Faculty Collaboration Database

Refined mapping of the renal failure RF-3 quantitative trait locus. J Am Soc Nephrol 2011 Mar;22(3):518-25

Date

12/04/2010

Pubmed ID

21127141

Pubmed Central ID

PMC3060445

DOI

10.1681/ASN.2010060661

Scopus ID

2-s2.0-79952347866 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

Rf-3, a quantitative trait locus (QTL) on rat chromosome 3, affects the development of CKD in Fawn-Hooded Hypertensive (FHH) rats. This QTL spans 110 Mb and approximately 1400 genes; therefore, narrowing the position of this locus is necessary to elucidate potential candidate genes. Here, we used congenic models and comparative genomics to refine the Rf-3 candidate region. We generated congenic lines carrying smaller intervals (subcongenics) of the Rf-3 region and used these lines to reduce the Rf-3 candidate region by 94% (to 7.1 Mb). We used comparative genomics to identify QTL for both nephropathy and albuminuria in the syntenic region of this interval for both human and mouse. We also used the overlapping homologous regions to reduce the number of likely positional candidate genes to 13 known or predicted genes. By combining congenic models and cross-species studies, we narrowed the list of candidate genes to a level that we could sequence the whole interval to further identify the causative gene in future studies.

Author List

O'Meara CC, Lazar J, Hoffman M, Moreno C, Jacob HJ

Author

Caitlin C. O'Meara PhD Associate Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Albuminuria
Animals
Blood Pressure
Chromosome Mapping
Chronic Disease
Disease Models, Animal
Humans
Kidney Diseases
Mice
Quantitative Trait Loci
Rats
Rats, Inbred Strains
Renal Insufficiency