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Multiple quantitative trait loci modify the heart failure phenotype in murine cardiomyopathy.

Publication ,  Journal Article
Le Corvoisier, P; Park, H-Y; Carlson, KM; Marchuk, DA; Rockman, HA
Published in: Hum Mol Genet
December 1, 2003

The variability in outcome of heart failure patients depends on a number of factors including differences in their genetic background. To identify novel genes that modify the human heart failure phenotype, we used a strategy of quantitative trait locus (QTL) mapping in an experimental mouse model of dilated cardiomyopathy induced by cardiac-specific overexpression of calsequestrin and characterized by a strong strain-specific variability in the phenotype. We identified two novel QTLs, Hrtfm3 (heart failure modifier 3) on chromosome (Chr) 4 and Hrtfm4 on Chr 18, significantly linked to survival with likelihood ratio statistics (LRS) of 19.9 and 23.6 respectively (corresponding to LOD scores of 4.3 and 5.1). Two other QTLs, Hrtfm5 on Chr 2 and Hrtfm6 on Chr 13, were significantly linked to cardiac function as measured by echocardiographic fractional shortening (LRS 22.1 and 15.2 respectively, LOD score 4.8 and 3.3) and left ventricular end-diastolic diameter (LRS 23.5 and 18.8, LOD score 5.1 and 4.1). Importantly, Hrtfm5 was not significantly linked to survival. A significant interaction was found between Hrtfm4 and two other QTLs (Hrtfm6 and a QTL near to the marker D19Mit88) for fractional shortening with a LRS of 34.6 and 26.5 respectively (LOD score 7.5 and 5.8). These data show that the effect of genetic background on murine heart failure is complex and result from the action of several loci that differentially modify the cardiac phenotype. The identification of these novel modifier genes will serve as strong candidates for the discovery of modifiers in human heart failure.

Duke Scholars

Published In

Hum Mol Genet

DOI

ISSN

0964-6906

Publication Date

December 1, 2003

Volume

12

Issue

23

Start / End Page

3097 / 3107

Location

England

Related Subject Headings

  • Survival Analysis
  • Quantitative Trait Loci
  • Phenotype
  • Mice
  • Male
  • Lod Score
  • Heart Failure
  • Genetics & Heredity
  • Female
  • Crosses, Genetic
 

Citation

APA
Chicago
ICMJE
MLA
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Le Corvoisier, P., Park, H.-Y., Carlson, K. M., Marchuk, D. A., & Rockman, H. A. (2003). Multiple quantitative trait loci modify the heart failure phenotype in murine cardiomyopathy. Hum Mol Genet, 12(23), 3097–3107. https://doi.org/10.1093/hmg/ddg333
Le Corvoisier, Philippe, Hyun-Young Park, Kerri M. Carlson, Douglas A. Marchuk, and Howard A. Rockman. “Multiple quantitative trait loci modify the heart failure phenotype in murine cardiomyopathy.Hum Mol Genet 12, no. 23 (December 1, 2003): 3097–3107. https://doi.org/10.1093/hmg/ddg333.
Le Corvoisier P, Park H-Y, Carlson KM, Marchuk DA, Rockman HA. Multiple quantitative trait loci modify the heart failure phenotype in murine cardiomyopathy. Hum Mol Genet. 2003 Dec 1;12(23):3097–107.
Le Corvoisier, Philippe, et al. “Multiple quantitative trait loci modify the heart failure phenotype in murine cardiomyopathy.Hum Mol Genet, vol. 12, no. 23, Dec. 2003, pp. 3097–107. Pubmed, doi:10.1093/hmg/ddg333.
Le Corvoisier P, Park H-Y, Carlson KM, Marchuk DA, Rockman HA. Multiple quantitative trait loci modify the heart failure phenotype in murine cardiomyopathy. Hum Mol Genet. 2003 Dec 1;12(23):3097–3107.

Published In

Hum Mol Genet

DOI

ISSN

0964-6906

Publication Date

December 1, 2003

Volume

12

Issue

23

Start / End Page

3097 / 3107

Location

England

Related Subject Headings

  • Survival Analysis
  • Quantitative Trait Loci
  • Phenotype
  • Mice
  • Male
  • Lod Score
  • Heart Failure
  • Genetics & Heredity
  • Female
  • Crosses, Genetic