Diane
P.
Genereux
Epigenetic
Biology: mathematical and molecular approaches
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RESEARCH
My goal is to understand the molecular origins of epigenetic stability and change, and their implications for population genetics and genome evolution.
My current focus is on epigenetic regulation as mediated by DNA methylation. In particular, I am asking:
How precisely is epigenetic information transmitted across generations of somatic cells?
The epigenetic information encoded by DNA methylation is transmitted
with good --- but imperfect --- fidelity. We have developed
mathematical models (Genereux et al. 2005, Fu et al. 2010) to quantify the fidelity with which
this information is transmitted, and molecular techniques (Genereux et al. 2008) to
collect the highly reliable epigenetic data necessary to measure these
fidelities. In our most recent work (Fu et al., in press), we investigate the molecular properties of the methyltransferase enzymes that are responsible for transmitting epigenetic information from parent to daughter strands of DNA.
How
does epigenetic
information emerge during organismal development?
In mammals, the epigenetic information encoded by DNA methylation is
erased --- and then reestablished --- at every generation. In collaboration with Jamie Goodson and Minseung Choi, I am using vertebrate and plant models to investigate these dynamics.
How is
epigenetic
information altered in
disease and aging?
Abnormal loss, and abnormal gain, of DNA methylation can lead to
disease phenotypes in human. We have developed molecular and
mathematical approaches to investigate the epigenetic states that lead
to the cognitive impairment characteristic of fragile X syndrome
(Stöger et al. 2011). I have developed theoretical approaches (Genereux 2009) to
investigate the impact of cellular-population structure on epigenetic
changes in cancer and aging. In my current work, I am applying our statistical models to ask how the transmission of epigenetic information over rounds of cell division is perturbed in individuals with fragile X syndrome.
How
did epigenetic
regulation evolve, and how has it shaped population genetics and genome evolution?
There are many opportunities for genetic and epigenetic information to
interact. DNA methylation is mutagenic when transmitted through the
germ line, and a gene that is epigenetically silenced in a
given
individual becomes transiently invisible to natural
selection. In my current work (Genereux and Laird, in final preparation), I am using mathematical approaches to investigate the historical, molecular, and cultural factors that have shaped and will shape the contemporary and future epidemiology of fragile X syndrome, a genetic/epigenetic disease. A
long-term goal is to understand the role of evolution processes in tuning the ability of individual loci to undergo epigenetic change in response to environmental signals.
Biology Publications
Audrey Q. Fu, Diane P. Genereux, Reinhard Stöger,
Charles
D. Laird, and Matthew Stephens in press. Statistical Inference of In Vivo Properties of Human DNA
Methyltransferases from Double-Stranded Methylation Patterns. PLoS One.
Reinhard Stöger, Diane P. Genereux, Randi J. Hagerman, Paul J. Hagerman, Flora Tassone, Charles D. Laird. 2011. Testing the FMR1 promoter for mosaicism in DNA methylation among CpG sites, strands, and cells in FMR1-expressing males with fragile X syndrome. PLoS One 6(8):
e23648. .pdf
Audrey Q. Fu, Diane P. Genereux, Reinhard Stöger,
Charles
D. Laird, and Matthew Stephens, 2010. Statistical inference of
transmission fidelity of DNA methylation patterns over somatic cell
divisions in mammals. Annals of
Applied Statistics 4:
871-892. .pdf
Diane P. Genereux, 2009.
Asymmetric Strand Segregation: Epigenetic
Costs of Genetic Fidelity? PLoS
Genetics 5(6): e1000509.
.pdf
Diane P. Genereux, Winslow C.
Johnson, Alice F. Burden, Reinhard
Stöger, Charles D. Laird, 2008. Errors in the
Bisulfite
Conversion of DNA: Modulating
Inappropriate- and Failed-Conversion Frequencies. Nucleic Acids
Research 36:e150..pdf
Diane P. Genereux, Brooks E.
Miner, Carl T. Bergstrom, Charles D.
Laird, 2005. A population-epigenetic model to infer site-specific
methylation rates from double-stranded DNA methylation patterns. Proceedings
of the
National Academy of the Sciences. 102: 5802. .pdf
Diane P. Genereux and John M.
Logsdon, Jr. 2003. Much Ado about
Bacteria-to-Vertebrate Lateral Gene Transfer. Trends
in
Genetics. 19: 191-195..pdf
Teaching Publications
Diane P. Genereux and Carl T. Bergstrom, 2005. Evolution in Action:
Understanding Antibiotic Resistance in Evolutionary
Science and Society: Educating a New Generation,
Joel Cracraft and Rodger W. Bybee, eds., published by National Association of
Biology Teachers. .pdf
Diane Genereux and Brianna Huntsberger. 1999. Service matters: the engaged campus. Campus Compact, Providence, Rhode Island. Barbara Caron, ed.
Contact
Information
Diane Genereux
Department of
Biology
University of Washington
Box 351800
Seattle, WA 98195-1800
Phone: (206) 616-9385
Fax: (206) 543-3041
genereux@u.washington.edu
Last modified 18 February 2012.