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PROFESSOR HOWARD COOKE, FRSE FMedSci

Chromosomes and Gene Expression: Associate

 


Howard Cooke

Contact Details

E-mail address: howard.cooke@hgu.mrc.ac.uk
Telephone: +44 (0)131 332 2471
Fax: +44 (0)131 467 8456
Address: Medical Research Council
Human Genetics Unit
Western General Hospital
Crewe Road
Edinburgh EH4 2XU
Research Programme: Genes Involved in the Germ Line

 

 

Research Areas

About 12% of couples are infertile according to the WHO definition. Both partners contribute approximately equally to this. In over half the cases of male infertility the underlying cause is difficult to determine. There are reasons for thinking that genetic causes are at work in over half of these cases but many genes are needed for the production of sperm. The Y chromosome (only present in males) is a favoured place to look for such genes and we are working on a relative of one of these.
To spread the net wider we have used micro-array analysis in mice and identified two new genes required for fertility. The proteins these genes encode are key components of the meiotic machinery in mammals, without them chromosomes do not pair properly and germ cells die through apoptosis and the animals are sterile. We are working to understand the mechanisms underlying this and its relevance to human fertility.

Recent Publications

  • Bolcun-Filas, E.; Speed, R.; Taggart, M.; Grey, C.;de Massy, B.; Benavente, R. and Cooke, H.J. Mutation of the Mouse Syce1 Gene Disrupts Synapsis and Suggests a Link Between Synaptonemal Complex Structural Components and DNA Repair. PLoS Genetics 5(2):e1000393, 2009
    PubMed Abstract
  • Wojtasz, L.; Daniel, K.; Roig, I.; Bolcun-Filas, E.; Xu, H.; Boonsanay, V.; Eckmann, C.R.; Cooke, H.J.; Jasin, M.; Keeney, S.; McKay, M.J. and Toth, A. Mouse HORMAD1 and HORMAD2, Two Conserved Meiotic Chromosomal Proteins, Are Depleted from Synapsed Chromosome Axes with the Help of TRIP13 AAA-ATPase. PLoS Genet. 5(10):e1000702, 2009 PubMed Abstract
  • Hamer, G.; Wang, H.; Bolcun-Filas, E.; Cooke, H.J.; Benavente, R. and Hoog, C. Progression of meiotic recombination requires structural maturation of the central element of the synaptonemal complex. J Cell Sci 121:2445-2451, 2008 PubMed Abstract
  • Ollinger, R.; Childs, A.J.; Burgess, H.M.; Speed, R.M.; Lundegaard, P.R.; Reynolds, N.; Gray, N.K.; Cooke, H.J. and Adams, I.R. Deletion of the pluripotency-associated Tex19.1 gene causes activation of endogenous retroviruses and defective spermatogenesis in mice.
    PLoS Genet     4(9):e1000199, 2008 PubMed Abstract
  • Bolcun-Filas, E.; Costa, Y.; Speed, R.; Taggart, M.; Benavente, R.; de Rooij, D.G. and Cooke, H.J. SYCE2 is required for synaptonemal complex assembly, double strand break repair, and homologous recombination. J Cell Biol 176(6):741-747, 2007 PubMed Abstract
  • Costa, Y. and Cooke, H.J. Dissecting the mammalian synaptonemal complex using targeted mutations. Chromosome Res 15(5):579-589, 2007 PubMed Abstract
  • Reynolds, N.; Collier, B.; Bingham, V.; Gray, N.K. and Cooke, H.J. Translation of the synaptonemal complex component Sycp3 is enhanced in vivo by the germ cell specific regulator Dazl.
    RNA     13(7):974-981, 2007 PubMed Abstract