Complete genome sequencing and variant analysis of a Pakistani individual

Abstract

We sequenced the genome of a Pakistani male at 25.5x coverage using massively parallel sequencing technology. More than 90% of the sequence reads were mapped to the human reference genome. In subsequent analysis, we identified 3,224,311 single-nucleotide polymorphisms (SNPs), of which 388,532 (12% of the total SNPs) had not been previously recorded in single nucleotide polymorphism database (dbSNP) or the 1000 Genomes Project database. The 5991 non-synonymous coding variants were screened for deleterious or disease-associated SNPs. Analysis of genes with deleterious SNPs identified 'retinoic acid signaling' and 'regulation of transcription' as the enriched Gene Ontology terms. Scanning of non-synonymous SNPs against the OMIM revealed several disease and phenotype-associated variants in Pakistani genome. Comparative analysis with Indian genome sequence revealed >1.8 million shared SNPs; 32% of which were annotated in ~14,000 genes. Gene Ontology (GO) terms analysis of these genes identified 'response to jasmonic acid stimulus', 'aminoglycoside antibiotic metabolic process' and 'glycoside metabolic process' with considerable enrichment. A total of 59,558 of small indels (1-5 bp) and 16,063 large structural variations were found; 54% of which was novel. Substantial number of novel structural variations discovered in Pakistani genome enforced previous inferences that (a) structural variations are major type of variation in the genome and (b) compared with SNPs, they putatively exhibit equivalent or superior functional roles. This genome sequence information will be an important reference for population-wide genomics studies of ethnically diverse South Asian subcontinent.

Impact of copy number variations burden on coding genome in humans using integrated high resolution arrays

“…Some of these pathways were also found enriched in the variations reported from a recent study (Azim et al, 2013). Some of these pathways were also found enriched in the variations reported from a recent study (Azim et al, 2013).…”

Whole genome sequencing data of multiple individuals of Pakistani descent

“…Additionally, independent groups have recently published two Indian and two Pakistani genomes with an overall 25-30× sequencing coverage [16][17][18][19] . Recently, the GenomeAsia 100 K project reported genomes of 1,739 individuals, including 113 individuals of Pakistani origin (https://browser.genomeasia100k.org).…”

An integrated Asian human SNV and indel benchmark combining multiple sequencing methods

“…For example, targeted DNA-HiSeq [8] identified 1,281 SNVs in 193 genes in the Asian reference sample YH that could not be detected in the original study [5]. The 193 genes are associated with hereditary diseases with a higher incidence in the Chinese population, a clear example of the need for high quality reference genomes in addition to NA12878 [7]. It is now apparent that a combination of long read, short read, and linked-read sequencing is required to fully characterize human reference genomes[9].…”

“…Significant insights have been gained from NA12878, but it is appreciated that reference genomes from additional populations are needed [4]. Several Asian genomes are now available from individuals of Chinese [5], Korean [6] and Pakistani [7] descent. However, the majority of these studied used next-generation sequencing (NGS) platforms to generate short reads and could not resolve SNVs and indels located in complex regions.…”