Polymorphic gene for human carbonic anhydrase II: a molecular disease marker located on chromosome 8.

A panel of 28 mouse-human somatic cell hybrids of known karyotype was screened for the presence of the human carbonic anhydrase II (CA II) gene, which encodes one of the three well-characterized, genetically distinct carbonic anhydrase isozymes (carbonate dehydratase; carbonate hydro-lyase, EC 4.2.1.1). The human and mouse CA II genes can be clearly distinguished by Southern blot analysis of BamHI-digested genomic DNA with a mouse CA II cDNA hybridization probe. The two major hybridizing fragments in mouse were 15 and 6.0 kilobase pairs, and in human they were 15 and 4.3 kilobase pairs. Analysis of the somatic cell hybrids by this technique identified those containing human CA II gene sequences. Segregation analysis of the molecular marker and chromosomes in cell hybrids indicated a clear correlation between the presence of chromosome 8 and the human CA II gene (CA2). This finding provides the second polymorphic marker for human chromosome 8 and, moreover, a molecular disease marker, because human CA II deficiency has recently been linked to an autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification.