Insights into the Genetic Structure and Diversity of 38 South Asian Indians from Deep Whole-Genome Sequencing

Abstract

South Asia possesses a significant amount of genetic diversity due to considerable intergroup differences in culture and language. There have been numerous reports on the genetic structure of Asian Indians, although these have mostly relied on genotyping microarrays or targeted sequencing of the mitochondria and Y chromosomes. Asian Indians in Singapore are primarily descendants of immigrants from Dravidian-language–speaking states in south India, and 38 individuals from the general population underwent deep whole-genome sequencing with a target coverage of 30X as part of the Singapore Sequencing Indian Project (SSIP). The genetic structure and diversity of these samples were compared against samples from the Singapore Sequencing Malay Project and populations in Phase 1 of the 1,000 Genomes Project (1 KGP). SSIP samples exhibited greater intra-population genetic diversity and possessed higher heterozygous-to-homozygous genotype ratio than other Asian populations. When compared against a panel of well-defined Asian Indians, the genetic makeup of the SSIP samples was closely related to South Indians. However, even though the SSIP samples clustered distinctly from the Europeans in the global population structure analysis with autosomal SNPs, eight samples were assigned to mitochondrial haplogroups that were predominantly present in Europeans and possessed higher European admixture than the remaining samples. An analysis of the relative relatedness between SSIP with two archaic hominins (Denisovan, Neanderthal) identified higher ancient admixture in East Asian populations than in SSIP. The data resource for these samples is publicly available and is expected to serve as a valuable complement to the South Asian samples in Phase 3 of 1 KGP.

The GenomeAsia 100K Project enables genetic discoveries across Asia

“…We accessed publicly available high-coverage, whole-genome FASTQ files from previous studies of human genetic variation [52][53][54][55] and combined these with 1,267 high-coverage genomes generated as part of this project. Full details on the samples chosen for sequencing and the informed consent processes for these samples can be found in Supplementary Information 1.…”

Population Stratification in Genetic Association Studies

“…2012] is also widely used for most populations, with the Haplotype Reference Consortium (HRC) panel [McCarthy, et al 2016] becoming more commonly utilized recently. However, construction of population-specific reference sets through whole genome sequencing is becoming increasingly more common [Low-Kam, et al 2016] (French-Canadian); [Tang, et al 2016] (Australian Aboriginal; exome); [Higasa, et al 2016] (Japanese); [Thareja, et al 2015](Persian Kuwaiti); [Huang, et al 2015] (UK10K, United Kingdom), [Kawai, et al 2015] (1KJPN, Japanese); [Wong, et al 2014] (South Asian Indians); [Kim, et al 2014] (Korean); [Deelen, et al 2014] (GoNL, Netherlands); [Carmi, et al 2014] (Ashkenazi); [Wong, et al 2013] (Asian Malays)), though some of these (i.e. UK10K and GoNL) have also been included in the HRC.…”

Reconstructing genetic history of Siberian and Northeastern European populations

“…To examine the genetic relationships of Siberian and Eastern European populations relative to other populations in the world, we integrated publicly available raw sequencing data from 32 high-coverage modern genomes representing 18 populations (Supplemental Table S2; Wong et al 2013Wong et al , 2014Zhou et al 2013;Jeong et al 2014;Prufer et al 2014), ancient genomes (Supplemental Table S3), and variant calls from the two hominin genomes, the Neanderthal and Denisova individuals (Meyer et al 2012) in our analysis. We sought to minimize potential biases stemming from the use of different sequencing platforms, different read mapping tools, different SNP calling tools, and downstream variant filters.…”

“…To further understand the genetic relationships and ancient history of indigenous Northeastern European and Siberian populations, spanning thousands to tens of thousands of years, we performed deep genome sequencing of 28 individuals (with an average sequence coverage depth of 38×), representing 14 major ethnic groups from Northeastern Europe and Siberia, including undersurveyed Western Siberian groups (Table 1), and compared them to 32 publicly available high-coverage modern genomes from 18 populations (Supplemental Table S2; Wong et al 2013Wong et al , 2014Zhou et al 2013;Jeong et al 2014;Prufer et al 2014), two hominin genomes, the Neanderthal , and Denisova genomes (Meyer et al 2012), as well as 46 publicly available ancient genomes from other studies (Supplemental Table S3). …”