Absence of linkage between inflammatory bowel disease and selected loci on chromosomes 3, 7, 12, and 16.
OBJECTIVE
Linkage data derived from genome-wide scans of inflammatory bowel disease (IBD) sibling-pair families have identified 4 loci on chromosomes 3, 7, 12, and 16 as potential sites for IBD susceptibility genes. The aim of this study was to investigate whether linkage analysis of another independently collected set of sibling pairs with IBD would provide further evidence of linkage between these previously reported loci and IBD.


METHODS
Using the MAPMAKER/SIBS program, the segregation of 21 microsatellite marker loci spanning the 4 putative IBD gene loci was analyzed in a study population comprising 161 families with 114 Crohn's disease, 36 ulcerative colitis, and 50 mixed IBD sibling pairs from the Greater Toronto area.


RESULTS
The results of multipoint linkage analysis showed no evidence for linkage between IBD and each of the 21 marker loci studied; the logarithm of odds scores in all instances were less than 0.8. These linkage data were found, by exclusion mapping analysis, to exclude values of lambdas ranging from 1.5 to 3.0, depending on the locus evaluated.


CONCLUSIONS
The loci previously suggested as representing IBD susceptibility loci are not linked to IBD in the Toronto population examined in this analysis.
Rioux
J D
JD
Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, Cambridge, Massachusetts, USA.
Daly
M J
MJ
Green
T
T
Stone
V
V
Lander
E S
ES
Hudson
T J
TJ
Steinhart
A H
AH
Bull
S
S
Cohen
Z
Z
Greenberg
G
G
Griffiths
A
A
McLeod
R
R
Silverberg
M
M
Williams
C N
CN
Siminovitch
K A
KA
D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008126:Lod Score; D018895:Microsatellite Repeats / Q000235:genetics