Campus Event Calendar
Event Entry
What and Who
Systematic Investigation of Genetic Variability in the Human Genome –- Implications for Disease Susceptibility.
Dr. Jan Freudenberg
Institute of Human Genetics of the University of Bonn
Talk
AG 1, AG 2, AG 3, AG 4, AG 5
MPI Audience
Note: We use this to send email in the morning.
Date, Time and Location
Wednesday, 7 July 2004
16:15
-- Not specified --
46.1 - MPII
023
Saarbrücken
Abstract
Medically important traits, such as susceptibility to disease and
response to therapy, are influenced by inheritance and vary in the
population. For identification of sequence variants underlying
inherited phenotype variation, SNP-based linkage disequilibrium (LD)
mapping is a widely applied strategy. Bioinformatic challenges in
LD-mapping studies include the prediction of disease relevant genes
and variants based on knowledge gathered in genome databases.
In order to fulfill these tasks, we have implemented efficient
strategies to access knowledge from various genome databases.
Furthermore, bioinformatic support is required for individual
resequencing experiments, which are necessary to gain a
comprehensive overview of sequence variation in selected
genomic regions. We resequenced coding regions of a large
set of human genes, using a sample representative for the
European population. The minor allele frequency (MAF), an
indicator of weak purifying selection, was lowest in radical
amino acid alterations. In non-coding sequences, a decreased
MAF was displayed by variants, which are located in CpG islands
or located in genomic regions conserved between human and rodents.
Since only a small fraction of low-frequency variants is found
in public SNP databases, these potentially functional variants
obtain distinctively lower database coverage. However,
particularly those variants appear to be under weak purifying
selection and thus seem to play a role in the etiology of
inherited diseases. Therefore, it is necessary to develop
new research strategies, which are founded in a more general
understanding of inherited disease.
response to therapy, are influenced by inheritance and vary in the
population. For identification of sequence variants underlying
inherited phenotype variation, SNP-based linkage disequilibrium (LD)
mapping is a widely applied strategy. Bioinformatic challenges in
LD-mapping studies include the prediction of disease relevant genes
and variants based on knowledge gathered in genome databases.
In order to fulfill these tasks, we have implemented efficient
strategies to access knowledge from various genome databases.
Furthermore, bioinformatic support is required for individual
resequencing experiments, which are necessary to gain a
comprehensive overview of sequence variation in selected
genomic regions. We resequenced coding regions of a large
set of human genes, using a sample representative for the
European population. The minor allele frequency (MAF), an
indicator of weak purifying selection, was lowest in radical
amino acid alterations. In non-coding sequences, a decreased
MAF was displayed by variants, which are located in CpG islands
or located in genomic regions conserved between human and rodents.
Since only a small fraction of low-frequency variants is found
in public SNP databases, these potentially functional variants
obtain distinctively lower database coverage. However,
particularly those variants appear to be under weak purifying
selection and thus seem to play a role in the etiology of
inherited diseases. Therefore, it is necessary to develop
new research strategies, which are founded in a more general
understanding of inherited disease.
Contact
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Ruth Schneppen-Christmann, 06/29/2004 13:04 -- Created document.