The second forensic application offered by Y chromosome markers is in testing for the paternity of male offspring. Already in 1985, and therefore seven years before the first hypervariable Y-STR marker was discovered, it was suggested based on statistical considerations that the use of polymorphic Y markers should increase the chance to detect non-paternity compared with their autosomal counterparts (Chakraborty, 1985). Polymorphic Y-chromosomal markers are especially useful in deficiency cases where the alleged father of a male child is deceased. Such cases can only be solved via autosomal STR profiling with a high degree of certainty if both parents of the putative father are available for DNA analysis. Only the complete genotypes of the grandparents allow a reliable reconstruction of the STR alleles inherited from the deceased putative father to his child, given the mother's profile. However, many cases are brought to paternity testing where none or only one parent of the deceased alleged father is available for DNA analysis. In those cases involving a male child, Y-STR haplo-typing can identify the biological father if a biological male relative of any grade of relationship is available for testing to replace the deceased alleged father in the Y chromosome DNA analysis. Since Y-chromosomal STR haplotypes are identical between male relatives (unless rare mutation events occur), finding matching haplotypes between the male child and any biological paternal relative of the putative father will provide evidence in favour of the biological paternity of the deceased putative father (or any of his contemporary male relatives). Conversely, finding haplotype differences between the child and the male relative will exclude the deceased alleged father from paternity. However, the number of generations that separate the alleged father from his male relative used for Y chromosome analysis will increase the probability that mutations will introduce differences between the male relative and the child, despite the deceased male being the true father of the child. Thus, mutation rate estimates of the Y-STRs used for testing need to be taken into account in calculating paternity probabilities (Rolf et al., 2001). Therefore, knowledge about mutation rates for the Y-STRs used in forensics is important (Kayser and Sajantila, 2001).
The first study to estimate mutation rates for Y-STRs used in forensics applied deep-rooting pedigrees and revealed an average rate of 2.1 x 10-3 mutations per locus per generation (Heyer et al., 1997). In principle, mutation rate estimates should include the uncertainty caused by potential non-biological paternity, being especially crucial in pedigree studies where paternity cannot be established directly. However, in this study the biological paternal relationships within the pedigrees used for Y-STR mutation rate estimation were confirmed by additional analysis of the Y-chromosomal minisatellite MSY1 (Jobling et al., 1999). The first comprehensive study establishing Y-STR mutation rates based on father-son pairs of (autosomal) DNA-proven biological paternity revealed an average rate of 2.8 x 10-3 mutations per locus per generation (Kayser et al., 2000b). Subsequent, additional studies using father-son pairs confirmed previously obtained mutation rates (Ballard et al., 2005; Budowle et al., 2005; Dupuy et al., 2004; Gusmao et al., 2005) and a summary of mutation rate estimates for Y-STR markers commonly used in forensics is available from the YHRD website. Given the hypervariability of Y-STR haplotypes with sufficient loci included (e.g. the minimal haplotype), paternally unrelated males normally show differences at many Y-STRs. If two minimal haplotypes show differences at only one or two loci involving only one or two repeats, a relationship between the two respective male individuals needs to be considered, given the available knowledge about Y-STR mutation rates. It has been suggested that exclusion constellations at three or more Y-STRs need to be established before an exclusion of paternity can be concluded (Kayser et al., 1998; Kayser and Sajantila, 2001). Mutations at STRs, independent of whether they are located on the autosomes or on the sex chromosomes, are results of errors during DNA replication and mismatch repair. Single-strand slippage within the repetitive sequence of the STR locus can lead to a gain or a loss of repeats, usually of single repeat units.
Another feature of Y-STRs that is of relevance for forensic applications (although not for paternity testing) concerns the rare occurrence of additional Y-STR alleles (Kayser and Sajantila, 2001). Two mutational events lead to the observation of additional Y-STR alleles: first, a Y-chromosomal duplication including the STR locus occurs, and subsequently a slippage mutation results in allelic differences between the original STR and the copy. Additional Y-STR alleles were observed at almost all Y-STRs used in forensics (Butler et al., 2005) and can be misinterpreted as the involvement of multiple males when detected in a crime scene sample.
In principle, the absence of recombination between Y-specific markers allows the identification of non-biological paternity after many (male) generations in pedigree analysis. Thus, disputed paternity cases from historical times involving male offspring can be resolved today by testing Y-chromosomal polymorphisms in true paternal male descendants. This has been done in many cases, with the most prominent being that of the former U.S. President Thomas Jefferson and the children of Sally Hemmings, one of his slaves (Foster et al., 1998). It could be shown that Y-chromosomal profiles based on Y-SNPs, Y-STRs and a Y minisatellite of a fourth-generation male descendant of Easton Hemings Jefferson, one of Sally Hemmings sons, and four sixth- and seventh-generation descendants of Field Jefferson, Thomas Jefferson's father's brother, were identical. From the Y-chromosome data it was concluded that either Thomas Jefferson or one of his contempory male-line relatives, including his brother Randolph, had fathered Easton Hemings Jefferson. Unfortunately no living male descendants of Randolph Jefferson were available for testing.
In the same way that Y chromosome DNA analysis can be used for paternity testing and forensic stain analysis, it can also be used for identifying the biological remains of missing persons, including cases of mass disasters (Corach et al., 2001). Reference material of known living relatives is needed, as for autosomal DNA analysis, but the advantage of Y (and mitochondrial DNA) markers over autosomal markers is that relationships can be established and individuals identified, even if only reference samples of distant relatives are available for analysis. This can be highly relevant in mass disasters such as the 2004 Tsunami disaster in Southeast Asia, where entire families died and close relatives were therefore not available as references for autosomal DNA testing.
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