Download The Twelfth Annual Janet L. Norwood Award Dr. Kathryn Roeder

The Twelfth Annual
Janet L. Norwood Award
For Outstanding Achievement by a Woman
in the Statistical Sciences
Dr. Kathryn Roeder
Wednesday, September 11, 2013
9:30 AM
The Edge of Chaos Atrium
Lister Hill Library, 4th floor
1700 University Boulevard
Birmingham AL
http://theedgeofchaos.org/
Seminar Title:
Statistics and Genetics Open a Window into Autism
Seminar Abstract:
Rare variants identified from DNA sequence, especially de novo loss of function (LoF)
mutations, have identified genes involved in risk for autism spectrum disorders (ASD). Multiple de
novo LoF mutations in the same gene demonstrate that gene affects risk. De novo mutations occur
twofold more often in ASD probands than their siblings, implying that half of the genes hit are risk
genes. He et al. (2013) extract more information by using a statistical model, called TADA for
Transmission And De novo Association, that integrates data from family and case-control studies to
infer the likelihood a gene affects risk. Still, given limited sequence data, can we garner yet more
information? Progress has been made as part of a collaborative effort to develop systems biological
approaches to understanding ASD pathophysiology. Using ASD risk genes as foci, we hypothesize that
genes expressed at the same developmental period and brain region, and with highly correlated coexpression, are functionally interrelated and more likely to affect risk. To find these genes we model
two kinds of data: gene co-expression in specific brain regions and periods of development; and the
TADA results from published sequencing studies. We model the ensemble data as a Hidden Markov
Random Field, in which the graph structure is determined by gene co-expression and the model
combines these interrelationships with node-specific observations: gene identity; expression; genetic
data; and whether it affects risk, which will be estimated. This analysis identifies ≈100 genes that
plausibly affect risk, many novel and others implicated despite relatively weak genetic evidence. We
will describe how these results can be used to expand our understanding of the genetics of ASD (e.g.,
nominating genes for targeted sequencing in new samples) and ASD neurobiology.
http://www.soph.uab.edu/ssg/norwoodaward/twelfthaward
The University of Alabama at Birmingham
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