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

다국어 초록 (Multilingual Abstract)

Background: Relatives share more genomic regions than unrelated individuals, with closer relatives sharing more regions. This concept, paired with the increased availability of highthroughput single nucleotide polymorphism (SNP) genotyping technologies, has made it feasible to measure the shared chromosomal regions between individuals to assess their level of relation to each other. However, such techniques have remained in the conceptual rather than practical stages in terms of applying measures or indices. Recently, we developed an index called “genetic distance-based index of chromosomal sharing (GD-ICS)” utilizing large-scale SNP data from Korean family samples and demonstrated its potential for practical applications in kinship determination. In the current study, we present validation results from various real cases demonstrating the utility of this method in resolving complex familial relationships where information obtained from traditional short tandem repeats (STRs) or lineage markers is inconclusive.
Methods: We obtained large-scale SNP data through microarray analysis from Korean individuals involving 13 kinship cases and calculated GD-ICS values using the method described in our previous study. Based on the GD-ICS reference constructed for Korean families, each disputed kinship was evaluated and validated using a combination of traditional STRs and lineage markers.
Results: The cases comprised those A) that were found to be inconclusive using the traditional approach, B) for which it was difficult to apply traditional testing methods, and C) that were more conclusively resolved using the GD-ICS method. This method has overcome the limitations faced by traditional STRs in kinship testing, particularly in a paternity case with STR mutational events and in confirming distant kinship where the individual of interest is unavailable for testing. It has also been demonstrated to be effective in identifying various relationships without specific presumptions and in confirming a lack of genetic relatedness between individuals.
Conclusion: This method has been proven effective in identifying familial relationships across diverse complex and practical scenarios. It is not only useful when traditional testing methods fail to provide conclusive results, but it also enhances the resolution of challenging kinship cases, which suggests its applicability in various types of practical casework.

참고문헌 (Reference)

1 Lindner I, "Usefulness of SNPs as supplementary markers in a paternity case with 3 genetic incompatibilities at autosomal and Y chromosomal loci" 41 (41): 117-121, 2014

2 정수진 ; 이재원 ; 이숭덕 ; 이승환 ; 박수정 ; 김종식 ; 이효정, "Statistical evaluation of common relationships using STR markers in Korean population" 10 (10): 107-115, 2016

3 Delaneau O, "Shape-IT : new rapid and accurate algorithm for haplotype inference" 9 (9): 540-, 2008

4 Morimoto C, "Pairwise kinship analysis by the index of chromosomal sharing using high-density single nucleotide polymorphisms" 11 (11): e0160287-, 2016

5 Purcell S, "PLINK : a tool set for whole-genome association and population-based linkage analyses" 81 (81): 559-575, 2007

6 Pinto N, "Optimizing the information increase through the addition of relatives and genetic markers in identification and kinship cases" 40 : 210-218, 2019

7 Sun M, "On the use of dense SNP marker data for the identification of distant relative pairs" 107 : 14-25, 2016

8 Hong SB, "Korean population genetic data and concordance for the PowerPlex® ESX 17, AmpFlSTR Identifiler®, and PowerPlex® 16 systems" 7 (7): e47-e51, 2013

9 Turrina S, "Kinship analysis : assessment of related vs unrelated based on defined pedigrees" 130 (130): 113-119, 2016

10 Pu CE, "Increasing the confidence in half-sibship determination based upon 15 STR loci" 15 (15): 373-377, 2008

11 Li R, "Improved pairwise kinship analysis using massively parallel sequencing" 38 : 77-85, 2019

12 de Vries JH, "Impact of SNP microarray analysis of compromised DNA on kinship classification success in the context of investigative genetic genealogy" 56 : 102625-, 2022

13 Hill WG, "Identification of pedigree relationship from genome sharing" 3 (3): 1553-1571, 2013

14 Kling D, "Forensic genealogy-A comparison of methods to infer distant relationships based on dense SNP data" 42 : 113-124, 2019

15 Snedecor J, "Fast and accurate kinship estimation using sparse SNPs in relatively large database searches" 61 : 102769-, 2022

16 Tamura T, "Evaluation of advanced multiplex short tandem repeat systems in pairwise kinship analysis" 17 (17): 320-325, 2015

17 Chu MC, "Effects of DNA degradation and genotype imputation on high-density SNP microarray in pairwise kinship analysis" 60 : 102158-, 2023

18 Morimoto C, "Discrimination of relationships with the same degree of kinship using chromosomal sharing patterns estimated from high-density SNPs" 33 : 10-16, 2018

19 Thomson JA, "Analysis of disputed single-parent/child and sibling relationships using 16 STR loci" 115 (115): 128-134, 2001

20 Kim YL, "Allele frequencies of 15 STR loci using AmpF/STR Identifiler kit in a Korean population" 136 (136): 92-95, 2003

21 Cho Sohee ; Shin Eunsoon ; Park Yoon Gi ; Choi Seung Ho ; Choe Eun Kyung ; Bae Jung Ho ; Lee Jong-Eun ; 이숭덕, "A novel approach of kinship determination based on the physical length of genetically shared regions of chromosomes" 46 (46): 577-587, 2024

22 Li L, "A case of false mother included with 46 autosomal STR markers" 6 (6): 9-, 2015