Genomic organization and chromosomal localization of the human Coxsackievirus B-adenovirus receptor gene

Myocarditis and dilated cardiomyopathy (DCM) are common causes of morbidity and mortality in children. Many studies have implicated the enteroviruses and, particularly, the Coxsackievirus-B family as etiologic agents of the a cquired forms of these diseases. However, we have shown the group-C adenovi ruses to be as commonly detected as enteroviruses in the myocardium of chil dren and adults with these diseases. It has remained something of a conundr um why two such divergent virus families cause these diseases. The recent d escription of the common human Coxsackievirus B-adenovirus receptor (CAR) o ffers at least a partial explanation. In order to characterize the CAR gene , we screened a bacterial artificial chromosomal (BAC) library (RPCI11) usi ng a polymerase chain reaction (PCR) product derived from the 3' end of the CAR cDNA sequence. This identified 13 BACs that were further characterized by PCR amplification of seven contiguous regions of the entire cDNA sequen ce. Eleven of the BACs were determined to encode pseudogenes while the othe r two BACs (131J5 and 246M1) encoded the presumed functional gene. PCR ampl ification of a monochromosomal hybrid panel indicated the presence of pseud ogenes on chromosomes 15, 18, and 21 while the functional gene is encoded o n chromosome 21. Fluorescence in situ hybridization analysis indicated that the gene is located at 21q11.2. DNA sequencing of BACs 131J5 and 246M1 rev ealed the presence of seven exons. The DNA sequences have been determined f or each exon-intron boundary, and putative promoter sequences and transcrip tion initiation sites identified. No consensus polyadenylation signal was i dentified.