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Direct assignment of the human beta B2 and beta B3 crystallin genes to 22q11.2----q12: markers for neurofibromatosis 2.

We have isolated a human probe specific for the beta B3 crystallin gene (CRYB3) and hybridized it to Southern blots of human X rodent cell hybrids with known human chromosomal constitution. In this way we could directly assign CRYB3 to chromosome 22. Cell hybrids with translocation chromosomes containing distinct portions of chromosomes 22 were used to regionally localize the gene to 22q11.2----q12. Owing to its known close proximity to the beta B3 crystallin gene, the beta B2-1 crystallin gene (CRYB2-1) also maps in this region. A second beta B2 crystallin gene, beta B2-2 (CRYB2-2), not linked to the CRYB2-1/CRYB3 cluster, could be localized in the same region. This implies that the three known beta B crystallin genes are all within 22q11.2----q12. This small region contains D22S1, the only marker that shows no recombination with neurofibromatosis 2. Therefore, the beta B crystallin genes on chromosome 22 might be markers for this disease. Two DNA fragments revealing useful polymorphisms associated with the beta B crystallin genes were identified. One detects a two-system MspI restriction fragment length polymorphism specific for the CRYB2-1/CRYB3 cluster. The other detects an informative PstI polymorphism that is in linkage equilibrium with the MspI polymorphism.