Over the past few years, the Y chromosome has emerged as a crucial investigative tool, gaining significant applications in multiple disciplines such as forensics, anthropology, and genetics. Standard Y-STRs are particularly useful for identifying male donors in mixed deoxyribonucleic acid (DNA) samples dominated by female DNA, in tracing male patrilineal lineage, and in disaster victim identification. Nonetheless, their limited ability to distinguish closely related males has constrained their forensic utility. Evidence from multiple studies shows that rapidly mutating (RM) Y-STR markers improve male differentiation owing to their elevated mutation rates. Recent advances in RM Y-STR research include marker discovery, panel validation, and development of multiplex assays. RM Y-STRs have demonstrated effectiveness in male relative differentiation, kinship analysis, and analysis of complex mixtures with multiple contributors. Beyond forensic casework, RM Y-STRs hold promise in clinical contexts, particularly in investigating unexplained infertility and assessing reproductive risks. The advanced genotyping approaches, such as capillary electrophoresis, massively parallel sequencing (MPS), and the use of advanced computational analytical methods, have further enhanced their utility. Nevertheless, their implementation is complicated by interpretive challenges and inconsistencies in mutation rates across populations. Addressing these challenges through further research on additional RM Y-STRs, establishing standardised methods for determining mutation rates, and expanding databases like the Y chromosome Haplotype Reference Database (YHRD) to include RM Y-STR markers is crucial to fully leverage the potential of RM Y-STR markers.
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