Post by djoser-xyyman on Oct 22, 2018 11:14:18 GMT -5
www.ashg.org/2018meeting/pages/online-planner.shtml
2018 Meeting Online Planner and Abstract
PgmNr 372: Uganda genomes resource enables inferences into population history and genomic discovery in Africa.
Authors:
D. Gurdasani 1,2; T. Carstensen 1,2; S. Fatumo 1,2,3; G. Chen 4; CS. Franklin 1; J. Prado-Martinez 1; H. Bouman 1; Uganda Genomes Resource Investigators
Genomic studies in African populations provide unique opportunities to understand disease aetiology, human genetic diversity and population history in a regional and a global context. In the largest study of its kind to date, comprising genome-wide data from 6,400 individuals from ***rural*** Uganda, and including whole-genome sequence from 1,978 individuals, we find evidence of geographically correlated fine-scale population substructure, as well ascomplex admixture from eastern African hunter-gatherer and Eurasian populations. We highlight the value of the largest sequence panel from Africa to date as a global resource for population genetics, imputation and understanding the mutational spectrum and its clinical relevance in African populations. Examining 34 cardiometabolic traits, we demonstrate systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genetic and environmental factors on traits. In the first multi-trait pan-African GWAS of up to 14,126 individuals, we identify 10 novel loci associated with anthropometric, haematological, lipid and glycemic traits. Our findings suggest that several functionally important signals at known and novel loci may be driven by differentiated variants within and specific to Africa, highlighting the utility of inclusion of diverse study populations in African GWAS. We provide a rich new genomic and phenotypic resource for researchers in Africa and globally.
PgmNr 2771: Building human reference genomes for Africa.
Authors:
M.O. Pollard 1,2; E. Karakoc 1,2; T. Porter 1,2; J. Prado Martinez 1; C. Pomilla 1,2; on behalf of GDAP investigators
The current version of the human reference GRCh38 is largely a mosaic of European haplotypes with limited contribution from genome sequences from Africa. As such, using the current human reference genome for global population studies may bias inferences, including for population genetics and genomic discovery.
Recent attempts to broaden the repertoire of reference haplotypes, and develop population specific references have shown that these enable discovery of novel regions within the genome, and provide a resource for improved mapping and subsequent variant calling. The high levels of genetic diversity in Africa, highlight the need for a high resolution resource of genome assemblies representing genetic diversity across Africa. Here, we present the African reference resource, comprised of 43 individuals with highly contiguous assemblies from 23 populations across Africa. These data have been assembled using a combination of approaches, including 42 genomes on the 10x Chromium platform, and one Zulu genome sequenced at 55x coverage and 30x coverage on the PacBio and 10x Chromium platforms, respectively. We also created BioNano optical maps for this sample to perform assembly scaffolding, quality control and the discovery of structural variation.
Our assemblies using different platforms show a high degree of concordance with regard to structural variants. We use the Africa reference genome resource to identify novel population specific sequences and structural variation. Development of a resource of reference genomes across Africa will enable population genetics research, and genomic discovery using sequencing studies from this region and globally.
PgmNr 2686: New insights into the genetic basis and evolutionary history of lactase persistence in Africa.
Authors:
A. Ranciaro 1; M.C. Campbell 2; E. Eyerman 1; S. Thompson 1; W. Beggs 1; S.W. Mpoloka 3; G.G. Mokone 4; T. Nyambo 5; D.W. Meskel 6; G. Belay 6; M. Meredith Yeager 7; S. Channock 8; S.A. Tishkoff 1
Lactase persistence (LP) is a recent adaptive trait in humans and has evolved mainly in populations that practice milk production. Prior studies of African populations have identified novel common variants in intron 13 of the MCM6gene (a known candidate enhancer region for LCT) associated with LP primarily in pastoralists. While these variants account for a large proportion of the phenotypic variance, there may be additional polymorphisms that contribute to the LP trait. To test this hypothesis, we resequenced 555bp of intron 13 of MCM6, in ~1,500 African individuals from diverse populations in Ethiopia, Tanzania and Botswana. We also genotyped these same individuals using the Illumina Omni 5M SNP array, and integrated our sequencing data with the 5M genotype data to detect signatures of selection. In addition, we performed the lactose tolerance test for a subset of ~450 individuals.Based on our analyses, we identified for the first time the presence of the C-14010 and G-13915 variants in the Hadza hunter-gatherers from Tanzania. We also observed the G-13915 variant in the Burunge and Maasai populations from Tanzania, which has never previously been reported. Furthermore, we confirmed the presence of the G-13907 and the G-13915 alleles in Ethiopia. In addition, we detected a strong association between LP and genomic regions on several chromosomes in the Maasai pastoralists based on Fisher’s Exact Test, suggesting candidate regions that might contribute to LP in this population. Overall, this large-scale study offers new insights into the genetic basis and evolutionary history of LP in Africa.
PgmNr 2719: Investigating Sardinian population history with ancient DNA.
Authors:
J.H. Marcus 1; C. Posth 7,8; H. Ringbauer 1; L. Lai 11; C. Sidore 4,5,6; J. Beckett 13; H. Al-asadi 2,3; A. Furtwängler 8; M. Zoledziewska 4; C. Chiang 12; K. Dey 3; M. Gradoli 14; G. Abecasis 5; D. Schlessinger 9; R. Skeates 10; J. Krause 7,8; J. Novembre 1,2; F. Cucca 4,6
The sequencing of ancient DNA (aDNA) has provided new understanding into human movement and demography for many regions around the globe. For mainland Europe, ancient DNA studies have revealed a dynamic history, with major inferred population influxes due to Neolithic and Bronze Age expansions. The population of the Mediterranean island of Sardinia has been notable in these studies–typically aDNA samples of the early Neolithic on mainland Europe cluster with modern Sardinian samples. The standing model is that Sardinia had a high influx of Neolithic ancestry followed by relative isolation from the mainland and subsequent Bronze Age expansions. To gain further insight, we analyze genome-wide capture data (~1.2 millions SNPs) of 26 ancient Sardinians spanning the Neolithic, Copper Age, and Bronze Age, including individuals from Sardinia's Nuragic culture. Merging this novel data with 998 previously studied aDNA samples from across Europe and throughout the last ten millennia, we are able to place the ancient Sardinian samples into the broader context of the peopling of Europe. We confirm that ancient Sardinian samples show a strong affinity to early Neolithic samples and a near complete absence of the “Steppe” ancestry associated with Bronze Age expansions on the mainland. Interestingly, we also detect elevated affinities with pre-Neolithic peoples of Europe. Moreover, we studied genetic change through time within Sardinia. To this end, we analyzed whole-genome sequence data from approximately 1,500 modern Sardinian individuals, densely sampled across much of the island. Using our ancient samples enables us to detect significant signs of recent admixture, in particular with a strong influence from the Mediterranean region. We also find that populations from the more isolated mountainous provinces of Sardinia are less admixed and have experienced high levels of genetic drift. Overall, our analysis allows us to shed new light on the intriguing history of the peopling of Sardinia.