frayling, Timothy M.; Islam, Muhammad; Jafar, Tazeen H.; Erdmann, Jeanette; Kulkarni, Smita R.; Bornstein, Stefan R.; Grässler, Jürgen; Groop, Leif; Voight, Benjamin F.; Kettunen, Johannes; Howard, Philip; Taylor, Andrew; Guarrera, Simonetta; Ricceri, Fulvio; Emilsson, Valur; Plump, Andrew; Barroso, Inês; Khaw, Kay-Tee; Weder, Alan B.; Hunt, Steven C.; Bergman, Richard N.; Collins, Francis S.; Bonnycastle, Lori L.; Scott, Laura J.; Stringham, Heather M.; Peltonen, Leena; Perola, Markus; Vartiainen, Erkki; Brand, Stefan-Martin; Staessen, Jan A.; Wang, Thomas J.; Burton, Paul R.; SolerArtigas, Maria; Dong, Yanbin; Snieder, Harold; Wang, Xiaoling; Zhu, Haidong; Lohman, Kurt K.; Rudock, Megan E.; Heckbert, Susan R.; Smith, Nicholas L.; Wiggins, Kerri L.; Shriner, Daniel; Veldre, Gudrun; Viigimaa, Margus; Kinra, Sanjay; Prabhakaran, Dorairajan; Tripathy, Vikal; Langefeld, Carl D.; Rosengren, Annika; Thelle, Dag S.; MariaCorsi, Anna; Singleton, Andrew; Forrester, Terrence; Hilton, Gina; McKenzie, Colin A.; Salako, Tunde; Iwai, Naoharu; Kita, Yoshikuni; Ogihara, Toshio; Ohkubo, Takayoshi; Okamura, Tomonori; Ueshima, Hirotsugu; Umemura, Satoshi; Eyheramendy, Susana; Meitinger, Thomas; Wichmann, H.-Erich; Cho, Yoon Shin; Kim, Hyung-Lae; Lee, Jong-Young; Scott, James; Sehmi, Joban S.; Zhang, Weihua; Hedblad, Bo; Nilsson, Peter; Smith, George Davey; Wong, Andrew; Narisu, Narisu; Stančáková, Alena; Raffel, Leslie J.; Yao, Jie; Kathiresan, Sekar; O'Donnell, Chris; Schwartz, Steven M.; Arfan Ikram, M.; Longstreth, Will T.; Seshadri, Sudha; Shrine, Nick R.G.; Wain, Louise V.; Morken, Mario A.; Swift, Amy J.; Laitinen, Jaana; Prokopenko, Inga; Zitting, Paavo; Cooper, Jackie A.; Humphries, Steve E.; Danesh, John; Rasheed, Asif; Goel, Anuj; Hamsten, Anders; Watkins, Hugh; Bakker, Stephan J.L.; van Gilst, Wiek H.; Janipalli, Charles S.; Radha Mani, K.; Yajnik, Chittaranjan S.; Hofman, Albert; Mattace-Raso, Francesco U.S.; Oostra, Ben A.; Demirkan, Ayse; Isaacs, Aaron; Rivadeneira, Fernando; Lakatta, Edward G.; Orru, Marco; Scuteri, Angelo; Ala-Korpela, Mika; Kangas, Antti J.; Lyytikäinen, Leo-Pekka; Soininen, Pasi; Tukiainen, Taru; Würz, Peter; Twee-Hee Ong, Rick; Dörr, Marcus; Kroemer, Heyo K.; Völker, Uwe; Völzke, Henry; Galan, Pilar; Hercberg, Serge; Lathrop, Mark; Zelenika, Diana; Deloukas, Panos; Mangino, Massimo; Spector, Tim D.; Zhai, Guangju; Meschia, James F.; Nalls, Michael A.; Sharma, Pankaj; Terzic, Janos; Kranthi Kumar, M.J.; Denniff, Matthew; Zukowska-Szczechowska, Ewa; Wagenknecht, Lynne E.; Fowkes, Gerald R.; Charchar, Fadi J.; Schwarz, Peter E.H.; Hayward, Caroline; Guo, Xiuqing; Bots, Michiel L.; Brand, Eva; Samani, Nilesh J.; Polasek, Ozren; Talmud, Philippa J.; Nyberg, Fredrik; Kuh, Diana; Laan, Maris; Hveem, Kristian; Palmer, Lyle J.; van der Schouw, Yvonne T.; Casas, Juan P.; Mohlke, Karen L.; Vineis, Paolo; Raitakari, Olli; Wong, Tien Y.; Shyong Tai, E.; Laakso, Markku; Rao, Dabeeru C.; Harris, Tamara B.; Morris, Richard W.; Dominiczak, Anna F.; Kivimaki, Mika; Marmot, Michael G.; Miki, Tetsuro; Saleheen, Danish; Chandak, Giriraj R.; Coresh, Josef; Navis, Gerjan; Salomaa, Veikko; Han, Bok-Ghee; Kooner, Jaspal S.; Melander, Olle; Ridker, Paul M.; Bandinelli, Stefania; Gyllensten, Ulf B.; Wright, Alan F.; Wilson, James F.; Ferrucci, Luigi; Farrall, Martin; Tuomilehto, Jaakko; Pramstaller, Peter P.; Elosua, Roberto; Soranzo, Nicole; Sijbrands, Eric J.G.; Altshuler, David; Loos, Ruth J.F.; Shuldiner, Alan R.; Gieger, Christian; Meneton, Pierre; Uitterlinden, Andre G.; Wareham, Nicholas J.; Gudnason, Vilmundur; Rettig, Rainer; Uda, Manuela; Strachan, David P.; Witteman, Jacqueline C.M.; Hartikainen, Anna-Liisa; Beckmann, Jacques S.; Boerwinkle, Eric; Boehnke, Michael; Larson, Martin G.; Järvelin, Marjo-Riitta; Psaty, Bruce M.; Abecasis, Gonçalo R.; Elliott, Paul; van Duijn , Cornelia M.; Newton-Cheh, Christopher

2011-01-01

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity. PMID:21378095

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.

PubMed

Fox, Ervin R; Young, J Hunter; Li, Yali; Dreisbach, Albert W; Keating, Brendan J; Musani, Solomon K; Liu, Kiang; Morrison, Alanna C; Ganesh, Santhi; Kutlar, Abdullah; Ramachandran, Vasan S; Polak, Josef F; Fabsitz, Richard R; Dries, Daniel L; Farlow, Deborah N; Redline, Susan; Adeyemo, Adebowale; Hirschorn, Joel N; Sun, Yan V; Wyatt, Sharon B; Penman, Alan D; Palmas, Walter; Rotter, Jerome I; Townsend, Raymond R; Doumatey, Ayo P; Tayo, Bamidele O; Mosley, Thomas H; Lyon, Helen N; Kang, Sun J; Rotimi, Charles N; Cooper, Richard S; Franceschini, Nora; Curb, J David; Martin, Lisa W; Eaton, Charles B; Kardia, Sharon L R; Taylor, Herman A; Caulfield, Mark J; Ehret, Georg B; Johnson, Toby; Chakravarti, Aravinda; Zhu, Xiaofeng; Levy, Daniel

2011-06-01

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity.

Genetic Variability of the Grey Wolf Canis lupus in the Caucasus in Comparison with Europe and the Middle East: Distinct or Intermediary Population?

PubMed Central

Pilot, Małgorzata; Dąbrowski, Michał J.; Hayrapetyan, Vahram; Yavruyan, Eduard G.; Kopaliani, Natia; Tsingarska, Elena; Bujalska, Barbara; Kamiński, Stanisław; Bogdanowicz, Wiesław

2014-01-01

Despite continuous historical distribution of the grey wolf (Canis lupus) throughout Eurasia, the species displays considerable morphological differentiation that resulted in delimitation of a number of subspecies. However, these morphological discontinuities are not always consistent with patterns of genetic differentiation. Here we assess genetic distinctiveness of grey wolves from the Caucasus (a region at the border between Europe and West Asia) that have been classified as a distinct subspecies C. l. cubanensis. We analysed their genetic variability based on mtDNA control region, microsatellite loci and genome-wide SNP genotypes (obtained for a subset of the samples), and found similar or higher levels of genetic diversity at all these types of loci as compared with other Eurasian populations. Although we found no evidence for a recent genetic bottleneck, genome-wide linkage disequilibrium patterns suggest a long-term demographic decline in the Caucasian population – a trend consistent with other Eurasian populations. Caucasian wolves share mtDNA haplotypes with both Eastern European and West Asian wolves, suggesting past or ongoing gene flow. Microsatellite data also suggest gene flow between the Caucasus and Eastern Europe. We found evidence for moderate admixture between the Caucasian wolves and domestic dogs, at a level comparable with other Eurasian populations. Taken together, our results show that Caucasian wolves are not genetically isolated from other Eurasian populations, share with them the same demographic trends, and are affected by similar conservation problems. PMID:24714198

High levels of genetic diversity in Spodoptera exempta NPV from Tanzania.

PubMed

Redman, Elizabeth M; Wilson, Kenneth; Grzywacz, David; Cory, Jenny S

2010-10-01

The African armyworm, Spodoptera exempta, is a major pest in sub-Saharan Africa. A nucleopolyhedrovirus (NPV) is often recorded in later population outbreaks and can cause very high levels of mortality. Research has been addressing whether this NPV can be developed into a strategic biological control agent. As part of this study, the variation in natural populations of NPV is being studied. An isolate of S. exempta NPV was cloned in vivo and found to contain at least 17 genetically-distinct genotypes. These genotypes varied in size from approximately 115 to 153 kb. Copyright 2010 Elsevier Inc. All rights reserved.

Characterization of Genetic Loci That Affect Susceptibility to Inflammatory Bowel Diseases in African Americans

PubMed Central

Cutler, David J.; Zwick, Michael E.; Taylor, Kent D.; Datta, Lisa W.; Maranville, Joseph C.; Liu, Zhenqiu; Ellis, Shannon; Chopra, Pankaj; Alexander, Jonathan S.; Baldassano, Robert N.; Cross, Raymond K.; Dassopoulos, Themistocles; Dhere, Tanvi A.; Duerr, Richard H.; Hanson, John S.; Hou, Jason K.; Hussain, Sunny Z.; Isaacs, Kim L.; Kachelries, Kelly E; Kader, Howard; Kappelman, Michael D.; Katz, Jeffrey; Kellermayer, Richard; Kirschner, Barbara S.; Kuemmerle, John F.; Kumar, Archana; Kwon, John H.; Lazarev, Mark; Mannon, Peter; Moulton, Dedrick E.; Osuntokun, Bankole O.; Patel, Ashish; Rioux, John D.; Rotter, Jerome I.; Saeed, Shehzad; Scherl, Ellen J.; Silverberg, Mark S.; Silverman, Ann; Targan, Stephan R.; Valentine, John F.; Wang, Ming-Hsi; Simpson, Claire L.; Bridges, S. Louis; Kimberly, Robert P.; Rich, Stephen S.; Cho, Judy H.; Rienzo, Anna Di; Kao, Linda W.H.

2015-01-01

Background & Aims Inflammatory bowel disease (IBD) has familial aggregation in African Americans (AAs), but little is known about the molecular genetic susceptibility. Mapping studies using the Immunochip genotyping array expand the number of susceptibility loci for IBD in Caucasians to 163, but the contribution of the 163 loci and European admixture to IBD risk in AAs is unclear. We performed a genetic mapping study using the Immunochip to determine whether IBD susceptibility loci in Caucasians also affect risk in AAs and identify new associated loci. Methods We recruited AAs with IBD and without IBD (controls) from 34 IBD centers in the US; additional controls were collected from 4 other immunochip studies. Association and admixture loci were mapped for 1088 patients with Crohn's disease (CD), 361 with ulcerative colitis (UC), 62 with IBD type-unknown (IBDU), and 1797 controls; 130,241 autosomal single-nucleotide polymorphisms (SNPs) were analyzed. Results The strongest associations were observed between UC and HLA rs9271366 (P=7.5e–6), CD and 5p13.1 rs4286721 (P=3.0e–6), and IBD and KAT2A rs730086 (P=2.3e–6). Additional suggestive associations (P<4.2e-5) were observed between CD and IBD and African-specific SNPs in STAT5A and STAT3; between IBD and SNPs in IL23R, IL12B, and C2 open reading frame 43; and between UC and SNPs near HDAC11 and near LINC00994. The latter 3 loci have not been previously associated with IBD, but require replication. Established Caucasian associations were replicated in AAs (P<3.1e-4) at NOD2, IL23R, 5p15.3, and IKZF3. Significant admixture (P<3.9e–4) was observed for 17q12-17q21.31 (IZKF3 through STAT3), 10q11.23-10q21.2, 15q22.2–15q23, and 16p12.2–16p12.1. Network analyses showed significant enrichment (false discovery rate <1e–5) in genes that encode members of the JAK–STAT, cytokine, and chemokine signaling pathways, as well those involved in pathogenesis of measles. Conclusions In a genetic analysis of 3308 AA IBD

Factors associated with African Americans' enrollment in a national cancer genetics registry.

PubMed

Skinner, C S; Schildkraut, J M; Calingaert, B; Hoyo, C; Crankshaw, S S; Fish, L; Susswein, L; Jasper, C; Reid, L

2008-01-01

This study explored whether reactions to the Cancer Genetics Network (CGN) or CGN enrollment differed by receipt of a standard informational brochure versus a targeted version addressing factors previously associated with African Americans' health behavior decisions and research participation. The 262 participants, identified through tumor registries or clinic contacts, were mailed brochures and completed phone interviews. When asked whether - based on the brochure - they were or were not 'leaning toward' CGN enrollment, about 75% of both standard and targeted groups reported leaning toward. When given the opportunity at the end of the interview, 68% enrolled in the CGN. Trust was strongly related to enrollment. Less education, less satisfaction with cancer care, and individualistic rather than collective orientation were associated with lower trust. Education was also bivariately associated with enrollment, but mediation analysis indicated that the operational mechanism of education's influence on enrollment was through trust. Copyright 2008 S. Karger AG, Basel.

Landscape genetics indicate recently increased habitat fragmentation in African forest-associated chafers.

PubMed

Eberle, Jonas; Rödder, Dennis; Beckett, Marc; Ahrens, Dirk

2017-05-01

Today, indigenous forests cover less than 0.6% of South Africa's land surface and are highly fragmented. Most forest relicts are very small and typically occur in fire-protected gorges along the eastern Great Escarpment. Yet, they hold a unique and valuable fauna with high endemism and ancient phylogenetic lineages, fostered by long-term climatic stability and complex microclimates. Despite numerous studies on southern African vegetation cover, the current state of knowledge about the natural extension of indigenous forests is rather fragmentary. We use an integrated approach of population-level phylogeography and climatic niche modeling of forest-associated chafer species to assess connectivity and extent of forest habitats since the last glacial maximum. Current and past species distribution models ascertained potential fluctuations of forest distribution and supported a much wider potential current extension of forests based on climatic data. Considerable genetic admixture of mitochondrial and nuclear DNA among many populations and an increase in mean population mutation rate in Extended Bayesian Skyline Plots of all species indicated more extended or better connected forests in the recent past (<5 kya). Genetic isolation of certain populations, as revealed by population differentiation statistics (GST'), as well as landscape connectivity statistics and habitat succession scenarios suggests considerable loss of habitat connectivity. As major anthropogenic influence is likely, conservational actions need to be considered. © 2017 John Wiley & Sons Ltd.

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

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.

The potential European genetic predisposition for non-contact anterior cruciate ligament injury.

PubMed

Astur, Diego Costa; Andrade, Edilson; Arliani, Gustavo Gonçalves; Debieux, Pedro; Loyola, Leonor Casilla; Dos Santos, Sidney Emanuel Batista; Burbano, Rommel Mario Rodriguez; Leal, Mariana Ferreira; Cohen, Moises

2018-05-04

Previous research has provided evidence of a hereditary predisposition for anterior cruciate ligament (ACL) injury. The purpose of this study was to evaluate the association between ancestral population genetics and risk of non-contact ACL injuries. Blood samples were collected from 177 individuals with a history of non-contact ACL injury and 556 non-injured control individuals for analysis of the genetic material through the use of a panel of 48 INDELs ancestry genetic markers from three ancestral origins. Among patients with non-contact ACL injury, 82% were male and 18% were female. In the control group, 78% were male, and 22% were female. The mean age of the non-contact ACL injury group was 31.7 years (± 10.2), and the control group was 33.8 years (± 13.2). The individual genetic contribution from INDELs of each ancestral origin varied considerably: ranging between 1.5-94.8% contribution for INDELs of African origin (mean of 21.4% of INDELs); between 2 and 96.1% contribution for INDELs of European origin (mean of 66.7% of INDELs); and between 1.3-96.4% contribution for INDELs of Amerindian origin (mean of 11.7% of INDELs). When comparing paired subjects from the non-contact ACL and control groups, the genetic analysis showed that the European ancestry score was higher in the non-contact ACL group than control group (0.70 ± 0.21 vs 0.63 ± 0.22 respectively, p < 0.001), whereas African ancestry scores (ACL group 0.18 ± 0.18 vs control group 0.24 ± 0.21, p < 0.001) and Amerindian ancestry scores (ACL group 0.11 ± 0.09 vs control group 0.12 ± 0.10, n.s.) were lower among the non-contact ACL group than in controls. European INDELs markers were found to represent a potential genetic predisposition for non-contact ACL injuries when compared to African and Amerindian INDELs. This study has the potential to correlate a measurable and distinct genetic marker with risk of a non-contact ACL injury. Thus, it increases knowledge

Variable association of reactive intermediate genes with systemic lupus erythematosus in populations with different African ancestry.

PubMed

Ramos, Paula S; Oates, James C; Kamen, Diane L; Williams, Adrienne H; Gaffney, Patrick M; Kelly, Jennifer A; Kaufman, Kenneth M; Kimberly, Robert P; Niewold, Timothy B; Jacob, Chaim O; Tsao, Betty P; Alarcón, Graciela S; Brown, Elizabeth E; Edberg, Jeffrey C; Petri, Michelle A; Ramsey-Goldman, Rosalind; Reveille, John D; Vilá, Luis M; James, Judith A; Guthridge, Joel M; Merrill, Joan T; Boackle, Susan A; Freedman, Barry I; Scofield, R Hal; Stevens, Anne M; Vyse, Timothy J; Criswell, Lindsey A; Moser, Kathy L; Alarcón-Riquelme, Marta E; Langefeld, Carl D; Harley, John B; Gilkeson, Gary S

2013-06-01

Little is known about the genetic etiology of systemic lupus erythematosus (SLE) in individuals of African ancestry, despite its higher prevalence and greater disease severity. Overproduction of nitric oxide (NO) and reactive oxygen species are implicated in the pathogenesis and severity of SLE, making NO synthases and other reactive intermediate-related genes biological candidates for disease susceptibility. We analyzed variation in reactive intermediate genes for association with SLE in 2 populations with African ancestry. A total of 244 single-nucleotide polymorphisms (SNP) from 53 regions were analyzed in non-Gullah African Americans (AA; 1432 cases and 1687 controls) and the genetically more homogeneous Gullah of the Sea Islands of South Carolina (133 cases and 112 controls). Single-marker, haplotype, and 2-locus interaction tests were computed for these populations. The glutathione reductase gene GSR (rs2253409; p = 0.0014, OR 1.26, 95% CI 1.09-1.44) was the most significant single SNP association in AA. In the Gullah, the NADH dehydrogenase NDUFS4 (rs381575; p = 0.0065, OR 2.10, 95% CI 1.23-3.59) and NO synthase gene NOS1 (rs561712; p = 0.0072, OR 0.62, 95% CI 0.44-0.88) were most strongly associated with SLE. When both populations were analyzed together, GSR remained the most significant effect (rs2253409; p = 0.00072, OR 1.26, 95% CI 1.10-1.44). Haplotype and 2-locus interaction analyses also uncovered different loci in each population. These results suggest distinct patterns of association with SLE in African-derived populations; specific loci may be more strongly associated within select population groups.

Genetic Characterization of Spondweni and Zika Viruses and Susceptibility of Geographically Distinct Strains of Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus (Diptera: Culicidae) to Spondweni Virus

DTIC Science & Technology

2016-10-26

1 Genetic characterization of Spondweni and Zika viruses and susceptibility of geographically distinct strains of Aedes aegypti, Aedes albopictus...substantial genetic and vector susceptibility data exist for ZIKV, less is 5 known for its sister flavivirus, Spondweni virus (SPONV). Both ZIKV and SPONV...have 6 been known to circulate in Africa since the mid-1900s, but neither has been genetically 7 characterized by gene and compared in parallel

A genetically diverse but distinct North American population of Sarcocystis neurona includes an overrepresented clone described by 12 microsatellite alleles.

PubMed

Asmundsson, Ingrid M; Dubey, J P; Rosenthal, Benjamin M

2006-09-01

The population genetics and systematics of most coccidians remain poorly defined despite their impact on human and veterinary health. Non-recombinant parasite clones characterized by distinct transmission and pathogenesis traits persist in the coccidian Toxoplasma gondii despite opportunities for sexual recombination. In order to determine whether this may be generally true for tissue-cyst forming coccidia, and to address evolutionary and taxonomic problems within the genus Sarcocystis, we characterized polymorphic microsatellite markers in Sarcocystis neurona, the major causative agent of equine protozoal myeloencephalitis (EPM). Bayesian statistical modeling, phylogenetic reconstruction based on genotypic chord distances, and analyses of linkage disequilibrium were employed to examine the population structure within S. neurona and closely related Sarcocystis falcatula isolates from North and South America. North American S. neurona were clearly differentiated from those of South America and also from isolates of S. falcatula. Although S. neurona is characterized by substantial allelic and genotypic diversity typical of interbreeding populations, one genotype occurs with significantly excessive frequency; thus, some degree of asexual propagation of S. neurona clones may naturally occur. Finally, S. neurona isolated from disparate North American localities and diverse hosts (opossums, a Southern sea otter, and horses) comprise a single genetic population. Isolates associated with clinical neurological disease bear no obvious distinction as measured by these presumably neutral genetic markers.

African Swine Fever Epidemic, Poland, 2014-2015.

PubMed

Śmietanka, Krzysztof; Woźniakowski, Grzegorz; Kozak, Edyta; Niemczuk, Krzysztof; Frączyk, Magdalena; Bocian, Łukasz; Kowalczyk, Andrzej; Pejsak, Zygmunt

2016-07-01

In Poland, African swine fever (ASF) emerged in February 2014; by August 2015, the virus had been detected in >130 wild boar and in pigs in 3 backyard holdings. We evaluated ASF spread in Poland during these 18 months. Phylogenetic analysis indicated repeated incursions of genetically distinct ASF viruses of genotype II; the number of cases positively correlated wild boar density; and disease spread was very slow. More cases were reported during summer than autumn. The 18-month prevalence of ASF in areas under various animal movement restrictions was 18.6% among wild boar found dead or killed by vehicles and only 0.2% in hunted wild boar. Repeated introductions of the virus into the country, the primary role of wild boar in virus maintenance, and the slow spread of the disease indicate a need for enhanced biosecurity at pig holdings and continuous and intensive surveillance for fast detection of ASF.

Genome-wide Ancestry and Demographic History of African-Descendant Maroon Communities from French Guiana and Suriname.

PubMed

Fortes-Lima, Cesar; Gessain, Antoine; Ruiz-Linares, Andres; Bortolini, Maria-Cátira; Migot-Nabias, Florence; Bellis, Gil; Moreno-Mayar, J Víctor; Restrepo, Berta Nelly; Rojas, Winston; Avendaño-Tamayo, Efren; Bedoya, Gabriel; Orlando, Ludovic; Salas, Antonio; Helgason, Agnar; Gilbert, M Thomas P; Sikora, Martin; Schroeder, Hannes; Dugoujon, Jean-Michel

2017-11-02

The transatlantic slave trade was the largest forced migration in world history. However, the origins of the enslaved Africans and their admixture dynamics remain unclear. To investigate the demographic history of African-descendant Marron populations, we generated genome-wide data (4.3 million markers) from 107 individuals from three African-descendant populations in South America, as well as 124 individuals from six west African populations. Throughout the Americas, thousands of enslaved Africans managed to escape captivity and establish lasting communities, such as the Noir Marron. We find that this population has the highest proportion of African ancestry (∼98%) of any African-descendant population analyzed to date, presumably because of centuries of genetic isolation. By contrast, African-descendant populations in Brazil and Colombia harbor substantially more European and Native American ancestry as a result of their complex admixture histories. Using ancestry tract-length analysis, we detect different dates for the European admixture events in the African-Colombian (1749 CE; confidence interval [CI]: 1737-1764) and African-Brazilian (1796 CE; CI: 1789-1804) populations in our dataset, consistent with the historically attested earlier influx of Africans into Colombia. Furthermore, we find evidence for sex-specific admixture patterns, resulting from predominantly European paternal gene flow. Finally, we detect strong genetic links between the African-descendant populations and specific source populations in Africa on the basis of haplotype sharing patterns. Although the Noir Marron and African-Colombians show stronger affinities with African populations from the Bight of Benin and the Gold Coast, the African-Brazilian population from Rio de Janeiro has greater genetic affinity with Bantu-speaking populations from the Bight of Biafra and west central Africa. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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

Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype

PubMed Central

Toyota, Minoru; Ohe-Toyota, Mutsumi; Ahuja, Nita; Issa, Jean-Pierre J.

2000-01-01

Colorectal cancers (CRCs) are characterized by multiple genetic (mutations) and epigenetic (CpG island methylation) alterations, but it is not known whether these evolve independently through stochastic processes. We have recently described a novel pathway termed CpG island methylator phenotype (CIMP) in CRC, which is characterized by the simultaneous methylation of multiple CpG islands, including several known genes, such as p16, hMLH1, and THBS1. We have now studied mutations in K-RAS, p53, DPC4, and TGFβRII in a panel of colorectal tumors with or without CIMP. We find that CIMP defines two groups of tumors with significantly different genetic lesions: frequent K-RAS mutations were found in CIMP+ CRCs (28/41, 68%) compared with CIMP− cases (14/47, 30%, P = 0.0005). By contrast, p53 mutations were found in 24% (10/41) of CIMP+ CRCs vs. 60% (30/46) of CIMP− cases (P = 0.002). Both of these differences were independent of microsatellite instability. These interactions between CIMP, K-RAS mutations, and p53 mutations were preserved in colorectal adenomas, suggesting that they occur early in carcinogenesis. The distinct combinations of epigenetic and genetic alterations in each group suggest that activation of oncogenes and inactivation of tumor suppressor genes is related to the underlying mechanism of generating molecular diversity in cancer, rather than simply accumulate stochastically during cancer development. PMID:10639144

Investigating the Association of Genetic Admixture and Donor/Recipient Genetic Disparity with Transplant Outcomes

PubMed Central

Madbouly, Abeer; Wang, Tao; Haagenson, Michael; Paunic, Vanja; Vierra-Green, Cynthia; Fleischhauer, Katharina; Hsu, Katharine C.; Verneris, Michael R.; Majhail, Navneet S.; Lee, Stephanie J.; Spellman, Stephen R.; Maiers, Martin

2017-01-01

Disparities in survival after allogeneic hematopoietic cell transplantation have been reported for some race and ethnic groups despite comparable HLA matching. Individuals’ ethnic and race groups, as reported through self-identification, can change over time due to multiple sociological factors. We studied the effect of two measures of genetic similarity in 1,378 recipients who underwent myeloablative first allogeneic hematopoietic cell transplantation between 1995 and 2011 and their unrelated 10-of-10 HLA-A, -B, -C, -DRB1 and DQB1 matched donors. The studied factors were: i) Donor and recipient genetic ancestral admixture, and ii) Pairwise donor/recipient genetic distance. Increased African genetic admixture for either transplant recipients or donors was associated with increased risk of overall mortality (HR=2.26, p=0.005 and HR=3.09, p=0.0002 respectively), Transplant Related Mortality (HR=3.3, p=0.0003 and HR=3.86, p=0.0001 respectively) and decreased Disease Free Survival (HR=1.9, p=0.02 and HR=2.46, p=0.002 respectively). The observed effect, albeit statistically significant, was relevant to small subset of the studied population and was notably correlated with self-reported African-American race. We were not able to control for other non-genetic factors such as access to healthcare or other socio-economic factors, however the results suggest the influence of a genetic driver. Our findings confirm what has been previously reported for African-American recipients and show similar results for donors. No significant association was found with donor/recipient genetic distance. PMID:28263917

Pregnancy, parturition and preeclampsia in women of African ancestry.

PubMed

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

2014-06-01

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

Pregnancy, parturition and preeclampsia in women of African ancestry

PubMed Central

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

2014-01-01

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

Genetically distinct populations of northern shrimp, Pandalus borealis, in the North Atlantic: adaptation to different temperatures as an isolation factor.

PubMed

Jorde, Per Erik; Søvik, Guldborg; Westgaard, Jon-Ivar; Albretsen, Jon; André, Carl; Hvingel, Carsten; Johansen, Torild; Sandvik, Anne Dagrun; Kingsley, Michael; Jørstad, Knut Eirik

2015-04-01

The large-scale population genetic structure of northern shrimp, Pandalus borealis, was investigated over the species' range in the North Atlantic, identifying multiple genetically distinct groups. Genetic divergence among sample localities varied among 10 microsatellite loci (range: FST = -0.0002 to 0.0475) with a highly significant average (FST = 0.0149; P < 0.0001). In contrast, little or no genetic differences were observed among temporal replicates from the same localities (FST = 0.0004; P = 0.33). Spatial genetic patterns were compared to geographic distances, patterns of larval drift obtained through oceanographic modelling, and temperature differences, within a multiple linear regression framework. The best-fit model included all three factors and explained approximately 29% of all spatial genetic divergence. However, geographic distance and larval drift alone had only minor effects (2.5-4.7%) on large-scale genetic differentiation patterns, whereas bottom temperature differences explained most (26%). Larval drift was found to promote genetic homogeneity in parts of the study area with strong currents, but appeared ineffective across large temperature gradients. These findings highlight the breakdown of gene flow in a species with a long pelagic larval phase (up to 3 months) and indicate a role for local adaptation to temperature conditions in promoting evolutionary diversification and speciation in the marine environment. © 2015 John Wiley & Sons Ltd.

[North African and Southeast Asian nasopharyngeal carcinomas: between the resemblance and the dissemblance].

PubMed

Ayadi, W; Khabir, A; Hadhri-Guiga, B; Fki, L; Toumi, N; Siala, W; Charfi, S; Fendri, A; Makni, H; Boudawara, T; Ghorbel, A; Gargouri, A; Jlidi, R; Gargouri, R; Busson, P; Drira, M; Daoud, J; Frikha, M; Hammami, A; Karray-Hakim, H

2010-04-01

Nasopharyngeal carcinoma (NPC) is an unusual head and neck cancer because of its unequal geographical distribution and its consistent association with the Epstein-Barr virus (EBV). This malignant tumor poses a serious public health problem in many countries, especially in Southeast Asia and North Africa where the recorded incidence are highest. During the past decade, a growing number of studies were undertaken to define the molecular basis of NPC. However, the analysis of several clinical and biological parameters of North African and Southeast Asian NPCs has shown notable differences, suggesting that they could result from a distinct combination of etiological factors. One intriguing characteristic of North African NPC, concerns its bimodal age distribution with a secondary peak of incidence in the range of 15-25 years, not observed in Asian NPC. In this juvenile form of NPC, immuno-histochemistry assay has shown that the two key proteins controlling the apoptotic-survival balance p53 and Bcl-2 are less frequently expressed whereas the transmembrane tyrosine-kinase receptor c-kit and the main EBV oncoprotein LMP1 were more abundant. In addition, the EBV serological alterations are less informative for the diagnosis of the juvenile compared to the adult form. In addition, most North African NPCs contain EBV strains with genetic polymorphisms distinct from those described in the Southeast Asia series (predominance of F, D, H1-H2, XhoI+ and f, C, H, XhoI- respectively). In contrast, studies relating on tumor chromosomal alterations or aberrant promoter methylation result in data very similar to those obtained from the Southeast Asia series, supporting the concept of a common molecular basis for all NPC regardless of patient geographic origin.

Distinct virulence of Rift Valley fever phlebovirus strains from different genetic lineages in a mouse model.

PubMed

Ikegami, Tetsuro; Balogh, Aaron; Nishiyama, Shoko; Lokugamage, Nandadeva; Saito, Tais B; Morrill, John C; Shivanna, Vinay; Indran, Sabarish V; Zhang, Lihong; Smith, Jennifer K; Perez, David; Juelich, Terry L; Morozov, Igor; Wilson, William C; Freiberg, Alexander N; Richt, Juergen A

2017-01-01

Rift Valley fever phlebovirus (RVFV) causes high rates of abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral transmission occurs via mosquito vectors in endemic areas, which necessitates regular vaccination of susceptible livestock animals to prevent the RVF outbreaks. Although ZH501 strain has been used as a challenge strain for past vaccine efficacy studies, further characterization of other RVFV strains is important to optimize ruminant and nonhuman primate RVFV challenge models. This study aimed to characterize the virulence of wild-type RVFV strains belonging to different genetic lineages in outbred CD1 mice. Mice were intraperitoneally infected with 1x103 PFU of wild-type ZH501, Kenya 9800523, Kenya 90058, Saudi Arabia 200010911, OS1, OS7, SA75, Entebbe, or SA51 strains. Among them, mice infected with SA51, Entebbe, or OS7 strain showed rapid dissemination of virus in livers and peracute necrotic hepatitis at 2-3 dpi. Recombinant SA51 (rSA51) and Zinga (rZinga) strains were recovered by reverse genetics, and their virulence was also tested in CD1 mice. The rSA51 strain reproduced peracute RVF disease in mice, whereas the rZinga strain showed a similar virulence with that of rZH501 strain. This study showed that RVFV strains in different genetic lineages display distinct virulence in outbred mice. Importantly, since wild-type RVFV strains contain defective-interfering RNA or various genetic subpopulations during passage from original viral isolations, recombinant RVFV strains generated by reverse genetics will be better suitable for reproducible challenge studies for vaccine development as well as pathological studies.

Distinct virulence of Rift Valley fever phlebovirus strains from different genetic lineages in a mouse model

PubMed Central

Balogh, Aaron; Nishiyama, Shoko; Lokugamage, Nandadeva; Saito, Tais B.; Morrill, John C.; Shivanna, Vinay; Indran, Sabarish V.; Zhang, Lihong; Smith, Jennifer K.; Perez, David; Juelich, Terry L.; Morozov, Igor; Wilson, William C.; Freiberg, Alexander N.; Richt, Juergen A.

2017-01-01

Rift Valley fever phlebovirus (RVFV) causes high rates of abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral transmission occurs via mosquito vectors in endemic areas, which necessitates regular vaccination of susceptible livestock animals to prevent the RVF outbreaks. Although ZH501 strain has been used as a challenge strain for past vaccine efficacy studies, further characterization of other RVFV strains is important to optimize ruminant and nonhuman primate RVFV challenge models. This study aimed to characterize the virulence of wild-type RVFV strains belonging to different genetic lineages in outbred CD1 mice. Mice were intraperitoneally infected with 1x103 PFU of wild-type ZH501, Kenya 9800523, Kenya 90058, Saudi Arabia 200010911, OS1, OS7, SA75, Entebbe, or SA51 strains. Among them, mice infected with SA51, Entebbe, or OS7 strain showed rapid dissemination of virus in livers and peracute necrotic hepatitis at 2–3 dpi. Recombinant SA51 (rSA51) and Zinga (rZinga) strains were recovered by reverse genetics, and their virulence was also tested in CD1 mice. The rSA51 strain reproduced peracute RVF disease in mice, whereas the rZinga strain showed a similar virulence with that of rZH501 strain. This study showed that RVFV strains in different genetic lineages display distinct virulence in outbred mice. Importantly, since wild-type RVFV strains contain defective-interfering RNA or various genetic subpopulations during passage from original viral isolations, recombinant RVFV strains generated by reverse genetics will be better suitable for reproducible challenge studies for vaccine development as well as pathological studies. PMID:29267298

Genetic profile of a multi-ethnic population from Guiné-Bissau (west African coast) using the new PowerPlex 16 System kit.

PubMed

Gonçalves, Rita; Jesus, José; Fernandes, Ana Teresa; Brehm, António

2002-09-10

Allele and haplotype frequencies of 15 chromosome STR loci included in the kit PowerPlex16 System from Promega, were determined in a sample of unrelated males from Guiné-Bissau, a country from the west African coast. All individuals were subjected to an interview in order to make sure that their ancestors belonged to the same ethnic group. This way we intended to look for possible inter-ethnic differences. PowerPlex 16 includes STRs not studied before in any multi-ethnic population. The kit includes two new allele markers (Penta D and Penta E), which are very useful either in forensics or population genetic studies. The Guinean population presents significant differences when compared with other African populations.

Shared versus distinct genetic contributions of mental wellbeing with depression and anxiety symptoms in healthy twins.

PubMed

Routledge, Kylie M; Burton, Karen L O; Williams, Leanne M; Harris, Anthony; Schofield, Peter R; Clark, C Richard; Gatt, Justine M

2016-10-30

Mental wellbeing and mental illness symptoms are typically conceptualized as opposite ends of a continuum, despite only sharing about a quarter in common variance. We investigated the normative variation in measures of wellbeing and of depression and anxiety in 1486 twins who did not meet clinical criteria for an overt diagnosis. We quantified the shared versus distinct genetic and environmental variance between wellbeing and depression and anxiety symptoms. The majority of participants (93%) reported levels of depression and anxiety symptoms within the healthy range, yet only 23% reported a wellbeing score within the "flourishing" range: the remainder were within the ranges of "moderate" (67%) or "languishing" (10%). In twin models, measures of wellbeing and of depression and anxiety shared 50.09% of variance due to genetic factors and 18.27% due to environmental factors; the rest of the variance was due to unique variation impacting wellbeing or depression and anxiety symptoms. These findings suggest that an absence of clinically-significant symptoms of depression and anxiety does not necessarily indicate that an individual is flourishing. Both unique and shared genetic and environmental factors may determine why some individuals flourish in the absence of symptoms while others do not. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cytochrome and sulfotransferase gene variation in north African populations.

PubMed

Fernández-Santander, Ana; Novillo, Apolonia; Gaibar, María; Romero-Lorca, Alicia; Moral, Pedro; Sánchez-Cuenca, David; Amir, Nadir; Chaabani, Hassen; Harich, Nourdin; Esteban, Maria Esther

2016-08-01

To describe the diversity of four cytochrome and four sulfotransferase polymorphisms in six north African samples. Scarce data have been compiled for these samples despite the rich genetic background of north African populations. CYP3A4*1B, CYP3A4*17, CYP3A4*3, CYP3A5*3, SULT1A1*2, SULT1A2*2, SULT1A2*3 and SULT1E1*2 polymorphisms were explored in 556 individuals from Morocco, Algeria, Tunisia and Libya. Allele frequencies in our samples largely exceeded the variation ranges described for European populations, especially for CYP3A4*1B, SULT1A1*2 and SULT1A2*3. North African populations are heterogeneous, genetically diverse and show a considerable sub-Saharan African contribution for markers associated with increased risk of prostate cancer and with differential drug metabolism.

Variable association of reactive intermediate genes with systemic lupus erythematosus (SLE) in populations with different African ancestry

PubMed Central

Ramos, Paula S.; Oates, James C.; Kamen, Diane L.; Williams, Adrienne H.; Gaffney, Patrick M.; Kelly, Jennifer A.; Kaufman, Kenneth M.; Kimberly, Robert P.; Niewold, Timothy B.; Jacob, Chaim O.; Tsao, Betty P.; Alarcón, Graciela S.; Brown, Elizabeth E.; Edberg, Jeffrey C.; Petri, Michelle A.; Ramsey-Goldman, Rosalind; Reveille, John D.; Vilá, Luis M.; James, Judith A.; Guthridge, Joel M.; Merrill, Joan T.; Boackle, Susan A.; Freedman, Barry I.; Scofield, R. Hal; Stevens, Anne M.; Vyse, Timothy J.; Criswell, Lindsey A.; Moser, Kathy L.; Alarcón-Riquelme, Marta E.; Langefeld, Carl D.; Harley, John B.; Gilkeson, Gary S.

2013-01-01

Objective Little is known about the genetic etiology of systemic lupus erythematosus (SLE) in individuals of African ancestry, despite its higher prevalence and greater disease severity. Overproduction of nitric oxide (NO) and reactive oxygen species are implicated in the pathogenesis and severity of SLE, making NO synthases and other reactive intermediate related genes biological candidates for disease susceptibility. This study analyzed variation in reactive intermediate genes for association with SLE in two populations with African ancestry. Methods A total of 244 SNPs from 53 regions were analyzed in non-Gullah African Americans (AA; 1432 cases and 1687 controls) and the genetically more homogeneous Gullah of the Sea Islands of South Carolina (133 cases and 112 controls) and. Single-marker, haplotype, and two-locus interaction tests were computed for these populations. Results The glutathione reductase gene GSR (rs2253409, P=0.0014, OR [95% CI]=1.26 [1.09–1.44]) was the most significant single-SNP association in AA. In the Gullah, the NADH dehydrogenase NDUFS4 (rs381575, P=0.0065, OR [95%CI]=2.10 [1.23–3.59]) and nitric oxide synthase gene NOS1 (rs561712, P=0.0072, OR [95%CI]=0.62 [0.44–0.88]) were most strongly associated with SLE. When both populations were analyzed together, GSR remained the most significant effect (rs2253409, P=0.00072, OR [95%CI]=1.26 [1.10–1.44]). Haplotype and two-locus interaction analyses also uncovered different loci in each population. Conclusion These results suggest distinct patterns of association with SLE in African-derived populations; specific loci may be more strongly associated within select population groups. PMID:23637325

Perceptions of family history and genetic testing and feasibility of pedigree development among African Americans with hypertension

PubMed Central

Pettey, Christina M; McSweeney, Jean C; Stewart, Katharine E; Price, Elvin T; Cleves, Mario A; Heo, Seongkum; Souder, Elaine

2016-01-01

Background Pedigree development, family history, and genetic testing are thought to be useful in improving outcomes of chronic illnesses such as hypertension (HTN). However, the clinical utility of pedigree development is still unknown. Further, little is known about African Americans’ (AAs’) perceptions of family history and genetic testing. Aims This study examined the feasibility of developing pedigrees for AAs with HTN and explored perceptions of family history and genetic research among AAs with HTN. Methods The US Surgeon General’s My Family Health Portrait was administered, and 30–60 minute in-person individual interviews were conducted. Descriptive statistics were used to analyze pedigree data. Interview transcripts were analyzed with content analysis and constant comparison. Results Twenty-nine AAs with HTN were recruited from one free clinic (15 women, 14 men; mean age 49 years, SD 9.6). Twenty-six (90%) reported their family history in sufficient detail to develop a pedigree. Perceptions of family history included knowledge of HTN in the family, culturally influenced family teaching about HTN, and response to family history of HTN. Most participants agreed to future genetic testing and DNA collection because they wanted to help others; some said they needed more information and others expressed a concern for privacy. Conclusion The majority of AAs in this sample possessed extensive knowledge of HTN within their family and were able to develop a three generation pedigree with assistance. The majority were willing to participate in future genetic research. PMID:25322748

Perceptions of family history and genetic testing and feasibility of pedigree development among African Americans with hypertension.

PubMed

Pettey, Christina M; McSweeney, Jean C; Stewart, Katharine E; Price, Elvin T; Cleves, Mario A; Heo, Seongkum; Souder, Elaine

2015-02-01

Pedigree development, family history, and genetic testing are thought to be useful in improving outcomes of chronic illnesses such as hypertension (HTN). However, the clinical utility of pedigree development is still unknown. Further, little is known about the perceptions of African Americans (AAs) of family history and genetic testing. This study examined the feasibility of developing pedigrees for AAs with HTN and explored perceptions of family history and genetic research among AAs with HTN. The US Surgeon General's My Family Health Portrait was administered, and 30-60 min in-person individual interviews were conducted. Descriptive statistics were used to analyze pedigree data. Interview transcripts were analyzed with content analysis and constant comparison. Twenty-nine AAs with HTN were recruited from one free clinic (15 women, 14 men; mean age 49 years, standard deviation (SD) 9.6). Twenty-six (90%) reported their family history in sufficient detail to develop a pedigree. Perceptions of family history included knowledge of HTN in the family, culturally influenced family teaching about HTN, and response to family history of HTN. Most participants agreed to future genetic testing and DNA collection because they wanted to help others; some said they needed more information and others expressed a concern for privacy. The majority of AAs in this sample possessed extensive knowledge of HTN within their family and were able to develop a three-generation pedigree with assistance. The majority were willing to participate in future genetic research. © The European Society of Cardiology 2014.

Ethiopian highlands as a cradle of the African fossorial root-rats (genus Tachyoryctes), the genetic evidence.

PubMed

Šumbera, Radim; Krásová, Jarmila; Lavrenchenko, Leonid A; Mengistu, Sewnet; Bekele, Afework; Mikula, Ondřej; Bryja, Josef

2018-09-01

Root-rats of the genus Tachyoryctes (Spalacidae) are subterranean herbivores occupying open humid habitats in the highlands of Eastern Africa. There is strong disagreement about species diversity of the genus, because some authors accept two species, while others more than ten. Species with relatively high surface activity, the giant root-rat Tachyoryctes macrocephalus, which is by far largest member of the genus, and the more fossorial African root-rat Tachyoryctes splendens, which eventually has been divided up to 12-13 species, represent two major morphological forms within the genus. In our study, we carried out a multilocus analysis of root-rats' genetic diversity based on samples from 41 localities representing most of Tachyoryctes geographic distribution. Using two mitochondrial and three nuclear genes, we found six main genetic clades possibly representing separate species. These clades were organised into three basal groups whose branching is not well resolved, probably due to fast radiation in the late Pliocene and early Pleistocene. Climatic changes in that time, i.e. fast and repeated changes between extremely dry and humid conditions, which both limited root-rat dispersal, probably stimulated their initial genetic diversification. Contrary to expectation based on the largest root-rat diversity in Kenya (up to eight species by some authors), we found the highest diversity in the Ethiopian highlands, because all but one putative species occur there. All individuals outside of Ethiopia belong to a single recently diverged and expanded clade. This species should bear the name T. annectens (Thomas, 1891), and all other names of taxa described from outside of Ethiopia should be considered its junior synonyms. However, to solve taxonomic issues, future detailed morphological analyses should be conducted on all main clades together with genetic analysis of material from areas of their supposed contact. One of the most interesting findings of the study is the

Co-circulation of genetically distinct groups of avian paramyxovirus type 1 in pigeon Newcastle disease in Iran.

PubMed

Rezaei Far, A; Peighambari, S M; Pourbakhsh, S A; Ashtari, A; Soltani, M

2017-02-01

Pigeons are considered as one of the major natural reservoirs in the epidemiology of Newcastle disease (ND). In this study, the partial sequence of fusion protein gene of 17 pigeon-origin ND viruses (NDVs) isolated during 2012-2013 in Iran was analysed. Since the studied isolates showed F0 protein cleavage sites compatible with velogenic NDVs, all were considered as virulent NDVs. Two isolates carried 112RRQKRF117 as the cleavage site motif, whereas the rest demonstrated 112KRQKRF117 motif which just recently has been reported among Iranian virulent NDVs. Phylogenetic analysis divided all these diverse isolates in two distinct clusters within class II genotype VI. Based on the partial fusion protein gene sequence, 15 out of 17 isolates showed the highest genetic identity to subgenotype VIb/2 and the other two isolates were placed in a distinct genetic group of genotype VI. Based on recent findings, at least two different sublineages of genotype VI are causing the ND outbreaks in the pigeon population and are circulating simultaneously along with virulent NDVs of genotype VII in various species in Iran. The continuing circulation of a diverse group of virulent NDVs as an enzootic in widespread species such as pigeon can cause outbreaks in commercial poultry flocks and also failure in controlling programmes. Therefore, the constant monitoring and awareness of the virus characteristics should be considered in controlling programmes against ND in Iran.

Differences in Allergic Sensitization by Self-reported Race and Genetic Ancestry

PubMed Central

Yang, James J.; Burchard, Esteban G.; Choudhry, Shweta; Johnson, Christine C.; Ownby, Dennis R.; Favro, David; Chen, Justin; Akana, Matthew; Ha, Connie; Kwok, Pui-Yan; Krajenta, Richard; Havstad, Suzanne L.; Joseph, Christine L.; Seibold, Max A.; Shriver, Mark D.; Williams, L. Keoki

2010-01-01

Background Many allergic conditions occur more frequently in African-American patients when compared with white patients; however it is not known whether this represents genetic predisposition or disparate environmental exposures. Objective To assess the relationship of self-reported race and genetic ancestry to allergic sensitization. Methods We included 601 women enrolled in a population-based cohort study whose self-reported race was African-American or white. Genetic ancestry was estimated using markers that differentiate West African and European ancestry. We assessed the relationship between allergic sensitization (defined as ≥1 allergen-specific IgE result) and both self-reported race and genetic ancestry. Regression models adjusted for socio-demographic variables, environmental exposures, and location of residence. Results The average proportion of West African ancestry in African-American participants was 0.69, whereas the mean proportion of European ancestry in white participants was 0.79. Self-reported African-American race was associated with allergic sensitization when compared with those who reported being white (adjusted odds ratio [aOR] 2.19; 95% confidence interval [CI] 1.22 – 3.93) even after adjusting for other variables. Genetic ancestry was not significantly associated with allergic sensitization after accounting for location of residence (aOR 2.09 for urban vs. suburban residence, 95% CI 1.32 −3.31). Conclusion Self-reported race and location of residence appeared to be more important predictors of allergic sensitization when compared with genetic ancestry, suggesting that the disparity in allergic sensitization by race may be primarily due to environmental factors rather than genetic differences. Clinical Implications These data suggest that efforts to eliminate disparities in allergic sensitization should focus on contributing environmental factors. PMID:19014772

Transancestral mapping and genetic load in systemic lupus erythematosus.

PubMed

Langefeld, Carl D; Ainsworth, Hannah C; Cunninghame Graham, Deborah S; Kelly, Jennifer A; Comeau, Mary E; Marion, Miranda C; Howard, Timothy D; Ramos, Paula S; Croker, Jennifer A; Morris, David L; Sandling, Johanna K; Almlöf, Jonas Carlsson; Acevedo-Vásquez, Eduardo M; Alarcón, Graciela S; Babini, Alejandra M; Baca, Vicente; Bengtsson, Anders A; Berbotto, Guillermo A; Bijl, Marc; Brown, Elizabeth E; Brunner, Hermine I; Cardiel, Mario H; Catoggio, Luis; Cervera, Ricard; Cucho-Venegas, Jorge M; Dahlqvist, Solbritt Rantapää; D'Alfonso, Sandra; Da Silva, Berta Martins; de la Rúa Figueroa, Iñigo; Doria, Andrea; Edberg, Jeffrey C; Endreffy, Emőke; Esquivel-Valerio, Jorge A; Fortin, Paul R; Freedman, Barry I; Frostegård, Johan; García, Mercedes A; de la Torre, Ignacio García; Gilkeson, Gary S; Gladman, Dafna D; Gunnarsson, Iva; Guthridge, Joel M; Huggins, Jennifer L; James, Judith A; Kallenberg, Cees G M; Kamen, Diane L; Karp, David R; Kaufman, Kenneth M; Kottyan, Leah C; Kovács, László; Laustrup, Helle; Lauwerys, Bernard R; Li, Quan-Zhen; Maradiaga-Ceceña, Marco A; Martín, Javier; McCune, Joseph M; McWilliams, David R; Merrill, Joan T; Miranda, Pedro; Moctezuma, José F; Nath, Swapan K; Niewold, Timothy B; Orozco, Lorena; Ortego-Centeno, Norberto; Petri, Michelle; Pineau, Christian A; Pons-Estel, Bernardo A; Pope, Janet; Raj, Prithvi; Ramsey-Goldman, Rosalind; Reveille, John D; Russell, Laurie P; Sabio, José M; Aguilar-Salinas, Carlos A; Scherbarth, Hugo R; Scorza, Raffaella; Seldin, Michael F; Sjöwall, Christopher; Svenungsson, Elisabet; Thompson, Susan D; Toloza, Sergio M A; Truedsson, Lennart; Tusié-Luna, Teresa; Vasconcelos, Carlos; Vilá, Luis M; Wallace, Daniel J; Weisman, Michael H; Wither, Joan E; Bhangale, Tushar; Oksenberg, Jorge R; Rioux, John D; Gregersen, Peter K; Syvänen, Ann-Christine; Rönnblom, Lars; Criswell, Lindsey A; Jacob, Chaim O; Sivils, Kathy L; Tsao, Betty P; Schanberg, Laura E; Behrens, Timothy W; Silverman, Earl D; Alarcón-Riquelme, Marta E; Kimberly, Robert P; Harley, John B; Wakeland, Edward K; Graham, Robert R; Gaffney, Patrick M; Vyse, Timothy J

2017-07-17

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10 -8 ), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.

Transancestral mapping and genetic load in systemic lupus erythematosus

PubMed Central

Langefeld, Carl D.; Ainsworth, Hannah C.; Graham, Deborah S. Cunninghame; Kelly, Jennifer A.; Comeau, Mary E.; Marion, Miranda C.; Howard, Timothy D.; Ramos, Paula S.; Croker, Jennifer A.; Morris, David L.; Sandling, Johanna K.; Almlöf, Jonas Carlsson; Acevedo-Vásquez, Eduardo M.; Alarcón, Graciela S.; Babini, Alejandra M.; Baca, Vicente; Bengtsson, Anders A.; Berbotto, Guillermo A.; Bijl, Marc; Brown, Elizabeth E.; Brunner, Hermine I.; Cardiel, Mario H.; Catoggio, Luis; Cervera, Ricard; Cucho-Venegas, Jorge M.; Dahlqvist, Solbritt Rantapää; D’Alfonso, Sandra; Da Silva, Berta Martins; de la Rúa Figueroa, Iñigo; Doria, Andrea; Edberg, Jeffrey C.; Endreffy, Emőke; Esquivel-Valerio, Jorge A.; Fortin, Paul R.; Freedman, Barry I.; Frostegård, Johan; García, Mercedes A.; de la Torre, Ignacio García; Gilkeson, Gary S.; Gladman, Dafna D.; Gunnarsson, Iva; Guthridge, Joel M.; Huggins, Jennifer L.; James, Judith A.; Kallenberg, Cees G. M.; Kamen, Diane L.; Karp, David R.; Kaufman, Kenneth M.; Kottyan, Leah C.; Kovács, László; Laustrup, Helle; Lauwerys, Bernard R.; Li, Quan-Zhen; Maradiaga-Ceceña, Marco A.; Martín, Javier; McCune, Joseph M.; McWilliams, David R.; Merrill, Joan T.; Miranda, Pedro; Moctezuma, José F.; Nath, Swapan K.; Niewold, Timothy B.; Orozco, Lorena; Ortego-Centeno, Norberto; Petri, Michelle; Pineau, Christian A.; Pons-Estel, Bernardo A.; Pope, Janet; Raj, Prithvi; Ramsey-Goldman, Rosalind; Reveille, John D.; Russell, Laurie P.; Sabio, José M.; Aguilar-Salinas, Carlos A.; Scherbarth, Hugo R.; Scorza, Raffaella; Seldin, Michael F.; Sjöwall, Christopher; Svenungsson, Elisabet; Thompson, Susan D.; Toloza, Sergio M. A.; Truedsson, Lennart; Tusié-Luna, Teresa; Vasconcelos, Carlos; Vilá, Luis M.; Wallace, Daniel J.; Weisman, Michael H.; Wither, Joan E.; Bhangale, Tushar; Oksenberg, Jorge R.; Rioux, John D.; Gregersen, Peter K.; Syvänen, Ann-Christine; Rönnblom, Lars; Criswell, Lindsey A.; Jacob, Chaim O.; Sivils, Kathy L.; Tsao, Betty P.; Schanberg, Laura E.; Behrens, Timothy W.; Silverman, Earl D.; Alarcón-Riquelme, Marta E.; Kimberly, Robert P.; Harley, John B.; Wakeland, Edward K.; Graham, Robert R.; Gaffney, Patrick M.; Vyse, Timothy J.

2017-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10−8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE. PMID:28714469

Population genetics of Vibrio vulnificus: identification of two divisions and a distinct eel-pathogenic clone.

PubMed

Gutacker, Michaela; Conza, Nadine; Benagli, Cinzia; Pedroli, Ambra; Bernasconi, Marco Valerio; Permin, Lise; Aznar, Rosa; Piffaretti, Jean-Claude

2003-06-01

Genetic relationships among 62 Vibrio vulnificus strains of different geographical and host origins were analyzed by multilocus enzyme electrophoresis (MLEE), random amplification of polymorphic DNA (RAPD), and sequence analyses of the recA and glnA genes. Out of 15 genetic loci analyzed by MLEE, 11 were polymorphic. Cluster analysis identified 43 distinct electrophoretic types (ETs) separating the V. vulnificus population into two divisions (divisions I and II). One ET (ET 35) included all indole-negative isolates from diseased eels worldwide (biotype 2). A second ET (ET 2) marked all of the strains from Israel isolated from patients who handled St. Peter's fish (biotype 3). RAPD analysis of the 62 V. vulnificus isolates identified 26 different profiles separated into two divisions as well. In general, this subdivision was comparable (but not identical) to that observed by MLEE. Phylogenetic analysis of 543 bp of the recA gene and of 402 bp of the glnA gene also separated the V. vulnificus population into two major divisions in a manner similar to that by MLEE and RAPD. Sequence data again indicated the overall subdivision of the V. vulnificus population into different biotypes. In particular, indole-negative eel-pathogenic isolates (biotype 2) on one hand and the Israeli isolates (biotype 3) on the other tended to cluster together in both gene trees. None of the methods showed an association between distinct clones and human clinical manifestations. Furthermore, except for the Israeli strains, only minor clusters comprising geographically related isolates were observed. In conclusion, all three approaches (MLEE, RAPD, and DNA sequencing) generated comparable but not always equivalent results. The significance of the two divisions (divisions I and II) still remains to be clarified, and a reevaluation of the definition of the biotypes is also needed.

The African Diaspora: History, Adaptation and Health

PubMed Central

Rotimi, Charles N.; Tekola-Ayele, Fasil; Baker, Jennifer L.; Shriner, Daniel

2017-01-01

The trans-Atlantic slave trade brought millions of Africans to the New World. Advances in genomics are providing novel insights into the history and health of Africans and the diasporan populations. Recent examples reviewed here include the unraveling of substantial hunter-gatherer and “Eurasian” admixtures across sub-Saharan Africa, expanding our understanding of ancestral African genetics; the global ubiquity of mixed ancestry; the revealing of African ancestry in Latin Americans that likely derived from the slave trade; and understanding of the ancestral backgrounds of APOL1 and LPL found to influence kidney disease and lipid levels, respectively, providing specific insights into disease etiology and health disparities. PMID:27644073

The African diaspora: history, adaptation and health.

PubMed

Rotimi, Charles N; Tekola-Ayele, Fasil; Baker, Jennifer L; Shriner, Daniel

2016-12-01

The trans-Atlantic slave trade brought millions of Africans to the New World. Advances in genomics are providing novel insights into the history and health of Africans and the diasporan populations. Recent examples reviewed here include the unraveling of substantial hunter-gatherer and 'Eurasian' admixtures across sub-Saharan Africa, expanding our understanding of ancestral African genetics; the global ubiquity of mixed ancestry; the revealing of African ancestry in Latin Americans that likely derived from the slave trade; and understanding of the ancestral backgrounds of APOL1 and LPL found to influence kidney disease and lipid levels, respectively, providing specific insights into disease etiology and health disparities. Published by Elsevier Ltd.

Large-scale pattern of genetic differentiation within African rainforest trees: insights on the roles of ecological gradients and past climate changes on the evolution of Erythrophleum spp (Fabaceae).

PubMed

Duminil, Jerome; Brown, Richard P; Ewédjè, Eben-Ezer B K; Mardulyn, Patrick; Doucet, Jean-Louis; Hardy, Olivier J

2013-09-12

The evolutionary events that have shaped biodiversity patterns in the African rainforests are still poorly documented. Past forest fragmentation and ecological gradients have been advocated as important drivers of genetic differentiation but their respective roles remain unclear. Using nuclear microsatellites (nSSRs) and chloroplast non-coding sequences (pDNA), we characterised the spatial genetic structure of Erythrophleum (Fabaceae) forest trees in West and Central Africa (Guinea Region, GR). This widespread genus displays a wide ecological amplitude and taxonomists recognize two forest tree species, E. ivorense and E. suaveolens, which are difficult to distinguish in the field and often confused. Bayesian-clustering applied on nSSRs of a blind sample of 648 specimens identified three major gene pools showing no or very limited introgression. They present parapatric distributions correlated to rainfall gradients and forest types. One gene pool is restricted to coastal evergreen forests and corresponds to E. ivorense; a second one is found in gallery forests from the dry forest zone of West Africa and North-West Cameroon and corresponds to West-African E. suaveolens; the third gene pool occurs in semi-evergreen forests and corresponds to Central African E. suaveolens. These gene pools have mostly unique pDNA haplotypes but they do not form reciprocally monophyletic clades. Nevertheless, pDNA molecular dating indicates that the divergence between E. ivorense and Central African E. suaveolens predates the Pleistocene. Further Bayesian-clustering applied within each major gene pool identified diffuse genetic discontinuities (minor gene pools displaying substantial introgression) at a latitude between 0 and 2°N in Central Africa for both species, and at a longitude between 5° and 8°E for E. ivorense. Moreover, we detected evidence of past population declines which are consistent with historical habitat fragmentation induced by Pleistocene climate changes. Overall

Large-scale pattern of genetic differentiation within African rainforest trees: insights on the roles of ecological gradients and past climate changes on the evolution of Erythrophleum spp (Fabaceae)

PubMed Central

2013-01-01

Background The evolutionary events that have shaped biodiversity patterns in the African rainforests are still poorly documented. Past forest fragmentation and ecological gradients have been advocated as important drivers of genetic differentiation but their respective roles remain unclear. Using nuclear microsatellites (nSSRs) and chloroplast non-coding sequences (pDNA), we characterised the spatial genetic structure of Erythrophleum (Fabaceae) forest trees in West and Central Africa (Guinea Region, GR). This widespread genus displays a wide ecological amplitude and taxonomists recognize two forest tree species, E. ivorense and E. suaveolens, which are difficult to distinguish in the field and often confused. Results Bayesian-clustering applied on nSSRs of a blind sample of 648 specimens identified three major gene pools showing no or very limited introgression. They present parapatric distributions correlated to rainfall gradients and forest types. One gene pool is restricted to coastal evergreen forests and corresponds to E. ivorense; a second one is found in gallery forests from the dry forest zone of West Africa and North-West Cameroon and corresponds to West-African E. suaveolens; the third gene pool occurs in semi-evergreen forests and corresponds to Central African E. suaveolens. These gene pools have mostly unique pDNA haplotypes but they do not form reciprocally monophyletic clades. Nevertheless, pDNA molecular dating indicates that the divergence between E. ivorense and Central African E. suaveolens predates the Pleistocene. Further Bayesian-clustering applied within each major gene pool identified diffuse genetic discontinuities (minor gene pools displaying substantial introgression) at a latitude between 0 and 2°N in Central Africa for both species, and at a longitude between 5° and 8°E for E. ivorense. Moreover, we detected evidence of past population declines which are consistent with historical habitat fragmentation induced by Pleistocene climate

Population genetics of Glossina palpalis palpalis from central African sleeping sickness foci.

PubMed

Melachio, Trésor Tito Tanekou T T; Simo, Gustave; Ravel, Sophie; De Meeûs, Thierry; Causse, Sandrine; Solano, Philippe; Lutumba, Pascal; Asonganyi, Tazoacha; Njiokou, Flobert

2011-07-18

Glossina palpalis palpalis (Diptera: Glossinidae) is widespread in west Africa, and is the main vector of sleeping sickness in Cameroon as well as in the Bas Congo Province of the Democratic Republic of Congo. However, little is known on the structure of its populations. We investigated G. p. palpalis population genetic structure in five sleeping sickness foci (four in Cameroon, one in Democratic Republic of Congo) using eight microsatellite DNA markers. A strong isolation by distance explains most of the population structure observed in our sampling sites of Cameroon and DRC. The populations here are composed of panmictic subpopulations occupying fairly wide zones with a very strong isolation by distance. Effective population sizes are probably between 20 and 300 individuals and if we assume densities between 120 and 2000 individuals per km2, dispersal distance between reproducing adults and their parents extends between 60 and 300 meters. This first investigation of population genetic structure of G. p. palpalis in Central Africa has evidenced random mating subpopulations over fairly large areas and is thus at variance with that found in West African populations of G. p. palpalis. This study brings new information on the isolation by distance at a macrogeographic scale which in turn brings useful information on how to organise regional tsetse control. Future investigations should be directed at temporal sampling to have more accurate measures of demographic parameters in order to help vector control decision.

Antigenic and genetic characterization of serotype G2 human rotavirus strains from the African continent.

PubMed

Page, N A; Steele, A D

2004-02-01

Serotype G2 rotavirus strains were isolated in seven countries on the African continent during 1999 and 2000. To investigate the associated DS-1 genogroup characteristics, subgroup (VP6) enzyme-linked immunosorbent assay, polyacrylamide gel electrophoresis, and P genotyping were performed on 10 G2 strains. The antigenic and genetic variation of the gene encoding the major neutralization glycoprotein (VP7) was also investigated by using G2-specific monoclonal antibodies and sequence analysis. Alterations in the characteristic DS-1 genogroup gene constellations were more likely to occur in the VP4 gene, and three genotypes were observed: P[4], P[6], and a dual P[4]-P[6] type. The failure of G2-specific monoclonal antibodies to type African G2 strains was more likely due to improper storage of the original stool, although G2 monotypes were detected. Phylogenetic analyses revealed clusters of serotype G2 strains that were more commonly associated with seasons during which G2 was predominant. No rotavirus vaccine trials have been conducted in an area where G2 strains were the predominant circulating serotype, and the continued surveillance of rotavirus epidemics in Africa will be preparation for future vaccine implementation in an area that clearly needs these preventative medicines.

al mena: a comprehensive resource of human genetic variants integrating genomes and exomes from Arab, Middle Eastern and North African populations.

PubMed

Koshy, Remya; Ranawat, Anop; Scaria, Vinod

2017-10-01

Middle East and North Africa (MENA) encompass very unique populations, with a rich history and encompasses characteristic ethnic, linguistic and genetic diversity. The genetic diversity of MENA region has been largely unknown. The recent availability of whole-exome and whole-genome sequences from the region has made it possible to collect population-specific allele frequencies. The integration of data sets from this region would provide insights into the landscape of genetic variants in this region. We integrated genetic variants from multiple data sets systematically, available from this region to create a compendium of over 26 million genetic variations. The variants were systematically annotated and their allele frequencies in the data sets were computed and available as a web interface which enables quick query. As a proof of principle for application of the compendium for genetic epidemiology, we analyzed the allele frequencies for variants in transglutaminase 1 (TGM1) gene, associated with autosomal recessive lamellar ichthyosis. Our analysis revealed that the carrier frequency of selected variants differed widely with significant interethnic differences. To the best of our knowledge, al mena is the first and most comprehensive repertoire of genetic variations from the Arab, Middle Eastern and North African region. We hope al mena would accelerate Precision Medicine in the region.

Genetic Characterization of Circulating African Swine Fever Viruses in Nigeria (2007-2015).

PubMed

Luka, P D; Achenbach, J E; Mwiine, F N; Lamien, C E; Shamaki, D; Unger, H; Erume, J

2017-10-01

Sequencing and analysis of three discrete genome regions of African swine fever viruses (ASFV) from archival samples collected in 2007-2011 and active and passive surveillance between 2012 and 2015 in Nigeria were carried out. Analysis was conducted by genotyping of three single-copy African swine fever (ASF) genes. The E183L and B646L genes that encode structural proteins p54 and p72, respectively, were utilized to delineate genotypes before intragenotypic resolution by characterization of the tetrameric amino acid repeat region within the hypervariable central variable region of the B602L gene. The results showed no variation in the p72 and p54 gene regions sequenced. Phylogeny of p72 sequences revealed that all the Nigerian isolates belonged to genotype I, while that of the p54 recovered the Ia genotype. Analysis of B602L gene revealed the differences in the number of tetrameric repeats. Four new variants (Tet-15, Tet-17a, Tet-17b and Tet-48) were recovered, while a fifth variant (Tet-20) was the most widely distributed in the country displacing Tet-36 reported previously in 2003-2006. The viruses responsible for ASF outbreaks in Nigeria are from very closely related but mutated variants of the virus that have been circulating since 1997. A practical implication of the genetic variability of the Nigerian viral isolates in this study is the need for continuous sampling and analysis of circulating viruses, which will provide epidemiological information on the evolution of ASFV in the field versus new incursion for informed strategic control of the disease in the country. © 2016 Blackwell Verlag GmbH.

Who Are the Okinawans? Ancestry, Genome Diversity, and Implications for the Genetic Study of Human Longevity From a Geographically Isolated Population

PubMed Central

Hsueh, Wen-Chi; He, Qimei; Willcox, D. Craig; Nievergelt, Caroline M.; Donlon, Timothy A.; Kwok, Pui-Yan; Suzuki, Makoto; Willcox, Bradley J.

2014-01-01

Isolated populations have advantages for genetic studies of longevity from decreased haplotype diversity and long-range linkage disequilibrium. This permits smaller sample sizes without loss of power, among other utilities. Little is known about the genome of the Okinawans, a potential population isolate, recognized for longevity. Therefore, we assessed genetic diversity, structure, and admixture in Okinawans, and compared this with Caucasians, Chinese, Japanese, and Africans from HapMap II, genotyped on the same Affymetrix GeneChip Human Mapping 500K array. Principal component analysis, haplotype coverage, and linkage disequilibrium decay revealed a distinct Okinawan genome—more homogeneity, less haplotype diversity, and longer range linkage disequilibrium. Population structure and admixture analyses utilizing 52 global reference populations from the Human Genome Diversity Cell Line Panel demonstrated that Okinawans clustered almost exclusively with East Asians. Sibling relative risk (λs) analysis revealed that siblings of Okinawan centenarians have 3.11 times (females) and 3.77 times (males) more likelihood of centenarianism. These findings suggest that Okinawans are genetically distinct and share several characteristics of a population isolate, which are prone to develop extreme phenotypes (eg, longevity) from genetic drift, natural selection, and population bottlenecks. These data support further exploration of genetic influence on longevity in the Okinawans. PMID:24444611

Shorter telomere length in Europeans than in Africans due to polygenetic adaptation.

PubMed

Hansen, Matthew E B; Hunt, Steven C; Stone, Rivka C; Horvath, Kent; Herbig, Utz; Ranciaro, Alessia; Hirbo, Jibril; Beggs, William; Reiner, Alexander P; Wilson, James G; Kimura, Masayuki; De Vivo, Immaculata; Chen, Maxine M; Kark, Jeremy D; Levy, Daniel; Nyambo, Thomas; Tishkoff, Sarah A; Aviv, Abraham

2016-06-01

Leukocyte telomere length (LTL), which reflects telomere length in other somatic tissues, is a complex genetic trait. Eleven SNPs have been shown in genome-wide association studies to be associated with LTL at a genome-wide level of significance within cohorts of European ancestry. It has been observed that LTL is longer in African Americans than in Europeans. The underlying reason for this difference is unknown. Here we show that LTL is significantly longer in sub-Saharan Africans than in both Europeans and African Americans. Based on the 11 LTL-associated alleles and genetic data in phase 3 of the 1000 Genomes Project, we show that the shifts in allele frequency within Europe and between Europe and Africa do not fit the pattern expected by neutral genetic drift. Our findings suggest that differences in LTL within Europeans and between Europeans and Africans is influenced by polygenic adaptation and that differences in LTL between Europeans and Africans might explain, in part, ethnic differences in risks for human diseases that have been linked to LTL. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Asthma progression to airway remodeling and bone marrow eosinophil responses in genetically distinct strains of mice.

PubMed

Hogan, Mary Beth; Piktel, Debra; Hubbs, Ann F; McPherson, Leslie E; Landreth, Kenneth S

2008-12-01

Patient factors that cause long-term airway remodeling are largely unidentified. This suggests that genetic differences may determine which asthmatic patients develop airway remodeling. A murine model with repeated allergen exposure leading to peribronchial fibrosis in complement factor 5 (C5)-deficient A/J mice has been used to study asthma progression. No studies have addressed the systemic effects of allergen sensitization or chronic allergen exposure on bone marrow eosinophilopoiesis in this mouse strain. To investigate bone marrow eosinophil responses during acute sensitization and chronic allergen exposure using genetically distinct mouse strains differing in persistent airway reactivity and remodeling. The C5-sufficient BALB/c and C5-deficient A/J mice were repetitively exposed to intranasal ovalbumin for 12 weeks. Subsequently, the mice were evaluated for airway eosinophilia, mucus-containing goblet cells, and peribronchial fibrosis. Both strains of mice were also acutely sensitized to ovalbumin. Bone marrow eosinophil progenitor cells and mature eosinophils were enumerated. BALB/c and A/J mice have similar bone marrow responses after acute allergen exposure, with elevations in bone marrow eosinophil progenitor cell and eosinophil numbers. After chronic allergen exposure, only C5-deficient A/J mice that developed peribronchial fibrosis exhibited bone marrow eosinophilia. BALB/c mice lacked peribronchial fibrosis and extinguished accelerated eosinophil production after long-term allergen challenge. Chronic airway remodeling after repeated allergen exposure in genetically different mice correlated with differences in long-term bone marrow eosinophilopoiesis. Preventing asthma from progressing to chronic airway remodeling with fibrosis may involve identifying genetically determined influences on bone marrow responses to chronic allergen exposure.

Genetic variation in N- and C-terminal regions of bovine DNAJA1 heat shock protein gene in African, Asian and American cattle.

PubMed

Ajayi, Oyeyemi O; Peters, Sunday O; De Donato, Marcos; Mujibi, F Denis; Khan, Waqas A; Hussain, Tanveer; Babar, Masroor E; Imumorin, Ikhide G; Thomas, Bolaji N

2018-01-01

DNAJA1 or heat shock protein 40 (Hsp40) is associated with heat adaptation in various organisms. We amplified and sequenced a total of 1,142 bp of bovine Hsp40 gene representing the critical N-terminal (NTR) and C-terminal (CTR) regions in representative samples of African, Asian and American cattle breeds. Eleven and 9 different haplotypes were observed in the NTR in Asian and African breeds respectively while in American Brangus, only two mutations were observed resulting in two haplotypes. The CTR appears to be highly conserved between cattle and yak. In-silico functional analysis with PANTHER predicted putative deleterious functional impact of c.161 T>A; p. V54Q while alignment of bovine and human NTR-J domains revealed that p.Q19H, p.E20Q and p. E21X mutations occurred in helix 2 and p.V54Q missense mutation occurred in helix 3 respectively. The 124 bp insertion found in the yak DNAJA1 ortholog may have significant functional relevance warranting further investigation. Our results suggest that these genetic differences may be concomitant with population genetic history and possible functional consequences for climate adaptation in bovidae.

Two Genetic Loci Produce Distinct Carbohydrate-Rich Structural Components of the Pseudomonas aeruginosa Biofilm Matrix

PubMed Central

Friedman, Lisa; Kolter, Roberto

2004-01-01

Pseudomonas aeruginosa forms biofilms, which are cellular aggregates encased in an extracellular matrix. Molecular genetics studies of three common autoaggregative phenotypes, namely wrinkled colonies, pellicles, and solid-surface-associated biofilms, led to the identification of two loci, pel and psl, that are involved in the production of carbohydrate-rich components of the biofilm matrix. The pel gene cluster is involved in the production of a glucose-rich matrix material in P. aeruginosa strain PA14 (L. Friedman and R. Kolter, Mol. Microbiol. 51:675-690, 2004). Here we investigate the role of the pel gene cluster in P. aeruginosa strain ZK2870 and identify a second genetic locus, termed psl, involved in the production of a mannose-rich matrix material. The 11 predicted protein products of the psl genes are homologous to proteins involved in carbohydrate processing. P. aeruginosa is thus able to produce two distinct carbohydrate-rich matrix materials. Either carbohydrate-rich matrix component appears to be sufficient for mature biofilm formation, and at least one of them is required for mature biofilm formation in P. aeruginosa strains PA14 and ZK2870. PMID:15231777

Two genetic loci produce distinct carbohydrate-rich structural components of the Pseudomonas aeruginosa biofilm matrix.

PubMed

Friedman, Lisa; Kolter, Roberto

2004-07-01

Pseudomonas aeruginosa forms biofilms, which are cellular aggregates encased in an extracellular matrix. Molecular genetics studies of three common autoaggregative phenotypes, namely wrinkled colonies, pellicles, and solid-surface-associated biofilms, led to the identification of two loci, pel and psl, that are involved in the production of carbohydrate-rich components of the biofilm matrix. The pel gene cluster is involved in the production of a glucose-rich matrix material in P. aeruginosa strain PA14 (L. Friedman and R. Kolter, Mol. Microbiol. 51:675-690, 2004). Here we investigate the role of the pel gene cluster in P. aeruginosa strain ZK2870 and identify a second genetic locus, termed psl, involved in the production of a mannose-rich matrix material. The 11 predicted protein products of the psl genes are homologous to proteins involved in carbohydrate processing. P. aeruginosa is thus able to produce two distinct carbohydrate-rich matrix materials. Either carbohydrate-rich matrix component appears to be sufficient for mature biofilm formation, and at least one of them is required for mature biofilm formation in P. aeruginosa strains PA14 and ZK2870. Copyright 2004 American Society for Microbiology

Measuring Type 2 Diabetes Mellitus Knowledge and Perceptions of Risk in Middle-Class African Americans

ERIC Educational Resources Information Center

Spears, Erica C.; Guidry, Jeffrey J.; Harvey, Idethia S.

2018-01-01

There is a paucity in the literature examining the African American middle-class. Most studies of African Americans and Type 2 Diabetes Mellitus (T2DM) have concentrated on lower-SES individuals, or make no distinction between African Americans of varying socio-economic positions. Middle-class African Americans are vulnerable in ways often…

Racial and ethnic variations in knowledge and attitudes about genetic testing.

PubMed

Singer, Eleanor; Antonucci, Toni; Van Hoewyk, John

2004-01-01

This study was designed to shed light on whether differences in utilization of genetic testing by African-Americans, Latinos, and non-Hispanic Whites are due primarily to different preferences, or whether they instead reflect other values and beliefs or differential access. It explores the values, attitudes, and beliefs of African-Americans, Latinos, and non-Hispanic Whites with respect to genetic testing by means of a telephone survey of representative samples of these three groups. The study finds clear evidence that Latinos and African-Americans are, if anything, more likely to express preferences for both prenatal and adult genetic testing than White respondents. At the same time, they hold other beliefs and attitudes that may conflict with, and override, these preferences in specific situations. African-Americans and Latinos are also less knowledgeable about genetic testing than non-Hispanic Whites, and they are less likely to have the financial resources or insurance coverage that would facilitate access to testing.

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

Genetic diversity and differentiation among insular honey bee populations in the southwest Indian Ocean likely reflect old geographical isolation and modern introductions.

PubMed

Techer, Maéva Angélique; Clémencet, Johanna; Simiand, Christophe; Turpin, Patrick; Garnery, Lionel; Reynaud, Bernard; Delatte, Hélène

2017-01-01

With globalization the Western honey bee has become a nearly cosmopolitan species, but it was originally restricted to the Old World. This renowned model of biodiversity has diverged into five evolutionary lineages and several geographic "subspecies." If Apis mellifera unicolor is indubitably an African subspecies endemic to Madagascar, its relationship with honey bees from three archipelagos in the southwest Indian Ocean (SWIO) hotspot of biodiversity is misunderstood. We compared recent mtDNA diversity data to an original characterization of the nuclear diversity from honey bees in the Mascarenes and Comoros archipelagos, using 14 microsatellites, but also additional mtDNA tRNALeu-cox2 analysis. Our sampling offers the most comprehensive dataset for the SWIO populations with a total of 3,270 colonies from 10 islands compared with 855 samples from Madagascar, 113 from Africa, and 138 from Europe. Comprehensive mitochondrial screening confirmed that honey bees from La Réunion, Mauritius, and Comoros archipelagos are mainly of African origin (88.1% out of 2,746 colonies) and that coexistence with European lineages occurs only in the Mascarenes. PCA, Bayesian, and genetic differentiation analysis showed that African colonies are not significantly distinct on each island, but have diversified among islands and archipelagos. FST levels progressively decreased in significance from European and African continental populations, to SWIO insular and continental populations, and finally among islands from the same archipelago. Among African populations, Madagascar shared a nuclear background with and was most closely related to SWIO island populations (except Rodrigues). Only Mauritius Island presented clear cytoplasmic disequilibrium and genetic structure characteristic of an admixed population undergoing hybridization, in this case, between A. m. unicolor and A. m. ligustica, A. m. carnica and A. m. mellifera-like individuals. Finally, global genetic clustering analysis

Genetic diversity and differentiation among insular honey bee populations in the southwest Indian Ocean likely reflect old geographical isolation and modern introductions

PubMed Central

Clémencet, Johanna; Simiand, Christophe; Turpin, Patrick; Garnery, Lionel; Reynaud, Bernard; Delatte, Hélène

2017-01-01

With globalization the Western honey bee has become a nearly cosmopolitan species, but it was originally restricted to the Old World. This renowned model of biodiversity has diverged into five evolutionary lineages and several geographic “subspecies.” If Apis mellifera unicolor is indubitably an African subspecies endemic to Madagascar, its relationship with honey bees from three archipelagos in the southwest Indian Ocean (SWIO) hotspot of biodiversity is misunderstood. We compared recent mtDNA diversity data to an original characterization of the nuclear diversity from honey bees in the Mascarenes and Comoros archipelagos, using 14 microsatellites, but also additional mtDNA tRNALeu-cox2 analysis. Our sampling offers the most comprehensive dataset for the SWIO populations with a total of 3,270 colonies from 10 islands compared with 855 samples from Madagascar, 113 from Africa, and 138 from Europe. Comprehensive mitochondrial screening confirmed that honey bees from La Réunion, Mauritius, and Comoros archipelagos are mainly of African origin (88.1% out of 2,746 colonies) and that coexistence with European lineages occurs only in the Mascarenes. PCA, Bayesian, and genetic differentiation analysis showed that African colonies are not significantly distinct on each island, but have diversified among islands and archipelagos. FST levels progressively decreased in significance from European and African continental populations, to SWIO insular and continental populations, and finally among islands from the same archipelago. Among African populations, Madagascar shared a nuclear background with and was most closely related to SWIO island populations (except Rodrigues). Only Mauritius Island presented clear cytoplasmic disequilibrium and genetic structure characteristic of an admixed population undergoing hybridization, in this case, between A. m. unicolor and A. m. ligustica, A. m. carnica and A. m. mellifera-like individuals. Finally, global genetic clustering

Bat trait, genetic and pathogen data from large-scale investigations of African fruit bats, Eidolon helvum.

PubMed

Peel, Alison J; Baker, Kate S; Hayman, David T S; Suu-Ire, Richard; Breed, Andrew C; Gembu, Guy-Crispin; Lembo, Tiziana; Fernández-Loras, Andrés; Sargan, David R; Fooks, Anthony R; Cunningham, Andrew A; Wood, James L N

2016-08-01

Bats, including African straw-coloured fruit bats (Eidolon helvum), have been highlighted as reservoirs of many recently emerged zoonotic viruses. This common, widespread and ecologically important species was the focus of longitudinal and continent-wide studies of the epidemiological and ecology of Lagos bat virus, henipaviruses and Achimota viruses. Here we present a spatial, morphological, demographic, genetic and serological dataset encompassing 2827 bats from nine countries over an 8-year period. Genetic data comprises cytochrome b mitochondrial sequences (n=608) and microsatellite genotypes from 18 loci (n=544). Tooth-cementum analyses (n=316) allowed derivation of rare age-specific serologic data for a lyssavirus, a henipavirus and two rubulaviruses. This dataset contributes a substantial volume of data on the ecology of E. helvum and its viruses and will be valuable for a wide range of studies, including viral transmission dynamic modelling in age-structured populations, investigation of seasonal reproductive asynchrony in wide-ranging species, ecological niche modelling, inference of island colonisation history, exploration of relationships between island and body size, and various spatial analyses of demographic, morphometric or serological data.

Use and Misuse of Speech Diagnostics for African American Students

ERIC Educational Resources Information Center

Baugh, John

2015-01-01

Many African American students have been tested using speech pathology diagnostics that are ill suited to their distinctive linguistic circumstances. Slave descendants of African origin share a unique linguistic heritage in contrast and comparison to every other immigrant group residing within America. In an effort to overcome the legacy of…

Host switch during evolution of a genetically distinct hantavirus in the American shrew mole (Neurotrichus gibbsii)

PubMed Central

Kang, Hae Ji; Bennett, Shannon N.; Dizney, Laurie; Sumibcay, Laarni; Arai, Satoru; Ruedas, Luis A.; Song, Jin-Won; Yanagihara, Richard

2009-01-01

A genetically distinct hantavirus, designated Oxbow virus (OXBV), was detected in tissues of an American shrew mole (Neurotrichus gibbsii), captured in Gresham, Oregon, in September 2003. Pairwise analysis of full-length S- and M- and partial L-segment nucleotide and amino acid sequences of OXBV indicated low sequence similarity with rodent-borne hantaviruses. Phylogenetic analyses using maximum-likelihood and Bayesian methods, and host-parasite evolutionary comparisons, showed that OXBV and Asama virus, a hantavirus recently identified from the Japanese shrew mole (Urotrichus talpoides), were related to soricine shrew-borne hantaviruses from North America and Eurasia, respectively, suggesting parallel evolution associated with cross-species transmission. PMID:19394994

The Evolution of Human Genetic and Phenotypic Variation in Africa

PubMed Central

Campbell, Michael C.

2010-01-01

Africa is the birthplace of modern humans, and is the source of the geographic expansion of ancestral populations into other regions of the world. Indigenous Africans are characterized by high levels of genetic diversity within and between populations. The pattern of genetic variation in these populations has been shaped by demographic events occurring over the last 200,000 years. The dramatic variation in climate, diet, and exposure to infectious disease across the continent has also resulted in novel genetic and phenotypic adaptations in extant Africans. This review summarizes some recent advances in our understanding of the demographic history and selective pressures that have influenced levels and patterns of diversity in African populations. PMID:20178763

Genetically defined race, but not sex, is associated with higher humoral and cellular immune responses to measles vaccination

PubMed Central

Voigt, Emily A.; Ovsyannikova, Inna G.; Haralambieva, Iana H.; Kennedy, Richard B.; Larrabee, Beth R.; Schaid, Daniel J.; Poland, Gregory A.

2017-01-01

In addition to host genetic and environmental factors, variations in immune responses to vaccination are influenced by demographic variables, such as race and sex. The influence of genetic race and sex on measles vaccine responses is not well understood, yet important for the development of much-needed improved measles vaccines with lower failure rates. We assessed associations between genetically defined race and sex with measles humoral and cellular immunity after measles vaccination in three independent and geographically distinct cohorts totaling 2,872 healthy racially diverse children, older adolescents, and young adults. We found no associations between biological sex and either humoral or cellular immunity to measles vaccine, and no correlation between humoral and cellular immunity in these study subjects. Genetically defined race was, however, significantly associated with both measles vaccine-induced humoral and cellular immune responses, with subjects genetically classified as having African-American ancestry demonstrating significantly higher antibody and cell-mediated immune responses relative to subjects of Caucasian ancestry. This information may be useful in designing novel measles vaccines that are optimally effective across human genetic backgrounds. PMID:27591105

Comprehensive Evaluation of the Association of APOE Genetic Variation with Plasma Lipoprotein Traits in U.S. Whites and African Blacks

PubMed Central

Radwan, Zaheda H.; Wang, Xingbin; Waqar, Fahad; Pirim, Dilek; Niemsiri, Vipavee; Hokanson, John E.; Hamman, Richard F.; Bunker, Clareann H.; Barmada, M. Michael; Demirci, F. Yesim; Kamboh, M. Ilyas

2014-01-01

Although common APOE genetic variation has a major influence on plasma LDL-cholesterol, its role in affecting HDL-cholesterol and triglycerides is not well established. Recent genome-wide association studies suggest that APOE also affects plasma variation in HDL-cholesterol and triglycerides. It is thus important to resequence the APOE gene to identify both common and uncommon variants that affect plasma lipid profile. Here, we have sequenced the APOE gene in 190 subjects with extreme HDL-cholesterol levels selected from two well-defined epidemiological samples of U.S. non-Hispanic Whites (NHWs) and African Blacks followed by genotyping of identified variants in the entire datasets (623 NHWs, 788 African Blacks) and association analyses with major lipid traits. We identified a total of 40 sequence variants, of which 10 are novel. A total of 32 variants, including common tagSNPs (≥5% frequency) and all uncommon variants (<5% frequency) were successfully genotyped and considered for genotype-phenotype associations. Other than the established associations of APOE*2 and APOE*4 with LDL-cholesterol, we have identified additional independent associations with LDL-cholesterol. We have also identified multiple associations of uncommon and common APOE variants with HDL-cholesterol and triglycerides. Our comprehensive sequencing and genotype-phenotype analyses indicate that APOE genetic variation impacts HDL-cholesterol and triglycerides in addition to affecting LDL-cholesterol. PMID:25502880

Genetic Determinants Influencing Human Serum Metabolome among African Americans

PubMed Central

Yu, Bing; Zheng, Yan; Alexander, Danny; Morrison, Alanna C.; Coresh, Josef; Boerwinkle, Eric

2014-01-01

Phenotypes proximal to gene action generally reflect larger genetic effect sizes than those that are distant. The human metabolome, a result of multiple cellular and biological processes, are functional intermediate phenotypes proximal to gene action. Here, we present a genome-wide association study of 308 untargeted metabolite levels among African Americans from the Atherosclerosis Risk in Communities (ARIC) Study. Nineteen significant common variant-metabolite associations were identified, including 13 novel loci (p<1.6×10−10). These loci were associated with 7–50% of the difference in metabolite levels per allele, and the variance explained ranged from 4% to 20%. Fourteen genes were identified within the nineteen loci, and four of them contained non-synonymous substitutions in four enzyme-encoding genes (KLKB1, SIAE, CPS1, and NAT8); the other significant loci consist of eight other enzyme-encoding genes (ACE, GATM, ACY3, ACSM2B, THEM4, ADH4, UGT1A, TREH), a transporter gene (SLC6A13) and a polycystin protein gene (PKD2L1). In addition, four potential disease-associated paths were identified, including two direct longitudinal predictive relationships: NAT8 with N-acetylornithine, N-acetyl-1-methylhistidine and incident chronic kidney disease, and TREH with trehalose and incident diabetes. These results highlight the value of using endophenotypes proximal to gene function to discover new insights into biology and disease pathology. PMID:24625756

Pleistocene aridification cycles shaped the contemporary genetic architecture of Southern African baboons.

PubMed

Sithaldeen, Riashna; Ackermann, Rebecca Rogers; Bishop, Jacqueline M

2015-01-01

Plio-Pleistocene environmental change influenced the evolutionary history of many animal lineages in Africa, highlighting key roles for both climate and tectonics in the evolution of Africa's faunal diversity. Here, we explore diversification in the southern African chacma baboon Papio ursinus sensu lato and reveal a dominant role for increasingly arid landscapes during past glacial cycles in shaping contemporary genetic structure. Recent work on baboons (Papio spp.) supports complex lineage structuring with a dominant pulse of diversification occurring 1-2Ma, and yet the link to palaeoenvironmental change remains largely untested. Phylogeographic reconstruction based on mitochondrial DNA sequence data supports a scenario where chacma baboon populations were likely restricted to refugia during periods of regional cooling and drying through the Late Pleistocene. The two lineages of chacma baboon, ursinus and griseipes, are strongly geographically structured, and demographic reconstruction together with spatial analysis of genetic variation point to possible climate-driven isolating events where baboons may have retreated to more optimum conditions during cooler, drier periods. Our analysis highlights a period of continuous population growth beginning in the Middle to Late Pleistocene in both the ursinus and the PG2 griseipes lineages. All three clades identified in the study then enter a state of declining population size (Nef) through to the Holocene; this is particularly marked in the last 20,000 years, most likely coincident with the Last Glacial Maximum. The pattern recovered here conforms to expectations based on the dynamic regional climate trends in southern Africa through the Pleistocene and provides further support for complex patterns of diversification in the region's biodiversity.

Pauci- and Multibacillary Leprosy: Two Distinct, Genetically Neglected Diseases

PubMed Central

Gaschignard, Jean; Grant, Audrey Virginia; Thuc, Nguyen Van; Orlova, Marianna; Cobat, Aurélie; Huong, Nguyen Thu; Ba, Nguyen Ngoc; Thai, Vu Hong; Abel, Laurent; Schurr, Erwin; Alcaïs, Alexandre

2016-01-01

After sustained exposure to Mycobacterium leprae, only a subset of exposed individuals develops clinical leprosy. Moreover, leprosy patients show a wide spectrum of clinical manifestations that extend from the paucibacillary (PB) to the multibacillary (MB) form of the disease. This “polarization” of leprosy has long been a major focus of investigation for immunologists because of the different immune response in these two forms. But while leprosy per se has been shown to be under tight human genetic control, few epidemiological or genetic studies have focused on leprosy subtypes. Using PubMed, we collected available data in English on the epidemiology of leprosy polarization and the possible role of human genetics in its pathophysiology until September 2015. At the genetic level, we assembled a list of 28 genes from the literature that are associated with leprosy subtypes or implicated in the polarization process. Our bibliographical search revealed that improved study designs are needed to identify genes associated with leprosy polarization. Future investigations should not be restricted to a subanalysis of leprosy per se studies but should instead contrast MB to PB individuals. We show the latter approach to be the most powerful design for the identification of genetic polarization determinants. Finally, we bring to light the important resource represented by the nine-banded armadillo model, a unique animal model for leprosy. PMID:27219008

The complete nucleotide sequences of the 5 genetically distinct plastid genomes of Oenothera, subsection Oenothera: II. A microevolutionary view using bioinformatics and formal genetic data.

PubMed

Greiner, Stephan; Wang, Xi; Herrmann, Reinhold G; Rauwolf, Uwe; Mayer, Klaus; Haberer, Georg; Meurer, Jörg

2008-09-01

A unique combination of genetic features and a rich stock of information make the flowering plant genus Oenothera an appealing model to explore the molecular basis of speciation processes including nucleus-organelle coevolution. From representative species, we have recently reported complete nucleotide sequences of the 5 basic and genetically distinguishable plastid chromosomes of subsection Oenothera (I-V). In nature, Oenothera plastid genomes are associated with 6 distinct, either homozygous or heterozygous, diploid nuclear genotypes of the 3 basic genomes A, B, or C. Artificially produced plastome-genome combinations that do not occur naturally often display interspecific plastome-genome incompatibility (PGI). In this study, we compare formal genetic data available from all 30 plastome-genome combinations with sequence differences between the plastomes to uncover potential determinants for interspecific PGI. Consistent with an active role in speciation, a remarkable number of genes have high Ka/Ks ratios. Different from the Solanacean cybrid model Atropa/tobacco, RNA editing seems not to be relevant for PGIs in Oenothera. However, predominantly sequence polymorphisms in intergenic segments are proposed as possible sources for PGI. A single locus, the bidirectional promoter region between psbB and clpP, is suggested to contribute to compartmental PGI in the interspecific AB hybrid containing plastome I (AB-I), consistent with its perturbed photosystem II activity.

African-American wildland memories

Treesearch

Cassandra Y. Johnson; J. Michael Bowker

2004-01-01

Collective memory can be used conceptually to examine African-American perceptions of wildlands and black interaction with such places. The middle--American view of wildlands frames these terrains as refuges--pure and simple, sanctified places distinct from the profanity of human modification. However, wild, primitive areas do not exist in the minds of all Americans as...

Analysis of betaS and betaA genes in a Mexican population with African roots.

PubMed

Magaña, María Teresa; Ongay, Zoyla; Tagle, Juan; Bentura, Gilberto; Cobián, José G; Perea, F Javier; Casas-Castañeda, Maricela; Sánchez-López, Yoaly J; Ibarra, Bertha

2002-01-01

To investigate the origin of the beta(A) and beta(S) genes in a Mexican population with African roots and a high frequency of hemoglobin S, we analyzed 467 individuals (288 unrelated) from different towns in the states of Guerrero and Oaxaca in the Costa Chica region. The frequency of the sickle-cell trait was 12.8%, which may represent a public health problem. The frequencies of the beta-haplotypes were determined from 350 nonrelated chromosomes (313 beta(A) and 37 beta(S)). We observed 15 different beta(A) haplotypes, the most common of which were haplotypes 1 (48.9%), 2 (13.4%), and 3 (13.4%). The calculation of pairwise distributions and Nei's genetic distance analysis using 32 worldwide populations showed that the beta(A) genes are more closely related to those of Mexican Mestizos and North Africans. Bantu and Benin haplotypes and haplotype 9 were related to the beta(S) genes, with frequencies of 78.8, 18.2, and 3.0%, respectively. Comparison of these haplotypes with 17 other populations revealed a high similitude with the population of the Central African Republic. These data suggest distinct origins for the beta(A) and beta(S) genes in Mexican individuals from the Costa Chica region.

Genetic and environmental influences on skeletal muscle phenotypes as a function of age and sex in large, multigenerational families of African heritage.

PubMed

Prior, Steven J; Roth, Stephen M; Wang, Xiaojing; Kammerer, Candace; Miljkovic-Gacic, Iva; Bunker, Clareann H; Wheeler, Victor W; Patrick, Alan L; Zmuda, Joseph M

2007-10-01

The aim of this study was to estimate the heritability of and environmental contributions to skeletal muscle phenotypes (appendicular lean mass and calf muscle cross-sectional area) in subjects of African descent and to determine whether heritability estimates are impacted by sex or age. Body composition was measured by dual-energy X-ray absorptiometry and computed tomography in 444 men and women aged 18 yr and older (mean: 43 yr) from eight large, multigenerational Afro-Caribbean families (family size range: 21-112). Using quantitative genetic methods, we estimated heritability and the association of anthropometric, lifestyle, and medical variables with skeletal muscle phenotypes. In the overall group, we estimated the heritability of lean mass and calf muscle cross-sectional area (h(2) = 0.18-0.23, P < 0.01) and contribution of environmental factors to these phenotypes (r(2) = 0.27-0.55, P < 0.05). In our age-specific analysis, the heritability of leg lean mass was lower in older vs. younger individuals (h(2) = 0.05 vs. 0.23, respectively, P = 0.1). Sex was a significant covariate in our models (P < 0.001), although sex-specific differences in heritability varied depending on the lean mass phenotype analyzed. High genetic correlations (rho(G) = 0.69-0.81; P < 0.01) between different lean mass measures suggest these traits share a large proportion of genetic components. Our results demonstrate the heritability of skeletal muscle traits in individuals of African heritage and that heritability may differ as a function of sex and age. As the loss of skeletal muscle mass is related to metabolic abnormalities, disability, and mortality in older individuals, further research is warranted to identify specific genetic loci that contribute to these traits in general and in a sex- and age-specific manner.

Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates.

PubMed

Hemmings, Sîan M J; Kinnear, Craig J; Lochner, Christine; Niehaus, Dana J H; Knowles, James A; Moolman-Smook, Johanna C; Corfield, Valerie A; Stein, Dan J

2004-09-30

There is increasing evidence that obsessive-compulsive disorder (OCD) is mediated by genetic factors. Although the precise mechanism of inheritance is unclear, recent evidence has pointed towards the involvement of the serotonergic and dopaminergic systems in the disorder's development. Furthermore, early-onset OCD appears to be a subtype that exhibits distinct clinical features and that is associated with greater familial loading. In the present investigation, South African OCD patients (n=252) were stratified according to age of onset and were clinically assessed. Additionally, selected variants in genes encoding serotonergic and dopaminergic components were investigated in a Caucasian OCD subset (n=180). This subgroup was further stratified to evaluate the role that these candidate genes may play in the genetically homogeneous Afrikaner subset (n=80). Analysis of the clinical data revealed an association between early age of onset and an increased frequency of tics, Tourette's disorder, and trichotillomania (TTM). The genetic studies yielded statistically significant results when the allelic distributions of genetic variants in the dopamine receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data support a role for the dopaminergic system, which may be relevant to the development of early-onset OCD.

A mitochondrial analysis reveals distinct founder effect signatures in Canarian and Balearic goats.

PubMed

Ferrando, A; Manunza, A; Jordana, J; Capote, J; Pons, A; Pais, J; Delgado, T; Atoche, P; Cabrera, B; Martínez, A; Landi, V; Delgado, J V; Argüello, A; Vidal, O; Lalueza-Fox, C; Ramírez, O; Amills, M

2015-08-01

In the course of human migrations, domestic animals often have been translocated to islands with the aim of assuring food availability. These founder events are expected to leave a genetic footprint that may be recognised nowadays. Herewith, we have examined the mitochondrial diversity of goat populations living in the Canarian and Balearic archipelagos. Median-joining network analysis produced very distinct network topologies for these two populations. Indeed, a majority of Canarian goats shared a single ancestral haplotype that segregated in all sampled islands, suggesting a single founder effect followed by a stepping-stone pattern of diffusion. This haplotype also was present in samples collected from archaeological assemblies at Gran Canaria and Lanzarote, making evident its widespread distribution in ancient times. In stark contrast, goats from Majorca and Ibiza did not share any mitochondrial haplotypes, indicating the occurrence of two independent founder events. Furthermore, in Majorcan goats, we detected the segregation of the mitochondrial G haplogroup that has only been identified in goats from Egypt, Iran and Turkey. This finding suggests the translocation of Asian and/or African goats to Majorca, possibly as a consequence of the Phoenician and Carthaginian colonisations of this island. © 2015 Stichting International Foundation for Animal Genetics.

HLA similarities indicate shared genetic risk in 21-hydroxylase autoantibody positive South African and United States Addison's disease.

PubMed

Ross, I L; Babu, S; Armstrong, T; Zhang, L; Schatz, D; Pugliese, A; Eisenbarth, G; Baker Ii, P

2014-10-01

Genetic similarities between patients from the United States and South African (SA) Addison's Disease (AD) strengthen evidence for genetic association. SA-AD (n = 73), SA healthy controls (N = 78), and US-AD patients (N = 83) were genotyped for DQA1, DQB1, DRB1, and HLA-B alleles. Serum was tested for the quantity of 21OH-AA and IFNα-AA at the Barbara Davis Center. Although not as profound as in US-AD, in SA-AD 21OH-AA + subjects the predominantly associated risk haplotypes were DRB1*0301-DQB1*0201 (DR3), DRB1*04xx-DQB1*0302 (DR4), and the combined DR3/4 genotype. DQB1*0302 associated DRB1*04xx haplotypes conferred higher risk than those DRB1*04xx haplotypes associated with other DQB1 alleles. We found negative association in 21OH-AA + SA-AD for DQA1*0201-DQB1*0202 and DQA1*0101-DQB1*0501 vs SA controls, and positive association for DQA1*0401-DQB1*0402 vs US-AD. Apart from the class II DR3 haplotype, HLA-B8 did not have an independent effect; however together DR3 and HLA-B8 conferred the highest risk vs 21OH-AA negative SA-AD and SA-controls. HLA-B7 (often with DR4) conferred novel risk in 21OH-AA + SA-AD vs controls. This study represents the first comparison between South African and United States AD populations utilizing genotyping and serology performed at the same center. SA-AD and US-AD 21OH-AA + patients share common HLA risk haplotypes including DR4 (with HLA-B7) and DR3 (with HLA-B8), strengthening previously described HLA associations and implicating similar genetic etiology. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Loci associated with skin pigmentation identified in African populations

PubMed Central

Crawford, Nicholas G.; Kelly, Derek E.; Hansen, Matthew E. B.; Beltrame, Marcia H.; Fan, Shaohua; Bowman, Shanna L.; Jewett, Ethan; Ranciaro, Alessia; Thompson, Simon; Lo, Yancy; Pfeifer, Susanne P.; Jensen, Jeffrey D.; Campbell, Michael C.; Beggs, William; Hormozdiari, Farhad; Mpoloka, Sununguko Wata; Mokone, Gaonyadiwe George; Nyambo, Thomas; Meskel, Dawit Wolde; Belay, Gurja; Haut, Jake; Rothschild, Harriet; Zon, Leonard; Zhou, Yi; Kovacs, Michael A.; Xu, Mai; Zhang, Tongwu; Bishop, Kevin; Sinclair, Jason; Rivas, Cecilia; Elliot, Eugene; Choi, Jiyeon; Li, Shengchao A.; Hicks, Belynda; Burgess, Shawn; Abnet, Christian; Watkins-Chow, Dawn E.; Oceana, Elena; Song, Yun S.; Eskin, Eleazar; Brown, Kevin M.; Marks, Michael S.; Loftus, Stacie K.; Pavan, William J.; Yeager, Meredith; Chanock, Stephen; Tishkoff, Sarah

2017-01-01

Despite the wide range of skin pigmentation in humans, little is known about its genetic basis in global populations. Examining ethnically diverse African genomes, we identify variants in or near SLC24A5, MFSD12, DDB1, TMEM138, OCA2 and HERC2 that are significantly associated with skin pigmentation. Genetic evidence indicates that the light pigmentation variant at SLC24A5 was introduced into East Africa by gene flow from non-Africans. At all other loci, variants associated with dark pigmentation in Africans are identical by descent in southern Asian and Australo-Melanesian populations. Functional analyses indicate that MFSD12 encodes a lysosomal protein that affects melanogenesis in zebrafish and mice, and that mutations in melanocyte-specific regulatory regions near DDB1/TMEM138 correlate with expression of UV response genes under selection in Eurasians. PMID:29025994

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

African Swine Fever Epidemic, Poland, 2014–2015

PubMed Central

Woźniakowski, Grzegorz; Kozak, Edyta; Niemczuk, Krzysztof; Frączyk, Magdalena; Bocian, Łukasz; Kowalczyk, Andrzej; Pejsak, Zygmunt

2016-01-01

In Poland, African swine fever (ASF) emerged in February 2014; by August 2015, the virus had been detected in >130 wild boar and in pigs in 3 backyard holdings. We evaluated ASF spread in Poland during these 18 months. Phylogenetic analysis indicated repeated incursions of genetically distinct ASF viruses of genotype II; the number of cases positively correlated wild boar density; and disease spread was very slow. More cases were reported during summer than autumn. The 18-month prevalence of ASF in areas under various animal movement restrictions was 18.6% among wild boar found dead or killed by vehicles and only 0.2% in hunted wild boar. Repeated introductions of the virus into the country, the primary role of wild boar in virus maintenance, and the slow spread of the disease indicate a need for enhanced biosecurity at pig holdings and continuous and intensive surveillance for fast detection of ASF. PMID:27314611

Population-genetic properties of differentiated copy number variations in cattle.

PubMed

Xu, Lingyang; Hou, Yali; Bickhart, Derek M; Zhou, Yang; Hay, El Hamidi Abdel; Song, Jiuzhou; Sonstegard, Tad S; Van Tassell, Curtis P; Liu, George E

2016-03-23

While single nucleotide polymorphism (SNP) is typically the variant of choice for population genetics, copy number variation (CNV) which comprises insertion, deletion and duplication of genomic sequence, is an informative type of genetic variation. CNVs have been shown to be both common in mammals and important for understanding the relationship between genotype and phenotype. However, CNV differentiation, selection and its population genetic properties are not well understood across diverse populations. We performed a population genetics survey based on CNVs derived from the BovineHD SNP array data of eight distinct cattle breeds. We generated high resolution results that show geographical patterns of variations and genome-wide admixture proportions within and among breeds. Similar to the previous SNP-based studies, our CNV-based results displayed a strong correlation of population structure and geographical location. By conducting three pairwise comparisons among European taurine, African taurine, and indicine groups, we further identified 78 unique CNV regions that were highly differentiated, some of which might be due to selection. These CNV regions overlapped with genes involved in traits related to parasite resistance, immunity response, body size, fertility, and milk production. Our results characterize CNV diversity among cattle populations and provide a list of lineage-differentiated CNVs.

Rainbow Nation's "Ubuntu": Discovering Distinctness as a Spectrum through South African Literature

ERIC Educational Resources Information Center

Smith, Colin Bridges

2007-01-01

Apartheid created more than physical distances between color groups; South Africa is made up of people with often separated minds. Leaders of the democratic government draw from and modify the ancient African tribal value called "ubuntu" as the philosophic basis for their cultural strategy of unification. Sandra Chait has pointed out…

Genetic modulators of sickle cell disease in French Guiana: Markers of the slave trade.

PubMed

Simonnet, Christine; Elanga, Narcisse; Joly, Philippe; Vaz, Tania; Nacher, Mathieu

2016-11-01

Sickle cell disease (SCD) is the leading genetic disease in French Guiana, reflecting the predominantly African ancestry of the Guianese population. Our purpose was to characterize the genetic modulators of SCD in order to retrace the origin of the population in light of the slave trade. We have studied the sickle cell genotype, the βS haplotypes, the alpha and beta thalassemia and the UGT1A1 promoter polymorphisms in 224 Guianese patients with SCD. The genotypes of SCD were HbSS 65.6%, HbSC 24.5%, and HbS-beta thalassemia 9.4%. The most frequent βS haplotypes were the Benin haplotype (65.9% of the chromosomes) and the Bantu (20.5%). Alpha thalassemic deletions were present in 37% of the patients and homozygosity for the (TA)7 allele of the UGT1A1 promoter in 21.4%. When the patients' origins were considered, 3 groups, Noir Marron, Haitians and Creoles, displayed distinctive characteristics. The HbSC genotype, the Benin haplotype, and the homozygous UGT1A1 genotype TA7/TA7 were significantly more frequent in Noir Marron. The Haitian patients were characterized by the occurrence of alpha-thalassemia and beta-thalassemia and by a higher prevalence of the Bantu haplotype. In the group of Creole patients, the genotype HbSS was predominant but the other modulators of SCD were associated with intermediate risk. The results highlight the genetic diversity of the Guianese population and are concordant with historical data on the slave trade showing a West African origin for Noir Marron and a Central African origin for Haitians, while Guianese Creoles are highly admixed. Am. J. Hum. Biol. 28:811-816, 2016. © 2016Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The Genetic Legacy of Religious Diversity and Intolerance: Paternal Lineages of Christians, Jews, and Muslims in the Iberian Peninsula

PubMed Central

Adams, Susan M.; Bosch, Elena; Balaresque, Patricia L.; Ballereau, Stéphane J.; Lee, Andrew C.; Arroyo, Eduardo; López-Parra, Ana M.; Aler, Mercedes; Grifo, Marina S. Gisbert; Brion, Maria; Carracedo, Angel; Lavinha, João; Martínez-Jarreta, Begoña; Quintana-Murci, Lluis; Picornell, Antònia; Ramon, Misericordia; Skorecki, Karl; Behar, Doron M.; Calafell, Francesc; Jobling, Mark A.

2008-01-01

Most studies of European genetic diversity have focused on large-scale variation and interpretations based on events in prehistory, but migrations and invasions in historical times could also have had profound effects on the genetic landscape. The Iberian Peninsula provides a suitable region for examination of the demographic impact of such recent events, because its complex recent history has involved the long-term residence of two very different populations with distinct geographical origins and their own particular cultural and religious characteristics—North African Muslims and Sephardic Jews. To address this issue, we analyzed Y chromosome haplotypes, which provide the necessary phylogeographic resolution, in 1140 males from the Iberian Peninsula and Balearic Islands. Admixture analysis based on binary and Y-STR haplotypes indicates a high mean proportion of ancestry from North African (10.6%) and Sephardic Jewish (19.8%) sources. Despite alternative possible sources for lineages ascribed a Sephardic Jewish origin, these proportions attest to a high level of religious conversion (whether voluntary or enforced), driven by historical episodes of social and religious intolerance, that ultimately led to the integration of descendants. In agreement with the historical record, analysis of haplotype sharing and diversity within specific haplogroups suggests that the Sephardic Jewish component is the more ancient. The geographical distribution of North African ancestry in the peninsula does not reflect the initial colonization and subsequent withdrawal and is likely to result from later enforced population movement—more marked in some regions than in others—plus the effects of genetic drift. PMID:19061982

Genetics Home Reference: complement component 8 deficiency

MedlinePlus

... in people with Hispanic, Japanese, or African Caribbean heritage, whereas type II primarily occurs in people of Northern European descent. Related Information What information about a genetic condition can statistics provide? Why are some genetic ...

Distinct Genetic Signatures for Variability in Total and Free Serum Thyroxine Levels in Four Sets of Recombinant Inbred Mice

PubMed Central

Lu, Lu; Aliesky, Holly A.; Williams, Robert W.; Rapoport, Basil

2011-01-01

C3H/He and BALB/c mice have elevated serum thyroxine levels associated with low deiodinase type-1 activity whereas C57BL/6 (B6) mice have low thyroxine levels and elevated deiodinase type-1 activity. High-resolution genetic maps are available for four sets of recombinant inbred (RI) mice derived from B6 parents bred to C3H/He, BALB/c, DBA/2, or A strains. Total and free T4 (T-T4 and F-T4) levels in females from these RI sets (BXH, CXB, BXD, and AXBXA) were analyzed to test two hypotheses: first, serum T4 variability is linked to the deiodinase type-1 gene; second, because of their shared B6 parent, the RI sets will share linkages responsible for T-T4 or F-T4 variability. A number of chromosomes (Chr) and loci were linked to T-T4 (Chr 1, 4, 13, 11) or F-T4 (Chr 1, 6, 13, 18, 19). Linkage between T-T4 and Chr 4 was limited to CXB and BXH strains, but the locus was distinct from the deiodinase type-1 gene. Surprisingly, many linkages were unique providing “genetic signatures” for T-T4 or F-T4 in each set of RI mice. Indeed, the strongest linkage between T-T4 (or F-T4) and a Chr 2 locus (logarithm of the odds scores >4.4) was only observed in AXBXA strains. Some loci corresponded to genes/Chr associated in humans with variable TSH or T-T4 levels. Unlike inbred mice, human populations are extremely diverse. Consequently, our data suggest that the contributions of unique chromosomes/loci controlling T-T4 and F-T4 in distinct human subgroups are likely to be “buried” in genetic analyses of heterogeneous human populations. PMID:21209025

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

PubMed Central

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

2016-01-01

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

GENETIC AND ENVIRONMENTAL RISK FOR MAJOR DEPRESSION IN AFRICAN-AMERICAN AND EUROPEAN-AMERICAN WOMEN

PubMed Central

Duncan, Alexis E.; Munn-Chernoff, Melissa A.; Hudson, Darrell L.; Eschenbacher, Michaela A.; Agrawal, Arpana; Grant, Julia D.; Nelson, Elliot C.; Waldron, Mary; Glowinski, Anne L.; Sartor, Carolyn E.; Bucholz, Kathleen K.; Madden, Pamela A.F.; Heath, Andrew C.

2014-01-01

It is unknown whether there are racial differences in the heritability of major depressive disorder (MDD) because most psychiatric genetic studies have been conducted in samples comprised largely of white non-Hispanics. To examine potential differences between African-American (AA) and European-American (EA) young adult women in (1) DSM-IV MDD prevalence, symptomatology and risk factors and (2) genetic and/or environmental liability to MDD, we analyzed data from a large, population representative sample of twins ascertained from birth records (n= 550 AA and n=3226 EA female twins) aged 18–28 years at the time of MDD assessment by semi-structured psychiatric interview. AA women were more likely to have MDD risk factors; however, there were no significant differences in lifetime MDD prevalence between AA and EA women after adjusting for covariates (Odds Ratio = 0.88, 95% confidence interval: 0.67–1.15 ). Most MDD risk factors identified among AAs were also associated with MDD at similar magnitudes among EAs. Although the MDD heritability point estimate was higher among AA than EA women in a model with paths estimated separately by race (56%, 95% CI: 29%–78% vs. 41%, 95% CI: 29%–52%), the best-fitting model was one in which additive genetic and nonshared environmental paths for AA and EA women were constrained to be equal (A = 43%, 33%–53% and E = 57%, 47%–67%). Despite a marked elevation in the prevalence of environmental risk exposures related to MDD among AA women, there were no significant differences in lifetime prevalence or heritability of MDD between AA and EA young women. PMID:24910290

Genetic structure of a unique admixed population: implications for medical research.

PubMed

Patterson, Nick; Petersen, Desiree C; van der Ross, Richard E; Sudoyo, Herawati; Glashoff, Richard H; Marzuki, Sangkot; Reich, David; Hayes, Vanessa M

2010-02-01

STATEMENT: In naming population groups, we think a chief aim is to use terms that the group members use themselves, or find familiar and comfortable. The terms used in this manuscript to describe populations are as historically correct as possible and are chosen so as not to offend any population group. Two of the authors (DCP and REvdR) belong to the Coloured population, with one of the authors (REvdR) having contributed extensively to current literature on the history of the Coloured people of South Africa and served as Vice-President of the South African Institute of Race Relations. According to the 2001 South African census (http://www.statssa.gov.za/census01/HTML/CInBrief/CIB2001.pdf), "Statistics South Africa continues to classify people by population group, in order to monitor progress in moving away from the apartheid-based discrimination of the past. However, membership of a population group is now based on self-perception and self-classification, not on a legal definition. Five options were provided on the questionnaire, Black African, Coloured, Indian or Asian, White and Other. Responses in the category 'Other' were very few and were therefore imputed". We have elected to use the term Bushmen rather than San to refer to the hunter-gatherer people of Southern Africa. Although they have no collective name for themselves, this decision was based on the term Bushmen (or Bossiesman) being the more familiar to the communities themselves, while the term San is the more accepted academic classification. Understanding human genetic structure has fundamental implications for understanding the evolution and impact of human diseases. In this study, we describe the complex genetic substructure of a unique and recently admixed population arising approximately 350 years ago as a direct result of European settlement in South Africa. Analysis was performed using over 900 000 genome-wide single nucleotide polymorphisms in 20 unrelated ancestry-informative marker selected

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-10-01

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

Divergent pattern of nuclear genetic diversity across the range of the Afromontane Prunus africana mirrors variable climate of African highlands

PubMed Central

Kadu, Caroline A. C.; Konrad, Heino; Schueler, Silvio; Muluvi, Geoffrey M.; Eyog-Matig, Oscar; Muchugi, Alice; Williams, Vivienne L.; Ramamonjisoa, Lolona; Kapinga, Consolatha; Foahom, Bernard; Katsvanga, Cuthbert; Hafashimana, David; Obama, Crisantos; Geburek, Thomas

2013-01-01

Background and Aims Afromontane forest ecosystems share a high similarity of plant and animal biodiversity, although they occur mainly on isolated mountain massifs throughout the continent. This resemblance has long provoked questions on former wider distribution of Afromontane forests. In this study Prunus africana (one of the character trees of Afromontane forests) is used as a model for understanding the biogeography of this vegetation zone. Methods Thirty natural populations from nine African countries covering a large part of Afromontane regions were analysed using six nuclear microsatellites. Standard population genetic analysis as well as Bayesian and maximum likelihood models were used to infer genetic diversity, population differentiation, barriers to gene flow, and recent and all migration among populations. Key Results Prunus africana exhibits strong divergence among five main Afromontane regions: West Africa, East Africa west of the Eastern Rift Valley (ERV), East Africa east of the ERV, southern Africa and Madagascar. The strongest divergence was evident between Madagascar and continental Africa. Populations from West Africa showed high similarity with East African populations west of the ERV, whereas populations east of the ERV are closely related to populations of southern Africa, respectively. Conclusions The observed patterns indicate divergent population history across the continent most likely associated to Pleistocene changes in climatic conditions. The high genetic similarity between populations of West Africa with population of East Africa west of the ERV is in agreement with faunistic and floristic patterns and provides further evidence for a historical migration route. Contrasting estimates of recent and historical gene flow indicate a shift of the main barrier to gene flow from the Lake Victoria basin to the ERV, highlighting the dynamic environmental and evolutionary history of the region. PMID:23250908

A distinct alleles and genetic recombination of pmrCAB operon in species of Acinetobacter baumannii complex isolates.

PubMed

Kim, Dae Hun; Ko, Kwan Soo

2015-07-01

To investigate pmrCAB sequence divergence in 5 species of Acinetobacter baumannii complex, a total of 80 isolates from a Korean hospital were explored. We evaluated nucleotide and amino acid polymorphisms of pmrCAB operon, and phylogenetic trees were constructed for each gene of prmCAB operon. Colistin and polymyxin B susceptibility was determined for all isolates, and multilocus sequence typing was also performed for A. baumannii isolates. Our results showed that each species of A. baumannii complex has divergent pmrCAB operon sequences. We identified a distinct pmrCAB allele allied with Acinetobacter nosocomialis in gene trees. Different grouping in each gene tree suggests sporadic recombination or emergence of pmrCAB genes among Acinetobacter species. Sequence polymorphisms among Acinetobacter species might not be associated with colistin resistance. We revealed that a distinct pmrCAB allele may be widespread across the continents such as North America and Asia and that sporadic genetic recombination or emergence of pmrCAB genes might occur. Copyright © 2015 Elsevier Inc. All rights reserved.

African human mtDNA phylogeography at-a-glance.

PubMed

Rosa, Alexandra; Brehem, António

2011-01-01

The mitochondrial DNA (mtDNA) genetic system has long proven to be useful for studying the demographic history of our species, since their proposed Southeast/East African origin 200 kya. Despite the weak archaeological and anthropologic records, which render a difficult understanding of early intra- continental migrations, the phylogenetic L0-L1'6 split at about 140-160 kya is thought to represent also an early sub-structuring of small and isolated communities in South and East Africa. Regional variation accumulated over the following millennia, with L2 and L3 lineages arising in Central and East Africa 100-75 kya. Their sub-Saharan dispersal not later than 60 kya, largely overwhelmed the L0'1 distribution, nowadays limited to South African Khoisan and Central African Pygmies. Cyclic expansions and retractions of the equatorial forest between 40 kya and the "Last Glacial Aridity Maximum" were able to reduce the genetic diversity of modern humans. Surviving regional-specific lineages have emerged from the Sahelian refuge areas, repopulating the region and contributing to the overall West African genetic similarity. Particular L1- L3 lineages mirror the substantial population growth made possible by moister and warmer conditions of the Sahara's Wet Phase and the adoption of agriculture and iron smelting techniques. The diffusion of the farming expertise from a Central African source towards South Africa was mediated by the Bantu people 3 kya. The strong impact of their gene flow almost erased the pre-existent maternal pool. Non-L mtDNAs testify for Eurasian lineages that have enriched the African maternal pool at different timeframes: i) Near and Middle Eastern influences in Upper Palaeolithic, probably link to the spread of Afro-Asiatic languages; ii) particular lineages from West Eurasia around or after the glacial period; iii) post-glacial mtDNA signatures from the Franco-Cantabrian refugia, that have crossed the Strait of Gibraltar and iv) Eurasian lineages

Phylogeny and genetic structure of Erophaca (Leguminosae), a East-West Mediterranean disjunct genus from the Tertiary.

PubMed

Casimiro-Soriguer, Ramón; Talavera, María; Balao, Francisco; Terrab, Anass; Herrera, Javier; Talavera, Salvador

2010-07-01

The genus Erophaca comprises a single herbaceous perennial species with two subspecies distributed at opposite ends of the Mediterranean region. We used nrDNA ITS to investigate the phylogeny of the genus, and AFLP markers (9 primers, 20 populations) to establish the genetic relationship between subspecies, and among populations at each side of the Gibraltar Strait. According to nrDNA ITS, Erophaca is monophyletic, old (Miocene), and sister to the Astragalean clade. Life form attributes and molecular clock estimates suggest that Erophaca is one of the many Tertiary relicts that form part of the present Mediterranean flora. Within the occidental subspecies, European plants are clearly derived from North-African populations (Morocco) which, despite being rare on a regional scale, present the highest genetic diversity (as estimated by private and rare fragment numbers). In general, genetic diversity decreased with increasing distance from Morocco. AFLP and nrDNA ITS markers evidenced that the Eastern and the Western subspecies are genetically distinct. Possible causes for their disjunct distribution are discussed. Copyright 2010 Elsevier Inc. All rights reserved.

A cryptic mitochondrial DNA link between North European and West African dogs.

PubMed

Adeola, Adeniyi C; Ommeh, Sheila C; Song, Jiao-Jiao; Olaogun, S Charles; Sanke, Oscar J; Yin, Ting-Ting; Wang, Guo-Dong; Wu, Shi-Fang; Zhou, Zhong-Yin; Lichoti, Jacqueline K; Agwanda, Bernard R; Dawuda, Philip M; Murphy, Robert W; Peng, Min-Sheng; Zhang, Ya-Ping

2017-03-20

Domestic dogs have an ancient origin and a long history in Africa. Nevertheless, the timing and sources of their introduction into Africa remain enigmatic. Herein, we analyse variation in mitochondrial DNA (mtDNA) D-loop sequences from 345 Nigerian and 37 Kenyan village dogs plus 1530 published sequences of dogs from other parts of Africa, Europe and West Asia. All Kenyan dogs can be assigned to one of three haplogroups (matrilines; clades): A, B, and C, while Nigerian dogs can be assigned to one of four haplogroups A, B, C, and D. None of the African dogs exhibits a matrilineal contribution from the African wolf (Canis lupus lupaster). The genetic signal of a recent demographic expansion is detected in Nigerian dogs from West Africa. The analyses of mitochondrial genomes reveal a maternal genetic link between modern West African and North European dogs indicated by sub-haplogroup D1 (but not the entire haplogroup D) coalescing around 12,000 years ago. Incorporating molecular anthropological evidence, we propose that sub-haplogroup D1 in West African dogs could be traced back to the late-glacial dispersals, potentially associated with human hunter-gatherer migration from southwestern Europe. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Race, Gender, and Genetic Polymorphism Contribute to Variability in Acetaminophen Pharmacokinetics, Metabolism, and Protein-Adduct Concentrations in Healthy African-American and European-American Volunteers.

PubMed

Court, Michael H; Zhu, Zhaohui; Masse, Gina; Duan, Su X; James, Laura P; Harmatz, Jerold S; Greenblatt, David J

2017-09-01

Over 30 years ago, black Africans from Kenya and Ghana were shown to metabolize acetaminophen faster by glucuronidation and slower by oxidation compared with white Scottish Europeans. The objectives of this study were to determine whether similar differences exist between African-Americans and European-Americans, and to identify genetic polymorphisms that could explain these potential differences. Acetaminophen plasma pharmacokinetics and partial urinary metabolite clearances via glucuronidation, sulfation, and oxidation were determined in healthy African-Americans (18 men, 23 women) and European-Americans (34 men, 20 women) following a 1-g oral dose. There were no differences in acetaminophen total plasma, glucuronidation, or sulfation clearance values between African-Americans and European-Americans. However, median oxidation clearance was 37% lower in African-Americans versus European-Americans (0.57 versus 0.90 ml/min per kilogram; P = 0.0001). Although acetaminophen total or metabolite clearance values were not different between genders, shorter plasma half-life values (by 11-14%; P < 0.01) were observed for acetaminophen, acetaminophen glucuronide, and acetaminophen sulfate in women versus men. The UGT2B15*2 polymorphism was associated with variant-allele-number proportional reductions in acetaminophen total clearance (by 15-27%; P < 0.001) and glucuronidation partial clearance (by 23-48%; P < 0.001). UGT2B15 *2/*2 genotype subjects also showed higher acetaminophen protein-adduct concentrations than *1/*2 (by 42%; P = 0.003) and *1/*1 (by 41%; P = 0.003) individuals. Finally, CYP2E1 *1D/*1D genotype African-Americans had lower oxidation clearance than *1C/*1D (by 42%; P = 0.041) and *1C/*1C (by 44%; P = 0.048) African-Americans. Consequently, African-Americans oxidize acetaminophen more slowly than European-Americans, which may be partially explained by the CYP2E1*1D polymorphism. UGT2B15*2 influences acetaminophen pharmacokinetics in both African

Admixture mapping of lung cancer in 1812 African-Americans.

PubMed

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

2011-03-01

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

Glacial vicariance in Eurasia: mitochondrial DNA evidence from Scots pine for a complex heritage involving genetically distinct refugia at mid-northern latitudes and in Asia Minor

PubMed Central

Naydenov, Krassimir; Senneville, Sauphie; Beaulieu, Jean; Tremblay, Francine; Bousquet, Jean

2007-01-01

Background At the last glacial maximum, Fennoscandia was covered by an ice sheet while the tundra occupied most of the rest of northern Eurasia. More or less disjunct refugial populations of plants were dispersed in southern Europe, often trapped between mountain ranges and seas. Genetic and paleobotanical evidences indicate that these populations have contributed much to Holocene recolonization of more northern latitudes. Less supportive evidence has been found for the existence of glacial populations located closer to the ice margin. Scots pine (Pinus sylvestris L.) is a nordic conifer with a wide natural range covering much of Eurasia. Fractures in its extant genetic structure might be indicative of glacial vicariance and how different refugia contributed to the current distribution at the continental level. The population structure of Scots pine was investigated on much of its Eurasian natural range using maternally inherited mitochondrial DNA polymorphisms. Results A novel polymorphic region of the Scots pine mitochondrial genome has been identified, the intron 1 of nad7, with three variants caused by insertions-deletions. From 986 trees distributed among 54 populations, four distinct multi-locus mitochondrial haplotypes (mitotypes) were detected based on the three nad7 intron 1 haplotypes and two previously reported size variants for nad1 intron B/C. Population differentiation was high (GST = 0.657) and the distribution of the mitotypes was geographically highly structured, suggesting at least four genetically distinct ancestral lineages. A cosmopolitan lineage was widely distributed in much of Europe throughout eastern Asia. A previously reported lineage limited to the Iberian Peninsula was confirmed. A new geographically restricted lineage was found confined to Asia Minor. A new lineage was restricted to more northern latitudes in northeastern Europe and the Baltic region. Conclusion The contribution of the various ancestral lineages to the current

Solo status and self-construal: being distinctive influences racial self-construal and performance apprehension in African American women.

PubMed

Sekaquaptewa, Denise; Waldman, Andrew; Thompson, Mischa

2007-10-01

A preliminary study and main experiment tested the hypothesis that racial solo status (being the only member of one's race in a group) increases racial self-construal among African Americans. The preliminary study showed that African American men and women reported greater collectivist (i.e., group-based) over individualist self-construal under solo compared to nonsolo status, whereas Whites did not. The main experiment showed that the increased collectivism among African American solo women appears to be strongly reflected in racial identity becoming a salient aspect of self-construal. African American participants were also more likely than Whites to perceive that their anticipated performance would be generalized to their race, to feel like representatives of their race, and to show greater performance apprehension (indirectly evidenced by increased self-handicapping) when in racial solo status. The implications of solo status for African Americans in evaluative situations (such as academic testing sessions) are discussed. 2007 APA

Novel recurrently mutated genes in African American colon cancers.

PubMed

Guda, Kishore; Veigl, Martina L; Varadan, Vinay; Nosrati, Arman; Ravi, Lakshmeswari; Lutterbaugh, James; Beard, Lydia; Willson, James K V; Sedwick, W David; Wang, Zhenghe John; Molyneaux, Neil; Miron, Alexander; Adams, Mark D; Elston, Robert C; Markowitz, Sanford D; Willis, Joseph E

2015-01-27

We used whole-exome and targeted sequencing to characterize somatic mutations in 103 colorectal cancers (CRC) from African Americans, identifying 20 new genes as significantly mutated in CRC. Resequencing 129 Caucasian derived CRCs confirmed a 15-gene set as a preferential target for mutations in African American CRCs. Two predominant genes, ephrin type A receptor 6 (EPHA6) and folliculin (FLCN), with mutations exclusive to African American CRCs, are by genetic and biological criteria highly likely African American CRC driver genes. These previously unsuspected differences in the mutational landscapes of CRCs arising among individuals of different ethnicities have potential to impact on broader disparities in cancer behaviors.

Genetic variants in microRNAs and breast cancer risk in African American and European American women

PubMed Central

Yao, Song; Graham, Kelly; Shen, Jie; Sucheston Campbell, Lara E.; Singh, Prashant; Zirpoli, Gary; Roberts, Michelle; Ciupak, Gregory; Davis, Warren; Hwang, Helena; Khoury, Thaer; Bovbjerg, Dana H.; Jandorf, Lina; Pawlish, Karen S.; Bandera, Elisa V.; Liu, Song; Ambrosone, Christine B.; Zhao, Hua

2013-01-01

MicroRNAs (miRNAs) are an integral part of the post-transcriptional machinery of gene expression and have been implicated in the carcinogenic cascade. Single nucleotide polymorphisms (SNPs) in miRNAs and risk of breast cancer have been evaluated in populations of European or Asian ancestry, but not among women of African ancestry. Here we examined 145 SNPs in 6 miRNA processing genes and in 78 miRNAs which target genes known to be important in breast cancer among 906 African American (AA) and 653 European American (EA) cases and controls enrolled in the Women’s Circle of Health Study (WCHS). Allele frequencies of most SNPs (87%) differed significantly by race. We found a number of SNPs in miRNAs and processing genes in association with breast cancer overall or stratified by estrogen receptor (ER) status. Several associations were significantly different by race, with none of the associations being significant in both races. Using a polygenic risk score to combine the effects of multiple SNPs, we found significant associations with the score in each subgroup analysis. For ER-positive cancer, each unit increment of the risk score was associated with a 51% increased risk in AAs (OR=1.51, 95% CI=1.30–1.74, p=3.3*10−8) and a 73% increased risk in EAs (OR=1.73, 95% CI=1.45–2.06, p=1.4*10−9). These data show, for the first time, that miRNA-related genetic variations may underlie the etiology of breast cancer in both populations of African and European ancestries. Future studies are needed to validate our findings and to explore the underlying mechanisms. PMID:24062209

Revealing hidden species diversity in closely related species using nuclear SNPs, SSRs and DNA sequences - a case study in the tree genus Milicia.

PubMed

Daïnou, Kasso; Blanc-Jolivet, Céline; Degen, Bernd; Kimani, Priscilla; Ndiade-Bourobou, Dyana; Donkpegan, Armel S L; Tosso, Félicien; Kaymak, Esra; Bourland, Nils; Doucet, Jean-Louis; Hardy, Olivier J

2016-12-01

Species delimitation in closely related plant taxa can be challenging because (i) reproductive barriers are not always congruent with morphological differentiation, (ii) use of plastid sequences might lead to misinterpretation, (iii) rare species might not be sampled. We revisited molecular-based species delimitation in the African genus Milicia, currently divided into M. regia (West Africa) and M. excelsa (from West to East Africa). We used 435 samples collected in West, Central and East Africa. We genotyped SNP and SSR loci to identify genetic clusters, and sequenced two plastid regions (psbA-trnH, trnC-ycf6) and a nuclear gene (At103) to confirm species' divergence and compare species delimitation methods. We also examined whether ecological niche differentiation was congruent with sampled genetic structure. West African M. regia, West African and East African M. excelsa samples constituted three well distinct genetic clusters according to SNPs and SSRs. In Central Africa, two genetic clusters were consistently inferred by both types of markers, while a few scattered samples, sympatric with the preceding clusters but exhibiting leaf traits of M. regia, were grouped with the West African M. regia cluster based on SNPs or formed a distinct cluster based on SSRs. SSR results were confirmed by sequence data from the nuclear region At103 which revealed three distinct 'Fields For Recombination' corresponding to (i) West African M. regia, (ii) Central African samples with leaf traits of M. regia, and (iii) all M. excelsa samples. None of the plastid sequences provide indication of distinct clades of the three species-like units. Niche modelling techniques yielded a significant correlation between niche overlap and genetic distance. Our genetic data suggest that three species of Milicia could be recognized. It is surprising that the occurrence of two species in Central Africa was not reported for this well-known timber tree. Globally, our work highlights the importance

The African honey bee: factors contributing to a successful biological invasion.

PubMed

Scott Schneider, Stanley; DeGrandi-Hoffman, Gloria; Smith, Deborah Roan

2004-01-01

The African honey bee subspecies Apis mellifera scutellata has colonized much of the Americas in less than 50 years and has largely replaced European bees throughout its range in the New World. The African bee therefore provides an excellent opportunity to examine the factors that influence invasion success. We provide a synthesis of recent research on the African bee, concentrating on its ability to displace European honey bees. Specifically, we consider (a) the genetic composition of the expanding population and the symmetry of gene flow between African and European bees, (b) the mechanisms that favor the preservation of the African genome, and (c) the possible range and impact of the African bee in the United States.

Aggressive Versus Nonaggressive Antisocial Behavior: Distinctive Etiological Moderation by Age

PubMed Central

Burt, S. Alexandra; Neiderhiser, Jenae M.

2015-01-01

Research has supported the existence of distinct behavioral patterns, demographic correlates, and etiologic mechanisms for aggressive (AGG) versus nonaggressive but delinquent (DEL) antisocial behavior. Though behavioral genetic studies have the potential to further crystallize these dimensions, inconsistent results have limited their contribution. These inconsistencies may stem in part from the limited attention paid to the impact of age. In the current study, the authors thus examined age-related etiological moderation of AGG and DEL antisocial behavior in a sample of 720 sibling pairs (ranging in age from 10 to 18 years) with varying degrees of genetic relatedness. Results reveal that the magnitude of genetic and environmental influences on AGG remained stable across adolescence. By contrast, genetic influences on DEL increased dramatically with age, whereas shared environmental influences decreased. Subsequent longitudinal analyses fully replicated these results. Such findings highlight etiological distinctions between aggression and delinquency, and offer insights into the expression of genetic influences during development. PMID:19586186

Genetic micro-epidemiology of malaria in Papua Indonesia: Extensive P. vivax diversity and a distinct subpopulation of asymptomatic P. falciparum infections.

PubMed

Pava, Zuleima; Noviyanti, Rintis; Handayuni, Irene; Trimarsanto, Hidayat; Trianty, Leily; Burdam, Faustina H; Kenangalem, Enny; Utami, Retno A S; Tirta, Yusrifar K; Coutrier, Farah; Poespoprodjo, Jeanne R; Price, Ric N; Marfurt, Jutta; Auburn, Sarah

2017-01-01

Genetic analyses of Plasmodium have potential to inform on transmission dynamics, but few studies have evaluated this on a local spatial scale. We used microsatellite genotyping to characterise the micro-epidemiology of P. vivax and P. falciparum diversity to inform malaria control strategies in Timika, Papua Indonesia. Genotyping was undertaken on 713 sympatric P. falciparum and P. vivax isolates from a cross-sectional household survey and clinical studies conducted in Timika. Standard population genetic measures were applied, and the data was compared to published data from Kalimantan, Bangka, Sumba and West Timor. Higher diversity (HE = 0.847 vs 0.625; p = 0.017) and polyclonality (46.2% vs 16.5%, p<0.001) were observed in P. vivax versus P. falciparum. Distinct P. falciparum substructure was observed, with two subpopulations, K1 and K2. K1 was comprised solely of asymptomatic infections and displayed greater relatedness to isolates from Sumba than to K2, possibly reflecting imported infections. The results demonstrate the greater refractoriness of P. vivax versus P. falciparum to control measures, and risk of distinct parasite subpopulations persisting in the community undetected by passive surveillance. These findings highlight the need for complimentary new surveillance strategies to identify transmission patterns that cannot be detected with traditional malariometric methods.

Evolution of foraging behaviour: Deep intra-generic genetic divergence between territorial and non-territorial southern African patellid limpets.

PubMed

Mmonwa, Kolobe L; Teske, Peter R; McQuaid, Christopher D; Barker, Nigel P

2017-12-01

Southern Africa is a biodiversity hotspot of patellid limpets, with three genera (Helcion, Cymbula and Scutellastra) identified and described in the region. Scutellastra is the most diverse and most frequently studied of these and, along with Cymbula, includes species with territorial and non-territorial foraging behaviours. We used three mitochondrial markers (12S rRNA, 16S rRNA and COI) and one nuclear marker (ATPSβ intron) to assess evolutionary relationships among species of Cymbula and Scutellastra with these two foraging behaviours and to identify which foraging mode is the more ancient. Maximum Likelihood and Bayesian Inference phylogenetic analyses revealed that the species sharing a foraging type are monophyletic in both genera. Territoriality is a derived character, as the clades with this foraging type are nested within a tree that otherwise comprises non-territorial taxa. These include Helcion, which was recovered as sister to the Cymbula/Scutellastra clade, and the next basal genus, Patella, which is ancestral to all southern African patellogastropods. Deep genetic divergence between the two foraging traits reflects strong adaptive effects of resource partitioning in the evolution of southern African patellid limpets. Copyright © 2017 Elsevier Inc. All rights reserved.

Pediatric Cystic Nephroma Is Morphologically, Immunohistochemically, and Genetically Distinct From Adult Cystic Nephroma.

PubMed

Li, Yunjie; Pawel, Bruce R; Hill, Dana A; Epstein, Jonathan I; Argani, Pedram

2017-04-01

The term cystic nephroma has traditionally been used to refer to 2 neoplasms, a lesion in adults that is now thought to be part of the spectrum of mixed epithelial stromal tumor (MEST) and a pediatric lesion that has been associated with mutations in the DICER1 gene. A direct detailed morphologic, immunohistochemical, and genetic comparison of these 2 lesions has not been performed. In this study, we compare the morphologic features, immunoreactivity for estrogen receptor and inhibin, and DICER1 genetic status of 12 adult cystic nephroma/MEST (median age 50.5 y, all females) and 7 pediatric cystic nephroma (median age 1.3 y, male:female=6:1). Both lesions (11 of 12 adult cases, 6 of 7 pediatric cases) frequently demonstrated subepithelial accentuation of stromal cellularity, though the increased cellularity frequently included inflammatory cells in the pediatric cases. All adult and pediatric cases labeled for estrogen receptor; however, whereas most (83%) of adult cases labeled for inhibin at least focally, no pediatric case labeled for inhibin. Most adult cases (58%) demonstrated wavy, ropy collagen in association with cellular stroma, whereas this was not found in pediatric cases. 86% of pediatric cases demonstrated DICER1 mutations, whereas only 1 of 10 adult cases demonstrated a DICER1 mutation. In summary, although cellular stroma and estrogen receptor immunoreactivity are commonly present in both adult and pediatric cystic nephroma, ropy collagen and inhibin immunoreactivity are far more common in adult cystic nephroma/MEST, whereas DICER1 mutations are far more prevalent in pediatric cystic nephroma. These results support the current World Health Organization Classification's separation of adult and pediatric cystic nephromas as distinct entities.

Genetic variants associated with fetal hemoglobin levels show the diverse ethnic origin in Colombian patients with sickle cell anemia.

PubMed

Fong, Cristian; Menzel, Stephan; Lizarralde, María Alejandra; Barreto, Guillermo

2015-01-01

Fetal hemoglobin is an important factor in modulating the severity of sickle cell anemia. Its level in peripheral blood underlies strong genetic determination. Associated loci with increased levels of fetal hemoglobin display population-specific allele frequencies. We investigated the presence and effect of known common genetic variants promoting fetal hemoglobin persistence (rs11886868, rs9399137, rs4895441, and rs7482144) in 60 Colombian patients with sickle cell anemia. Four single nucleotide polymorphisms (SNP) were genotyped by restriction fragment length polymorphisms (RFLP) and the use of the TaqMan procedure. Fetal hemoglobin (HbF) from these patients was quantified using the oxyhemoglobin alkaline denaturation technique. Genotype frequencies were compared with frequencies reported in global reference populations. We detected genetic variants in the four SNPs, reported to be associated with higher HbF levels for all four SNPs in the Colombian patients. Genetic association between SNPs and HbF levels did not reach statistical significance. The frequency of these variants reflected the specific ethnic make-up of our patient population: A high prevalence of rs7482144-'A' reflects the West-African origin of the sickle cell mutation, while high frequencies of rs4895441-'G' and rs11886868-'C' point to a significant influence of an Amerindian ethnic background in the Colombian sickle cell disease population. These results showed that in the sickle cell disease population in Colombia there is not a unique genetic background, but two (African and Amerindian). This unique genetic situation will provide opportunities for a further study of these loci, such as fine-mapping and molecular-biological investigation. Colombian patients are expected to yield a distinctive insight into the effect of modifier loci in sickle cell disease.

Genetic and environmental risk for major depression in African-American and European-American women.

PubMed

Duncan, Alexis E; Munn-Chernoff, Melissa A; Hudson, Darrell L; Eschenbacher, Michaela A; Agrawal, Arpana; Grant, Julia D; Nelson, Elliot C; Waldron, Mary; Glowinski, Anne L; Sartor, Carolyn E; Bucholz, Kathleen K; Madden, Pamela A F; Heath, Andrew C

2014-08-01

It is unknown whether there are racial differences in the heritability of major depressive disorder (MDD) because most psychiatric genetic studies have been conducted in samples comprised largely of white non-Hispanics. To examine potential differences between African-American (AA) and European-American (EA) young adult women in (1) Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) MDD prevalence, symptomatology, and risk factors, and (2) genetic and/or environmental liability to MDD, we analyzed data from a large population-representative sample of twins ascertained from birth records (n = 550 AA and n = 3226 EA female twins) aged 18-28 years at the time of MDD assessment by semi-structured psychiatric interview. AA women were more likely to have MDD risk factors; however, there were no significant differences in lifetime MDD prevalence between AA and EA women after adjusting for covariates (odds ratio = 0.88, 95% confidence interval [CI]: 0.67-1.15). Most MDD risk factors identified among AA women were also associated with MDD at similar magnitudes among EA women. Although the MDD heritability point estimate was higher among AA women than EA women in a model with paths estimated separately by race (56%, 95% CI: 29-78% vs. 41%, 95% CI: 29-52%), the best fitting model was one in which additive genetic and non-shared environmental paths for AA and EA women were constrained to be equal (A = 43%, 33-53% and E = 57%, 47-67%). In spite of a marked elevation in the prevalence of environmental risk exposures related to MDD among AA women, there were no significant differences in lifetime prevalence or heritability of MDD between AA and EA young women.

Human Genetic Ancestral Composition Correlates with the Origin of Mycobacterium leprae Strains in a Leprosy Endemic Population.

PubMed

Cardona-Castro, Nora; Cortés, Edwin; Beltrán, Camilo; Romero, Marcela; Badel-Mogollón, Jaime E; Bedoya, Gabriel

2015-01-01

Recent reports have suggested that leprosy originated in Africa, extended to Asia and Europe, and arrived in the Americas during European colonization and the African slave trade. Due to colonization, the contemporary Colombian population is an admixture of Native-American, European and African ancestries. Because microorganisms are known to accompany humans during migrations, patterns of human migration can be traced by examining genomic changes in associated microbes. The current study analyzed 118 leprosy cases and 116 unrelated controls from two Colombian regions endemic for leprosy (Atlantic and Andean) in order to determine possible associations of leprosy with patient ancestral background (determined using 36 ancestry informative markers), Mycobacterium leprae genotype and/or patient geographical origin. We found significant differences between ancestral genetic composition. European components were predominant in Andean populations. In contrast, African components were higher in the Atlantic region. M. leprae genotypes were then analyzed for cluster associations and compared with the ancestral composition of leprosy patients. Two M. leprae principal clusters were found: haplotypes C54 and T45. Haplotype C54 associated with African origin and was more frequent in patients from the Atlantic region with a high African component. In contrast, haplotype T45 associated with European origin and was more frequent in Andean patients with a higher European component. These results suggest that the human and M. leprae genomes have co-existed since the African and European origins of the disease, with leprosy ultimately arriving in Colombia during colonization. Distinct M. leprae strains followed European and African settlement in the country and can be detected in contemporary Colombian populations.

The genetic prehistory of southern Africa.

PubMed

Pickrell, Joseph K; Patterson, Nick; Barbieri, Chiara; Berthold, Falko; Gerlach, Linda; Güldemann, Tom; Kure, Blesswell; Mpoloka, Sununguko Wata; Nakagawa, Hirosi; Naumann, Christfried; Lipson, Mark; Loh, Po-Ru; Lachance, Joseph; Mountain, Joanna; Bustamante, Carlos D; Berger, Bonnie; Tishkoff, Sarah A; Henn, Brenna M; Stoneking, Mark; Reich, David; Pakendorf, Brigitte

2012-01-01

Southern and eastern African populations that speak non-Bantu languages with click consonants are known to harbour some of the most ancient genetic lineages in humans, but their relationships are poorly understood. Here, we report data from 23 populations analysed at over half a million single-nucleotide polymorphisms, using a genome-wide array designed for studying human history. The southern African Khoisan fall into two genetic groups, loosely corresponding to the northwestern and southeastern Kalahari, which we show separated within the last 30,000 years. We find that all individuals derive at least a few percent of their genomes from admixture with non-Khoisan populations that began ∼1,200 years ago. In addition, the East African Hadza and Sandawe derive a fraction of their ancestry from admixture with a population related to the Khoisan, supporting the hypothesis of an ancient link between southern and eastern Africa.

Teachers' Conceptions About the Genetic Determinism of Human Behaviour: A Survey in 23 Countries

NASA Astrophysics Data System (ADS)

Castéra, Jérémy; Clément, Pierre

2014-02-01

This work analyses the answers to a questionnaire from 8,285 in-service and pre-service teachers from 23 countries, elaborated by the Biohead-Citizen research project, to investigate teachers' conceptions related to the genetic determinism of human behaviour. A principal components analysis is used to assess the main trends in all the interviewed teachers' conceptions. This illustrates that innatism is present in two distinct ways: in relation to individuals (e.g. genetic determinism to justify intellectual likeness between individuals such as twins) or in relation to groups of humans (e.g. genetic determinism to justify gender differences or the superiority of some human ethnic groups). A between-factor analysis discriminates between countries, showing very significant differences. There is more innatism among teachers' conceptions in African countries and Lebanon than in European countries, Brazil and Australia. Among the other controlled parameters, only two are significantly independent of the country: the level of training and the level of knowledge of biology. A co-inertia analysis shows a strong correlation between non-citizen attitudes towards and innatist conceptions of genetic determinism regarding human groups. We discuss these findings and their implications for education.

Genomic Tools for Evolution and Conservation in the Chimpanzee: Pan troglodytes ellioti Is a Genetically Distinct Population

PubMed Central

Myers, Simon; Hellenthal, Garrett; Nerrienet, Eric; Bontrop, Ronald E.; Freeman, Colin; Donnelly, Peter; Mundy, Nicholas I.

2012-01-01

In spite of its evolutionary significance and conservation importance, the population structure of the common chimpanzee, Pan troglodytes, is still poorly understood. An issue of particular controversy is whether the proposed fourth subspecies of chimpanzee, Pan troglodytes ellioti, from parts of Nigeria and Cameroon, is genetically distinct. Although modern high-throughput SNP genotyping has had a major impact on our understanding of human population structure and demographic history, its application to ecological, demographic, or conservation questions in non-human species has been extremely limited. Here we apply these tools to chimpanzee population structure, using ∼700 autosomal SNPs derived from chimpanzee genomic data and a further ∼100 SNPs from targeted re-sequencing. We demonstrate conclusively the existence of P. t. ellioti as a genetically distinct subgroup. We show that there is clear differentiation between the verus, troglodytes, and ellioti populations at the SNP and haplotype level, on a scale that is greater than that separating continental human populations. Further, we show that only a small set of SNPs (10–20) is needed to successfully assign individuals to these populations. Tellingly, use of only mitochondrial DNA variation to classify individuals is erroneous in 4 of 54 cases, reinforcing the dangers of basing demographic inference on a single locus and implying that the demographic history of the species is more complicated than that suggested analyses based solely on mtDNA. In this study we demonstrate the feasibility of developing economical and robust tests of individual chimpanzee origin as well as in-depth studies of population structure. These findings have important implications for conservation strategies and our understanding of the evolution of chimpanzees. They also act as a proof-of-principle for the use of cheap high-throughput genomic methods for ecological questions. PMID:22396655

Genomic tools for evolution and conservation in the chimpanzee: Pan troglodytes ellioti is a genetically distinct population.

PubMed

Bowden, Rory; MacFie, Tammie S; Myers, Simon; Hellenthal, Garrett; Nerrienet, Eric; Bontrop, Ronald E; Freeman, Colin; Donnelly, Peter; Mundy, Nicholas I

2012-01-01

In spite of its evolutionary significance and conservation importance, the population structure of the common chimpanzee, Pan troglodytes, is still poorly understood. An issue of particular controversy is whether the proposed fourth subspecies of chimpanzee, Pan troglodytes ellioti, from parts of Nigeria and Cameroon, is genetically distinct. Although modern high-throughput SNP genotyping has had a major impact on our understanding of human population structure and demographic history, its application to ecological, demographic, or conservation questions in non-human species has been extremely limited. Here we apply these tools to chimpanzee population structure, using ∼700 autosomal SNPs derived from chimpanzee genomic data and a further ∼100 SNPs from targeted re-sequencing. We demonstrate conclusively the existence of P. t. ellioti as a genetically distinct subgroup. We show that there is clear differentiation between the verus, troglodytes, and ellioti populations at the SNP and haplotype level, on a scale that is greater than that separating continental human populations. Further, we show that only a small set of SNPs (10-20) is needed to successfully assign individuals to these populations. Tellingly, use of only mitochondrial DNA variation to classify individuals is erroneous in 4 of 54 cases, reinforcing the dangers of basing demographic inference on a single locus and implying that the demographic history of the species is more complicated than that suggested analyses based solely on mtDNA. In this study we demonstrate the feasibility of developing economical and robust tests of individual chimpanzee origin as well as in-depth studies of population structure. These findings have important implications for conservation strategies and our understanding of the evolution of chimpanzees. They also act as a proof-of-principle for the use of cheap high-throughput genomic methods for ecological questions.

HLA-DRB1 Analysis Identified a Genetically Unique Subset within Rheumatoid Arthritis and Distinct Genetic Background of Rheumatoid Factor Levels from Anticyclic Citrullinated Peptide Antibodies.

PubMed

Hiwa, Ryosuke; Ikari, Katsunori; Ohmura, Koichiro; Nakabo, Shuichiro; Matsuo, Keitaro; Saji, Hiroh; Yurugi, Kimiko; Miura, Yasuo; Maekawa, Taira; Taniguchi, Atsuo; Yamanaka, Hisashi; Matsuda, Fumihiko; Mimori, Tsuneyo; Terao, Chikashi

2018-04-01

HLA-DRB1 is the most important locus associated with rheumatoid arthritis (RA) and anticitrullinated protein antibodies (ACPA). However, fluctuations of rheumatoid factor (RF) over the disease course have made it difficult to define fine subgroups according to consistent RF positivity for the analyses of genetic background and the levels of RF. A total of 2873 patients with RA and 2008 healthy controls were recruited. We genotyped HLA-DRB1 alleles for the participants and collected consecutive data of RF in the case subjects. In addition to RF+ and RF- subsets, we classified the RF+ subjects into group 1 (constant RF+) and group 2 (seroconversion). We compared HLA-DRB1 alleles between the RA subsets and controls and performed linear regression analysis to identify HLA-DRB1 alleles associated with maximal RF levels. Omnibus tests were conducted to assess important amino acid positions. RF positivity was 88%, and 1372 and 970 RF+ subjects were classified into groups 1 and 2, respectively. RF+ and RF- showed similar genetic associations to ACPA+ and ACPA- RA, respectively. We found that shared epitope (SE) was more enriched in group 2 than 1, p = 2.0 × 10 -5 , and that amino acid position 11 showed a significant association between 1 and 2, p = 2.7 × 10 -5 . These associations were independent of ACPA positivity. SE showed a tendency to be negatively correlated with RF titer (p = 0.012). HLA-DRB1*09:01, which reduces ACPA titer, was not associated with RF levels (p = 0.70). The seroconversion group was shown to have distinct genetic characteristics. The genetic architecture of RF levels is different from that of ACPA.

Molecular Comparison and Evolutionary Analyses of VP1 Nucleotide Sequences of New African Human Enterovirus 71 Isolates Reveal a Wide Genetic Diversity

PubMed Central

Nougairède, Antoine; Joffret, Marie-Line; Deshpande, Jagadish M.; Dubot-Pérès, Audrey; Héraud, Jean-Michel

2014-01-01

Most circulating strains of Human enterovirus 71 (EV-A71) have been classified primarily into three genogroups (A to C) on the basis of genetic divergence between the 1D gene, which encodes the VP1 capsid protein. The aim of the present study was to provide further insights into the diversity of the EV-A71 genogroups following the recent description of highly divergent isolates, in particular those from African countries, including Madagascar. We classified recent EV-A71 isolates by a large comparison of 3,346 VP1 nucleotidic sequences collected from GenBank. Analysis of genetic distances and phylogenetic investigations indicated that some recently-reported isolates did not fall into the genogroups A-C and clustered into three additional genogroups, including one Indian genogroup (genogroup D) and 2 African ones (E and F). Our Bayesian phylogenetic analysis provided consistent data showing that the genogroup D isolates share a recent common ancestor with the members of genogroup E, while the isolates of genogroup F evolved from a recent common ancestor shared with the members of the genogroup B. Our results reveal the wide diversity that exists among EV-A71 isolates and suggest that the number of circulating genogroups is probably underestimated, particularly in developing countries where EV-A71 epidemiology has been poorly studied. PMID:24598878

Pelagic Life and Depth: Coastal Physical Features in West Africa Shape the Genetic Structure of the Bonga Shad, Ethmalosa fimbriata

PubMed Central

Durand, Jean-Dominique; Guinand, Bruno; Dodson, Julian J.; Lecomte, Frédéric

2013-01-01

The bonga shad, Ethmalosa fimbriata, is a West African pelagic species still abundant in most habitats of its distribution range and thought to be only recently affected by anthropogenic pressure (habitat destruction or fishing pressure). Its presence in a wide range of coastal habitats characterised by different hydrodynamic processes, represents a case study useful for evaluating the importance of physical structure of the west African shoreline on the genetic structure of a small pelagic species. To investigate this question, the genetic diversity of E. fimbriata was assessed at both regional and species range scales, using mitochondrial (mt) and nuclear DNA markers. Whereas only three panmictic units were identified with mtDNA at the large spatial scale, nuclear genetic markers (EPIC: exon-primed intron-crossing) indicated a more complex genetic pattern at the regional scale. In the northern-most section of shad’s distribution range, up to 4 distinct units were identified. Bayesian inference as well as spatial autocorrelation methods provided evidence that gene flow is impeded by the presence of deep-water areas near the coastline (restricting the width of the coastal shelf), such as the Cap Timiris and the Kayar canyons in Mauritania and Senegal, respectively. The added discriminatory power provided by the use of EPIC markers proved to be essential to detect the influence of more subtle, contemporary processes (e.g. gene flow, barriers, etc.) acting within the glacial refuges identified previously by mtDNA. PMID:24130890

Comparative multivariate analysis of biometric traits of West African Dwarf and Red Sokoto goats.

PubMed

Yakubu, Abdulmojeed; Salako, Adebowale E; Imumorin, Ikhide G

2011-03-01

The population structure of 302 randomly selected West African Dwarf (WAD) and Red Sokoto (RS) goats was examined using multivariate morphometric analyses. This was to make the case for conservation, rational management and genetic improvement of these two most important Nigerian goat breeds. Fifteen morphometric measurements were made on each individual animal. RS goats were superior (P<0.05) to the WAD for the body size and skeletal proportions investigated. The phenotypic variability between the two breeds was revealed by their mutual responses in the principal components. While four principal components were extracted for WAD goats, three components were obtained for their RS counterparts with variation in the loading traits of each component for each breed. The Mahalanobis distance of 72.28 indicated a high degree of spatial racial separation in morphology between the genotypes. The Ward's option of the cluster analysis consolidated the morphometric distinctness of the two breeds. Application of selective breeding to genetic improvement would benefit from the detected phenotypic differentiation. Other implications for management and conservation of the goats are highlighted.

African American Adolescents' Perceptions of Ethnic Socialization and Racial Socialization as Distinct Processes

ERIC Educational Resources Information Center

Paasch-Anderson, Julie; Lamborn, Susie D.

2014-01-01

Ethnic socialization and racial socialization were examined as discrete concepts using a semistructured interview to assess message content for each form of socialization. We were interested in whether adolescents distinguished between these forms of socialization. Fifty-five African American 11th- and 12th-grade students were asked separate…

IGF2R Genetic Variants, Circulating IGF2 Concentrations and Colon Cancer Risk in African Americans and Whites

PubMed Central

Hoyo, Cathrine; Murphy, Susan K.; Schildkraut, Joellen M.; Vidal, Adriana C.; Skaar, David; Millikan, Robert C.; Galanko, Joseph; Sandler, Robert S.; Jirtle, Randy; Keku, Temitope

2012-01-01

The Mannose 6 Phosphate/Insulin-like Growth Factor Receptor-2 (IGF2R) encodes a type-1 membrane protein that modulates availability of the potent mitogen, IGF2. We evaluated the associations between IGF2R non-synonymous genetic variants (c.5002G>A, Gly1619Arg(rs629849), and c.901C>G, Leu252Val(rs8191754)), circulating IGF2 levels, and colon cancer (CC) risk among African American and White participants enrolled in the North Carolina Colon Cancer Study (NCCCS). Generalized linear models were used to compare circulating levels of IGF2 among 298 African American and 518 White controls. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of IGF2R genetic variants and CC risk. Women homozygous for the IGF2R c.5002 G>A allele, had higher mean levels of circulating IGF2, 828 (SD=321) ng/ml compared to non-carriers, 595 (SD=217) ng/ml (p-value=0.01). This pattern was not apparent in individuals homozygous for the IGF2R c.901 C>G variant. Whites homozygous for the IGF2R c.901 C>G variant trended towards a higher risk of CC, OR=2.2 [95% CI(0.9–5.4)], whereas carrying the IGF2R c.5002 G>A variant was not associated with CC risk. Our findings support the hypothesis that being homozygous for the IGF2R c.5002 G>A modulates IGF2 circulating levels in a sex-specific manner, and while carrying the IGF2R c.901 C>G may increase cancer risk, the mechanism may not involve modulation of circulating IGF2. PMID:22377707

IGF2R genetic variants, circulating IGF2 concentrations and colon cancer risk in African Americans and Whites.

PubMed

Hoyo, Cathrine; Murphy, Susan K; Schildkraut, Joellen M; Vidal, Adriana C; Skaar, David; Millikan, Robert C; Galanko, Joseph; Sandler, Robert S; Jirtle, Randy; Keku, Temitope

2012-01-01

The Mannose 6 Phosphate/Insulin-like Growth Factor Receptor-2 (IGF2R) encodes a type-1 membrane protein that modulates availability of the potent mitogen, IGF2. We evaluated the associations between IGF2R non-synonymous genetic variants (c.5002G>A, Gly1619Arg(rs629849), and c.901C>G, Leu252Val(rs8191754)), circulating IGF2 levels, and colon cancer (CC) risk among African American and White participants enrolled in the North Carolina Colon Cancer Study (NCCCS). Generalized linear models were used to compare circulating levels of IGF2 among 298 African American and 518 White controls. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of IGF2R genetic variants and CC risk. Women homozygous for the IGF2R c.5002 G>A allele, had higher mean levels of circulating IGF2, 828 (SD=321) ng/ml compared to non-carriers, 595 (SD=217) ng/ml (p-value=0.01). This pattern was not apparent in individuals homozygous for the IGF2R c.901 C>G variant. Whites homozygous for the IGF2R c.901 C>G variant trended towards a higher risk of CC, OR=2.2 [95% CI(0.9-5.4)], whereas carrying the IGF2R c.5002 G>A variant was not associated with CC risk. Our findings support the hypothesis that being homozygous for the IGF2R c.5002 G>A modulates IGF2 circulating levels in a sex-specific manner, and while carrying the IGF2R c.901 C>G may increase cancer risk, the mechanism may not involve modulation of circulating IGF2.

Biomarkers in the Detection of Prostate Cancer in African Americans

DTIC Science & Technology

2015-09-01

of PrCas in AAs. These may be inherited genetic factors, DNA mutations in the tumor or epigenetic changes secondary to or interacting with other... genetic admixture. This finding suggests that in AAs, ancestry genotyping may be helpful in assessing individual PrCa risk and provide useful...identified African Americans showed genetic evidence of ancestry admixture; in our Birmingham AA subjects this admixture was almost entirely from

Triple-negative breast cancer in African-American women: disparities versus biology

PubMed Central

Dietze, Eric C.; Sistrunk, Christopher; Miranda-Carboni, Gustavo; O’Regan, Ruth; Seewaldt, Victoria L.

2017-01-01

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects BRCA1 mutation carriers and young women of African origin. There is evidence that African-American women with TNBC have worse clinical outcomes than women of European descent. However, it is unclear whether survival differences persist after adjusting for disparities in access to health-care treatment, co-morbid disease and income. It remains controversial whether TNBC in African-American women is a molecularly distinct disease or whether African-American women have a higher incidence of aggressive biology driven by disparities: there is evidence in support of both. Understanding the relative contributions of biology and disparities is essential for improving the poor survival rate of African-American women with TNBC. PMID:25673085

Triple-negative breast cancer in African-American women: disparities versus biology.

PubMed

Dietze, Eric C; Sistrunk, Christopher; Miranda-Carboni, Gustavo; O'Regan, Ruth; Seewaldt, Victoria L

2015-04-01

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects BRCA1 mutation carriers and young women of African origin. There is evidence that African-American women with TNBC have worse clinical outcomes than women of European descent. However, it is unclear whether survival differences persist after adjusting for disparities in access to health-care treatment, co-morbid disease and income. It remains controversial whether TNBC in African-American women is a molecularly distinct disease or whether African-American women have a higher incidence of aggressive biology driven by disparities: there is evidence in support of both. Understanding the relative contributions of biology and disparities is essential for improving the poor survival rate of African-American women with TNBC.

Resequencing of the CETP gene in American whites and African blacks: Association of rare and common variants with HDL-cholesterol levels

PubMed Central

Pirim, Dilek; Wang, Xingbin; Niemsiri, Vipavee; Radwan, Zaheda H.; Bunker, Clareann H.; Hokanson, John E.; Hamman, Richard F.; Barmada, M. Michael; Demirci, F. Yesim; Kamboh, M. Ilyas

2015-01-01

Background Cholesteryl ester transfer protein (CETP) plays a crucial role in lipid metabolism. Associations of common CETP variants with variation in plasma lipid levels, and/or CETP mass/activity have been extensively studied and well-documented; however, the effects of uncommon/rare CETP variants on plasma lipid profile remain undefined. Hence, resequencing of the gene in extreme phenotypes and follow-up rare-variant association analyses are essential to fill this gap. Objective To identify common and uncommon/rare variants in the CETP gene by resequencing the entire gene and test the effects of both common and uncommon/rare CETP variants on plasma lipid traits in two genetically distinct populations. Methods and Results The entire CETP gene plus flanking regions were resequenced in 190 individuals comprising 95 non-Hispanic Whites (NHWs) and 95 African blacks with extreme HDL-C levels. A total of 279 sequence variants were identified, of which 25 were novel. Selected variants were genotyped in the entire samples of 623 NHWs and 788 African blacks and 184 QC-passed variants were tested in relation to plasma lipid traits by using gene-based, single-site, haplotype and rare variant association analyses (SKAT-O). Two novel and independent associations of rs1968905 and rs289740 with HDL-C were identified in African blacks. Using SKAT-O analysis, we also identified rare variants with minor allele frequency <0.01 to be associated with HDL-C in both NHWs (P=0.024) and African blacks (P=0.009). Conclusions Our results point out that in addition to the common CETP variants, rare genetic variants in the CETP gene also contribute to the phenotypic variation of HDL-C in the general population. PMID:26683795

Identification of genetically and oceanographically distinct blooms of jellyfish

PubMed Central

Lee, Patricia L. M.; Dawson, Michael N; Neill, Simon P.; Robins, Peter E.; Houghton, Jonathan D. R.; Doyle, Thomas K.; Hays, Graeme C.

2013-01-01

Reports of nuisance jellyfish blooms have increased worldwide during the last half-century, but the possible causes remain unclear. A persistent difficulty lies in identifying whether blooms occur owing to local or regional processes. This issue can be resolved, in part, by establishing the geographical scales of connectivity among locations, which may be addressed using genetic analyses and oceanographic modelling. We used landscape genetics and Lagrangian modelling of oceanographic dispersal to explore patterns of connectivity in the scyphozoan jellyfish Rhizostoma octopus, which occurs en masse at locations in the Irish Sea and northeastern Atlantic. We found significant genetic structure distinguishing three populations, with both consistencies and inconsistencies with prevailing physical oceanographic patterns. Our analyses identify locations where blooms occur in apparently geographically isolated populations, locations where blooms may be the source or result of migrants, and a location where blooms do not occur consistently and jellyfish are mostly immigrant. Our interdisciplinary approach thus provides a means to ascertain the geographical origins of jellyfish in outbreaks, which may have wide utility as increased international efforts investigate jellyfish blooms. PMID:23287405

Genetic Variants Associated with Serum Thyroid Stimulating Hormone (TSH) Levels in European Americans and African Americans from the eMERGE Network

PubMed Central

Malinowski, Jennifer R.; Denny, Joshua C.; Bielinski, Suzette J.; Basford, Melissa A.; Bradford, Yuki; Peissig, Peggy L.; Carrell, David; Crosslin, David R.; Pathak, Jyotishman; Rasmussen, Luke; Pacheco, Jennifer; Kho, Abel; Newton, Katherine M.; Li, Rongling; Kullo, Iftikhar J.; Chute, Christopher G.; Chisholm, Rex L.; Jarvik, Gail P.; Larson, Eric B.; McCarty, Catherine A.; Masys, Daniel R.; Roden, Dan M.; de Andrade, Mariza; Ritchie, Marylyn D.; Crawford, Dana C.

2014-01-01

Thyroid stimulating hormone (TSH) hormone levels are normally tightly regulated within an individual; thus, relatively small variations may indicate thyroid disease. Genome-wide association studies (GWAS) have identified variants in PDE8B and FOXE1 that are associated with TSH levels. However, prior studies lacked racial/ethnic diversity, limiting the generalization of these findings to individuals of non-European ethnicities. The Electronic Medical Records and Genomics (eMERGE) Network is a collaboration across institutions with biobanks linked to electronic medical records (EMRs). The eMERGE Network uses EMR-derived phenotypes to perform GWAS in diverse populations for a variety of phenotypes. In this report, we identified serum TSH levels from 4,501 European American and 351 African American euthyroid individuals in the eMERGE Network with existing GWAS data. Tests of association were performed using linear regression and adjusted for age, sex, body mass index (BMI), and principal components, assuming an additive genetic model. Our results replicate the known association of PDE8B with serum TSH levels in European Americans (rs2046045 p = 1.85×10−17, β = 0.09). FOXE1 variants, associated with hypothyroidism, were not genome-wide significant (rs10759944: p = 1.08×10−6, β = −0.05). No SNPs reached genome-wide significance in African Americans. However, multiple known associations with TSH levels in European ancestry were nominally significant in African Americans, including PDE8B (rs2046045 p = 0.03, β = −0.09), VEGFA (rs11755845 p = 0.01, β = −0.13), and NFIA (rs334699 p = 1.50×10−3, β = −0.17). We found little evidence that SNPs previously associated with other thyroid-related disorders were associated with serum TSH levels in this study. These results support the previously reported association between PDE8B and serum TSH levels in European Americans and emphasize the need for additional genetic

Genetic variants associated with serum thyroid stimulating hormone (TSH) levels in European Americans and African Americans from the eMERGE Network.

PubMed

Malinowski, Jennifer R; Denny, Joshua C; Bielinski, Suzette J; Basford, Melissa A; Bradford, Yuki; Peissig, Peggy L; Carrell, David; Crosslin, David R; Pathak, Jyotishman; Rasmussen, Luke; Pacheco, Jennifer; Kho, Abel; Newton, Katherine M; Li, Rongling; Kullo, Iftikhar J; Chute, Christopher G; Chisholm, Rex L; Jarvik, Gail P; Larson, Eric B; McCarty, Catherine A; Masys, Daniel R; Roden, Dan M; de Andrade, Mariza; Ritchie, Marylyn D; Crawford, Dana C

2014-01-01

Thyroid stimulating hormone (TSH) hormone levels are normally tightly regulated within an individual; thus, relatively small variations may indicate thyroid disease. Genome-wide association studies (GWAS) have identified variants in PDE8B and FOXE1 that are associated with TSH levels. However, prior studies lacked racial/ethnic diversity, limiting the generalization of these findings to individuals of non-European ethnicities. The Electronic Medical Records and Genomics (eMERGE) Network is a collaboration across institutions with biobanks linked to electronic medical records (EMRs). The eMERGE Network uses EMR-derived phenotypes to perform GWAS in diverse populations for a variety of phenotypes. In this report, we identified serum TSH levels from 4,501 European American and 351 African American euthyroid individuals in the eMERGE Network with existing GWAS data. Tests of association were performed using linear regression and adjusted for age, sex, body mass index (BMI), and principal components, assuming an additive genetic model. Our results replicate the known association of PDE8B with serum TSH levels in European Americans (rs2046045 p = 1.85×10-17, β = 0.09). FOXE1 variants, associated with hypothyroidism, were not genome-wide significant (rs10759944: p = 1.08×10-6, β = -0.05). No SNPs reached genome-wide significance in African Americans. However, multiple known associations with TSH levels in European ancestry were nominally significant in African Americans, including PDE8B (rs2046045 p = 0.03, β = -0.09), VEGFA (rs11755845 p = 0.01, β = -0.13), and NFIA (rs334699 p = 1.50×10-3, β = -0.17). We found little evidence that SNPs previously associated with other thyroid-related disorders were associated with serum TSH levels in this study. These results support the previously reported association between PDE8B and serum TSH levels in European Americans and emphasize the need for additional genetic studies in more

Genetic Contributions to Disparities in Preterm Birth

PubMed Central

Anum, Emmanuel A.; Springel, Edward H.; Shriver, Mark D.; Strauss, Jerome F.

2008-01-01

Ethnic disparity in preterm delivery between African Americans and European Americans has existed for decades, and is likely the consequence of multiple factors, including socioeconomic status, access to care, environment, and genetics. This review summarizes existing information on genetic variation and its association with preterm birth in African Americans. Candidate gene-based association studies, in which investigators have evaluated particular genes selected primarily because of their potential roles in the process of normal and pathological parturition, provide evidence that genetic contributions from both mother and fetus account for some of the disparity in preterm births. To date, most attention has been focused on genetic variation in pro- and anti-inflammatory cytokine genes and their respective receptors. These genes, particularly the pro-inflammatory cytokine genes and their receptors, are linked to matrix metabolism since these cytokines increase expression of matrix degrading metalloproteinases. However, the role that genetic variants that are different between populations play in preterm birth cannot yet be quantified. Future studies based on genome wide association or admixture mapping may reveal other genes that contribute to disparity in prematurity. PMID:18787421

Evolutionary and demographic processes shaping geographic patterns of genetic diversity in a keystone species, the African forest elephant (Loxodonta cyclotis).

PubMed

Ishida, Yasuko; Gugala, Natalie A; Georgiadis, Nicholas J; Roca, Alfred L

2018-05-01

The past processes that have shaped geographic patterns of genetic diversity may be difficult to infer from current patterns. However, in species with sex differences in dispersal, differing phylogeographic patterns between mitochondrial (mt) and nuclear (nu) DNA may provide contrasting insights into past events. Forest elephants ( Loxodonta cyclotis ) were impacted by climate and habitat change during the Pleistocene, which likely shaped phylogeographic patterns in mitochondrial (mt) DNA that have persisted due to limited female dispersal. By contrast, the nuclear (nu) DNA phylogeography of forest elephants in Central Africa has not been determined. We therefore examined the population structure of Central African forest elephants by genotyping 94 individuals from six localities at 21 microsatellite loci. Between forest elephants in western and eastern Congolian forests, there was only modest genetic differentiation, a pattern highly discordant with that of mtDNA. Nuclear genetic patterns are consistent with isolation by distance. Alternatively, male-mediated gene flow may have reduced the previous regional differentiation in Central Africa suggested by mtDNA patterns, which likely reflect forest fragmentation during the Pleistocene. In species like elephants, male-mediated gene flow erases the nuclear genetic signatures of past climate and habitat changes, but these continue to persist as patterns in mtDNA because females do not disperse. Conservation implications of these results are discussed.

Knowledge-making distinctions in synthetic biology.

PubMed

O'Malley, Maureen A; Powell, Alexander; Davies, Jonathan F; Calvert, Jane

2008-01-01

Synthetic biology is an increasingly high-profile area of research that can be understood as encompassing three broad approaches towards the synthesis of living systems: DNA-based device construction, genome-driven cell engineering and protocell creation. Each approach is characterized by different aims, methods and constructs, in addition to a range of positions on intellectual property and regulatory regimes. We identify subtle but important differences between the schools in relation to their treatments of genetic determinism, cellular context and complexity. These distinctions tie into two broader issues that define synthetic biology: the relationships between biology and engineering, and between synthesis and analysis. These themes also illuminate synthetic biology's connections to genetic and other forms of biological engineering, as well as to systems biology. We suggest that all these knowledge-making distinctions in synthetic biology raise fundamental questions about the nature of biological investigation and its relationship to the construction of biological components and systems. (c) 2007 Wiley Periodicals, Inc.

Genetic micro-epidemiology of malaria in Papua Indonesia: Extensive P. vivax diversity and a distinct subpopulation of asymptomatic P. falciparum infections

PubMed Central

Pava, Zuleima; Noviyanti, Rintis; Handayuni, Irene; Trimarsanto, Hidayat; Trianty, Leily; Burdam, Faustina H.; Kenangalem, Enny; Utami, Retno A. S.; Tirta, Yusrifar K.; Coutrier, Farah; Poespoprodjo, Jeanne R.; Price, Ric N.; Marfurt, Jutta

2017-01-01

Background Genetic analyses of Plasmodium have potential to inform on transmission dynamics, but few studies have evaluated this on a local spatial scale. We used microsatellite genotyping to characterise the micro-epidemiology of P. vivax and P. falciparum diversity to inform malaria control strategies in Timika, Papua Indonesia. Methods Genotyping was undertaken on 713 sympatric P. falciparum and P. vivax isolates from a cross-sectional household survey and clinical studies conducted in Timika. Standard population genetic measures were applied, and the data was compared to published data from Kalimantan, Bangka, Sumba and West Timor. Results Higher diversity (HE = 0.847 vs 0.625; p = 0.017) and polyclonality (46.2% vs 16.5%, p<0.001) were observed in P. vivax versus P. falciparum. Distinct P. falciparum substructure was observed, with two subpopulations, K1 and K2. K1 was comprised solely of asymptomatic infections and displayed greater relatedness to isolates from Sumba than to K2, possibly reflecting imported infections. Conclusions The results demonstrate the greater refractoriness of P. vivax versus P. falciparum to control measures, and risk of distinct parasite subpopulations persisting in the community undetected by passive surveillance. These findings highlight the need for complimentary new surveillance strategies to identify transmission patterns that cannot be detected with traditional malariometric methods. PMID:28498860

Biomarkers in the Detection of Prostate Cancer in African Americans

DTIC Science & Technology

2015-09-01

AAs. These may be inherited genetic factors, DNA mutations in the tumor or epigenetic changes secondary to or interacting with other biological changes...WA) ancestry by AIMs genotyping, while a large proportion (40%) of the AAs diagnosed with no cancer on biopsy showed more than 25% EU genetic ...African Americans showed genetic evidence of ancestry admixture; in our Birmingham AA subjects this admixture was almost entirely from European ancestors

Insights into the Genetic History of French Cattle from Dense SNP Data on 47 Worldwide Breeds

PubMed Central

Gautier, Mathieu; Laloë, Denis; Moazami-Goudarzi, Katayoun

2010-01-01

Background Modern cattle originate from populations of the wild extinct aurochs through a few domestication events which occurred about 8,000 years ago. Newly domesticated populations subsequently spread worldwide following breeder migration routes. The resulting complex historical origins associated with both natural and artificial selection have led to the differentiation of numerous different cattle breeds displaying a broad phenotypic variety over a short period of time. Methodology/Principal Findings This study gives a detailed assessment of cattle genetic diversity based on 1,121 individuals sampled in 47 populations from different parts of the world (with a special focus on French cattle) genotyped for 44,706 autosomal SNPs. The analyzed data set consisted of new genotypes for 296 individuals representing 14 French cattle breeds which were combined to those available from three previously published studies. After characterizing SNP polymorphism in the different populations, we performed a detailed analysis of genetic structure at both the individual and population levels. We further searched for spatial patterns of genetic diversity among 23 European populations, most of them being of French origin, under the recently developed spatial Principal Component analysis framework. Conclusions/Significance Overall, such high throughput genotyping data confirmed a clear partitioning of the cattle genetic diversity into distinct breeds. In addition, patterns of differentiation among the three main groups of populations—the African taurine, the European taurine and zebus—may provide some additional support for three distinct domestication centres. Finally, among the European cattle breeds investigated, spatial patterns of genetic diversity were found in good agreement with the two main migration routes towards France, initially postulated based on archeological evidence. PMID:20927341

STRESS, RELATIONSHIP SATISFACTION, AND HEALTH AMONG AFRICAN AMERICAN WOMEN: GENETIC MODERATION OF EFFECTS

PubMed Central

Lei, Man-Kit; Beach, Steven R. H.; Simons, Ronald L.; Barr, Ashley B.; Cutrona, Carolyn E.; Philibert, Robert A.

2015-01-01

We examined whether romantic relationship satisfaction would serve as a link between early and later stressors which in turn would influence the Thyroid Function Index (TFI), an indicator of physiological stress response. Using the framework of genetic susceptibility theory combined with hypotheses derived from the vulnerability-stress-adaptation and stress-generation models, we tested whether the hypothesized mediational model would be conditioned by 5-HTTLPR genotype, with greater effects and stronger evidence of mediation among carriers of the “s” allele. In a sample of African American women in romantic relationships (n = 270), we found that 5-HTTLPR moderated each stage of the hypothesized mediational model in a “for better or for worse” manner. That is genetic polymorphisms function to exacerbate not only the detrimental impact of negative environments (i.e. “for worse effects”) but also the beneficial impact of positive environments (i.e. “for better effects”). The effect of early stress on relationship satisfaction was greater among carriers of the “short” allele than among those who did not carry the short allele, and was significantly different in both the “for better” and “for worse” direction. Likewise, the effect of relationship satisfaction on later stressors was moderated in a “for better” or “for worse” manner. Finally, impact on physiological stress, indexed using TFI level, indicated that the impact of later stressors on TFI level was greater in the presence of the short allele, and also followed a “for better” or “for worse” pattern. As expected, the proposed mediational model provided a better fit for “s” allele carriers. PMID:26376424