J Korean Med Sci.  2024 Jul;39(27):e198. 10.3346/jkms.2024.39.e198.

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

• Cho S
• Shin E
• Park Y
• You H
• Lee EY
• Lee JE
• Lee SD

• KMID: 2557779
• DOI: http://doi.org/10.3346/jkms.2024.39.e198

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.

Keyword

Kinship Analysis; Genetic Relatedness; Chromosomal Sharing; Korean Biobank Array; Koreans; Casework

Figure

• 

  Fig. 2 Distributions of GD-ICS values. (A) Each relationship in Korean reference data.9 (B) The cases investigated in this study.GD-ICS = genetic distance-based index of chromosomal sharing, cM = centimorgan, P-C = parent-child (1st), FS = full-siblings (1st), GP-GC = grandparent-grandchild (2nd), U-N = uncle/aunt-nephew/niece (2nd), GGP-GGC = great-grand parent-great-grandchild (3rd), FC = first cousins (3rd), GU-GN = granduncle/aunt-grand-nephew/niece (3rd), FCOR = first cousin once removed, GGU-GGN (4th) = great-granduncle/aunt-great-grandnephew/niece (4th), SC = second cousins (5th), FCTR = first cousin twice removed (5th), SCOR = second cousin once removed (6th), TC = third cousins (7th), F-C = father-child, M-C = mother-child, F-M = father-mother, M = male, F = female.

• 

  Fig. 1 Scenarios involving complex disputed relationships. (A) Case B3, (B) case B5, (C) case B6, (D) case C1, and (E) case C4.M = male, F = female.

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