Genomic DNA and cDNA encoding human SERCA1, the Ca2+-ATPase of fast-twitch skeletal muscle sarcoplasmic reticulum (the ATP2A1 gene on chromosome 16p12), were isolated and characterized. The cDNA encodes 994 amino acids. The genomic DNA is 26 kb long and contains 23 exons, one of which can be alternatively spliced. The locations of each of the exon/intron boundaries are the same as those previously identified in the rabbit ATP2A1 gene. Brody disease is an inherited disorder of skeletal muscle, characterized by exercise-induced impairment of muscle relaxation. It has been postulated to result from a deficiency in SERCA1. In a search for the genetic basis of Brody disease, the coding sequence of the ATP2A1 gene in one Brody patient and the full-length sequences of two SERCA1 cDNAs in two other, unrelated Brody patients were compared with normal ATP2A1 sequences. In all three cases, the coding and splice junction sequences were normal, indicating that the forms of Brody disease manifested in these three patients are not caused by mutations in the coding or splice junction regions of the ATP2A1 gene.
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