Structural variation on the short arm of the human Y chromosome: recurrent multigene deletions encompassing Amelogenin Y

Structural polymorphism is increasingly recognised as a major form of human genome variation, and is particularly prevalent on the Y chromosome. Assay of the Amelogenin Y gene (AMELY) on Yp is widely used in DNA-based sex testing, and sometimes reveals males who have interstitial deletions. In a collection of 45 deletion males from 12 populations, we used a combination of STS (sequence-tagged site) mapping, and binary-marker and Y-STR (short tandem repeat) haplotyping to understand the structural basis of this variation. 41/45 males carry indistinguishable deletions, 3.0-3.8Mb in size. Breakpoint mapping strongly implicates a mechanism of non-allelic homologous recombination between the proximal major array of TSPY-genecontaining repeats, and a single distal copy of TSPY; this is supported by estimation of TSPY copy number in deleted and non-deleted males. The remaining four males carry three distinct non-recurrent deletions (2.5-4.0Mb) which may be due to non-homologous mechanisms. Haplotyping shows that TSPY-mediated deletions have arisen seven times independently in the sample. One instance, represented by 30 chromosomes mostly of Indian origin within haplogroup J2e1*/M241, has a time-to-most-recent-commonancestor of ~7700 ± 1300 years. In addition to AMELY, deletion males all lack the genes PRKY and TBL1Y, and the rarer deletion classes also lack PCDH11Y. The persistence and expansion of deletion lineages, together with direct phenotypic evidence, suggests that absence of these genes has no major deleterious effects.