title: Pycnodysostosis: refined linkage and radiation hybrid analyses reduce the critical region to 2 cM at 1q21 and map two candidate genes.
abstract: Pycnodysostosis (PKND) is a rare, autosomal recessive skeletal dysplasia, which has been mapped previously to a 4-cM interval between D1S442 to D1S305 at chromosome 1q21. Only D1S498 did not recombine with the disease locus in a large, consanguineous Arab family with PKND. In the present studies, five new Généthon markers (D1S2343, D1S2344, D1S2345, D1S2346, and D1S2347) were tested against DNA from this family and against the Stanford G3 diploid radiation hybrid panel. The results permitted ordering of some loci previously mapped at no recombinant distance: D1S442-D1S2344-(D1S498/D1S2347)-(D1S2343/+ ++D1S2345)-D1S2346-D1S305.The PKND critical region was refined to the 2-cM interval from D1S2344 to D1S343/D1S2347. In addition, sequence-tagged sites were developed for the two PKND candidate genes, IL6R and MCL1. Use of radiation hybrids revealed that IL6R was tightly linked to D1S305, excluding it from the PKND critical region. MCL1 was most tightly linked to D1S498 and D1S2347, placing it within the critical region.
authors.affiliation: Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Gelb
authors.forename: E
authors.initials: E
authors.lastname: Spencer
authors.forename: S
authors.initials: S
authors.lastname: Obad
authors.forename: G J
authors.initials: GJ
authors.lastname: Edelson
authors.forename: S
authors.initials: S
authors.lastname: Faure
authors.forename: J
authors.initials: J
authors.lastname: Weissenbach
authors.forename: R J
authors.initials: RJ
authors.lastname: Desnick
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003241:Consanguinity; D017931:DNA Primers / Q000235:genetics; D004413:Dysostoses / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006822:Hybrid Cells; D008297:Male; D008969:Molecular Sequence Data
chemical_list: D017931:DNA Primers; D005819:Genetic Markers