Genetics Of Complex Traits In Murine Models


Inbred mouse strains offer tractable models for discovery of genetic factors predisposing to complex traits because genetic and environmental factors can be rigorously controlled. We have used linkage and GWAS approaches in inbred strains to map and identify genes for glomerulosclerosis (scarring of the glomerulus, the “filter” of the kidney) in murine models of HIV Associated nephropathy, diabetic kidney disease (db/db mice), developmental disorders of the kidney and experimental Adriamycin nephropathy. Most recently, in GWAS of inbred strains, we identified a new gene for elevated bile acid levels and diet-induced metabolic phenotypes.

Refinement of the Danforth mutation to a 13kb segment identifies a retrotransposon insertion upstream of Ptf1a.
(Natalia Papeta et al,J Am Soc Nephrol. 2011 )

GWAS identifies risk loci for fatty liver traits in mouse inbred strains
(Wei Wu et al, Hepatology. 2016)

Selected Publications

  1. Natalia Papeta et al. Refinement of the HIVAN1 Susceptibility Locus on Chr. 3A1-A3 via Generation of Sub-Congenic Strains PLoS One. 2016 Oct 13;11(10):e0163860. doi: 10.1371/journal.pone.0163860. eCollection 2016.
  2. Natalia Papeta et al. APOL1 variants increase risk for FSGS and HIVAN but not IgA nephropathy J Am Soc Nephrol. 2011 Nov;22(11):1991-6. doi: 10.1681/ASN.2011040434. Epub 2011 Oct 13.
  3. Natalia Papeta et al. The molecular pathogenesis of HIV-1 associated nephropathy: recent advances J Mol Med (Berl). 2011 May;89(5):429-36. doi: 10.1007/s00109-010-0719-x. Epub 2011 Jan 11.
  4. Ka T Chan et al. Accelerated development of collapsing glomerulopathy in mice congenic for the HIVAN1 locus Kidney Int. 2009 Feb;75(4):366-72. doi: 10.1038/ki.2008.625. Epub 2008 Dec 17.
  5. Ali G Gharavi et al. Mapping a locus for susceptibility to HIV-1-associated nephropathy to mouse chromosome 3 Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2488-93. doi: 10.1073/pnas.0308649100