Finer linkage mapping of primary osteoarthritis susceptibility loci on chromosomes 4 and 16 in families with affected women.
OBJECTIVE
To more finely linkage-map primary osteoarthritis (OA) susceptibility loci on chromosomes 4 and 16.


METHODS
Two hundred eighteen families, each with 2 or more women concordant for primary OA (ascertained by total hip replacement [THR] or total knee replacement), were genotyped using highly polymorphic microsatellite markers from chromosomes 4 and 16, at an average density of 1 marker every 4 cM. Two-point and multipoint linkage analyses were performed for all 218 families and for the 146 families from the 218 that included women concordant for THR (female-THR families).


RESULTS
A single region of linkage was identified on chromosome 4q, with a maximum multipoint logarithm of odds (LOD) score (MLS) of 3.1 in the 146 female-THR families. This locus was centered 79 cM from the 4p telomere and had a 1-LOD support interval of 4 cM. Two regions of linkage were identified on chromosome 16, the first on 16p with an MLS of 1.7 in the female-THR families and the second on 16q with an MLS of 1.9 in all 218 families. The first locus was centered 46 cM and the second 89 cM from the p-telomere. The 1-LOD support intervals were 12 cM and 10 cM, respectively.


CONCLUSIONS
Finer linkage mapping using a high density of microsatellite markers has narrowed female OA susceptibility loci on chromosomes 4 and 16. The regions have been narrowed sufficiently for association analysis.
Forster
Tracy
T
University of Oxford, Oxford, UK.
Chapman
Kay
K
Marcelline
Lucy
L
Mustafa
Zehra
Z
Southam
Lorraine
L
Loughlin
John
J
D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D002894:Chromosomes, Human, Pair 4; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D010003:Osteoarthritis / Q000235:genetics*