EXCLUSION OF BMP6 AS A CANDIDATE GENE FOR CLEIDOCRANIAL DYSPLASIA

Cleidocranial dysplasia (CCD) is an autosomal dominant, generalized sk eletal dysplasia in humans that has been mapped to the short arm of ch romosome 6, We report linkage of a CCD mutation to 6p21 in a large fam ily and exclude the bone morphogenetic protein 6 gene (BMP6) as a cand idate for the disease by cytogenetic localization and genetic recombin ation, CCD was linked with a maximal two-point LOD score of 7.22 with marker D6S452 at theta = 0. One relative with a recombination between D6S451 and D6S459 and another individual with a recombination between D6S465 and CCD places the mutation within a 7 cM region between D6S451 and D6S465 at 6p21, A phage P1 genomic clone spanning most of the BMP 6 gene hybridized to chromosome 6 in band region p23-p24 using FISH an alysis, placing this gene cytogenetically more distal than the region of linkage for CCD, We derived a new polymorphic marker from this same P1 clone and found recombinations between the marker and CCD in this family, The results confirm the map position of CCD on 6p21, further r efine the CCD genetic interval by identifying a recombination between D6S451 and D6S459, and exclude BMP6 as a candidate gene. (C) 1995 Wile y-Liss, Inc.