ANALYSIS OF HUMAN GENETIC VARIATIONS IN PAKISTANI POPULATION

Abstract

The diverse and cOIl1plex/heterogeneous Pakistani population is categorized into more than 18 ethnic groups. A properly reported forensic DNA database for this seventh largest population of the world is still not avai lable. This study contributes towards the development of a forensic DNA database of the Pakistani population comprising both autosomal short tandem repeat (STR) markers profiles and mitochondrial DNA (mtDNA) hyper-variable regions (HVRs) haplotypes. The obtained genetic data was used for phylogenetic and demographic analyses to study the structure of the Pakistani population. Additionally, the molecular diagnostic potential of the autosomal STRs was also evaluated for the detection of chromosomal aneuploidic conditions. DNA samples from 701 individuals belonging to the Punjabi, Pathan, Sindhi, Balochi and Hazara ethnic groups of Pakistan, were analyzed for fifteen short tandem repeat (STR) markers (TPOX, D2S1338, D3S1358, FGA, CSFIPO, D5S818, D7S820, D8S1179, THOl, VW A, D13S317, D 16S539, D18S51 , D19S433 and D21S 11) included in the AmpFISTR® Identifiler™ PCR amplification kit. Our data showed that four markers, D2S1338, D18S51 , D19S433 and FGA exhibit high power of discrimination, while TPOX was the least discriminative among all shldied loci. Subsequent analyses also revealed highly significant deviations from Hardy- Weinberg equilibrium at several loci in all the studied etlmic groups, which probably occurs due to frequently practiced inbreeding (consanguineous marriages) within each group. Further analyses with the clustering algorithm STRUCTURE, principal component analysis (PCA) and neighbour joining (NJ) tree did not show clear genetic differences among the five ethnic groups. However, differences were evident with Hazara ethnic group (emerged as a genetic out-group) when the analyses were perfo1111ed by using the data of 783 microsatellite markers from the HGDP-CEPH panel. Most of the STR markers in the Identifiler kit are valuable forensic tools but they are insufficient for elucidating the population stlUchlre or caphlring the demarcation and variation among the shldied ethnic groups of Pakistan. As the STR genotype frequency data from these five studied ethnic groups did not show any remarkable differences, it is not possible to assign ethnicity to an unknown DNA sample belonging to any of these ethnic groups on the basis of the data derived from 15 STRs.