title: Structural variation on the short arm of the human Y chromosome: recurrent multigene deletions encompassing Amelogenin Y.
abstract: Structural polymorphism is increasingly recognized 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 sequence-tagged site mapping, and binary-marker and Y-short tandem repeat haplotyping to understand the structural basis of this variation. Of the 45 deletion males, 41 carry indistinguishable deletions, 3.0-3.8 Mb 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 the estimation of TSPY copy number in deleted and non-deleted males. The remaining four males carry three distinct non-recurrent deletions (2.5-4.0 Mb), 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-common-ancestor of approximately 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.
authors.affiliation: Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK. maj4@le.ac.uk
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jobling
authors.forename: Iek Chi C
authors.initials: IC
authors.lastname: Lo
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Turner
authors.forename: Georgina R
authors.initials: GR
authors.lastname: Bowden
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Lee
authors.forename: Yali
authors.initials: Y
authors.lastname: Xue
authors.forename: Denise
authors.initials: D
authors.lastname: Carvalho-Silva
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Hurles
authors.forename: Susan M
authors.initials: SM
authors.lastname: Adams
authors.forename: Yuet Meng
authors.initials: YM
authors.lastname: Chang
authors.forename: Thirsa
authors.initials: T
authors.lastname: Kraaijenbrink
authors.forename: Jürgen
authors.initials: J
authors.lastname: Henke
authors.forename: Ginevra
authors.initials: G
authors.lastname: Guanti
authors.forename: Brian
authors.initials: B
authors.lastname: McKeown
authors.forename: Roland A H
authors.initials: RA
authors.lastname: van Oorschot
authors.forename: R John
authors.initials: RJ
authors.lastname: Mitchell
authors.forename: Peter
authors.initials: P
authors.lastname: de Knijff
authors.forename: Chris
authors.initials: C
authors.lastname: Tyler-Smith
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Parkin
mesh_terms: D053523:Amelogenin / Q000235:genetics*; D015820:Cadherins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D041322:Chromosomes, Human, Y / Q000737:chemistry*; D018628:Gene Dosage; D006239:Haplotypes; D006801:Humans; D008297:Male; D010802:Phylogeny; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000091363:Protocadherins; D015293:Transducin / Q000235:genetics
chemical_list: C507202:AMELY protein, human; D053523:Amelogenin; D015820:Cadherins; D018797:Cell Cycle Proteins; C468654:PCDH11Y protein, human; D000091363:Protocadherins; C485612:TBL1Y protein, human; C497749:TSPY1 protein, human; C109449:PRKY protein, human; D017346:Protein Serine-Threonine Kinases; D015293:Transducin