FACULTY LIST
Anne E. Kwitek, Ph.D.
Associate Professor
Phone: (414) 456-4346
Email: akwitek@mcw.edu Lab website: http://hmgc.mcw.edu/laboratories/kwitek/kwiteklabpage.asp
B.S. Biology, University of Wisconsin-Stevens Point
Ph.D. Genetics, University of Iowa
My laboratory focuses on identifying the genetic components of common multifactorial diseases - hypertension, diabetes and obesity in particular - using both rat models and human populations. We use genetic linkage strategies to genetically map genes, positionally clone genes, and/or test candidate genes within a specific region of the genome. We then use comparative genomics and comparative mapping to translate the data from the rat to human and back again via comparative genomics. Thus far we have positionally cloned a gene contributing to Type 1 Diabetes in the Biobreeding (BB) rat, identifying a mutation in a member of a novel gene family, Gimap5 , which causes T-cell lymphopenia and early progression to diabetes. We have also mapped loci that confer delayed onset of diabetes and are currently developing consomic and congenic rat strains to identify these protective factors.
We have also identified a gene contributing to obesity in human. The GHSR gene, which encodes the endogenous receptor for ghrelin (the major appetite stimulating hormone), was found within a QTL region for obesity and insulin resistance in a families of members of the TOPS organization. We have identified sequence variants (SNPs) and a corresponding haplotype within GHSR that is associated with obesity and BMI. Studies of the general population have confirmed both a susceptible and a resistant haplotype of GHSR associated with obesity and BMI.
We have developed algorithms and bioinformatics tools to generate comparative maps between rat, human and mouse and to better annotate QTL, disease, and phenotypes onto those maps to find potentially common mechanisms leading to disease across species. The tools are publicly available at the Rat Genome Database and the Human Phenome Database.
Recent Publications:
Baessler A, Hasinoff MJ, Fischer M, Reinhard W, Sonnenberg GE, Olivier M, Erdmann J, Schunkert H, Doering A, Jacob HJ, Comuzzie AG, Kissebah AH, Kwitek AE. Genetic linkage and association of the growth hormone secretagogue receptor (ghrelin receptor) gene in human obesity. Diabetes. 2005 Jan;54(1):259-67.
Bilusic M, Bataillard A, Tschannen MR, Gao L, Barreto NE, Vincent M, Wang T, Jacob HJ, Sassard J, Kwitek AE. Mapping the genetic determinants of hypertension, metabolic diseases, and related phenotypes in the lyon hypertensive rat. Hypertension. 2004 Nov;44(5):695-701.
Michalkiewicz M, Michalkiewicz T, Ettinger RA, Rutledge EA, Fuller JM, Moralejo DH, Van Yserloo B, MacMurray AJ, Kwitek AE, Jacob HJ, Lander ES, Lernmark A. Transgenic rescue demonstrates involvement of the Ian5 gene in T cell development in the rat. Physiol Genomics. 2004 Oct 4;19(2):228-32.
Kwitek AE, Gullings-Handley J, Yu J, Carlos DC, Orlebeke K, Nie J, Eckert J, Lemke A, Andrae JW, Bromberg S, Pasko D, Chen D, Scheetz TE, Casavant TL, Soares MB, Sheffield VC, Tonellato PJ, Jacob HJ. High-density rat radiation hybrid maps containing over 24,000 SSLPs, genes, and ESTs provide a direct link to the rat genome sequence. Genome Res. 2004 Apr;14(4):750-7.
Twigger SN, Nie J, Ruotti V, Yu J, Chen D, Li D, Mathis J, Narayanasamy V, Gopinath GR, Pasko D, Shimoyama M, De La Cruz N, Bromberg S, Kwitek AE, Jacob HJ, Tonellato PJ. Integrative genomics: in silico coupling of rat physiology and complex traits with mouse and human data. Genome Res. 2004 Apr;14(4):651-60.
Gibbs RA, Weinstock GM, et al; Rat Genome Sequencing Project Consortium, Genome sequence of the Brown Norway rat yields insights into mammalian evolution, Nature 428(6982):493-521, 2004.
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