Genetic variation for cardiac dysfunction in Drosophila.
BACKGROUND
Common diseases may be attributed to combinations of variant alleles, but there are few model systems where the interactions among such variants can be studied in controlled genetic crosses. While association studies are designed to detect common polymorphisms of moderate effect, new approaches are required to characterize the impact on disease of interactions among rare alleles.


RESULTS
We show that wild populations of Drosophila melanogaster harbor rare polymorphisms of major effect (RAME) that predispose flies to a specific disease phenotype, age-dependent cardiac dysfunction. A screen of fifty inbred wild-type lines revealed a continuous spectrum of pacing-induced heart failure that generally increases in frequency with age. High-speed video analysis of the inbred lines with high rates of inducible heart failure indicates specific defects in cardiac function, including arrhythmias and contractile disorders ('cardiomyopathies'). A combination of bulked segregant analysis and single feature polymorphism (SFP) detection localizes one of the cardiac susceptibility loci to the 97C interval on the fly genome.


CONCLUSIONS
Wild-type Drosophila, like humans, are predisposed to cardiac dysfunction. Identification of factors associated with these naturally occurring cardiac traits promises to provide important insights into the epidemiology of cardiac disease.
Ocorr
Karen A
KA
Center for Neuroscience and Aging, Burnham Institute for Medical Research, La Jolla, California, United States of America.
Crawley
Timothy
T
Gibson
Greg
G
Bodmer
Rolf
R
D000375:Aging / Q000235:genetics; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000503:physiopathology / Q000662:veterinary; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000662:veterinary; D020090:Chromosome Segregation / Q000235:genetics; D003433:Crosses, Genetic; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D008040:Genetic Linkage; D014644:Genetic Variation; D006331:Heart Diseases / Q000235:genetics*; D006333:Heart Failure / Q000235:genetics / Q000503:physiopathology / Q000662:veterinary; D006339:Heart Rate; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide