title: Improving empirical evidence on differentiating closely related men with RM Y-STRs: A comprehensive pedigree study from Pakistan.
abstract: Y-chromosomal short tandem repeat (Y-STR) markers are commonly used in forensic genetics. Male-specific haplotypes provided by commercial Y-STR kits allow discriminating between many - but not all - unrelated men, while they mostly fail to separate related ones. Aiming to improve male relative and paternal lineage differentiation, a set of 13 rapidly-mutating (RM) Y-STRs was previously identified and introduced to forensic Y-chromosome analysis. Recently, their value was highlighted by separating 99% of over 12,200 unrelated men from 111 global populations, as well as 29% of over 2500 male relative pairs, the vast majority were father-sons. Here, we provide improved empirical evidence on differentiating closely related men with RM Y-STRs, most notably beyond father-sons, where previous data were limited. After careful quality control including genetic relationship testing, we used 572 Pakistani men belonging to 99 2-4 generation pedigrees covering 1568 pairs of men related by 1-6 meioses. Of those, 45% were differentiated by one or more of the 13 RM Y-STR markers. In contrast, only 14.7% of a subset of 1484 pairs from 94 pedigrees were separated by the commercial AmpFlSTR Y-filer kit. Combining previously published and new data, an overall differentiation rate of 35.3% was revealed for the RM Y-STR set based on 4096 pairs of men related by 1-20 meioses, compared to 9.6% with Y-filer based on 3645 pairs. Using father-son pair data from the present and previous studies, we provide updated RM Y-STR mutation rates. Locus-specific mutation rates ranged from 2.0×10-3(7.0×10-4-4.3×10-3) to 6.9×10-2(6.1×10-2-7.9×10-2) based on 2741-3143 meioses, with an average rate across all 13 RM Y-STR markers of 1.8×10-2(1.7×10-2-1.9×10-2) based on 800 mutations from 44,922 meioses. The high haplotype diversity (h=0.9996) we observed among the unrelated men (N=105) underlines the value of this RM Y-STR set to differentiate paternal lineages even from endogamous populations such as from Pakistan.
authors: Department of Forensic Sciences, University of Health Sciences, Lahore, Pakistan; Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Atif
authors: A
authors: Adnan
authors: Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Arwin
authors: A
authors: Ralf
authors: Department of Forensic Sciences, University of Health Sciences, Lahore, Pakistan.
authors: Allah
authors: A
authors: Rakha
authors: Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Nefeli
authors: N
authors: Kousouri
authors: Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: m.kayser@erasmusmc.nl.
authors: Manfred
authors: M
authors: Kayser
mesh_terms: D041322:Chromosomes, Human, Y; D016172:DNA Fingerprinting; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D010154:Pakistan; D010375:Pedigree
chemical_list: D005819:Genetic Markers
keywords: Forensic genetics; Male lineage differentiation; Male relative differentiation; Mutation rate; RM Y-STRs; Y-chromosome