Genetic refinement and physical mapping of a chromosome 16q candidate region for inflammatory bowel disease.
Crohn's disease (CD) is a complex genetic disorder for which a susceptibility gene, IBD1, has been mapped within the pericentromeric region of chromosome 16. In order to refine the location of IBD1, 77 multiplex CD families were genotyped for 26 microsatellite markers evenly spaced by approximately 1 cM. Nonparametric linkage analyses exhibited a maximum NPL score of 3.49 (P=2.37x10(-4)) in a region centred by markers D16S3136, D16S3117 and D16S770. Simulation studies showed that the probability for IBD1 to be located in a 5 cM region around these markers was 70%. A 2.5 Mb YAC and BAC contig map spanning this genetic region on chromosome band 16q12 was built. TDT analyses demonstrated suggestive association between the 207 bp allele of D16S3136 (P<0.05) and a new biallellic marker hb27g11f-end (P=0.01). These markers were located in the hb27g11 and hb87b10 BAC clones from the contig. Taken together, the present results provide a crucial preliminary step before an exhaustive linkage disequilibrium mapping of putatively transcribed regions to identify IBD1.
Zouali
H
H
Fondation Jean Dausset CEPH, Paris, France.
Chamaillard
M
M
Lesage
S
S
Cézard
J P
JP
Colombel
J F
JF
Belaiche
J
J
Almer
S
S
Tysk
C
C
Montague
S
S
Gassull
M
M
Christensen
S
S
Finkel
Y
Y
Gower-Rousseau
C
C
Modigliani
R
R
Macry
J
J
Selinger-Leneman
H
H
Thomas
G
G
Hugot
J P
JP
D000483:Alleles; D015139:Blotting, Southern; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D020451:Contig Mapping; D003424:Crohn Disease / Q000235:genetics*; D020224:Expressed Sequence Tags; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D016324:Sequence Tagged Sites