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Human Molecular Genetics Advance Access published online on November 25, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi424
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© The Author 2005. Published by Oxford University Press. All rights reserved
Received September 14, 2005
Accepted November 10, 2005

Article

Telomere instability in the male germline

Duncan M. Baird 1 *, Bethan Britt-Compton 1, Jan Rowson 1, Nazar N. Amso 2, Linda Gregory 3, and David Kipling 1

1 Department of Pathology, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
2 Obstetrics and Gynaecology, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
3 Cardiff Assisted Reproduction Unit, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW, UK

* To whom correspondence should be addressed.
Duncan M. Baird, E-mail: bairddm{at}cardiff.ac.uk


  Abstract

Telomeres play a key role in upholding the integrity of the genome, and telomerase expression in spermatogonial stem cells is responsible for the maintenance of telomere length in the human male germline. We have previously described extensive allelic variation in somatic cell telomere length that is set in the zygote, the ultimate source of which may be the germline. This implies that despite telomerase activity substantial telomere length variation can be generated and tolerated in the germline; in order to investigate this further we have examined the nature of telomere length variation in the human male germline. Here we describe an analysis of both genome-wide telomere length and single molecule analysis of specific chromosome ends in human sperm. We observed individual specific differences in genome-wide telomere length. This variation may result from genetic differences within the components that determine the telomere length setting of each individual. Superimposed on the genome wide telomere length setting was a stochastic component of variation that generates germ-cells containing severely truncated telomeres. If not re-lengthened during early embryogenesis such telomeres may limit the replicative capacity of cells derived from the zygote and have the potential to create fusagenic chromosomes, unbalanced translocations and terminal micro-deletions. These data may have implications for the genetic determination of ageing, genetic disease and fertility.


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