Institute of Mathematics and Statistics,
University of Kent at Canterbury,
JOINT KENT AND SUSSEX SEMINAR
Wednesday, 15th December 1999
3:00pm Professor David Balding (University of Reading)
TITLE: Detecting gene regulatory sequences.
ABSTRACT: Now that much of the human and other genomes have been
sequenced, attention is focussing on how the information contained in
DNA sequences is converted into functioning proteins. Only
about 1% of the human genome consists of coding sequences ("genes" in
the traditional sense). Some of the remaining 99% is involved in
regulating how much, if any, of the protein which a
gene codes for is actually produced. Regulatory sequences can be
classified into two types: promoters and enhancers. The latter are
harder to detect as they can be remote from the gene that
they regulate, are relatively short (a few hundred base pairs), and
have no universal identifying characteristics. We implement a
statistical model to facilitate detection of regulatory regions
in long DNA sequences by looking for local excesses of short motifs
which may correspond to protein binding sites. The algorithm has some
flexibility to adjust the weights for different motifs in different
sequences.
4:30pm Professor David Clayton (University of Cambridge, MRC
Biostatistics Unit)
TITLE: Linkage disequilibrium mapping of disease susceptibility
genes inhuman populations.
ABSTRACT: The paper reviews recent work on statistical methods for
using linkage disequilibrium to locate disease susceptibility genes,
given a set of marker genes at known positions in the genome.
The paper starts by considering a simple deterministic model for
linkage disequilibrium and discusses recent attempts to elaborate it
to include the effects of stochastic influences, or ``drift'',
by the use of either Wright--Fisher models or by approaches based on
the coalescence of the genealogy of the sample of disease chromosomes.
Most of this first part of the paper concerns
a series of biallelic markers and, in this case, the models so far
proposed are hierarchical probability models for multivariate binary
data. Likelihoods are intractable and most approaches to
linkage disequilibrium mapping amount to marginal models for pairwise
associations between individual markers and the disease susceptibility
locus. Approaches to evaluation of a full
likelihood require Monte Carlo methods in order to integrate over the
large number of unknowns. The fact that the initial state of the
stochastic process which has led to present-day allele
frequencies is unknown is noted and its implications for the
hierarchical probability model is discussed. Difficulties and
opportunities arising as a result of more polymorphic markers and
extended marker haplotypes are indicated. Connections between the
hierarchical modelling approach and methods based upon identity by
descent and haplotype sharing by seemingly
unrelated cases are explored. Finally problems resulting from unknown
modes of inheritance, incomplete penetrance, and ``phenocopies'' are
briefly reviewed.
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Further details of the IMS seminar programme and abstracts of
forthcoming talks are available from:
http://www.ukc.ac.uk/IMS/statistics/people/T.Sapatinas/Seminars/
seminars.html
All are very welcome. The Seminars will be held in
Mathematics Lecture Theatre in the Institute of Mathematics and
Statistics, Cornwallis Building.
The following WWW page contain details of how to get to the campus,
and how to find your way around:
http://www.ukc.ac.uk/ukc/location.html
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Dr Theofanis Sapatinas,
Lecturer in Statistics,
Postal Address: Institute of Mathematics and Statistics,
University of Kent at Canterbury,
Canterbury, Kent CT2 7NF,
United Kingdom.
Tel: ++(44)-1227-827253
Fax: ++(44)-1227-827932
Email: [log in to unmask]
URL: http://www.ukc.ac.uk/IMS/statistics/people/T.Sapatinas/
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