Structural variation on the short arm of the human Y chromosome: recurrent multigene deletions encompassing Amelogenin Y.
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.
Jobling
Mark A
MA
Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK. maj4@le.ac.uk
Lo
Iek Chi C
IC
Turner
Daniel J
DJ
Bowden
Georgina R
GR
Lee
Andrew C
AC
Xue
Yali
Y
Carvalho-Silva
Denise
D
Hurles
Matthew E
ME
Adams
Susan M
SM
Chang
Yuet Meng
YM
Kraaijenbrink
Thirsa
T
Henke
Jürgen
J
Guanti
Ginevra
G
McKeown
Brian
B
van Oorschot
Roland A H
RA
Mitchell
R John
RJ
de Knijff
Peter
P
Tyler-Smith
Chris
C
Parkin
Emma J
EJ
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
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