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

Abstract

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-gene-containing 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 TSPYmediated 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-mostrecent-common-ancestor 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.

Great ape Y Chromosome and mitochondrial DNA phylogenies reflect subspecies structure and patterns of mating and dispersal

“…S5). Loss of these genes has also been documented in some human lineages (Jobling et al 2007) and includes a recurrent event sponsored by nonallelic homologous recombination between TSPY repeats. The same mechanism cannot apply in chimpanzees, since the TSPY loci lie on the opposite arm of the Y Chromosome.…”

Recurrence, submicroscopic complexity, and potential clinical relevance of copy gains detected by array CGH that are shown to be unbalanced insertions by FISH

“…First, this rearrangement may have arisen in a common ancestor shared by the families involved in this study and been subsequently transmitted through many generations. In this scenario, this insertion could represent an uncharacterized Y-chromosome variant that arose in recent human history (Hammer 1994;Jobling and Tyler-Smith 1995;Jobling et al 2007;Karafet et al 2008). Alternatively, because there is no known relationship between the family of proband 30 and those of probands 29 and 31, the observed recurrent rearrangements may represent two independent events, potentially mediated by genomic architecture present in the regions involved in the insertion.…”

Copy Number Variation of Testis-Specific Protein, Y-Encoded <i>(TSPY)</i> in 14 Different Breeds of Cattle <i>(Bos taurus)</i>

“…The length of the Y chromosome can differ significantly within a species [Jobling et al, 2007;Stranzinger et al, 2007]. Vast structural polymorphisms have been detected in both the heterochromatin and euchromatin of the Y chromosome.…”