TY  - JOUR
A1  - Friedrichs, Frauke
A1  - Zugck, Christian
A1  - Rauch, Gerd-Jörg
A1  - Ivandic, Boris
A1  - Weichenhan, Dieter
A1  - Müller-Bardorff, Margit
A1  - Meder, Benjamin
A1  - El Mokhtari, Nour Eddine
A1  - Regitz-Zagrosek, Vera
A1  - Hetzer, Roland
A1  - Schäfer, Arne
A1  - Schreiber, Stefan
A1  - Chen, Jian
A1  - Neuhaus, Isaac
A1  - Ji, Ruiru
A1  - Siemers, Nathan O.
A1  - Frey, Norbert
A1  - Rottbauer, Wolfgang
A1  - Katus, Hugo A.
A1  - Stoll, Monika
T1  - 
HBEGF, SRA1, and IK: Three cosegregating genes as determinants of cardiomyopathy
Y1  - 2009/03/01 
JF  - Genome Research 
JO  - Genome Research 
DO  - 10.1101/gr.076653.108 
UR  - http://genome.cshlp.org/content/early/2009/02/05/gr.076653.108.abstract 
N2  - 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. 
ER  -