BBSRC Ph.d. Studentship.
Supervisor. Prof.Chris Cannings.

***********Recombination in the MHC Region ***********************************

Suitable for a MATHS/STATS graduate with an interest in stochastic modelling
and applications.

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Joint project with Dr.Gerry Wilson, Division of Genetic and Molecular
Medicine, Umiversity of Sheffield.



As outlined below there will be data collected to inform
the modelling (this has just started). The project concerns 
genetic recombination, the process by which genetic material, which is
arranged linearly along the chromosomes, is shuffled. Essentially a point
process occurs along the pair of chromosomes e.g. ----*------*--- which results 
in the pair of chromosomes 1111111111111
                           2222222222222

producing either chromosome

       1111222222111  or  2222111111222
       
for transmission to offspring. It is this point process which we wish
to model (or approximate), and to investigate how it is affected by
detail at the moloecular level.                                     

Some more Biological details.
------------------------------
Recombination does not occur randomly throughout the human geneome;
rather there are regions with elevated rates, so called hot-spot, and regions 
with little or no recombination. DNA-motifs (short specific sequences)
are thought to be important in regulating DNA-crossover in bacteria, yeast 
and higher organisms. In humans hotspots in the MHC (major histocompatibilty
complex) have been reported but these are, as yet, poorly characterised.

Our project aims firstly to study recombination in a 4Mb region within the MHC
which contains a number of genes of importance in autoimmune rheumatic disease.
We shall obtain information on the recombination in this region using samples
of sperm from a number of sperm donors. Having isolated DNA which shows 
recombination over the 4Mb region we shall then narrow down the regions
where it has occurred sequentially until we have regions of length of the order
of 500kb within which the recombinations are known to occur. These will be
sequenced to provide the fine-grained information. We anticipate that a sample
of 1000 sperm from each of 20 men will provide us with some 500 recombinants,
which should allow us to investigate both the central question of DNA-motifs
affecting recombination but also give us the opportunity to examine
existing models of recombination, and to develop new models.

IF YOU ARE INTERESTED PLEASE CONTACT ME (PREFERABLY BY EMAIL) AT THE ADDRESS
BELOW.

              Chris Cannings.


Prof.Chris Cannings,
Division of Molecular and Genetic Medicine,
University of Sheffield,
M Floor,
Royal Hallamshire Hospital,
Sheffield S10 2JF.
Tel. (Office)                   44 O114 271 2252
Sec. (Sec. Beverley Jepson)     44 0114 278 2830
Fax                             44 0114 278 0125
Email                           [log in to unmask] 
WWW
http://www.shef.ac.uk/~mgm/staff/cannings/



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