Analysis of Multiple Polymorphisms in Candidate Genes

Cancer Research UK PhD Studentship October 2003 (re-advertisement)

Vacancy Reference: 4767

Cancer Research UK Genetic Epidemiology Division, St James's
University Hospital, Leeds

Maintenance Grant: £11,571 per annum

As a result of the Human Genome Project and the advent of rapid
high-throughout genotyping, dense maps of the human genome are
becoming available consisting of single nucleotide polymorphisms
(SNPs). For many complex diseases, association and linkage studies
have identified genes that are likely to be involved in disease
aetiology, but in most cases the exact functional polymorphism(s) and
the nature of the association are unknown. Multiple SNPs and other
polymorphisms exist in these genes or chromosomal regions, and these
polymorphisms generally display a complex pattern of linkage
disequilibrium.

This project will address several related statistical problems that
arise at this stage in the investigation of the genetic determinants
of complex diseases:

Having identified a candidate gene or region containing multiple
polymorphisms, and having carried out SNP discovery analyses, is it
necessary to genotype all SNPs in a subsequent association study? If
not, how should the optimal subset of SNPs be chosen?

Having identified and genotyped a set of SNPs in the gene or region,
how should these be used to test for association with disease or with
a quantitative trait?

The research will include a variety of approaches: consideration of
the problem from a theoretical viewpoint, simulation of appropriate
scenarios to evaluate different strategies, and application to real
data. The Genetic Epidemiology Division holds SNP data in candidate
genes for melanoma (and nevus density), and a trait related to
cardiovascular disease, and other applications are likely to be
generated during the course of the project.

This project would be suitable for a mathematics or statistics
graduate, or a numerate person with a degree in a related subject.

Supervisors: Jenny Barrett and Tim Bishop

Please contact Jenny Barrett (+44 113 206 6522 or 4573,
[log in to unmask] ) if you wish to discuss this informally.

To apply, please send a copy of your CV with a covering letter to:
Dr Jenny Barrett, Cancer Research UK Genetic Epidemiology Division,
Cancer Genetics Building,
St James's University Hospital, Beckett