title: 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.
authors.affiliation: Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
authors.forename: Muhammad Kamran
authors.initials: MK
authors.lastname: Azim
authors.forename: Chuanchun
authors.initials: C
authors.lastname: Yang
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Yan
authors.forename: Muhammad Iqbal
authors.initials: MI
authors.lastname: Choudhary
authors.forename: Asifullah
authors.initials: A
authors.lastname: Khan
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.forename: Huma
authors.initials: H
authors.lastname: Asif
authors.forename: Sana
authors.initials: S
authors.lastname: Sharif
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D063990:Gene Ontology; D015894:Genome, Human; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D010154:Pakistan; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics*