Finer linkage mapping of primary hip osteoarthritis susceptibility on chromosome 11q in a cohort of affected female sibling pairs.
OBJECTIVE
To finer linkage-map a primary osteoarthritis (OA) susceptibility locus as a prerequisite to linkage disequilibrium/association analysis.


METHODS
A 50-cM interval of chromosome 11q that we had previously identified as harboring susceptibility to hip OA in a female sibling-pair cohort was subjected to finer linkage mapping. Thirty-five microsatellite markers with a mean marker interval of 1.4 cM were genotyped in 146 families containing female sibling pairs who were concordant for hip OA, as ascertained by total hip replacement.


RESULTS
Two-point and multipoint linkage analysis revealed 2 distinct regions of linkage within the 50-cM interval. The first locus had a linkage interval of 11.9 cM and was centered at 81.5 cM from the 11p telomere, with a maximum multipoint logarithm of odds (LOD) score of 2.4. The second region had a linkage interval of 6.5 cM and was centered at 93.1 cM from the 11p telomere, with a maximum multipoint LOD score of 1.8.


CONCLUSIONS
Dense linkage mapping has highlighted the presence of 2 loci on chromosome 11q, each conferring susceptibility to hip OA. Both loci are sufficiently narrow for association analysis to be undertaken.
University of Oxford, Oxford, UK.
Kay
K
Chapman
Zehra
Z
Mustafa
Barbara
B
Dowling
Lorraine
L
Southam
Andrew
A
Carr
John
J
Loughlin
D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D018895:Microsatellite Repeats; D015207:Osteoarthritis, Hip / Q000235:genetics*