Simultaneous analysis of hundreds of Y-chromosomal SNPs for high-resolution paternal lineage classification using targeted semiconductor sequencing

Hum Mutat. 2015 Jan;36(1):151-9. doi: 10.1002/humu.22713. Epub 2014 Nov 27.

Abstract

SNPs from the non-recombining part of the human Y chromosome (Y-SNPs) are informative to classify paternal lineages in forensic, genealogical, anthropological, and evolutionary studies. Although thousands of Y-SNPs were identified thus far, previous Y-SNP multiplex tools target only dozens of markers simultaneously, thereby restricting the provided Y-haplogroup resolution and limiting their applications. Here, we overcome this shortcoming by introducing a high-resolution multiplex tool for parallel genotyping-by-sequencing of 530 Y-SNPs using the Ion Torrent PGM platform, which allows classification of 432 worldwide Y haplogroups. Contrary to previous Y-SNP multiplex tools, our approach covers branches of the entire Y tree, thereby maximizing the paternal lineage classification obtainable. We used a default DNA input amount of 10 ng per reaction but preliminary sensitivity testing revealed positive results from as little as 100 pg input DNA. Furthermore, we demonstrate that sample pooling using barcodes is feasible, allowing increased throughput for lower per-sample costs. In addition to the wetlab protocol, we provide a software tool for automated data quality control and haplogroup classification. The unique combination of ultra-high marker density and high sensitivity achievable from low amounts of potentially degraded DNA makes this new multiplex tool suitable for a wide range of Y-chromosome applications.

Keywords: Ion Torrent PGM; Y chromosome; Y-SNPs; haplogroup; male lineage identification; next-generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, Y / genetics*
  • Haplotypes
  • Humans
  • Male
  • Polymorphism, Single Nucleotide*
  • Sensitivity and Specificity
  • Sequence Analysis, DNA / economics
  • Sequence Analysis, DNA / instrumentation
  • Sequence Analysis, DNA / methods*
  • Software