Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
11149487
TITLE
Familial Paget's disease of bone: nonlinkage to the PDB1 and PDB2 loci on chromosomes 6p and 18q in a large pedigree.
ABSTRACT
Paget's disease of bone is a common condition characterized by bone pain, deformity, pathological fracture, and an increased incidence of osteosarcoma. Genetic factors play a role in the pathogenesis of Paget's disease but the molecular basis remains largely unknown. Susceptibility loci for Paget's disease of bone have been mapped to chromosome 6p21.3 (PDB1) and 18q21.1-q22 (PDB2) in different pedigrees. We have identified a large pedigree of over 250 individuals with 49 informative individuals affected with Paget's disease of bone; 31 of whom are available for genotypic analysis. The disease is inherited as an autosomal dominant trait in the pedigree with high penetrance by the sixth decade. Linkage analysis has been performed with markers at PDB1; these data show significant exclusion of linkage with log10 of the odds ratio (LOD) scores < -2 in this region. Linkage analysis of microsatellite markers from the PDB2 region has excluded linkage with this region, with a 30 cM exclusion region (LOD score < -2.0) centered on D18S42. These data confirm the genetic heterogeneity of Paget's disease of bone. Our hypothesis is that a novel susceptibility gene relevant to the pathogenesis of Paget's disease of bone lies elsewhere in the genome in the affected members of this pedigree and will be identified using a microsatellite genomewide scan followed by positional cloning.
DATE PUBLISHED
2001 Jan
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2001/01/10 11:00
medline 2001/03/07 10:01
entrez 2001/01/10 11:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Good D Good D D Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, Australia.
Busfield F Busfield F F
Duffy D Duffy D D
Lovelock PK Lovelock P K PK
Kesting JB Kesting J B JB
Cameron DP Cameron D P DP
Shaw JT Shaw J T JT
INVESTIGATORS
JOURNAL
VOLUME: 16
ISSUE: 1
TITLE: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
ISOABBREVIATION: J. Bone Miner. Res.
YEAR: 2001
MONTH: Jan
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0884-0431
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: J Bone Miner Res
COUNTRY: United States
ISSNLINKING: 0884-0431
NLMUNIQUEID: 8610640
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Aged, 80 and over
Australia
Chromosome Mapping
Chromosomes, Human, Pair 18 genetics
Chromosomes, Human, Pair 6 genetics
Female genetics
Genetic Heterogeneity genetics
Genetic Linkage genetics
Genetic Predisposition to Disease genetics
Humans genetics
Lod Score genetics
Male genetics
Microsatellite Repeats genetics
Middle Aged genetics
Osteitis Deformans physiopathology
Pedigree physiopathology
Phenotype physiopathology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's