•Numerous examples of the use of fine mapping strategies are available in the cardiovascular field but I have chosen this one from inflammatory bowel disease because it is from my colleague Gilles Thomas and it nicely demonstrates the subsequent steps of sequencing and functional studies.

•An approximately 9-cm linkage peak localized the IBD1 locus to the pericentromeric region of chromosome 1 with a maximum non-parametric LOD score of 3.49, as shown in panel a.  Fine mapping was concentrated on the area between markers D16S541 and D16S2623.  26 additional microsatellite  markers were tested in this region, the location of 9 of which are shown in panel B above.

•The third microsatellite from the left, D16S3136, was associated with the disease in 108 trios at p < 0.05, and the association was replicated in another 76 families at p < 0.01, though with a different allele.

•This difference in allelic associations at the same locus could be due to chance or could reflect a true association in two sets of families drawn from genetically distinct populations.  This would suggest that D16S3136 is in linkage disequilibrium with the disease-causing variant, though the microsatellites could have diverged after the disease-related variant arose.  We’ll come back to this example.