A novel approach of kinship determination based on the physical length of genetically shared regions of chromosomes

Abstract

Background Determination of genetic relatedness between individuals plays a crucial role in resolving numerous civil cases involving familial relationships and in forensic investigation concerning missing persons. Short tandem repeats (STRs), known for their high degree of DNA polymorphism, have traditionally been the primary choice of DNA markers in genetic testing, but their application for kinships testing is limited to cases involving close kinship. SNPs have emerged as promising supplementary markers for kinship determination. Nevertheless, the challenging remains in discriminating between third-degree or more distant relatives, such as first cousins, using SNPs. Objective To investigate a kinship analysis method for distant degree of familial relationships using high-density SNP data. Methods A high-density SNP data from 337 individuals of Korean families using Affymetrix Axiom KORV1.0-96 Array was obtained for this study. SNPs were aligned by chromosomal positions, and identity-by-state (IBS) was determined, and then shared regions as consecutive SNPs with IBS of 1 or 2 were investigated. The physical lengths of these IBS segments were measured and summed them to create an Index, as a measure of kinship. Results The kinship was determined by the physical length of shared chromosomal regions that are distinguished by each kinship. Using this method, the relationship was able be distinguished up to the fourth degree of kinship, and non-relatives were clearly distinguished from true relatives. We also found a potential for this approach to be used universally, regardless of microarray platforms for SNP genotyping and populations. Conclusion This method has a potential to determine the different degree of kinship between individuals and to distinguish non-relatives from true relatives, which can be of great help for practical applications in kinship determination.

Validation of the Utility of the Genetically Shared Regions of Chromosomes (GD-ICS) Measuring Method in Identifying Complicated Genetic Relatedness

“…Familial relationships in disputes were determined by comparing the calculated GD-ICS values for each case with the GD-ICS reference plot of 337 individuals of Korean families that have previously been reported . 9 The plot includes GD-ICS value distributions for first- to seventh-degree of kinship and unrelated individuals that were randomly generated between unrelated individuals from different families. Half-siblings (HSs) with the same genetic relatedness as a GP-GC and U-N were classified as 2nd-degree relatives.…”

“…The quality of the DNA samples could influence the variance of GD-ICS values in this approach, 9 as the reliability of microarray genotyping depends on sample qualities. 21 Although intact DNA from blood samples was used for SNP microarray analysis in the current study, various DNA sources may be employed in this analysis, thus resulting in the analysis of variable numbers of SNPs after quality control.…”

“…We investigated shared chromosomal regions between two individuals using a set of selected SNPs, following the method used in the previous study. 9 First, SNPs were aligned according to chromosomal positions, and SNP alleles from two individuals were then compared to investigate the identity-by-state (IBS) of each SNP. For example, IBS = 0 indicates AA vs. BB, while IBS = 1 and 2 indicates AA vs. AB and AA vs. AA, respectively.…”

“…In a previous study, we introduced an index called “genetic distance-based index of chromosomal sharing (GD-ICS)” based on this approach and established reference data for criteria determination using actual Korean family samples. 9 This established method is anticipated to be applicable in various scenarios of kinship disputes, but it is necessary to validate its application to real casework and evaluate its utility for respective scenarios based on the previous research. Here, we aimed to demonstrate the effectiveness of applying this approach to real casework in diverse scenarios of pairwise testing.…”