Identification of a Major Locus for Paget's Disease on Chromosome 10p13 in Families of British Descent

• DOI: 10.1359/jbmr.071004
• Publication Date: 2007-10-01T13:55:54Z
• Authors: Gavin JA Lucas; Phillip L Riches; Lynne J Hocking; Tim Cundy; Geoff C Nicholson; John P Walsh; Stuart H Ralston
• Keywords: Identification

Abstract Mutations of SQSTM1 are an important cause PDB, but other genes remain to be discovered. A major susceptibility locus for PDB was identified on chromosome 10p13 by a genome-wide linkage scan in families British descent, which accounted the vast majority cases not caused mutations. Introduction: Paget's disease bone (PDB) has strong genetic component, and several loci have been scans. We previously three using this approach chromosomes 5q35, 2q36, 62 mainly subsequently, mutations gene were found 23 from cohort. Here we reanalyzed results our search cohort who did Materials Methods: The study population consisted 210 individuals 39 predominantly descent with autosomal dominant inheritance whom had excluded mutation screening. average family size 5.44 ± 3.98 (SD) (range, 2-24 individuals). Genotyping performed standard techniques 382 microsatellite markers spaced at distance 9.06 cM throughout autosomes. Multipoint analysis GENEHUNTER program under models homogeneity heterogeneity. Results: parametric model nonparametric heterogeneity both showed evidence single (LOD score, +4.08) close marker D10S1653 41.43cM. No detected 2q36 population, candidate implicated pathogenesis excluded. Conclusions: conclude that there is find no support existence or population. lies within seems account development do carry