Karen Mohlke, PhD

Associate Professor

Research Interests

Key words: human genetics and genomics, diabetes, obesity, lipids, complex diseases

Common traits with complex inheritance patterns have both genetic and environmental causes. Type 2 diabetes and obesity are examples of complex metabolic disorders with a strong genetic component. Genetic association studies provide a promising approach to identify genes and nucleotide variants that alter disease susceptibility. Gene identification will likely result in better understanding of disease etiology, and has the potential to help identify at-risk individuals, to suggest new drug targets and therapies, and to assist in preventing disease.

Type 2 diabetes, obesity, lipids

The Mohlke lab uses genome-wide approaches to localize diabetes-susceptibility genes as part of the Finland United States Investigation of NIDDM Genetics (FUSION) study. This study includes more than 6000 Finnish individuals affected with type 2 diabetes or with normal glucose tolerance. To identify the underlying disease alleles, single nucleotide polymorphisms (SNPs) are tested for evidence of association with type 2 diabetes and related quantitative traits. SNPs being studied span the human genome, and special emphasis is given to SNPs located near a set of high priority genes. Common nonredundant SNPs are identified from genome databases and rare SNPs are identified by resequencing.

Weight gain

To investigate the role of genetics in weight gain and other traits associated with cardiovascular risk, the lab is partnering with investigators from the Cebu Longitudinal Health and Nutrition Survey (CLHNS). This study includes ~3700 individuals in the Philippines for whom 20 years of anthropometric, lifestyle, and environmental data exist. Traits include longitudinal weight gain and related obesity measures as well as the early origins of adult chronic diseases. In addition to examining the primary effects of genes, the lab is exploring the interaction of genes with environmental risk factors in disease pathogenesis.

Pathogenic mechanisms

A long-term goal of the Mohlke lab is to understand the biological function of susceptibility alleles identified through genome-wide studies. Hypothesizing that many common disease variants will have a regulatory effect on gene function, the lab is evaluating allelic expression differences in human and mouse tissue samples. Ultimately, the lab will create mouse models to compare high-and low-risk alleles in a whole-animal setting. Mice harboring the risk allele or haplotype will be used to examine interactions with diet, other environmental factors, and additional genes that may be relevant to diabetes, obesity and lipoprotein levels.

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