Vietnam exhibits great cultural and linguistic diversity, yet the genetic history of Vietnamese populations remains poorly understood. Previous studies focused mostly on the majority Kinh group,... Show moreVietnam exhibits great cultural and linguistic diversity, yet the genetic history of Vietnamese populations remains poorly understood. Previous studies focused mostly on the majority Kinh group, and thus the genetic diversity of the many other groups has not yet been investigated. Here we analyze complete mtDNA genome sequences and ~2.3 Mb sequences of the male-specific portion of the Y chromosome from the Kinh and 16 minority populations, encompassing all five language families present in Vietnam. We find highly variable levels of diversity within and between groups that do not correlate with either geography or language family. In particular, the Mang and Sila have undergone recent, independent bottlenecks, while the majority group, Kinh, exhibits low levels of differentiation with other groups. The two Austronesian-speaking groups, Giarai and Ede, show a potential impact of matrilocality on their patterns of variation. Overall, we find that isolation, coupled with limited contact involving some groups, has been the major factor influencing the genetic structure of Vietnamese populations, and that there is substantial genetic diversity that is not represented by the Kinh. Show less
Telomere length (TL) regulation is an important factor in ageing, reproduction and cancer development. Genetic, hereditary and environmental factors regulating TL are currently widely investigated,... Show moreTelomere length (TL) regulation is an important factor in ageing, reproduction and cancer development. Genetic, hereditary and environmental factors regulating TL are currently widely investigated, however, their relative contribution to TL variability is still understudied. We have used whole genome sequencing data of 250 family trios from the Genome of the Netherlands project to perform computational measurement of TL and a series of regression and genome-wide association analyses to reveal TL inheritance patterns and associated genetic factors. Our results confirm that TL is a largely heritable trait, primarily with mother's, and, to a lesser extent, with father's TL having the strongest influence on the offspring. In this cohort, mother's, but not father's age at conception was positively linked to offspring TL. Age-related TL attrition of 40 bp/year had relatively small influence on TL variability. Finally, we have identified TL-associated variations in ribonuclease reductase catalytic subunit M1 (RRM1 gene), which is known to regulate telomere maintenance in yeast. We also highlight the importance of multivariate approach and the limitations of existing tools for the analysis of TL as a polygenic heritable quantitative trait. Show less
X-inactivation is a well-established dosage compensation mechanism ensuring that X-chromosomal genes are expressed at comparable levels in males and females. Skewed X-inactivation is often... Show moreX-inactivation is a well-established dosage compensation mechanism ensuring that X-chromosomal genes are expressed at comparable levels in males and females. Skewed X-inactivation is often explained by negative selection of one of the alleles. We demonstrate that imbalanced expression of the paternal and maternal X-chromosomes is common in the general population and that the random nature of the X-inactivation mechanism can be sufficient to explain the imbalance. To this end, we analyzed blood-derived RNA and whole-genome sequencing data from 79 female children and their parents from the Genome of the Netherlands project. We calculated the median ratio of the paternal over total counts at all X-chromosomal heterozygous single-nucleotide variants with coverage ≥10. We identified two individuals where the same X-chromosome was inactivated in all cells. Imbalanced expression of the two X-chromosomes (ratios ≤0.35 or ≥0.65) was observed in nearly 50% of the population. The empirically observed skewing is explained by a theoretical model where X-inactivation takes place in an embryonic stage in which eight cells give rise to the hematopoietic compartment. Genes escaping X-inactivation are expressed from both alleles and therefore demonstrate less skewing than inactivated genes. Using this characteristic, we identified three novel escapee genes (SSR4, REPS2, and SEPT6), but did not find support for many previously reported escapee genes in blood. Our collective data suggest that skewed X-inactivation is common in the general population. This may contribute to manifestation of symptoms in carriers of recessive X-linked disorders. We recommend that X-inactivation results should not be used lightly in the interpretation of X-linked variants. Show less
Arias, L.; Schroder, R.; Hubner, A.; Barreto, G.; Stoneking, M.; Pakendorf, B. 2018
Human populations often exhibit contrasting patterns of genetic diversity in the mtDNA and the nonrecombining portion of the Y-chromosome (NRY), which reflect sex-specific cultural behaviors and... Show moreHuman populations often exhibit contrasting patterns of genetic diversity in the mtDNA and the nonrecombining portion of the Y-chromosome (NRY), which reflect sex-specific cultural behaviors and population histories. Here, we sequenced 2.3 Mb of the NRY from 284 individuals representing more than 30 Native American groups from Northwestern Amazonia (NWA) and compared these data to previously generated mtDNA genomes from the same groups, to investigate the impact of cultural practices on genetic diversity and gain new insights about NWA population history. Relevant cultural practices in NWA include postmarital residential rules and linguistic exogamy, a marital practice in which men are required to marry women speaking a different language. We identified 2,969 SNPs in the NRY sequences, only 925 of which were previously described. The NRY and mtDNA data showed different sex-specific demographic histories: female effective population size has been larger than that of males through time, which might reflect larger variance in male reproductive success. Both markers show an increase in lineage diversification beginning similar to 5,000 years ago, which may reflect the intensification of agriculture, technological innovations, and the expansion of regional trade networks documented in the archaeological evidence. Furthermore, we find similar excesses of NRY versus mtDNA between-population divergence at both the local and continental scale, suggesting long-term stability of female versus male migration. We also find evidence of the impact of sociocultural practices on diversity patterns. Finally, our study highlights the importance of analyzing high-resolution mtDNA and NRY sequences to reconstruct demographic history, since this can differ considerably between sexes. Show less
Vietnam is an important crossroads within Mainland Southeast Asia (MSEA) and a gateway to Island Southeast Asia, and as such exhibits high levels of ethnolinguistic diversity. However,... Show moreVietnam is an important crossroads within Mainland Southeast Asia (MSEA) and a gateway to Island Southeast Asia, and as such exhibits high levels of ethnolinguistic diversity. However, comparatively few studies have been undertaken of the genetic diversity of Vietnamese populations. In order to gain comprehensive insights into MSEA mtDNA phylogeography, we sequenced 609 complete mtDNA genomes from individuals belonging to five language families (Austroasiatic, Tai-Kadai, Hmong-Mien, Sino-Tibetan and Austronesian) and analyzed them in comparison with sequences from other MSEA countries and Taiwan. Within Vietnam, we identified 399 haplotypes belonging to 135 haplogroups; among the five language families, the sequences from Austronesian groups differ the most from the other groups. Phylogenetic analysis revealed 111 novel Vietnamese mtDNA lineages. Bayesian estimates of coalescence times and associated 95% HPD for these show a peak of mtDNA diversification around 2.5-3 kya, which coincides with the Dong Son culture, and thus may be associated with the agriculturally-driven expansion of this culture. Networks of major MSEA haplogroups emphasize the overall distinctiveness of sequences from Taiwan, in keeping with previous studies that suggested at most a minor impact of the Austronesian expansion from Taiwan on MSEA. We also see evidence for population expansions across MSEA geographic regions and language families. Show less
Tai-Kadai (TK) is one of the major language families in Mainland Southeast Asia (MSEA), with a concentration in the area of Thailand and Laos. Our previous study of 1234 mtDNA genome sequences... Show moreTai-Kadai (TK) is one of the major language families in Mainland Southeast Asia (MSEA), with a concentration in the area of Thailand and Laos. Our previous study of 1234 mtDNA genome sequences supported a demic diffusion scenario in the spread of TK languages from southern China to Laos as well as northern and northeastern Thailand. Here we add an additional 560 mtDNA genomes from 22 groups, with a focus on the TK-speaking central Thai people and the Sino-Tibetan speaking Karen. We find extensive diversity, including 62 haplogroups not reported previously from this region. Demic diffusion is still a preferable scenario for central Thais, emphasizing the expansion of TK people through MSEA, although there is also some support for gene flow between central Thai and native Austroasiatic speaking Mon and Khmer. We also tested competing models concerning the genetic relationships of groups from the major MSEA languages, and found support for an ancestral relationship of TK and Austronesian-speaking groups. Show less
Arias, L.; Barbieri, C.; Barreto, G.; Stoneking, M.; Pakendorf, B. 2018
Objectives: Northwestern Amazonia (NWA) is a center of high linguistic and cultural diversity. Several language families and linguistic isolates occur in this region, as well as different... Show moreObjectives: Northwestern Amazonia (NWA) is a center of high linguistic and cultural diversity. Several language families and linguistic isolates occur in this region, as well as different subsistence patterns, with some groups being foragers and others agriculturalists. In addition, speakers of Eastern Tukanoan languages are known for practicing linguistic exogamy, a marriage system in which partners are taken from different language groups. In this study, we use high-resolution mitochondrial DNA sequencing to investigate the impact of this linguistic and cultural diversity on the genetic relationships and population structure of NWA groups.Methods: We collected saliva samples from individuals representing 40 different NWA ethnolinguistic groups and sequenced 439 complete mitochondrial genomes to an average coverage of 1,0303.Results: The mtDNA data revealed that NWA populations have high genetic diversity with extensive sharing of haplotypes among groups. Moreover, groups who practice linguistic exogamy have higher genetic diversity, while the foraging Nukak have lower genetic diversity. We also find that rivers play a more important role than either geography or language affiliation in structuring the genetic relationships of populations.Discussion: Contrary to the view of NWA as a pristine area inhabited by small human populations living in isolation, our data support a view of high diversity and contact among different ethnolinguistic groups, with movement along rivers probably facilitating this contact. Additionally, we provide evidence for the impact of cultural practices, such as linguistic exogamy, on patterns of genetic variation. Overall, this study provides new data and insights into a remote and little-studied region of the world. Show less
Li, M.K.; Rothwell, R.; Vermaat, M.; Wachsmuth, M.; Schroder, R.; Laros, J.F.J.; ... ; Genome Netherlands Consortium 2016
Technological and cultural innovations as well as climate changes are thought to have influenced the diffusion of major language phyla in sub-Saharan Africa. The most widespread and the richest in... Show moreTechnological and cultural innovations as well as climate changes are thought to have influenced the diffusion of major language phyla in sub-Saharan Africa. The most widespread and the richest in diversity is the Niger-Congo phylum, thought to have originated in West Africa ∼10,000 years ago (ya). The expansion of Bantu languages (a family within the Niger-Congo phylum) ∼5,000 ya represents a major event in the past demography of the continent. Many previous studies on Y chromosomal variation in Africa associated the Bantu expansion with haplogroup E1b1a (and sometimes its sublineage E1b1a7). However, the distribution of these two lineages extends far beyond the area occupied nowadays by Bantu-speaking people, raising questions on the actual genetic structure behind this expansion. To address these issues, we directly genotyped 31 biallelic markers and 12 microsatellites on the Y chromosome in 1,195 individuals of African ancestry focusing on areas that were previously poorly characterized (Botswana, Burkina Faso, Democratic Republic of Congo, and Zambia). With the inclusion of published data, we analyzed 2,736 individuals from 26 groups representing all linguistic phyla and covering a large portion of sub-Saharan Africa. Within the Niger-Congo phylum, we ascertain for the first time differences in haplogroup composition between Bantu and non-Bantu groups via two markers (U174 and U175) on the background of haplogroup E1b1a (and E1b1a7), which were directly genotyped in our samples and for which genotypes were inferred from published data using linear discriminant analysis on short tandem repeat (STR) haplotypes. No reduction in STR diversity levels was found across the Bantu groups, suggesting the absence of serial founder effects. In addition, the homogeneity of haplogroup composition and pattern of haplotype sharing between Western and Eastern Bantu groups suggests that their expansion throughout sub-Saharan Africa reflects a rapid spread followed by backward and forward migrations. Overall, we found that linguistic affiliations played a notable role in shaping sub-Saharan African Y chromosomal diversity, although the impact of geography is clearly discernible. Show less
