Human Molecular Genetics Advance Access originally published online on December 22, 2006
Human Molecular Genetics 2007 16(3):307-316; doi:10.1093/hmg/ddl465
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Structural variation on the short arm of the human Y chromosome: recurrent multigene deletions encompassing Amelogenin Y
1 Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK, 2 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK, 3 Malaysian Forensic DNA Laboratory, Department of Chemistry, Jalan Sultan, Selangor, Malaysia, 4 MGC-Department of Human and Clinical Genetics, Leiden University Medical Centre, The Netherlands, 5 Institut für Blutgruppenforschung LGC GmbH, Köln, Germany, 6 Cattedra di Genetica Medica, Policlinico, Piazza Giulio Cesare, Bari, Italy, 7 Orchid Cellmark Ltd, Blacklands Way, Abingdon, UK, 8 Victoria Police Forensic Services Department, Melbourne, Victoria, Australia and 9 Department of Genetics and Human Variation, School of Molecular Sciences, La Trobe University, Melbourne, Australia
* To whom correspondence should be addressed. Tel: +44 1162523427; Fax: +44 1162523378; Email: maj4{at}le.ac.uk
Received October 20, 2006; Accepted December 8, 2006
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 
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.
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