Fast and Accurate Kinship Estimation Using Sparse SNPs in Relatively Large Database Searches

Abstract

Forensic genetic genealogy (FGG) has primarily relied upon dense single nucleotide polymorphism (SNP) profiles from forensic samples or unidentified human remains queried against online genealogy database(s) of known profiles generated with SNP microarrays or from whole genome sequencing (WGS). In these queries, SNPs are compared to database samples by locating contiguous stretches of shared SNP alleles that allow for detection of genomic segments that are identical by descent (IBD) among biological relatives (kinship). This segment-based approach, while robust for detecting distant relationships, generally requires DNA quantity and/or quality that are sometimes not available in forensic casework samples. By focusing on SNPs with maximal discriminatory power and using an algorithm designed for a sparser SNP set than those from microarray typing, performance similar to segment matching was reached even in difficult casework samples. This algorithm locates shared segments using kinship coefficients in "windows" across the genome. The windowed kinship algorithm is a modification of the PC-AiR and PC-Relate tools for genetic relatedness inference, referred to here as the "whole genome kinship" approach, that control for the presence of unknown or unspecified population substructure. Simulated and empirical data in this study, using DNA profiles comprised of 10,230 SNPs (10K multiplex) targeted by the ForenSeqTM Kintelligence Kit demonstrate that the windowed kinship approach performs comparably to segment matching for identifying first, second and third degree relationships, reasonably well for fourth degree relationships, and with fewer false kinship associations. Selection criteria for the 10K SNP PCR-based multiplex and functionality of the windowed kinship algorithm are described.

k2v: A Containerized Workflow for Creating VCF Files from Kintelligence Targeted Sequencing Data

“…The Kintelligence kit provides genotypes on 10,230 SNPs, of which 9,867 are kinship-informative SNPs used for SNP-based kinship analysis across populations, while the remaining 363 are used to inform biogeographical ancestry, identity, hair and eye color, and biological sex (Snedecor et al 2022). The Kintelligence kit integrates data analysis in a browser-based application, and also produces Excel and text file outputs containing genotype data in a custom format.…”