Whole genome sequencing of an ethnic Pathan (Pakhtun) from the north-west of Pakistan

Abstract

Background: Pakistan covers a key geographic area in human history, being both part of the Indus River region that acted as one of the cradles of civilization and as a link between Western Eurasia and Eastern Asia. This region is inhabited by a number of distinct ethnic groups, the largest being the Punjabi, Pathan (Pakhtuns), Sindhi, and Baloch.

Results: We analyzed the first ethnic male Pathan genome by sequencing it to 29.7-fold coverage using the Illumina HiSeq2000 platform. A total of 3.8 million single nucleotide variations (SNVs) and 0.5 million small indels were identified by comparing with the human reference genome. Among the SNVs, 129,441 were novel, and 10,315 nonsynonymous SNVs were found in 5,344 genes. SNVs were annotated for health consequences and high risk diseases, as well as possible influences on drug efficacy. We confirmed that the Pathan genome presented here is representative of this ethnic group by comparing it to a panel of Central Asians from the HGDP-CEPH panels typed for ~650 k SNPs. The mtDNA (H2) and Y haplogroup (L1) of this individual were also typical of his geographic region of origin. Finally, we reconstruct the demographic history by PSMC, which highlights a recent increase in effective population size compatible with admixture between European and Asian lineages expected in this geographic region.

Conclusions: We present a whole-genome sequence and analyses of an ethnic Pathan from the north-west province of Pakistan. It is a useful resource to understand genetic variation and human migration across the whole Asian continent.

Figure 1

Copy number variation regions in Pathan genome. Copy number variations counts distributed in each chromosome.

Figure 2

Admixture results of Pathan (PTN) individual to other ethnic groups in South Asia. Admixture results for K = 2 and K = 5 for the Pathan individual combined with eight ethnic genomes from HGDP dataset. The analysis was based on 643,281 SNVs. Each individual is represented by a vertical line, divided into colored segments that represent membership coefficients in the subgroups.

Figure 3

Inferred historical population sizes by Pairwise Sequential Markovian Coalescent analysis. PSMC (Pairwise Sequentially Markovian Coalescent) analysis was performed to reconstruct the demographic population history of Pathans, compared with a set of 11 HGDP genomes from around the world (Africa: Dinka, Yoruba, Mandenka, Mbuti, San; Asia: Dai, Han; Europe: French, Sardinian; Oceania: Papuan; Americas: Karitiana).