Understanding the Y chromosome variation by haplogroup and haplotype analyses in a Korean population

Abstract

Genetic variation on the non-recombining portion of the Y-chromosome contains information about the ancestral and geographical origin of biological samples as well as differentiation between male lineages. A molecular characterization of the Y-chromosome genetic structure was performed using a combination of Y-chromosomal single nucleotide polymorphisms (Y-SNPs) and Y-chromosomal short tandem repeats (Y-STRs) in a Korean population. Six multiplex PCRs followed by SBE reaction and two multiplex allele-specific PCR assays were developed for the identification of haplogroups in Koreans as well as haplogroups frequent in East Asians. Validation experiments demonstrated that the multiplex PCR systems followed by SBE reaction were optimized for analyzing low template and highly degraded DNA whereas a multiplex allele-specific PCR assay would be useful for simple and reliable determination of haplogroups in a large number of samples. In a test using DNA samples from Korean males, a total of 21 different haplogroups were identified by 33 Y-SNPs including the newly redefined markers (PK4, KL2 and P164) in haplogroup O. When genotyping the SNPs, phylogenetic nonequivalence was found between SNPs M117 and M133, which define haplogroup O3a2c1a, suggesting that the position of the M133 marker should be changed. This study has shown that the haplotypes consisting of DYS392, DYS393, DYS437, DYS438, DYS448 and DYS388 loci can preserve phylogenetic information by their relatively low mutation rates, and hence can be used to roughly distinguish Y-chromosome haplogroups, whereas more rapidly mutating Y-STRs such as DYS449 and DYS458 are useful for differentiating male lineages. At the relatively rapidly mutating DYS447, DYS449, DYS458 and DYS464 loci, unusually short alleles and intermediate alleles with common sequence structures are informative for elucidating the substructure within the context of a particular haplogroup. In addition, some deletion mutations in the DYS385 flanking region and the null allele at DYS448 were associated with a single haplogroup background. These variants support the hypothesis that the variant originated from a single mutational event like binary markers. The high-resolution haplogroup and haplotype data will improve our understanding of the Korean population substructure and will also help to infer haplogroup background or common ancestry.