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Mouse genome-wide association study identifies polymorphisms on chromosomes 4, 11, and 15 for age-related cardiac fibrosis

Overview of attention for article published in Mammalian Genome, April 2016
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Title
Mouse genome-wide association study identifies polymorphisms on chromosomes 4, 11, and 15 for age-related cardiac fibrosis
Published in
Mammalian Genome, April 2016
DOI 10.1007/s00335-016-9634-y
Pubmed ID
Authors

Qiaoli Li, Annerose Berndt, Beth A. Sundberg, Kathleen A. Silva, Victoria E. Kennedy, Clinton L. Cario, Matthew A. Richardson, Thomas H. Chase, Paul N. Schofield, Jouni Uitto, John P. Sundberg

Abstract

Dystrophic cardiac calcinosis (DCC), also called epicardial and myocardial fibrosis and mineralization, has been detected in mice of a number of laboratory inbred strains, most commonly C3H/HeJ and DBA/2J. In previous mouse breeding studies between these DCC susceptible and the DCC-resistant strain C57BL/6J, 4 genetic loci harboring genes involved in DCC inheritance were identified and subsequently termed Dyscalc loci 1 through 4. Here, we report susceptibility to cardiac fibrosis, a sub-phenotype of DCC, at 12 and 20 months of age and close to natural death in a survey of 28 inbred mouse strains. Eight strains showed cardiac fibrosis with highest frequency and severity in the moribund mice. Using genotype and phenotype information of the 28 investigated strains, we performed genome-wide association studies (GWAS) and identified the most significant associations on chromosome (Chr) 15 at 72 million base pairs (Mb) (P < 10(-13)) and Chr 4 at 122 Mb (P < 10(-11)) and 134 Mb (P < 10(-7)). At the Chr 15 locus, Col22a1 and Kcnk9 were identified. Both have been reported to be morphologically and functionally important in the heart muscle. The strongest Chr 4 associations were located approximately 6 Mb away from the Dyscalc 2 quantitative trait locus peak within the boundaries of the Extl1 gene and in close proximity to the Trim63 and Cap1 genes. In addition, a single-nucleotide polymorphism association was found on chromosome 11. This study provides evidence for more than the previously reported 4 genetic loci determining cardiac fibrosis and DCC. The study also highlights the power of GWAS in the mouse for dissecting complex genetic traits.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 14 100%

Demographic breakdown

Readers by professional status Count As %
Other 2 14%
Student > Bachelor 2 14%
Researcher 2 14%
Student > Ph. D. Student 2 14%
Lecturer 1 7%
Other 2 14%
Unknown 3 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 43%
Medicine and Dentistry 2 14%
Agricultural and Biological Sciences 2 14%
Pharmacology, Toxicology and Pharmaceutical Science 1 7%
Veterinary Science and Veterinary Medicine 1 7%
Other 0 0%
Unknown 2 14%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 April 2016.
All research outputs
#18,455,405
of 22,867,327 outputs
Outputs from Mammalian Genome
#1,004
of 1,126 outputs
Outputs of similar age
#218,956
of 299,116 outputs
Outputs of similar age from Mammalian Genome
#11
of 19 outputs
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