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Ira
M.
Hall
Degree(s): Ph.D. Graduate School: Watson School of Biological Sciences, Cold Spring Harbor Laboratory Primary Appointment: Assistant Professor of Biochemistry and Molecular Genetics Research Interests: Structural Genome Variation & Evolution; Genomic Instability; Epigenetic Inheritance Email Address: imh4y@virginia.edu |
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Biomedical Sciences Graduate Program(s) Research Description
Broadly speaking, I am interested in the behavior of heritable biological information. I want to understand how chromosomes, including DNA and associated epigenetic marks, change and adapt over relatively short time scales, and how these changes contribute to phenotypic variation and adaptive evolution. My general approach is to bring unbiased, genome-wide experimental and computational tools to bear on simple questions and tractable lineages.
Research in my laboratory is primarily focused on structural variation of mammalian genomes. Over the past several years it has become apparent that the genome is more labile than previously imagined. A substantial fraction of DNA (3-6%) in mammals is contained within large tracts of recently duplicated sequence, (known as segmental duplications) and any two normal human individuals differ in the copy number of >1000 discrete genomic segments (known as copy number variants, or CNVs), and by a smaller number of inversions. Because structural differences are large and often contain entire genes and conserved elements, their contribution to natural variation, evolution, and disease is potentially immense. We are interested in the underlying mutational process through which new structural variants arise. In recent work we utilized high resolution microarrays and pedigreed mice to identify spontaneous CNVs over ~1000 generations of inbreeding. We found that new CNVs arise through a highly nonrandom process: almost half were the product of recurrent mutation, and rates of change varied four orders of magnitude across different loci. We also identified a set of large gene-containing segments that mutate at exceptionally high rates in the germline of healthy individuals. We are currently addressing the following questions: How prevalent, really, is recurrent structural mutation? What is the molecular basis for extreme instability at certain loci? Are recurrent CNV loci functionally relevant? How variable are different cells and lineages from a single individual? A second topic of research in my lab is naturally occurring epigenetic variation. Epigenetic marks such DNA methylation and histone modification play a key role in directing gene expression patterns during development and in silencing selfish genetic elements, but exceedingly little is known about how the genomic distribution of these marks varies between individuals and populations of a species. This question has great importance for models of evolution, as well as for human disease. The distribution, function, and trans-generational stability of these marks is the subject of current and future work. Selected Publications Intranet Profile [To add/update Intranet profile information, read these instructions.]
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