Steven Munger, Ph.D., uses a systems genetics approach and advanced computational methods to study development and complex disease in advanced mouse populations.
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Steven Munger, Ph.D., uses a systems genetics approach and advanced computational methods to study development and complex disease in advanced mouse populations.
The genetic origins of most developmental disorders and diseases are complex and remain poorly understood. Rather than a single deleterious mutation, genetic susceptibility to common diseases is conferred by many variants that individually assert subtle effects but in certain combinations perturb cellular networks sufficiently to bias them to a disordered/diseased state. Classic single-gene experimental approaches fail to elucidate these interactions, but new integrative genomic and genetic approaches from the emerging field of “Systems Genetics” hold considerable promise.
The Munger lab combines experimental and computational methods with advanced mouse mapping populations to solve these complex genetic puzzles.
We examine the natural genetic variation driving individual differences in 1) susceptibility to sex reversal during primary sex determination of the gonad, 2) disease severity in a mouse model of Cornelia de Lange Syndrome, and 3) transcript and protein expression in the adult liver. We apply our genetic and genomics toolkit to predict causal variants and genetic interactions underlying phenotypic variability, validate these predictions at the bench with functional genomics methods, and ultimately seek to extend these results to inform patient diagnosis and treatment.