Next Generation Sequencing Plus (NGS+) with Y-chromosomal Markers for Forensic Pedigree Searches

Xiaoqin Qian,Jiayi Hou,Zheng Wang,Min Lang,Jing Liu,Tianzhen Gao,Yi Ye,Yiping Hou

doi:10.1038/s41598-017-11955-x

Abstract

There is high demand for forensic pedigree searches with Y-chromosome short tandem repeat (Y-STR) profiling in large-scale crime investigations. However, when two Y-STR haplotypes have a few mismatched loci, it is difficult to determine if they are from the same male lineage because of the high mutation rate of Y-STRs. Here we design a new strategy to handle cases in which none of pedigree samples shares identical Y-STR haplotype. We combine next generation sequencing (NGS), capillary electrophoresis and pyrosequencing under the term ‘NGS+’ for typing Y-STRs and Y-chromosomal single nucleotide polymorphisms (Y-SNPs). The high-resolution Y-SNP haplogroup and Y-STR haplotype can be obtained with NGS+. We further developed a new data-driven decision rule, FSindex, for estimating the likelihood for each retrieved pedigree. Our approach enables positive identification of pedigree from mismatched Y-STR haplotypes. It is envisaged that NGS+ will revolutionize forensic pedigree searches, especially when the person of interest was not recorded in forensic DNA database.

Highlights

Haplotype Name Minimal Yfiler conventional Y-chromosome short tandem repeat (Y-STR) rapidly mutating (RM) Y-STR RM Y-STR Yfiler Plus RM Y-STR RM Y-STR RM Y-STR
Y-STRs with capillary electrophoresis (CE), was applied to 100 father-son pairs to test for Y-STR mutations in paternal relatives
When rapidly mutating (RM) Y-STRs were introduced to the analysis, Yfiler Plus haplotype[23] analysis showed that 5 of the 8 mutation events were observed at RM Y-STRs, accounting for 62.5% of all mutations (Table 1, Supplementary Table S1)

Summary

Introduction

Haplotype Name Minimal Yfiler conventional Y-STR RM Y-STR RM Y-STR Yfiler Plus RM Y-STR RM Y-STR RM Y-STR. Y-SNP haplogroup analysis to forensic pedigree searches. In crime scene evidence comparisons, the presence of a discordant haplogroup in the reference sample indicates that both samples are derived from different MRCAs and the involved pedigree should be excluded from the scope of further investigations. We constructed a high-resolution Y-SNP haplogroup typing panel for forensic pedigree searches. We combined generation sequencing (NGS), capillary electrophoresis (CE) and pyrosequencing, under the term ‘NGS+’, for typing Y-SNPs and Y-STRs. We further developed a new data-driven decision rule, FSindex, for estimating the likelihood for each retrieved pedigree. Our approach enables positive identification of pedigree from mismatched Y-STR haplotypes. It is envisaged that NGS+ will revolutionize forensic pedigree searches, especially when the person of interest was not recorded in forensic DNA database

Methods

Results

Conclusion