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Arthritis Rheum. 2004 Jan;50(1):98-102.

Finer linkage mapping of primary osteoarthritis susceptibility loci on chromosomes 4 and 16 in families with affected women.

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University of Oxford, Oxford, UK.



To more finely linkage-map primary osteoarthritis (OA) susceptibility loci on chromosomes 4 and 16.


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).


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.


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.

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