Combined segregation and linkage analysis of inflammatory bowel disease in the IBD1 region using severity to characterise Crohn's disease and ulcerative colitis
Combined segregation and linkage analysis of inflammatory bowel disease in the IBD1 region using severity to characterise Crohn's disease and ulcerative colitis
Inflammatory bowel disease (IBD) is a chronic relapsing disorder affecting the gastro-intestinal tract and is subdivided into two main subtypes: Crohn's disease (CD) and ulcerative colitis (UC). Although the aetiology of IBD is unknown, a strong genetic susceptibility is suggested and different candidate regions have been identified for both CD and UC. The IBD1 region on chromosome 16 has been confirmed to be important for susceptibility to CD, whereas conflicting evidence has been obtained for UC. We performed a combined linkage and segregation analysis in the identified IBD1 region on a sample of 82 extended families with IBD using a parametric method implemented in the computer program COMDS. This approach allows simultaneous evaluation of linkage while estimating the mode of inheritance and to include severity of the trait to characterise the CD and UC phenotypes. Our results are consistent with the presence of a major gene in the IBD1 region close to D16S408 involved in both UC and CD. Furthermore, our data support evidence that a single mutation in the gene leads more frequently to UC, whereas inheritance of two mutant alleles results in the more severe CD. In our study the IBD1 locus was found to have a major role in IBD predisposition in the Italian population.
IBD1, Inflammatory bowel disease, Linkage, Segregation analysis
846-852
Forabosco, Paola
405fcfc5-369e-4b1c-81a9-8339b4033fa0
Collins, Andrew
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Latiano, Anna
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Annese, Vito
c7127dd0-6790-42d3-bd83-ea6ee06975a2
Clementi, Maurizio
5b53c83b-a79f-492c-b03b-13d49a907879
Andriulli, Angelo
68c8b305-f628-4fe8-abd3-877f58a36e5a
Fortina, Paolo
e92ac4aa-856f-4b8b-9c49-8385cecbef7b
Devoto, Marcella
c9ff9815-f2b5-4181-ba6d-6f04a9e162c0
Morton, Newton E.
c668e2be-074a-4a0a-a2ca-e8f51830ebb7
31 October 2000
Forabosco, Paola
405fcfc5-369e-4b1c-81a9-8339b4033fa0
Collins, Andrew
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Latiano, Anna
6fb79395-6e0a-4e87-80be-1603bbb8dd0f
Annese, Vito
c7127dd0-6790-42d3-bd83-ea6ee06975a2
Clementi, Maurizio
5b53c83b-a79f-492c-b03b-13d49a907879
Andriulli, Angelo
68c8b305-f628-4fe8-abd3-877f58a36e5a
Fortina, Paolo
e92ac4aa-856f-4b8b-9c49-8385cecbef7b
Devoto, Marcella
c9ff9815-f2b5-4181-ba6d-6f04a9e162c0
Morton, Newton E.
c668e2be-074a-4a0a-a2ca-e8f51830ebb7
Forabosco, Paola, Collins, Andrew, Latiano, Anna and Morton, Newton E.
,
et al.
(2000)
Combined segregation and linkage analysis of inflammatory bowel disease in the IBD1 region using severity to characterise Crohn's disease and ulcerative colitis.
European Journal of Human Genetics, 8 (11), .
(doi:10.1038/sj.ejhg.5200542).
Abstract
Inflammatory bowel disease (IBD) is a chronic relapsing disorder affecting the gastro-intestinal tract and is subdivided into two main subtypes: Crohn's disease (CD) and ulcerative colitis (UC). Although the aetiology of IBD is unknown, a strong genetic susceptibility is suggested and different candidate regions have been identified for both CD and UC. The IBD1 region on chromosome 16 has been confirmed to be important for susceptibility to CD, whereas conflicting evidence has been obtained for UC. We performed a combined linkage and segregation analysis in the identified IBD1 region on a sample of 82 extended families with IBD using a parametric method implemented in the computer program COMDS. This approach allows simultaneous evaluation of linkage while estimating the mode of inheritance and to include severity of the trait to characterise the CD and UC phenotypes. Our results are consistent with the presence of a major gene in the IBD1 region close to D16S408 involved in both UC and CD. Furthermore, our data support evidence that a single mutation in the gene leads more frequently to UC, whereas inheritance of two mutant alleles results in the more severe CD. In our study the IBD1 locus was found to have a major role in IBD predisposition in the Italian population.
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Published date: 31 October 2000
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Funding Information:
We thank the patients and their families who provided blood samples for the study. We also wish to thank Dr E Rappaport and two anonymous reviewers for their helpful comments and suggestions on this manuscript. The following investigators of the Italian Group for the Study of the Colon and Rectum (GISC) provided the family sample: G Iaquinto, I Sorrentini (Avellino); M Campieri, P Gionchetti, S Peruzzo (Bologna); D Valpiani, D Imperio (Forlì); G Frieri, MT Pimpo, R Caprilli (L’Aquila); S Giaccari, L Grasso (Galatina); G Riegler, F Morace, S Cucchiara (Napoli); A Andreoli, C Prantera, G Milite (Roma); GC Sturniolo, R D’Incà (Padova); M Astegiano, M Rizzetto, F Bresso, A Pera (Torino), G Lombardi, G Napolitano, A Piepoli, P Bovio (San Giovanni Rotondo). This work was supported in part by a grant from the Department of Pathology at the Children’s Hospital of Philadelphia, USA.
Keywords:
IBD1, Inflammatory bowel disease, Linkage, Segregation analysis
Identifiers
Local EPrints ID: 475432
URI: http://eprints.soton.ac.uk/id/eprint/475432
ISSN: 1018-4813
PURE UUID: 298c6c05-eb5a-4368-ad34-d57b6f0fae5b
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Date deposited: 17 Mar 2023 17:38
Last modified: 18 Mar 2024 02:38
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Contributors
Author:
Paola Forabosco
Author:
Anna Latiano
Author:
Vito Annese
Author:
Maurizio Clementi
Author:
Angelo Andriulli
Author:
Paolo Fortina
Author:
Marcella Devoto
Author:
Newton E. Morton
Corporate Author: et al.
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