New Insights on Human Y-chromosomal Variation for Forensic Familial Searching

Forensic DNA analysis has become the gold standard in the justice system to identify the perpetrator from biological traces found at the crime scene. Nevertheless, offender identification through standard DNA analysis can be challenging in mixed biological samples from sexual assault or murder cases. With a male perpetrator, as in the majority of the cases, it is possible to genotype for the male specific Y-chromosome (chrY). This analysis ignores any female victim DNA in mixed stains, facilitates exclusion of other male suspects from complicity and detects multiple male contributors. Due to the lack of chrY databases in most countries, other identification strategies have to be applied. Familial searching is a forensic method where chrY helps to find potential leads to identify the male offender through the search for relatives. ChrY acts as a unique tool since the majority is inherited from father to son in a relative conserved manner. The only source of genetic variation between men is the occurrence of mutations on Y-markers. ChrY analysis provides thus the opportunity to discriminate between families and to find distant or close biological relatives who share a most recent common ancestor (MRCA) with the perpetrator. However, in order to use familial searching as a more general tool in forensic casework, there are some important gaps in the knowledge concerning paternally transferred chrY variation. In this PhD dissertation, new insights into the patrilineal chrY transmission were gained to improve familial searching in forensic casework. First, the knowledge concerning Y-markers and their mutation rates was expanded by exploring chrY variation in deep-rooted family pedigrees. Second, hidden mutations between paternal relatives were investigated and analyzed in order to reveal all chrY variations. Third, the obtained detailed chrY mutability characteristics were used to develop an improved MRCA calculator (the ‘YMrCA’) to estimate the time between an offender and his relative. Fourth, as chrY is co-inherited with surnames in many populations, it was possible to gain insights into the strengths and factors influencing this correlation and to create a surname prediction model (the ‘Ysurnames’) for its possible use in familial searching. And finally, a chrY-specific panel (the ‘CSYseq’) was designed to enhance current Y-marker analysis resolution to sequence level, targeting a large number of interesting Y-markers with high discrimination power and easy interpretation in order to analyze many samples in a single assay.