Open AccessStructural variation on the short arm of the human Y chromosome: recurrent multigene deletions encompassing Amelogenin Y
Author(s) -
Mark A. Jobling,
Iek Chi C. Lo,
Daniel J. Turner,
Georgina R. Bowden,
Andrew C. Lee,
Yali Xue,
Denise Carvalho-Silva,
Matthew E. Hurles,
Susan M. Adams,
Yuet Meng Chang,
Thirsa Kraaijenbrink,
Jürgen Henke,
Ginevra Guanti,
Brian McKeown,
Roland A.H. van Oorschot,
Robert J. Mitchell,
Peter de Knijff,
Chris TylerSmith,
Emma J. Parkin
Publication year - 2006
Publication title -
human molecular genetics online/human molecular genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.811
H-Index - 276
eISSN - 1460-2083
pISSN - 0964-6906
DOI - 10.1093/hmg/ddl465
Subject(s) - biology , genetics , haplotype , breakpoint , haplogroup , y chromosome , gene , homologous chromosome , deletion mapping , copy number variation , structural variation , allele , chromosome , genome , amelogenin , x chromosome , human genome
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.