Search

Objectives From a genetic perspective, relatively little is known about how mass emigrations of African, European, and Asian peoples beginning in the 16th century affected Indigenous Caribbean populations. Therefore, we explored the impact of serial colonization on the genetic variation of the first Caribbean islanders. Materials and methods Sixty-four members of St. Vincent's Garifuna Community and 36 members of Trinidad's Santa Rosa First People's Community (FPC) of Arima were characterized for mitochondrial DNA and Y-chromosome diversity via direct sequencing and targeted SNP and STR genotyping. A subset of 32 Garifuna and 18 FPC participants were genotyped using the GenoChip 2.0 microarray. The resulting data were used to examine genetic diversity, admixture, and sex biased gene flow in the study communities. Results The Garifuna were most genetically comparable to African descendant populations, whereas the FPC were more similar to admixed American groups. Both communities also exhibited moderate frequencies of Indigenous American matrilines and patrilines. Autosomal SNP analysis indicated modest Indigenous American ancestry in these populations, while both showed varying degrees of African, European, South Asian, and East Asian ancestry, with patterns of sex-biased gene flow differing between the island communities. Discussion These patterns of genetic variation are consistent with historical records of migration, forced, or voluntary, and suggest that different migration events shaped the genetic make-up of each island community. This genomic study is the highest resolution analysis yet conducted with these communities, and provides a fuller understanding of the complex bio-histories of Indigenous Caribbean peoples in the Lesser Antilles.

PurposeUnderstanding the outcomes of returning individual genetic research results to participants is critical because some genetic variants are found to be associated with health outcomes and have become available for clinical testing.Materials and MethodsBRCA1/2-negative women with early-onset breast cancer, multiple primary cancers, or a family history of breast cancer who participated in a gene discovery cancer registry were offered the opportunity to learn their individual genetic research results of 24 breast cancer susceptibility genes with a genetic counselor after predisclosure genetic counseling. Outcomes included uptake of research results, knowledge, informed choice, psychosocial adjustment, uncertainty, satisfaction, and uptake of clinical confirmation testing.ResultsFour hundred two potential participants were contacted. One hundred ninety-four participants (48%) did not respond despite multiple attempts, and 85 participants (21%) actively or passively declined. One hundred seven participants (27%) elected for predisclosure counseling and were more likely to be younger, married, and white. Ninety percent of participants who had predisclosure counseling elected to receive their genetic research results, and 89% made an informed choice. Knowledge increased significantly after predisclosure counseling, and anxiety, intrusive cancer-specific distress, uncertainty, and depression declined significantly after receipt of results. General anxiety and intrusive cancer-specific distress declined significantly for both participants with a positive result and those with a negative result. Sixty-four percent of participants had clinical confirmation testing when recommended, including all participants with a mutation in a high-penetrance gene.ConclusionUptake of genetic research results may be lower than anticipated by hypothetical reports and small select studies. Participants who elected to receive research results with genetic providers did not experience increases in distress or uncertainty, but not all patients return for confirmation testing.

Background While there is increasing interest in sharing genetic research results with participants, how best to communicate the risks, benefits and limitations of research results remains unclear. Methods Participants who received genetic research results answered open and closed‐ended questions about their experiences receiving results and interest in and advantages and disadvantages of a web‐based alternative to genetic counseling. Results 107 BRCA1/2 negative women with a personal or family history of breast cancer consented to receive genetic research results and 82% completed survey items about their experience. Most participants reported there was nothing they disliked (74%) or would change (85%) about their predisclosure or disclosure session (78% and 89%). They most frequently reported liking the genetic counselor and learning new information. Only 24% and 26% would not be willing to complete predisclosure counseling or disclosure of results by a web‐based alternative, respectively. The most frequently reported advantages included convenience and reduced time. Disadvantages included not being able to ask questions, the risk of misunderstanding and the impersonal nature of the encounter. Conclusion Most participants receiving genetic research results report high satisfaction with telephone genetic counseling, but some may be willing to consider self‐directed web alternatives for both predisclosure genetic education and return of results.

2008 Background: Enthusiasm for precision oncology may obscure the complex psychosocial and ethical considerations for tumor genetic testing. Low patient genetic knowledge has been documented and heightens the risk for adverse experiences. We developed a web-based intervention to increase genetic knowledge and decrease distress among advanced cancer patients undergoing tumor genetic testing. Methods: 594 patients (80% from NCORP Community Sites) were recruited and randomized to web-intervention (n = 293) or usual care (n = 301), prior to receipt of tumor genetic test results. Primary outcomes were genetic knowledge, anxiety, depression, and cancer-specific distress measured at T0 (prior to intervention), T1 (post-intervention), T2 (after receipt of tumor results) and T3 (3 months post receipt of tumor results). Secondary outcomes included satisfaction, regret and disappointment. The effect of web-intervention was evaluated using t-test, multiple linear regression and logistic regression, with an intent-to-treat approach. Results: Patients randomized to web-intervention had better knowledge improvement than those randomized to usual care (T1-T0, p < 0.0001; T2-T0, p = 0.003). No difference was observed in change scores for anxiety, depression or cancer-specific distress. To find the moderators of intervention effect (including sex, age, education, and literacy) two 2-way interactions were noted with statistical significance: higher depression among those in the intervention arm versus the control arm for patients with lower literacy (p = 0.03); and lower cancer-specific distress among women in the intervention arm than with usual care but no such effect noted in men (p = 0.01). 71% of patients reported receiving tumor test results and this did not differ by arm. Only 20% of patients reported regret and disappointment at T2, which was more likely for those without a mutation of interest (MOI) detected vs those with a MOI detected (OR = 2.08, 95% CI, 1.13 to 3.83, p = 0.02). Conclusions: Web-based education prior to receipt of tumor genetic test results increases patient understanding of tumor genetic testing. While the intervention did not significantly reduce distress, results suggest that women who received the intervention had lower cancer-specific distress than those with usual care. Future refinements to the web-intervention are needed to address low literacy groups, men and patients with no actionable results. Clinical trial information: NCT02823652.

Multiple questions relating to contributions of cultural and demographical factors in the process of human geographical dispersal remain largely unanswered. India, a land of early human settlement and the resulting diversity is a good place to look for some of the answers. In this study, we explored the genetic structure of India using a diverse panel of 78 males genotyped using the GenoChip. Their genome-wide single-nucleotide polymorphism (SNP) diversity was examined in the context of various covariates that influence Indian gene pool. Admixture analysis of genome-wide SNP data showed high proportion of the Southwest Asian component in all of the Indian samples. Hierarchical clustering based on admixture proportions revealed seven distinct clusters correlating to geographical and linguistic affiliations. Convex hull overlay of Y-chromosomal haplogroups on the genome-wide SNP principal component analysis brought out distinct non-overlapping polygons of F*-M89, H*-M69, L1-M27, O2a-M95 and O3a3c1-M117, suggesting a male-mediated migration and expansion of the Indian gene pool. Lack of similar correlation with mitochondrial DNA clades indicated a shared genetic ancestry of females. We suggest that ancient male-mediated migratory events and settlement in various regional niches led to the present day scenario and peopling of India.

The linguistically distinctive Haida and Tlingit tribes of Southeast Alaska are known for their rich material culture, complex social organization, and elaborate ritual practices. However, much less is known about these tribes from a population genetic perspective. For this reason, we analyzed mtDNA and Y-chromosome variation in Haida and Tlingit populations to elucidate several key issues pertaining to the history of this region. These included the genetic relationships of Haida and Tlingit to other indigenous groups in Alaska and Canada; the relationship between linguistic and genetic data for populations assigned to the Na-Dene linguistic family, specifically, the inclusion of Haida with Athapaskan, Eyak, and Tlingit in the language family; the possible influence of matrilineal clan structure on patterns of genetic variation in Haida and Tlingit populations; and the impact of European entry into the region on the genetic diversity of these indigenous communities. Our analysis indicates that, while sharing a “northern” genetic profile, the Haida and the Tlingit are genetically distinctive from each other. In addition, Tlingit groups themselves differ across their geographic range, in part due to interactions of Tlingit tribes with Athapaskan and Eyak groups to the north. The data also reveal a strong influence of maternal clan identity on mtDNA variation in these groups, as well as the significant influence of non-native males on Y-chromosome diversity. These results yield new details about the histories of the Haida and Tlingit tribes in this region.

1531Background: How frequently research participants are interested in receiving genetic individual research results (IRR) and the best method for returning IRR remains unknown. Methods: Woman at t...

Puerto Rico and the surrounding islands rest on the eastern fringe of the Caribbean's Greater Antilles, located less than 100 miles northwest of the Lesser Antilles. Puerto Ricans are genetic descendants of pre-Columbian peoples, as well as peoples of European and African descent through 500 years of migration to the island. To infer these patterns of pre-Columbian and historic peopling of the Caribbean, we characterized genetic diversity in 326 individuals from the southeastern region of Puerto Rico and the island municipality of Vieques. We sequenced the mitochondrial DNA (mtDNA) control region of all of the samples and the complete mitogenomes of 12 of them to infer their putative place of origin. In addition, we genotyped 121 male samples for 25 Y-chromosome single nucleotide polymorphism and 17 STR loci. Approximately 60% of the participants had indigenous mtDNA haplotypes (mostly from haplogroups A2 and C1), while 25% had African and 15% European haplotypes. Three A2 sublineages were unique to the Greater Antilles, one of which was similar to Mesoamerican types, while C1b haplogroups showed links to South America, suggesting that people reached the island from the two distinct continental source areas. However, none of the male participants had indigenous Y-chromosomes, with 85% of them instead being European/Mediterranean and 15% sub-Saharan African in origin. West Eurasian Y-chromosome short tandem repeat haplotypes were quite diverse and showed similarities to those observed in southern Europe, North Africa and the Middle East. These results attest to the distinct, yet equally complex, pasts for the male and female ancestors of modern day Puerto Ricans.

For decades, the peopling of the Americas has been explored through the analysis of uniparentally inherited genetic systems in Native American populations and the comparison of these genetic data with current linguistic groupings. In northern North America, two language families predominate: Eskimo-Aleut and Na-Dene. Although the genetic evidence from nuclear and mtDNA loci suggest that speakers of these language families share a distinct biological origin, this model has not been examined using data from paternally inherited Y chromosomes. To test this hypothesis and elucidate the migration histories of Eskimoan- and Athapaskan-speaking populations, we analyzed Y-chromosomal data from Inuvialuit, Gwich’in, and Tłįchǫ populations living in the Northwest Territories of Canada. Over 100 biallelic markers and 19 chromosome short tandem repeats (STRs) were genotyped to produce a high-resolution dataset of Y chromosomes from these groups. Among these markers is an SNP discovered in the Inuvialuit that differentiates them from other Aboriginal and Native American populations. The data suggest that Canadian Eskimoan- and Athapaskan-speaking populations are genetically distinct from one another and that the formation of these groups was the result of two population expansions that occurred after the initial movement of people into the Americas. In addition, the population history of Athapaskan speakers is complex, with the Tłįchǫ being distinct from other Athapaskan groups. The high-resolution biallelic data also make clear that Y-chromosomal diversity among the first Native Americans was greater than previously recognized.

Y-chromosome Haplogroup O is the dominant lineage of East Asians, comprising more than a quarter of all males on the world; however, its internal phylogeny remains insufficiently investigated. In this study, we determined the phylogenetic position of recently defined markers (L127, KL1, KL2, P164, and PK4) in the background of Haplogroup O. In the revised tree, subgroup O3a-M324 is divided into two main subclades, O3a1-L127 and O3a2-P201, covering about 20 and 35% of Han Chinese people, respectively. The marker P164 is corrected from a downstream site of M7 to upstream of M134 and parallel to M7 and M159. The marker PK4 is also relocated from downstream of M88 to upstream of M95, separating the former O2(*) into two parts. This revision evidently improved the resolving power of Y-chromosome phylogeny in East Asia.

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

The name "Wampanoag" means "Eastern People" or "People of the First Light" in the local dialect of the Algonquian language. Once extensively populating the coastal lands and neighboring islands of the eastern United States, the Wampanoag people now consist of two federally recognized tribes, the Aquinnah and Mashpee, the state-recognized Seaconke Wampanoag tribe, and a number of bands and clans in present-day southern Massachusetts. Because of repeated epidemics and conflicts with English colonists, including King Philip's War of 1675-76, and subsequent colonial laws forbidding tribal identification, the Wampanoag population was largely decimated, decreasing in size from as many as 12,000 individuals in the 16th century to less than 400, as recorded in 1677. To investigate the influence of the historical past on its biological ancestry and native cultural identity, we analyzed genetic variation in the Seaconke Wampanoag tribe. Our results indicate that the majority of their mtDNA haplotypes belongs to West Eurasian and African lineages, thus reflecting the extent of their contacts and interactions with people of European and African descent. On the paternal side, Y-chromosome analysis identified a range of Native American, West Eurasian, and African haplogroups in the population, and also surprisingly revealed the presence of a paternal lineage that appears at its highest frequencies in New Guinea and Melanesia. Comparison of the genetic data with genealogical and historical information allows us to reconstruct the tribal history of the Seaconke Wampanoag back to at least the early 18th century.

Historical discourses about the Caribbean often chronicle West African and European influence to the general neglect of indigenous people's contributions to the contemporary region. Consequently, demographic histories of Caribbean people prior to and after European contact are not well understood. Although archeological evidence suggests that the Lesser Antilles were populated in a series of northward and eastern migratory waves, many questions remain regarding the relationship of the Caribbean migrants to other indigenous people of South and Central America and changes to the demography of indigenous communities post-European contact. To explore these issues, we analyzed mitochondrial DNA and Y-chromosome diversity in 12 unrelated individuals from the First Peoples Community in Arima, Trinidad, and 43 unrelated Garifuna individuals residing in St. Vincent. In this community-sanctioned research, we detected maternal indigenous ancestry in 42% of the participants, with the remainder having haplotypes indicative of African and South Asian maternal ancestry. Analysis of Y-chromosome variation revealed paternal indigenous American ancestry indicated by the presence of haplogroup Q-M3 in 28% of the male participants from both communities, with the remainder possessing either African or European haplogroups. This finding is the first report of indigenous American paternal ancestry among indigenous populations in this region of the Caribbean. Overall, this study illustrates the role of the region's first peoples in shaping the genetic diversity seen in contemporary Caribbean populations.

Behar, Doron M. et al.-- The Genographic Consortium, Different lines of evidence point to the resettlement of much of western and central Europe by populations from the Franco-Cantabrian region during the Late Glacial and Postglacial periods. In this context, the study of the genetic diversity of contemporary Basques, a population located at the epicenter of the Franco-Cantabrian region, is particularly useful because they speak a non-Indo-European language that is considered to be a linguistic isolate. In contrast with genome-wide analysis and Y chromosome data, where the problem of poor time estimates remains, a new timescale has been established for the human mtDNA and makes this genome the most informative marker for studying European prehistory. Here, we aim to increase knowledge of the origins of the Basque people and, more generally, of the role of the Franco-Cantabrian refuge in the postglacial repopulation of Europe. We thus characterize the maternal ancestry of 908 Basque and non-Basque individuals from the Basque Country and immediate adjacent regions and, by sequencing 420 complete mtDNA genomes, we focused on haplogroup H. We identified six mtDNA haplogroups, H1j1, H1t1, H2a5a1, H1av1, H3c2a, and H1e1a1, which are autochthonous to the Franco-Cantabrian region and, more specifically, to Basque-speaking populations. We detected signals of the expansion of these haplogroups at ∼4,000 years before present (YBP) and estimated their separation from the pan-European gene pool at ∼8,000 YBP, antedating the Indo-European arrival to the region. Our results clearly support the hypothesis of a partial genetic continuity of contemporary Basques with the preceding Paleolithic/Mesolithic settlers of their homeland., This work was supported by the Institut Pasteur, National Geographic, and the Histoire des populations et variation linguistique dans les Pyrénées de l'Ouest project, which received funding from the Conseil Régional d'Aquitaine, the Conseil Général des Pyrénées-Atlantiques, the Conseil des Elus du Pays-Basque, and the Centre National de la Recherche Scientifique interdisciplinary program Origine de l'Homme, des Langues et du Langage. This study also benefited from the support of Department of Hematology, Centre Hospitalier de la Côte Basque, in Bayonne, and Association Sang 64.