Ethnicity-specific pharmacogenetics: the case of warfarin in African Americans.

Using a derivation cohort (N=349), we developed the first warfarin dosing algorithm that includes recently discovered polymorphisms in VKORC1 and CYP2C9 associated with warfarin dose requirement in African Americans (AAs). We tested our novel algorithm in an independent cohort of 129 AAs and compared the dose prediction to the International Warfarin Pharmacogenetics Consortium (IWPC) dosing algorithms. Our algorithm explains more of the phenotypic variation (R(2)=0.27) than the IWPC pharmacogenomics (R(2)=0.15) or clinical (R(2)=0.16) algorithms. Among high-dose patients, our algorithm predicted a higher proportion of patients within 20% of stable warfarin dose (45% vs 29% and 2% in the IWPC pharmacogenomics and clinical algorithms, respectively). In contrast to our novel algorithm, a significant inverse correlation between predicted dose and percent West African ancestry was observed for the IWPC pharmacogenomics algorithm among patients requiring ⩾60 mg per week (ß=-2.04, P=0.02).

Implications of correlations between skin color and genetic ancestry for biomedical research.

Skin pigmentation is a central element of most discussions on 'race' and genetics. Research on the genetic basis of population variation in this phenotype, which is important in mediating both social experiences and environmental exposures, is sparse. We studied the relationship between pigmentation and ancestry in five populations of mixed ancestry with a wide range of pigmentation and ancestral proportions (African Americans from Washington, DC; African Caribbeans living in England; Puerto Ricans from New York; Mexicans from Guerrero; and Hispanics from San Luis Valley). The strength of the relationship between skin color and ancestry was quite variable, with the correlations ranging in intensity from moderately strong (Puerto Rico, rho = 0.633) to weak (Mexico, rho = 0.212). These results demonstrate the utility of ancestry-informative genetic markers and admixture methods and emphasize the need to be cautious when using pigmentation as a proxy of ancestry or when extrapolating the results from one admixed population to another.

Conceptualizing human variation.

What is the relationship between the patterns of biological and sociocultural variation in extant humans? Is this relationship accurately described, or best explained, by the term 'race' and the schema of 'racial' classification? What is the relationship between 'race', genetics and the demographic groups of society? Can extant humans be categorized into units that can scientifically be called 'races'? These questions underlie the discussions that address the explanations for the observed differences in many domains between named demographic groups across societies. These domains include disease incidence and prevalence and other variables studied by biologists and social scientists. Here, we offer a perspective on understanding human variation by exploring the meaning and use of the term 'race' and its relationship to a range of data. The quest is for a more useful approach with which to understand human biological variation, one that may provide better research designs and inform public policy.

A common nonsense mutation in EphB2 is associated with prostate cancer risk in African American men with a positive family history.

BACKGROUND: The EphB2 gene was recently implicated as a prostate cancer (PC) tumour suppressor gene, with somatic inactivating mutations occurring in approximately 10% of sporadic tumours. We evaluated the contribution of EphB2 to inherited PC susceptibility in African Americans (AA) by screening the gene for germline polymorphisms. METHODS: Direct sequencing of the coding region of EphB2 was performed on 72 probands from the African American Hereditary Prostate Cancer Study (AAHPC). A case-control association analysis was then carried out using the AAHPC probands and an additional 183 cases of sporadic PC compared with 329 healthy AA male controls. In addition, we performed an ancestry adjusted association study where we adjusted for individual ancestry among all subjects, in order to rule out a spurious association due to population stratification. RESULTS: Ten coding sequence variants were identified, including the K1019X (3055A-->T) nonsense mutation which was present in 15.3% of the AAHPC probands but only 1.7% of 231 European American (EA) control samples. We observed that the 3055A-->T mutation significantly increased risk for prostate cancer over twofold (Fisher's two sided test, p = 0.003). The T allele was significantly more common among AAHPC probands (15.3%) than among healthy AA male controls (5.2%) (odds ratio 3.31; 95% confidence interval 1.5 to 7.4; p = 0.008). The ancestry adjusted analyses confirmed the association. CONCLUSIONS: Our data show that the K1019X mutation in the EphB2 gene differs in frequency between AA and EA, is associated with increased risk for PC in AA men with a positive family history, and may be an important genetic risk factor for prostate cancer in AA.

Does prostate volume correlate with vitamin D deficiency among men undergoing prostate biopsy?

OBJECTIVES: Recent studies demonstrate vitamin D is inversely correlated with BPH and prostate cancer (PCa) incidence. We aim to clarify the associations of vitamin D with prostate volume. METHODS: This is an observational study investigating the associations of serum PSA, PSA density and prostate volume with serum 25-hydroxyvitamin D (25-OH D) in PCa patients and men with negative biopsies seen in outpatient urology clinics in Chicago, IL, USA. There were 571 men (40-79 years old) with elevated PSA or abnormal digital rectal examination with available prostate volume recorded from initial biopsy. The primary outcomes were the unadjusted associations of serum 25-OH D deficiency with prostate volume. The secondary outcomes were the adjusted associations using linear and logistic regression analysis. RESULTS: On univariate analysis, serum 25-OH D<20 ng ml-1 inversely correlated with prostate volume among all men undergoing transrectal ultrasonography (P=0.02), and this relationship remained significant for men with negative biopsy on stratified analysis. In adjusted models, controlling for age, serum PSA, 5-α reductase inhibitors use, obesity and PCa diagnosis, prostate volume was inversely associated with vitamin D (P<0.05) using serum vitamin D as a continuous and categorical variable. Logistic regression model also demonstrated an inverse association between vitamin D (continuous and categorical) and prostate volume ⩾40 grams. CONCLUSION: Serum 25-OH D levels are inversely associated with overall prostate volume and enlarged prostate gland (⩾40 grams), especially in men with benign prostatic disease. Given the largely non-toxic effect of supplementation, consideration should be given to assessing vitamin D levels in men with benign prostatic disease in addition, to malignant prostatic disease.

Germline BCL-2 sequence variants and inherited predisposition to prostate cancer.

Apoptosis is an essential physiological process that regulates cellular proliferation. Here, we explored the effect of DNA sequence variation within the BCL-2 gene on prostate cancer susceptibility in three clinical populations, consisting of 428 African Americans, 214 Jamaicans and 218 European Americans. We observed a 70% reduced risk for prostate cancer among the European Americans who had possessed two copies of a promoter variant -938C/A. Additionally, common BCL-2 haplotypes appeared to influence prostate cancer risk; however, studies in larger data sets are needed to confirm our findings. Our data suggest that inherited BCL-2 variants may be associated with a decrease in prostate cancer susceptibility.

Cyp17 promoter variant associated with prostate cancer aggressiveness in African Americans.

Androgens play an important role in the etiology of prostate cancer. The CYP17 gene encodes the cytochrome P450c17alpha enzyme, which is the rate-limiting enzyme in androgen biosynthesis. A T to C polymorphism in the 5' promoter region has recently been associated with prostate cancer. However, contradictory data exists concerning the risk allele. To investigate further the involvement of the CYP17 variant with prostate cancer, we typed the polymorphism in three different populations and evaluated its association with prostate cancer and clinical presentation in African Americans. We genotyped the CYP17 polymorphism in Nigerian (n = 56), European-American (n = 74), and African-American (n = 111) healthy male volunteers, along with African-American men affected with prostate cancer (n = 71), using pyrosequencing. Genotype and allele frequencies did not differ significantly across the different control populations. African-American men with the CC CYP17 genotype had an increased risk of prostate cancer (odds ratio, 2.8; 95% confidence interval, 1.0-7.4) compared with those with the TT genotype. A similar trend was observed between the homozygous variant genotype in African-American prostate cancer patients and clinical presentation. The CC genotype was significantly associated with higher grade and stage of prostate cancer (odds ratio, 7.1; 95% confidence interval, 1.4-36.1). The risk did not differ significantly by family history or age. Our results suggest that the C allele of the CYP17 polymorphism is significantly associated with increased prostate cancer risk and clinically advanced disease in African Americans.

In search of susceptibility genes for type 2 diabetes in West Africa: the design and results of the first phase of the AADM study.

PURPOSE: The purpose of this study is to map type 2 diabetes susceptibility genes in West African ancestral populations of African-Americans, through an international collaboration between West African and US investigators. DESIGN AND METHODS: Affected sib-pairs (ASP) along with unaffected spouse controls are being enrolled and examined in West Africa, with two sites established in Ghana (Accra and Kumasi) and three in Nigeria (Enugu, Ibadan, and Lagos). Eligible participants are invited to study clinics to obtain detailed epidemiologic, family, and medical history information. Blood samples are drawn from each participant to measure glucose, insulin, C-peptide, total cholesterol, LDL, HDL, triglycerides, albumin, creatinine, urea, uric acid, total calcium and to detect autoantibodies to glutamic acid decarboxylase (GAD). DNA is isolated from frozen white blood cells obtained from 20 ml of EDTA whole blood samples. RESULTS: With full informed consent, 162 individuals from 78 families have been enrolled and examined since the Africa America Diabetes Mellitus (AADM) study began in June of 1997. Logistics of field examinations and specimen shipping have been successfully established. At the end of the third year of field activity (September 2000) the AADM study will have enrolled and performed comprehensive examination on 400 ASP with type 2 diabetes, for a minimum of 800 cases and 200 controls from Ghana and Nigeria. At the current participation rate, the goal of 400 sib-pairs and 200 controls will be met before the scheduled closing date. CONCLUSIONS: The AADM study will create a comprehensive epidemiologic and genetic resource that will facilitate a powerful genome-wide search for West African susceptibility genes to type 2 diabetes.

Recruitment experience in the first phase of the African American Hereditary Prostate Cancer (AAHPC) study.

The African American Hereditary Prostate Cancer (AAHPC) Study is an ongoing multicenter genetic linkage study organized by Howard University and the National Human Genome Research Institute (NHGRI), with support from the Office for Research on Minority Health and the National Cancer Institute. The goals of the study are to: (i) look for evidence of involvement of chromosome 1q24-25 (HPC1) in African American men with hereditary prostate cancer (HPC) and (ii) conduct a genome-wide search for other loci associated with HPC in African American men. To accomplish these goals, a network has been established including Howard University, the NHGRI, and six Collaborative Recruitment Centers (CRCs). The CRCs are responsible for the identification and enrollment of 100 African American families. To date, 43 families have been enrolled. Recruitment strategies have included mass media campaigns, physician referrals, community health-fairs/prostate cancer screenings, support groups, tumor registries, as well as visits to churches, barber shops, and universities. By far, the most productive recruitment mechanisms have been physician referrals and tumor registries, yielding a total of 35 (81%) families. Approximately 41% (n = 3400) of probands initially contacted by phone or mail expressed interest in participating; the families of 2% of these met the eligibility criteria, and 75% of those families have been enrolled in the study, indicating a 0.5% recruitment yield (ratio of participants to contacts). As the first large-scale genetic linkage study of African Americans, on a common disease, the challenges and successes of the recruitment process for the AAHPC Study should serve to inform future efforts to involve this population in similar studies.

Clinical characteristics of African-American men with hereditary prostate cancer: the AAHPC Study.

INTRODUCTION: The African-American Hereditary Prostate Cancer (AAHPC) Study was designed to recruit African-American families fulfilling very stringent criteria of four or more members diagnosed with prostate cancer at a combined age at diagnosis of 65 years or less. This report describes the clinical characteristics of a sample of affected AAHPC family members. METHODS: In all, 92 African-American families were recruited into the study between 1998 and 2002. Complete clinical data including age and PSA at diagnosis, number of affected per family, stage, grade, and primary treatment were available on 154 affected males. Nonparametric Wilcoxon two-sample tests and Fisher's exact test (two-tailed), were performed to compare families with 4-6 and >6 affected males with respect to clinical characteristics. RESULTS: The mean number of affected men per family was 5.5, with a mean age at diagnosis of 61.0 (+/-8.4) years. Age at diagnosis, PSA and Gleason score did not show significant differences between the two groups of families. Based on the Gleason score, 77.2% of affected males had favorable histology. Significantly, there were marked differences between the two groups in the frequency of node-positive disease (P=0.01) and distant metastases (P=0.0001). Radical prostatectomy was the preferred primary therapy for 66.2% of all affected men followed by 20.8% who chose radiation therapy. CONCLUSIONS: Our findings suggest that affected males who carry the highest load of genetic factors are at the highest risk for early dissemination of disease, thus efforts at early diagnosis and aggressive therapeutic approaches may be warranted in these families. Since the primary therapy choices in our study favored definitive treatment (87.0%) when compared to the 1983 and 1995 SEER data in which 28 and 64% received definitive treatment, respectively, it appears that affected African-American men in multiplex families may be demonstrating the reported psycho-social impact of family history on screening practices and treatment decisions for prostate cancer.

Experimental oral carcinoma of the tongue and buccal mucosa: possible biologic markers linked to cancers at two anatomic sites.

The application of the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) can initiate and promote the development of oral squamous cell carcinoma of the tongue and buccal mucosa. In this study the level of expression of various markers related to the development of programmed cell death (PCD) in the respective oral carcinomas was analyzed. Sixteen male and female Syrian hamsters (Mesocrietus auratus) were treated with 0.05% DMBA for 16 weeks. Immunohistochemistry was used to observe the expression of p53, proliferating cell nuclear antigen (PCNA), Bcl-2, and nucleosome formation. Single-strand conformational polymorphism (SSCP) for exons 2-9 and sequence analysis of exon 9 of the p53 gene from normal buccal or tongue mucosa as well as the squamous cell carcinomas from the buccal mucosa or the tongue were determined. p53 (wild type) expression was significantly reduced in the tongue dysplastic mucosa or squamous cell carcinoma. The SSCP disclosed banding shifts or new bands in exons 2/3, 4, 8, and 9 for the tongue or buccal oral carcinomas (five of each). In exon 9 the mutation in codon 307 (ala)GCC-GTC(val) was present in the tongue but not in the buccal carcinoma. Other markers included the level of PCNA. PCNA was initially lower in the premalignant tongue lesions but increased in oral squamous cell carcinoma at both sites. In contrast, the amount of nucleosome formation in the tongue carcinomas was less than the level noted for buccal cancers but premalignant dysplasias in the tongue mucosa exhibited higher levels. The inhibitor of PCD, Bcl-2 was lower for dysplasias and carcinomas of the tongue compared to similar lesions of the buccal mucosa. These results indicate that oral carcinomas of different anatomical sites can exhibit differences in growth, oncogene mutation expression, and the development of PCD. The differences in Bcl-2 and nucleosome formation may signify their influence on oncogene expression and growth potential for developing transformed clones and established oral carcinomas.

African-American heredity prostate cancer study: a model for genetic research.

A genome-wide scan of high-risk prostate cancer families in North America has demonstrated linkage of a particular marker to Chromosome Iq (HPC11. An even greater proportion of African-American families have shown linkage to HPC 1. Therefore, investigators at the National Human Genome Research Institute [NHGRI] in collaboration with Howard University and a predominantly African-American group of urologists established the African-American Hereditary Prostate Cancer (AAHPC) Study Network to confirm the suggested linkage of HPC in African Americans with a gene on Chromosome 1. Blood samples from recruited families were sent to Howard University for extraction of DNA. The DNA was sent to NHGRI at NIH where the genotyping and genetic sequence analysis was conducted. Genotype data are merged with pedigree information so that statistical analysis can be performed to establish potential linkage. From March 1, 1998, to June 1, 1999, a total of 40 African-American families have been recruited who met the study criteria. Preliminary results suggest that racial/ethnicity grouping may affect the incidence and extent of linkage of prostate cancer to specific loci. The importance of these findings lays in the future treatment of genetic-based diseases.

African-American heredity prostate cancer study: a model for genetic research.

A genome-wide scan of high-risk prostate cancer families in North America has demonstrated linkage of a particular marker to Chromosome 1q (HPC1). An even greater proportion of African-American families have shown linkage to HPC1. Therefore, investigators at the National Human Genome Research Institute (NHGRI) in collaboration with Howard University and a predominantly African-American group of urologists established the African-American Hereditary Prostate Cancer (AAHPC) Study Network to confirm the suggested linkage of HPC in African Americans with a gene on Chromosome 1. Blood samples from recruited families were sent to Howard University for extraction of DNA. The DNA was sent to NHGRI at NIH where the genotyping and genetic sequence analysis was conducted. Genotype data are merged with pedigree information so that statistical analysis can be performed to establish potential linkage. From March 1, 1998, to June 1, 1999, a total of 40 African-American families have been recruited who met the study criteria. Preliminary results suggest that racial/ethnicity grouping may affect the incidence and extent of linkage of prostate cancer to specific loci. The importance of these findings lays in the future treatment of genetic-based diseases.

Identification of genetic risk associated with prostate cancer using ancestry informative markers.

BACKGROUND: Prostate cancer (PCa) is a common malignancy and a leading cause of cancer death among men in the United States with African-American (AA) men having the highest incidence and mortality rates. Given recent results from admixture mapping and genome-wide association studies for PCa in AA men, it is clear that many risk alleles are enriched in men with West African genetic ancestry. METHODS: A total of 77 ancestry informative markers (AIMs) within surrounding candidate gene regions were genotyped and haplotyped using Pyrosequencing in 358 unrelated men enrolled in a PCa genetic association study at the Howard University Hospital between 2000 and 2004. Sequence analysis of promoter region single-nucleotide polymorphisms (SNPs) to evaluate disruption of transcription factor-binding sites was conducted using in silico methods. RESULTS: Eight AIMs were significantly associated with PCa risk after adjusting for age and West African ancestry. SNP rs1993973 (intervening sequences) had the strongest association with PCa using the log-additive genetic model (P=0.002). SNPs rs1561131 (genotypic, P=0.007), rs1963562 (dominant, P=0.01) and rs615382 (recessive, P=0.009) remained highly significant after adjusting for both age and ancestry. We also tested the independent effect of each significantly associated SNP and rs1561131 (P=0.04) and rs1963562 (P=0.04) remained significantly associated with PCa development. After multiple comparisons testing using the false discovery rate, rs1993973 remained significant. Analysis of the rs156113-, rs1963562-rs615382l and rs1993973-rs585224 haplotypes revealed that the least frequently found haplotypes in this population were significantly associated with a decreased risk of PCa (P=0.032 and 0.0017, respectively). CONCLUSIONS: The approach for SNP selection utilized herein showed that AIMs may not only leverage increased linkage disequilibrium in populations to identify risk and protective alleles, but may also be informative in dissecting the biology of PCa and other health disparities.

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

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

The missing association: sequencing-based discovery of novel SNPs in VKORC1 and CYP2C9 that affect warfarin dose in African Americans.

It is well recognized that the genetic variants VKORC1-1639, CYP2C9*2, and CYP2C9*3 contribute to warfarin dose response. This has led to warfarin dosing algorithms that include these polymorphisms and explains between 47% and 56% of variability in dose in Caucasians. However, these polymorphisms explain significantly less of the variance in dose among African Americans. In order to identify novel variations that affect warfarin dose in African Americans, we used a targeted resequencing strategy that examined evolutionarily conserved sequences and regions of putative transcriptional binding. Through ethnicity-specific warfarin dose model building in 330 African Americans, we identified two novel genetic associations with higher warfarin dose, namely, VKORC1-8191 (rs61162043, P = 0.0041) and 18786 in CYP2C9 (rs7089580, P = 0.035). These novel finds are independent of the previous associations with these genes. Our regression model, encompassing both genetic and clinical variables, explained 40% of the variability in warfarin dose in African-American subjects, significantly more than any model thus far.

8q24 allelic imbalance and MYC gene copy number in primary prostate cancer.

Four independent regions within 8q24 near the MYC gene are associated with risk for prostate cancer (Pca). Here, we investigated allelic imbalance (AI) at 8q24 risk variants and MYC gene DNA copy number (CN) in 27 primary Pcas. Heterozygotes were observed in 24 of 27 patients at one or more 8q24 markers and 27% of the loci exhibited AI in tumor DNA. The 8q24 risk alleles were preferentially favored in the tumors. Increased MYC gene CN was observed in 33% of tumors, and the co-existence of increased MYC gene CN with AI at risk loci was observed in 86% (P<0.004 exact binomial test) of the informative tumors. No AI was observed in tumors, which did not reveal increased MYC gene CN. Higher Gleason score was associated with tumors exhibiting AI (P=0.04) and also with increased MYC gene CN (P=0.02). Our results suggest that AI at 8q24 and increased MYC gene CN may both be related to high Gleason score in Pca. Our findings also suggest that these two somatic alterations may be due to the same preferential chromosomal duplication event during prostate tumorigenesis.

NAT2 and NER genetic variants and sporadic prostate cancer susceptibility in African Americans.

Prostate cancer is a common malignancy that disproportionately affects African-American men. Environmental factors and variation in genes responsible for chemical and dietary carcinogen metabolism and DNA damage repair may modulate risk. Fourteen single nucleotide polymorphisms in NAT2 and four NER genes (ERCC1, XPF/ERCC4, XPG/ERCC5 and CSB/ERCC6) were genotyped in a case-control study of 254 African-American prostate cancer cases and 301 healthy controls from Washington, DC. Smoking status, BMI, age and genetic ancestry were included as covariates in the association analyses. We found that individuals homozygous for the XPG/ERCC5 -72C/T promoter polymorphism had a significant reduction in risk, for prostate cancer (OR=0.12; 95% CI=0.03-0.48). A haplotype trend regression test also revealed a protective effect for the haplotype bearing the T allele (P=0.003). In silica analyses suggest a functional implication for the promoter variant since it deletes a GCF transcriptional factor-binding site responsible for the downregulation of transcription. The protective effect of the promoter SNP on risk for prostate cancer was independent of smoking. In contrast, none of the SNPs typed for NAT2, ERCC1, ERCC4 and ERCC6 showed significant association with risk. Additional tests for genotype interactions were not significant. We note that there may be other factors, such as dietary exposures, which may modulate prostate cancer risk in combination with genetic variation within the NAT2 and NER genes. Our results, in combination with previous observations of LOH for ERCC5 in prostate tumors, provide further evidence for a role of XPG/ERCC5 in the etiology of prostate cancer.

Admixture and population stratification in African Caribbean populations.

Throughout biomedical research, there is growing interest in the use of ancestry informative markers (AIMs) to deconstruct racial categories into useful variables. Studies on recently admixed populations have shown significant population substructure due to differences in individual ancestry; however, few studies have examined Caribbean populations. Here we used a panel of 28 AIMs to examine the genetic ancestry of 298 individuals of African descent from the Caribbean islands of Jamaica, St. Thomas and Barbados. Differences in global admixture were observed, with Barbados having the highest level of West African ancestry (89.6%+/- 2.0) and the lowest levels of European (10.2%+/- 2.2) and Native American ancestry (0.2%+/- 2.0), while Jamaica possessed the highest levels of European (12.4%+/- 3.5) and Native American ancestry (3.2%+/- 3.1). St. Thomas, USVI had ancestry levels quite similar to African Americans in continental U.S. (86.8%+/- 2.2 West African, 10.6%+/- 2.3 European, and 2.6%+/- 2.1 Native American). Significant substructure was observed in the islands of Jamaica and St. Thomas but not Barbados (K=1), indicating that differences in population substructure exist across these three Caribbean islands. These differences likely stem from diverse colonial and historical experiences, and subsequent evolutionary processes. Most importantly, these differences may have significant ramifications for case-control studies of complex disease in Caribbean populations.

Mitochondrial and Y chromosome diversity in the English-speaking Caribbean.

The transatlantic slave trade lasted over three centuries and represents one of the largest forced migrations in human history. The biological repercussions are not well understood especially in African-Caribbean populations. This paper explores the effects of the forced migration, isolation, and admixture on genetic diversity using mitochondrial and Y chromosome markers for 501 individuals from Dominica, Grenada, Jamaica, St. Kitts, St. Lucia, St. Thomas, St. Vincent, and Trinidad. Genetic diversity and population genetic structure analyses of mitochondrial data and Y chromosome data indicate that there was no post-migration loss in genetic diversity in the African derived lineages. Genetic structure was observed between the islands for both genetic systems. This may be due to isolation, differences in the number and source of Africans imported, depopulation of indigenous populations, and/or differences in colonization history. Nearly 10% of the individuals belonged to a non-African mitochondrial haplogroup. In contrast, Y chromosome admixture estimates showed that there was nearly 30% European contribution to these Caribbean populations. This study sheds light on the history of Africans in the Americas as well as contributing to our understanding of the nature and extent of diversity within the African Diaspora.