Mutability of Y-chromosomal microsatellites: rates, characteristics, molecular bases, and forensic implications

Abstract

Nonrecombining Y-chromosomal microsatellites (Y-STRs) are widely used to infer population histories, discover genealogical relationships, and identify males for criminal justice purposes. Although a key requirement for their application is reliable mutability knowledge, empirical data are only available for a small number of Y-STRs thus far. To rectify this, we analyzed a large number of 186 Y-STR markers in nearly 2000 DNA-confirmed father-son pairs, covering an overall number of 352,999 meiotic transfers. Following confirmation by DNA sequence analysis, the retrieved mutation data were modeled via a Bayesian approach, resulting in mutation rates from 3.78 × 10(-4) (95% credible interval [CI], 1.38 × 10(-5) - 2.02 × 10(-3)) to 7.44 × 10(-2) (95% CI, 6.51 × 10(-2) - 9.09 × 10(-2)) per marker per generation. With the 924 mutations at 120 Y-STR markers, a nonsignificant excess of repeat losses versus gains (1.16:1), as well as a strong and significant excess of single-repeat versus multirepeat changes (25.23:1), was observed. Although the total repeat number influenced Y-STR locus mutability most strongly, repeat complexity, the length in base pairs of the repeated motif, and the father's age also contributed to Y-STR mutability. To exemplify how to practically utilize this knowledge, we analyzed the 13 most mutable Y-STRs in an independent sample set and empirically proved their suitability for distinguishing close and distantly related males. This finding is expected to revolutionize Y-chromosomal applications in forensic biology, from previous male lineage differentiation toward future male individual identification.

Figure 1

Mutation Rates of 186 Y-STR Markers Established from Father-Son Pair Analysis Distribution of 186 Y-STR markers according to their Bayesian-based mutation rates (with credible intervals) estimated from analyzing up to 1966 DNA-confirmed father-son pairs per marker. The 13 RM Y-STR markers ascertained for further family or pedigree analysis are highlighted in red, and the commonly used 17 Yfiler Y-STRs are in green. Multicopy Y-STRs are noted with a black insert diamond.

Figure 2

Correlation between the Length of the Longest Homogeneous Array, or the Total Number of Repeats within a Locus, and the Allele-Specific Mutation Rate from 267 Y-STR Loci Although the number of repeats present within a locus's longest homogenous array can be used to predict mutability, the total number of all repeats present within the locus has higher predictive value.

Figure 3

Relationship between Total Number of Repeats and Mutation Direction and Rate from 267 Y-STR Loci Repeat loss mutations (contractions) displayed an exponential relationship with the total number of repeats, with increasing loss rates at loci with higher numbers of repeats. Repeat gain mutations (expansions) showed a weak quadratic function, with a peak in gain rate at 19 total repeats.

Figure 4

Male Relative Differentiation with Newly Identified 13 RM Y-STRs and Commonly Used 17 Yfiler Y-STRs Results from differentiating between male relatives from analyzing 103 pairs from 80 male pedigrees, sorted according to the number of generations separating pedigree members, based on 13 RM Y-STRs (in red) and 17 Yfiler Y-STRs (in blue). Error bars represent 95% binomial confidence intervals. Note that these samples are independent from the father-son pairs initially used to establish the Y-STR mutation rates.