Post by djoser-xyyman on Sept 12, 2014 7:53:34 GMT -5
ASHG 2014
Here are some interesting up coming papers to look out for. ASHG 2014
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Capture of 390,000 SNPs in dozens of ancient central Europeans reveals a population turnover in Europe thousands of years after the advent of farming.
I. Lazaridis, W. Haak, N. Patterson, N. Rohland, S. Mallick, B. Llamas, S. Nordenfelt, E. Harney, A. Cooper, K. W. Alt, D. Reich.
To understand the population transformations that took place in Europe since the early Neolithic, we used a DNA capture technique to obtain reads covering ~390 thousand single nucleotide polymorphisms (SNPs) from a number of different archaeological cultures of central Europe (Germany and Hungary). The samples spanned the time period from 7,500 BP to 3,500 BP (Early Neolithic to Early Bronze Age periods) and most of them were previously studied using mtDNA (Brandt, Haak et al., Science, 2013). The captured SNPs include about 360,000 SNPs from the Affymetrix Human Origins Array that were discovered in African individuals, as well as about 30,000 SNPs chosen for other reasons (that are thought to have been affected by natural selection, or to have phenotypic effects, or are useful in determining Y-chromosome haplogroups). By analyzing this data together with a dataset of 2,345 present-day humans and other published ancient genomes, we show that late Neolithic inhabitants of central Europe belonging to the Corded Ware culture were not a continuation of the earlier occupants of the region. Our results highlight the importance of migration and major POPULATION TURNOVER IN EUROPE LONG AFTER THE ARRIVAL OF FARMING. * Contributed equally to this work
Insights into British and European population history from ancient DNA sequencing of Iron Age and Anglo-Saxon samples from Hinxton, England.
S. Schiffels, W. Haak, B. Llamas, E. Popescu, L. Loe, R. Clarke, A. Lyons, P. Paajanen, D. Sayer, R. Mortimer, C. Tyler-Smith, A. Cooper, R. Durbin.
British population history is shaped by a complex series of repeated immigration periods and associated changes in population structure. It is an open question however, to what extent each of these changes is reflected in the genetic ancestry of the current British population. Here we use ancient DNA sequencing to help address that question. We present whole genome sequences generated from five individuals that were found in archaeological excavations at the Wellcome Trust Genome Campus near Cambridge (UK), two of which are dated to around 2,000 years before present (Iron Age), and three to around 1,300 years before present (Anglo-Saxon period). Good preservation status allowed us to generate one high coverage sequence (12x) from an Iron Age individual, and four low coverage sequences (1x-4x) from the other samples. By providing the first ancient whole genome sequences from Britain, we get a unique picture of the ancestral populations in Britain before and after the Anglo-Saxon immigrations. We use modern genetic reference panels such as the 1000 Genomes Project to examine the relationship of these ancient samples with present day population genetic data. Results from principal component analysis suggest that all samples fall consistently within the broader Northern European context, which is also consistent with mtDNA haplogroups. In addition, we obtain a finer structural genetic classification from rare genetic variants and haplotype based methods such as FineStructure. Reflecting more recent genetic ancestry, results from these methods suggest SIGNIFICANT differences between the Iron Age and the Anglo-Saxon period samples when compared to other European samples. We find in particular that while the Anglo-Saxon samples resemble more closely the modern British population than the earlier samples, the Iron Age samples share more low frequency variation than the later ones with present day samples from southern Europe, in particular Spain (Iberians)(1000GP IBS). In addition the Anglo-Saxon period samples appear to share a stronger older component with Finnish (1000GP FIN) individuals. Our findings help characterize the ancestral European populations involved in major European MIGRATION MOVEMENTS INTO Britain in the last 2,000 years and thus provide more insights into the genetic history of people in northern Europe.
Fine-scale population structure in Europe.
S. Leslie, G. Hellenthal, S. Myers, P. Donnelly, International Multiple Sclerosis Genetics Consortium.
There is considerable interest in detecting and interpreting fine-scale population structure in Europe: as a signature of major events in the history of the populations of Europe, and because of the effect undetected population structure may have on disease association studies. Population structure appears to have been a minor concern for most of the recent generation of genome-wide association studies, but is likely to be important for the next generation of studies seeking associations to rare variants. Thus far, genetic studies across Europe have been limited to a small number of markers, or to methods that do not specifically account for the correlation structure in the genome due to linkage disequilibrium. Consequently, these studies were unable to group samples into clusters of similar ancestry on a fine (within country) scale with any confidence. We describe an analysis of fine-scale population structure using genome-wide SNP data on 6,209 individuals, sampled mostly from Western Europe. Using a recently published clustering algorithm (fineSTRUCTURE), adapted for specific aspects of our analysis, the samples were clustered purely as a function of genetic similarity, without reference to their known sampling locations. When plotted on a map of Europe one observes a striking association between the inferred clusters and geography. Interestingly, for the most part modern country boundaries are significant i.e. we see clear evidence of clusters that exclusively contain samples from a single country. At a high level we see: the Finns are the most differentiated from the rest of Europe (as might be expected); a clear divide between Sweden/Norway and the rest of Europe (including Denmark); and an obvious distinction between southern and northern Europe. We also observe considerable structure within countries on a hitherto unseen fine-scale - for example genetically distinct groups are detected along the coast of Norway. Using novel techniques we perform further analyses to examine the genetic relationships between the inferred clusters. We interpret our results with respect to geographic and linguistic divisions, as well as the historical and archaeological record. We believe this is the largest detailed analysis of very fine-scale human genetic structure and its origin within Europe. Crucial to these findings has been an approach to analysis that accounts for linkage disequilibrium.
The population structure and demographic history of Sardinia in relationship to neighboring populations.
J. Novembre, C. Chiang, J. Marcus, C. Sidore, M. Zoledziewska, M. Steri, H. Al-asadi, G. Abecasis, D. Schlessinger, F. Cucca.
Numerous studies have made clear that Sardinian populations are relatively isolated genetically from other populations of the Mediterranean, and more recently, intriguing connections between Sardinian ancestry and early Neolithic ancient DNA samples have been made. In this study, we analyze a whole-genome low-coverage sequencing dataset from 2120 Sardinians to more fully characterize patterns of genetic diversity in Sardinia. The study contains one subsample that contains individuals from across Sardinia and a second subsample that samples 4 villages from the more isolated Ogliastra region. We also merge the data with published reference data from Europe and North Africa. Overall Fst values of Sardinia to other European populations are low (less than 0.015); however using a novel method for visualizing genetic differentiation on a geographic map, we formally show how Sardinia is more differentiated than would be expected given its geographic distance from the mainland, consistent with periods of isolation. Applications of the software Admixture show how Sardinia populations differ in the levels of recent admixture with mainland European populations and that there are only minor contributions from North African populations to Sardinian ancestry. Notably the Sardinians from Ogliastra contain a distinct genetic cluster with minimal evidence of RECENT admixture with mainland Europe. We found frequency-based f3 tests and the tree-based algorithm Treemix both also show MINIMAL evidence of recent admixture. Given the relative isolation, one might expect to see a unique demographic history from neighboring populations. Using coalescent-based approaches, we find Sardinian populations have had more constant effective sizes over the past several thousand years than mainland European populations, which typically show evidence for rapid growth trajectories in the recent past. This unique demographic history has consequences for the abundance of putatively damaging and deleterious variants, and we use our data to address the prediction that the genetic architecture of disease traits is expected to involve fewer loci with a greater proportion of variants at common frequencies in Sardinia.
Population structure in African-Americans. S. Gravel, M. Barakatt, B. Maples, M. Aldrich, E. E. Kenny, C. D. Bustamante, S. Baharian.
We present a detailed population genetic study of 4 African-American cohorts comprising over 6000 genotyped individuals across US urban and rural communities: two nation-wide longitudinal cohorts, one biobank cohort, and the 1000 genomes ASW cohort. Ancestry analysis reveals a uniform breakdown of continental ancestry proportions across regions and urban/rural status, with 79% African, 19% European, and 1.5% Native American/Asian ancestries, with substantial between-individual variation. The Native Ancestry proportion is higher than previous estimates and is maintained after self-identified hispanics and individuals with substantial inferred Spanish ancestry are removed. This strongly supports direct admixture between Native Americans and African Americans on US territory, and linkage patterns suggest contact early after African-American arrival to the Americas. Local ancestry patterns and variation in ancestry proportions across individuals are broadly consistent with a single African-American population model with early Native American admixture and ongoing European gene flow in the South. The size and broad geographic sampling of our cohorts enables detailed analysis the geographic and cultural determinants of finer-scale population structure. Recent Identity-by-descent analysis reveals fine-scale structure consistent with the routes used during slavery and in the great African-American migrations of the twentieth century: east-to-west migrations in the south, and distinct south-to-north migrations into New England and the Midwest. These migrations follow transit routes available at the time, and are in stark contrast with European-American relatedness patterns.
Genetic testing of 400,000 individuals reveals the geography of ancestry in the United States. Y. Wang, J. M. Granka, J. K. Byrnes, M. J. Barber, K. Noto, R. E. Curtis, N. M. Natalie, C. A. Ball, K. G. Chahine.
The population of the United States is formed by the interplay of immigration, migration and admixture. Recent research (R. Sebro et al., ASHG 2013) has shed light on the U.S. demography by studying the self-reported ethnicity from the 2010 U.S. Census. However, self-reported ethnicity may not accurately represent true genetic ancestry and may therefore introduce unknown biases. Since launching its DNA service in May 2012, AncestryDNA has genotyped over 400, 000 individuals from the United States. Leveraging this huge volume of DNA data, we conducted a large-scale survey of the ancestry of the United States. We predicted genetic ethnicity for each individual, relying on a rigorously curated reference panel of 3,000 single-origin individuals. Combining that with birth locations, we explored how various ethnicities are distributed across the United States Our results reveal a distinct spatial distribution for each ethnicity. For example, we found that individuals from Massachusetts have the highest proportion of Irish genetic ancestry and individuals from New York have the highest proportion of Southern European genetic ancestry, indicating their unique immigration and migration histories. We also performed pairwise IBD analysis on the entire sample set and identified over 300 million shared genomic segments among all 400,000 individuals. From this data, we calculated the average amount of sharing for pairs of individuals born within the same state or from two different states. In general, we found the genetic sharing decreases as the geographic distance between two states increases. However, the pattern also varies substantially among the 50 states. In summary, our analysis has provided significant insight on the biogeographic patterns of the ancestry in the United States.
Statistical inference of archaic introgression and natural selection in Central African Pygmies. P. Hsieh, J. D. Wall, J. Lachance, S. A. Tishkoff, R. N. Gutenkunst, M. F. Hammer.
Recent evidence from ancient DNA studies suggests that genetic material introgressed from archaic forms of Homo, such as Neanderthals and Denisovans, into the ancestors of contemporary non-African populations. These findings also imply that hybridization may have given rise to some of adaptive novelties in anatomically modern humans (AMH) as they expanded from Africa into various ecological niches in Eurasia. Within Africa, fossil evidence suggests that AMH and a variety of archaic forms coexisted for much of the last 200,000 years. Here we present preliminary results leveraging high quality whole-genome data (>60X coverage) for three contemporary sub-Saharan African populations (Biaka, Baka, and Yoruba) from Central and West Africa to test for archaic admixture. With the current lack of African ancient DNA, especially in Central Africa due to its rainforest environment, our statistical inference approach provides an ALTERNATIVE means to understand the complex evolutionary dynamics among groups of the genus Homo. To identify candidate introgressive loci, we scan the genomes of 16 individuals and calculate S*, a summary statistic that was specifically designed by one of us (JDW) to detect archaic admixture. The significance of each candidate is assessed through extensive whole-genome level simulations using demographic parameters estimated by ∂a∂i to obtain a parametric distribution of S* values under the null hypothesis of no archaic introgression. As a complementary approach, top candidates are also examined by an approximate-likelihood computation method. The admixture time for each individual introgressive variant is inferred by estimating the decay of the genetic length of the diverged haplotype as a function of its underlying recombination rate. A neutrality test that controls for demography is performed for each candidate to test the hypothesis that introgressive variants rose to high frequency due to positive directional selection. Several genomic regions were identified by both selection and introgression scans, and we will discuss the possible genetic and functional properties of these “double-hits”. The present study represents one of the most comprehensive genomic surveys to date for evidence of archaic introgression to anatomically modern humans in Africa.
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Inferences about human history and natural selection from 280 complete genome sequences from 135 diverse populations. S. Mallick, D. Reich, Simons Genome Diversity Project Consortium.
The most powerful way to study population history and natural selection is to analyze whole genome sequences, which contain all the variation that exists in each individual. To date, genome-wide studies of history and selection have primarily analyzed data from single nucleotide polymorphism (SNP) arrays which are BIASED BY the choice of which SNPs to include. Alternatively they have analyzed sequence data that have been generated as part of medical genetic studies from populations with large census sizes, and thus do not capture the full scope of human genetic variation. Here we report high quality genome sequences (~40x average) from 280 individuals from 135 worldwide populations, including 45 Africans, 26 Native Americans, 27 Central Asians or Siberians, 46 East Asians, 25 Oceanians, 46 South Asians, and 71 West Eurasians. All samples were sequenced using an identical protocol at the same facility (Illumina Ltd.). We modified standard pipelines to eliminate biases that might confound population genetic studies. We report novel inferences, as well as a high resolution map that shows where archaic ancestry (Neanderthal and Denisovan) is distributed throughout the world. We compare and contrast the genomic landscape of the Denisovan introgression into mainland Eurasians to that in island Southeast Asians. We are making this dataset fully available on Amazon Web Services as a resource to the community, coincident with the American Society of Human Genetics meeting.
They are saying Hispanics are shorter because of Native American Ancestry
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Long-range haplotype mapping in Hispanic/Latinos reveals loci for short stature. G. Belbin, D. Ruderfer, K. Slivinski, M.C. Yee, J. Jeff, O. Gottesman, E.A. Stahl, R.J.F. Loos, E.P. Bottinger, E.E. Kenny.
The Hispanic/Latino (HL) population of Northern Manhattan represents a diverse recent diaspora population, with 95% of the individuals reporting having grandparents born outside of the United States. Of these 43% report grandparents born in Puerto Rico, 23% the Dominican Republic, 13% Central America, and 5%, 4%, and 2% from Mexico, South America, and Europe respectively. Despite complex patterns of migration, admixture, and diversity, strong signatures of cryptic relatedness persist amongst HLs. We have detected long-range genomic tract sharing (>3cM), or identity-by-descent (IBD), across 5,194 HL in the Mount Sinai BioMe Biobank. We observed an average population level IBD sharing of 0.0025 in HL, which is 2.5- and 5-fold higher than that observed in BioMe European- and African-American populations, respectively. We hypothesize that these patterns of recent migration and genetic drift may drive some otherwise rare functional alleles to detectable frequency. We clustered groups of homologous IBD tracts (n=112,250) segregating in this HL population. We observed that IBD clusters represent a class of low frequency alleles (median minor allele frequency =0.0077, s.d.=0.0015). We performed a genome-wide association of the IBD clusters, or ‘population-based linkage’, to detect loci implicated in height, a highly heritable polygenic trait. 15 independent loci surpassed our empirically derived genome-wide significance threshold of less than 4.4710-4, 11 of which replicated in an independent cohort of BioMe HLs. Strikingly, two regions confer strong recessive effects. In the case of the top hit on 9q32 (MAF less than 0.005; p less than8x10-6), homozygous non-referent individuals were shorter by 6” or 10”, for men or women, respectively, compared to the population mean (5’ 7” and 5’ 2” for men and women, respectively). In addition, IBD haplotypes in the 9q32 cluster harbored a significant enrichment of Native American ancestry (p less than 1x10-16). Finally, this interval contains a number of biologically compelling candidate genes, including COL27A1 and PALM2. This study demonstrates that rich population structure, rather than being a confounding factor in biomedical discovery efforts, may be leveraged to reveal novel genetic associations with complex human traits