GENES ENCODING THE H,K-ATPASE-ALPHA AND NA,K-ATPASE-ALPHA-3 SUBUNITS ARE LINKED ON MOUSE CHROMOSOME-7 AND HUMAN CHROMOSOME-19

We have used linkage analysis and fluorescence in situ hybridization t o determine the chromosomal organization and location of the mouse (At p4a) and human (ATP4A) genes encoding the H,K-ATPase a subunit. Linkag e analysis in recombinant inbred (BXD) strains of mice localized Atp4a to mouse Chromosome (Chr) 7. Segregation of restriction fragment leng th polymorphisms in backcross progeny of Mus musculus x Mus spretus ma ting confirmed this assignment and indicates that Atp4a and Atp1a3 (ge ne encoding the murine Na,K-ATPase alpha3 subunit) are linked and sepa rated by a distance of approximately 2 cM. Analysis of the segregation of simple sequence repeats suggested the gene order centromere-D7Mit2 1-D7Mit57/ Atp1a3-D7Mit72/Atp4a. A human Chr 19-enriched cosmid librar y was screened with both H,K-ATPase a and Na,K-ATPase alpha3 subunit c DNA probes to isolate the corresponding human genes (ATP4A and ATP1A3, respectively). Fluorescence in situ hybridization with gene-specific cosmid clones localized ATP4A to the q13.1 region, and proximal to ATP 1A3, which maps to the q13.2 region, of Chr 19. These results indicate that ATP4A and ATP1A3 are linked in both the mouse and human genomes.