CSYseq: The first Y-chromosome sequencing tool typing a large number of Y-SNPs and Y-STRs to unravel worldwide human population genetics

Abstract

Male-specific Y-chromosome (chrY) polymorphisms are interesting components of the DNA for population genetics. While single nucleotide polymorphisms (Y-SNPs) indicate distant evolutionary ancestry, short tandem repeats (Y-STRs) are able to identify close familial kinships. Detailed chrY analysis provides thus both biogeographical background information as paternal lineage identification. The rapid advancement of high-throughput massive parallel sequencing (MPS) technology in the past decade has revolutionized genetic research. Using MPS, single-base information of both Y-SNPs as Y-STRs can be analyzed in a single assay typing multiple samples at once. In this study, we present the first extensive chrY-specific targeted resequencing panel, the ‘CSYseq’, which simultaneously identifies slow mutating Y-SNPs as evolution markers and rapid mutating Y-STRs as patrilineage markers. The panel was validated by paired-end sequencing of 130 males, distributed over 65 deep-rooted pedigrees covering 1,279 generations. The CSYseq successfully targets 15,611 Y-SNPs including 9,014 phylogenetic informative Y-SNPs to identify 1,443 human evolutionary Y-subhaplogroup lineages worldwide. In addition, the CSYseq properly targets 202 Y-STRs, including 81 slow, 68 moderate, 27 fast and 26 rapid mutating Y-STRs to individualize close paternal relatives. The targeted chrY markers cover a high average number of reads (Y-SNP = 717, Y-STR = 150), easy interpretation, powerful discrimination capacity and chrY specificity. The CSYseq is interesting for research on different time scales: to identify evolutionary ancestry, to find distant family and to discriminate closely related males. Therefore, this panel serves as a unique tool valuable for a wide range of genetic-genealogical applications in interdisciplinary research within evolutionary, population, molecular, medical and forensic genetics.

Large-scale pedigree analysis highlights rapidly mutating Y-chromosomal short tandem repeats for differentiating patrilineal relatives and predicting their degrees of consanguinity

“…In addition, multiple models could be built for the same sets of Y-STRs, based on different mutation rate estimates, for example if it is shown that the locus-specific mutation rates strongly differ in the population of interest. This method of investigation may become more precise over time as the number of addressable and well-characterized Y-STRs increases, for example by using massively parallel sequencing-based methods for data generation (Claerhout et al 2021b ).…”

Recent advances in forensic biology and forensic DNA typing: INTERPOL review 2019–2022

“…A massively parallel sequencing tool was developed to analyze 859 Y-SNPs to infer 640 Y haplogroups [ 473 ]. Another MPS tool, the CSYseq panel, targeted 15,611 Y-SNPs to categorize 1443 Y-sub-haplogroup lineages worldwide along with 202 Y-STRs including 81 slow, 68 moderate, 27 fast, and 26 rapidly mutating Y-STRs to individualize close paternal relatives [ 474 ].…”

An Introductory Overview of Open-Source and Commercial Software Options for the Analysis of Forensic Sequencing Data

“…The software is a good starting point as a secondary analysis option with additional flexibility for those interested in building custom solutions for their more specific needs beyond standard reports [17,46,47]. The offered modular tools and customization are ideal for stutter analysis or the visualization of stutter restoration to the respective parent allele [48].…”