Case report on multilocus gene deletion and gene conversion at Y-STR loci

Area of Science:

• Forensic genetics
• Human genetics
• Molecular biology

Background:

• Y-chromosomal short tandem repeats (Y-STRs) are crucial for forensic applications like paternity testing and lineage tracing.
• Traditional mutation models, such as the stepwise mutation model (SMM), are insufficient for complex Y-STR mutations like gene deletion and conversion, especially at multi-copy loci.

Purpose of the Study:

• To investigate Y-STR mutation abnormalities, specifically gene conversion and deletion, in male pedigrees.
• To evaluate the limitations of the stepwise mutation model (SMM) in analyzing multi-copy Y-STR loci.
• To highlight the need for incorporating non-stepwise mutation mechanisms into forensic Y-STR analysis.

Main Methods:

• Utilized STR typing and next-generation sequencing (NGS) technologies.
• Genotyped biological samples from five father-son and father-cousin pairs.
• Employed the Yfiler™ Platinum Kit, Microreader™ RM-Y ID kit, and STRTyper Y68 Kit for STR typing.

Main Results:

• Observed a gene conversion mutation at the multi-copy locus DYS385ab in one case.
• Detected deletion of multiple Y-STR loci (DYS527ab, DYS387ab, DYF404S1, DYS464, DYS399S1, DYS626, DYS448) in four other cases.
• Demonstrated the inadequacy of SMM for accurately analyzing multi-copy Y-STR loci.

Conclusions:

• Y-STR mutation dynamics are more complex than SMM suggests, involving gene conversion and deletion.
• Current forensic methodologies require enhancement to account for non-stepwise mutation events at multi-copy Y-STR loci.
• This research provides critical insights for improving accuracy in forensic science and human genetics.