Mutation Rate Analysis of RM Y-STRs in Deep-Rooted Multi-Generational Punjabi Pedigrees from Pakistan

Abstract

Y chromosome short tandem repeat polymorphisms (Y-STRs) are important in many areas of human genetics. Y chromosomal STRs, being normally utilized in the field of forensics, exhibit low haplotype diversity in consanguineous populations and fail to discriminate among male relatives from the same pedigree. Rapidly mutating Y-STRs (RM Y-STRs) have received much attention in the past decade. These 13 RM Y-STRs have high mutation rates (>10−2) and have considerably higher haplotype diversity and discrimination capacity than conventionally used Y-STRs, showing remarkable power when it comes to differentiation in paternal lineages in endogamous populations. Previously, we analyzed two to four generations of 99 pedigrees with 1568 pairs of men covering one to six meioses from all over Pakistan and 216 male relatives from 18 deep-rooted endogamous Sindhi pedigrees covering one to seven meioses. Here, we present 861 pairs of men from 62 endogamous pedigrees covering one to six meioses from the Punjabi population of Punjab, Pakistan. Mutations were frequently observed at DYF399 and DYF403, while no mutation was observed at DYS526a/b. The rate of differentiation ranged from 29.70% (first meiosis) to 80.95% (fifth meiosis), while overall (first to sixth meiosis) differentiation was 59.46%. Combining previously published data with newly generated data, the overall differentiation rate was 38.79% based on 5176 pairs of men related by 1–20 meioses, while Yfiler differentiation was 9.24% based on 3864 pairs. Using father–son pair data from the present and previous studies, we also provide updated RM Y-STR mutation rates.

Mutation analysis for newly suggested 30 Y-STR loci with high mutation rates in Chinese father-son pairs

“…DYF387S1 was also found to have significantly higher mutation rate the Chinese population than in Austrian ( P value 0.0064). According to the previous mutation studies on DYF387S1, populations from central and southeastern China tend to show lower mutation rates 13 , 23 – 26 (0–10.27 × 10 –3 per meiosis, Supplementary Table S5 ) than the European populations (11.32–21.50 × 10 –3 per meiosis) 9 , 17 – 19 , 27 , and went higher in South Asians such as Pakistan (23.0–37.0 × 10 –3 per meiosis) 10 , 28 . Inconsistency in mutation rates within an ethnic group was also reported in the Pakistan group, which, like the Han Chinese, is also a largescale population 10 , 28 .…”

“…According to the previous mutation studies on DYF387S1, populations from central and southeastern China tend to show lower mutation rates 13 , 23 – 26 (0–10.27 × 10 –3 per meiosis, Supplementary Table S5 ) than the European populations (11.32–21.50 × 10 –3 per meiosis) 9 , 17 – 19 , 27 , and went higher in South Asians such as Pakistan (23.0–37.0 × 10 –3 per meiosis) 10 , 28 . Inconsistency in mutation rates within an ethnic group was also reported in the Pakistan group, which, like the Han Chinese, is also a largescale population 10 , 28 . However, the mutation rates for DYS449 and DYS570 were relatively low, consistent with previous findings in Chinese populations 20 , 23 , 24 and lower than in the European populations 9 , 17 .…”

Male Pedigree Toolbox: A Versatile Software for Y-STR Data Analyses

“…However, large father-son pair studies are labor and resource intensive, as for every genetic transfer (meiosis) tested, two DNA samples need to be analyzed. Y-STR studies in pedigrees are less common but more efficient, as information about the same number of meioses can be obtained by analyzing less samples [16][17][18]. Moreover, they allow for the determining of male relative differentiation rates also beyond the very close relative pairs available in father-son pairs.…”