Faculty Collaboration Database

Fine mapping of Lvm1: a quantitative trait locus controlling heart size independently of blood pressure. Pulm Pharmacol Ther 2006;19(1):70-3

Date

11/16/2005

Pubmed ID

16286240

DOI

10.1016/j.pupt.2005.02.010

Scopus ID

2-s2.0-27744536267 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

We have previously reported a quantitative trait locus (QTL) on rat chromosome 2 that influences heart size independently of blood pressure (Left Ventricular Mass Locus 1; Lvm1). The recent release of the rat genome sequence allowed us to retest and refine this relatively broad QTL with a view to identifying within it candidate genes worthy of structural investigation. We sought to achieve this 'fine mapping' by increasing the marker density within the interval and undertaking a linkage analysis in a previously defined population of F2 hybrids generated from inbred spontaneously hypertensive rats (SHR) of the Okamoto strain and Fischer rat (F344) progenitors. We were able to reconfirm and resolve Lvm1 from its original width of approximately 45 to 15 cM. By reference to the ENSEBL rat genome data bank, we identified within Lvm1 27 known genes, 109 predicted genes and 7 pseudogenes. Of the known genes, candidates include potential regulators of cardiac growth, a sodium channel and calcium channel as well as the fibroblast growth factor 2 gene. Located nearby the Lvm1 locus was the gene for the angiotensin Type 1B receptor. Given the evidence that the ligand for the angiotensin Type 1B receptor-angiotensin II-is a potent cardiotroph, we also consider this gene a potential candidate. The identification of the precise allelic variant(s) within Lvm1 involved in the control of pressure-independent cardiac growth awaits further molecular studies.

Author List

Di Nicolantonio R, Kostka V, Kwitek A, Jacob H, Thomas WG, Harrap SB

Author

Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin

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

Animals
Blood Pressure
Genetic Linkage
Genetic Markers
Humans
Hypertrophy, Left Ventricular
Organ Size
Physical Chromosome Mapping
Quantitative Trait Loci
Rats
Rats, Inbred F344
Rats, Inbred SHR
Receptor, Angiotensin, Type 2