Genetic analysis in Italian families with inflammatory bowel disease supports linkage to the IBD1 locus – A GISC study

Abstract

Epidemiological studies suggest that inherited factors influence susceptibility to inflammatory bowel disease (IBD), and some candidate loci have been described. In order to verify whether the same loci are responsible for predisposition to IBD in our population, we carried out a linkage study in a series of 58 Italian families with Crohn's disease (CD) and ulcerative colitis (UC). HLA-DQ alleles, motilin gene, and 34 microsatellites flanking the previously described loci on chromosomes 3, 6, 7, 12 and 16 were analysed by non-parametric linkage analysis in 16 and 23 families with CD and UC, respectively, and in 19 families where CD and UC coexisted. Non parametric analysis using GENEHUNTER yielded maximum NPL scores for marker D16S408 in all IBD families combined (2.71, P = 0.003), for marker D16S419 in CD (1.97, P = 0.026) and for marker D16S514 in UC families (2.44, P = 0.007). These markers map in the previously described IBD1 region. No significant linkage was found for markers of chromosomes 3, 6, 7 and 12. The present study performed in a Southern European population provides additional support for the conclusion that the IBD1 locus has a clear role in the genetic susceptibility to IBD.

Replication and extension studies of inflammatory bowel disease susceptibility regions confirm linkage to chromosome 6p (IBD3)

“…23,24,52,53 These studies also failed to see linkage. To date, six genome scans and four replication studies have failed to detect linkage to chromosome 7.…”

Combined segregation and linkage analysis of inflammatory bowel disease in the IBD1 region using severity to characterise Crohn's disease and ulcerative colitis

“…In our previous study 26 a peak multipoint non-parametric linkage score of 2.71 (P = 0.0035), corresponding to a lod score of 1.59 ( = 2.71 2 /2ln10) was obtained at the same marker identified in this analysis (namely D16S408), Number of extended families: CD only=21; UC only=38; CD/UC=23. Number of nuclear families: CD only=32; UC only=53; CD/UC=37.…”

“…[11][12][13][14][15][16] The importance of the candidate loci on chromosome 16 (IBD1, MIM 266600), chromosome 12 (IBD2, MIM 601458) and chromosome 6 (IBD3, MIM 604519) has been demonstrated in subsequent studies, [17][18][19][20][21][22][23][24][25][26] whereas the additional IBD loci need to be confirmed by further independent analyses.…”

“…26 We now present a parametric analysis performed on an extended sample employing combined segregation and linkage analysis in the identified IBD1 region. Using this approach it is possible to test linkage and to refine the mode of disease inheritance using the information provided by the linked marker, thus allowing more accurate estimates of the genetic parameters, such as gene frequency and penetrance and, consequently, a more powerful test for linkage.…”

Étude généalogique d'individus atteints de maladies inflammatoires chroniques non-spécifiques de l'intestin /

“…Cependant, les marqueurs utilisés sur les chromosomes 3, 6, 7 et 12 ne montrent pas de lien significatif (Annese & al., 1999 (Hampe & al., 1999).…”