X-inactivation
Hunt Willard (IGSP), Zhong Wang (IGSP), Sayan Mukherjee (IGSP)
A significant portion of genes on the inactivated human X chromosome
has been found to be transcriptionally active. We have investigated
the role of DNA sequence in this process. Using sequence feature, we
have created accurate classifiers that can distinguish genes that
escape inactivation from those that are subject to inactivation.
Related Publications:
- Wang Z, Willard HF, Mukherjee S, Furey TS (2006) Evidence of Influence of Genomic DNA Sequence on Human X Chromosome Inactivation. PLoS Comput Biol 2(9): e113.
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accompanying web site
DNA Hypermethylation in Cancer
Susan Murphy (IGSP)
In normal cells, DNA methylation contributes to gene regulation by
epigenetically silencing expression of certain genes. In cancer
cells, regions of the genome become aberrantly hypermethylated causing
the silencing of key genes that may contribute to the cancer phenotype. We are
investigating the relationship between DNA in regions around the
transcription start site of genes and their propensity of becoming
hypermethylated in cancer cells. Using these features, we are predicting
novel genes that are prone to hypermethylation. Predictions are being tested in
the Murphy lab in primary ovarian cancers.
Early Replicating DNA
David Kaufman (UNC-Chapl Hill),
Stephanie Cohen (UNC-Chapel Hill),
Norman Doggett (LANL)
We have identified regions of the genome that replicate early in S
phase in normal human fibroblasts. These regions have been found to
have distinct genomic profiles when compared to other later
replicating regions. Currently, we are developing a classifier to
predict early replicating regions. We also aim to explore whether the
replication timing of these regions has been evolutionarily conserved.
DNA Sequence and Association Studies
Beth Hauser (Center for Human Genetics, Duke University)
Association studies involve genotyping populations using a number of
polymorphic markers, usually single nucleotide polymorphisms (SNPs).
Correlations between certain polymorphisms a disease phenotype are
then used to identify regions of the genome that may be involved in
that disease. Generally, these regions of interest are large (>1Mb).
We are investigating the use of genome sequence features in the
analysis of association study data in order to help better identify
candidate genes or regulatory regions within these large regions of
association.
Evolutionarily Conserved dsRNA Structures in mRNAs
Increasingly, the importance of mRNA secondary structure in
post-transcriptional processing reactions, such as splicing and
editing, is being revealed. These secondary structures often are
evolutionarily conserved and involve the interaction of RNA bases long
distances from each other, even up to 10Kb. Current RNA folding
programs such as mfold and RNAfold cannot accurately
predict structures of large molecules. We are developing a method of
finding conserved double-stranded RNA (dsRNA) structures in the human
transcriptome.
