An unbalanced tri-allelic pattern at the D10S1248 locus: Characteristics, genetic basis and transmission. (November 2019)

• Record Type: Journal Article
• Authors: Xiao, Chao; Wei, Tian; Huang, Daixin
• Is Part Of: Legal medicine. Volume 41(2019)
• Publication Date: 2019-11
• Subjects: Short tandem repeat -- Tri-allelic pattern -- D10S1248 -- Somatic mutation -- Single nucleotide polymorphism -- Next-generation sequencing; Medical jurisprudence -- Periodicals; Forensic Medicine -- Periodicals; Médecine légale -- Périodiques; Medical jurisprudence; Periodicals; 614.1
• DOI: 10.1016/j.legalmed.2019.101627
• Languages: English
• ISSNs: 1344-6223

Abstract

Highlights: An unbalanced D10S1248 tri-allelic pattern 13/14/15 was investigated in a family. The coexistence of alleles was confirmed by SNP-STR typing and allelic sequencing. The pattern should stem from a somatic mutation in early embryonic development. The mutation of alleles 15 to 13 was determined using the rs2246538-D10S1248-rs2246512 marker. The allele 13 with the lowest peak height was identified by NGS as a stutter peak. Abstract: To address issues related to unbalanced tri-allelic patterns, an example at the D10S1248 locus characterized by the sum of heights of alleles 13 and 15 approximately equal to allele 14 was intensively investigated. The coexistence of these three alleles was confirmed by profiling the rs2246512-D10S1248 marker using fluorescently labelled primers and allelic sequencing. Multi-tissue genotyping revealed that this pattern had chimeric characteristics, and pedigree analysis found that allele 13 or allele 14 were inherited to offspring independently of the other two alleles. These evidences suggest that the pattern should stem from a somatic mutation in early embryonic development and that peak height ratio is not an accurate indicator of mutation time point and direction. The rs2246538-D10S1248-rs2246512 marker was subsequently used to determine the mutation from allele 15 to allele 13. Notably, allele 13 with the lowest peak height was misidentified as a stutter peak when genotyped using next generation sequencing.