The locus for bovine dilated cardiomyopathy maps to chromosome 18.

Bovine dilated cardiomyopathy (BDCMP) is a severe and terminal disease of the heart muscle observed in Holstein-Friesian cattle over the last 30 years. There is strong evidence for an autosomal recessive mode of inheritance for BDCMP. The objective of this study was to genetically map BDCMP, with the ultimate goal of identifying the causative mutation. A whole-genome scan using 199 microsatellite markers and one SNP revealed an assignment of BDCMP to BTA18. Fine-mapping on BTA18 refined the candidate region to the MSBDCMP06-BMS2785 interval. The interval containing the BDCMP locus was confirmed by multipoint linkage analysis using the software loki. The interval is about 6.7 Mb on the bovine genome sequence (Btau 3.1). The corresponding region of HSA19 is very gene-rich and contains roughly 200 genes. Although telomeric of the marker interval, TNNI3 is a possible positional and a functional candidate for BDCMP given its involvement in a human form of dilated cardiomyopathy. Sequence analysis of TNNI3 in cattle revealed no mutation in the coding sequence, but there was a G-to-A transition in intron 6 (AJ842179:c.378+315G>A). The analysis of this SNP using the study's BDCMP pedigree did not conclusively exclude TNNI3 as a candidate gene for BDCMP. Considering the high density of genes on the homologous region of HSA19, further refinement of the interval on BTA18 containing the BDCMP locus is needed.

[1]  P. Leifsson,et al.  Familial occurrence of bovine dilated cardiomyopathy in Denmark. , 2004, Journal of veterinary medicine. A, Physiology, pathology, clinical medicine.

[2]  J. Mogensen,et al.  Novel mutation in cardiac troponin I in recessive idiopathic dilated cardiomyopathy , 2004, The Lancet.

[3]  M. Pfister-Genskow,et al.  Construction and characterization of a bovine BAC library with four genome-equivalent coverage , 2001, Genetics Selection Evolution.

[4]  J. Martig,et al.  Evidence for autosomal recessive inheritance of a major gene for bovine dilated cardiomyopathy. , 1998, Journal of animal science.

[5]  S. Heath.  Markov chain Monte Carlo segregation and linkage analysis for oligogenic models. , 1997, American journal of human genetics.

[6]  A A Schäffer,et al.  Faster sequential genetic linkage computations. , 1993, American journal of human genetics.

[7]  J. Martig,et al.  Diagnosis of bovine cardiomyopathy by electrolyte and protein analysis. , 1993, Zentralblatt fur Veterinarmedizin. Reihe A.

[8]  R. Bahnemann,et al.  [Myocardial fibrosis of cattle in Hesse]. , 1992, Tierarztliche Praxis.

[9]  W. R. Kelly,et al.  Dilated (congestive) cardiomyopathy in a Friesian heifer. , 1990, Australian veterinary journal.

[10]  J. Martig,et al.  [Further cases of cardiomyopathy in cattle]. , 1985, DTW. Deutsche tierarztliche Wochenschrift.

[11]  C. Lobsiger,et al.  [Study of pulmonary vascular lesions in cows with cardiomyopathy]. , 1985, Schweizer Archiv fur Tierheilkunde.

[12]  J. Martig,et al.  [Incidence of cardiac insufficiency in cattle. Preliminary report]. , 1982, Schweizer Archiv fur Tierheilkunde.

[13]  R. Bradley,et al.  Cardiomyopathy in adult Holstein Friesian cattle in Britain. , 1991, Journal of comparative pathology.

[14]  C. Lobsiger,et al.  [Pathology of bovine cardiomyopathy]. , 1990, Schweizer Archiv fur Tierheilkunde.

[15]  L. Coulombel,et al.  A simple and efficient method for isolating high molecular weight DNA from mammalian sperm. , 1988, Nucleic acids research.