Pycnodysostosis: Refined linkage and radiation hybrid analyses reduce the critical region to 2 cM at 1q21 and map two candidate genes

Bruce D. Gelb, Eric Spencer, Suliman Obad, Gordon J. Edelson, Simon Faure, Jean Weissenbach, Robert J. Desnick

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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 Genethon 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 D1S2343/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.

Original languageEnglish
Pages (from-to)141-144
Number of pages4
JournalHuman Genetics
Volume98
Issue number2
DOIs
StatePublished - 1996

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