@article{Friedrichs01032009,
author = {Friedrichs, Frauke and Zugck, Christian and Rauch, Gerd-Jörg and Ivandic, Boris and Weichenhan, Dieter and Müller-Bardorff, Margit and Meder, Benjamin and El Mokhtari, Nour Eddine and Regitz-Zagrosek, Vera and Hetzer, Roland and Schäfer, Arne and Schreiber, Stefan and Chen, Jian and Neuhaus, Isaac and Ji, Ruiru and Siemers, Nathan O. and Frey, Norbert and Rottbauer, Wolfgang and Katus, Hugo A. and Stoll, Monika}, 
title = {HBEGF, SRA1, and IK: Three cosegregating genes as determinants of cardiomyopathy},
volume = {19}, 
number = {3}, 
pages = {395-403}, 
year = {2009}, 
doi = {10.1101/gr.076653.108}, 
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.}, 
URL = {http://genome.cshlp.org/content/19/3/395.abstract}, 
eprint = {http://genome.cshlp.org/content/19/3/395.full.pdf+html}, 
journal = {Genome Research} 
}