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• W2106396961 abstract "Human dilated cardiomyopathy (DCM), a disorder of the cardiac muscle, causes considerable morbidity and mortality and is one of the major causes of sudden cardiac death. Genetic factors play a role in the etiology and pathogenesis of DCM. Disease-associated genetic variations identified to date have been identified in single families or single sporadic patients and explain a minority of the etiology of DCM. We show that a 600-kb region of linkage disequilibrium (LD) on 5q31.2-3, harboring multiple genes, is associated with cardiomyopathy in three independent Caucasian populations (combined P-value = 0.00087). Functional assessment in zebrafish demonstrates that at least three genes, orthologous to loci in this LD block, HBEGF, IK, and SRA1, result independently in a phenotype of myocardial contractile dysfunction when their expression is reduced with morpholino antisense reagents. Evolutionary analysis across multiple vertebrate genomes suggests that this heart failure-associated LD block emerged by a series of genomic rearrangements across amphibian, avian, and mammalian genomes and is maintained as a cluster in mammals. Taken together, these observations challenge the simple notion that disease phenotypes can be traced to altered function of a single locus within a haplotype and suggest that a more detailed assessment of causality can be necessary." @default.
• W2106396961 created "2016-06-24" @default.
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• W2106396961 date "2008-12-08" @default.
• W2106396961 modified "2023-10-05" @default.
• W2106396961 title "<i>HBEGF, SRA1</i>, and <i>IK</i>: Three cosegregating genes as determinants of cardiomyopathy" @default.
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• W2106396961 doi "https://doi.org/10.1101/gr.076653.108" @default.
• W2106396961 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2661798" @default.
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• W2106396961 hasPublicationYear "2008" @default.
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