International collaboration provides convincing linkage replication in complex disease through analysis of a large pooled data set: Crohn disease and chromosome 16
| Autor: | Cavanaugh, J. A., Bryce, M. E., Stanford, P. M., Pavli, P., Vermeire, S., Peeters, M., Vlietinck, R., Rutgeerts, P., Rioux, J. D., Silverberg, M. S., Steinhart, A. H., Siminovitch, K. A., Hugot, J. P., Lesage, S., Zouali, H., Paavola, P., Halme, L., Färkkilä, M., Kontula, K., Annese, V., Forabosco, P., Fortina, P., Latiano, A., Van Heel, D., Parkes, M., Lench, N., Jewell, D., Brant, S. R., Bailey-Wilson, J. E., Panhuysen, C. I. M., Bayless, T. M., Cho, J. H., Bonen, D. K., Kirschner, B. S., Hanauer, S. B., Yang, H., Taylor, K., Targan, S. R., Rotter, J. I., Silver, J., Gulwani-Akolkar, B., Akolkar, P., Lin, X. -Y., Duerr, R. H., Zhang, L., Achkar, J. P., Baldassano, R. N., Daly, M. J., Risch, N. |
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| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Male
Genetic Linkage International Cooperation Ulcerative 0302 clinical medicine Chromosome Mapping Chromosomes Human Pair 12 Chromosomes Human Pair 16 Colitis Ulcerative Crohn Disease European Continental Ancestry Group Family Characteristics Female Genetic Heterogeneity Genetic Markers Genetic Predisposition to Disease Genotype Humans Jews Lod Score Microsatellite Repeats Models Genetic Nuclear Family Reproducibility of Results Statistics Nonparametric Genetics Genetics (clinical) Models Pair 12 Genetics(clinical) 0303 health sciences Statistics Articles Colitis 3. Good health symbols Microsatellite 030211 gastroenterology & hepatology Human Locus (genetics) Biology White People Chromosomes 03 medical and health sciences symbols.namesake Chromosome 16 Genetic Genetic linkage Nonparametric Genotyping Chromosome 12 030304 developmental biology Genetic heterogeneity Pair 16 Mendelian inheritance |
| Popis: | Numerous familial, non-Mendelian (i.e., complex) diseases have been screened by linkage analysis for regions harboring susceptibility genes. Except for rare, high-penetrance syndromes showing Mendelian inheritance, such as BRCA1 and BRCA2, most attempts have failed to produce replicable linkage findings. For example, in multiple sclerosis and other complex diseases, there have been many reports of significant linkage, followed by numerous failures to replicate. In inflammatory bowel disease (IBD), linkage to two regions has elsewhere been reported at genomewide significance levels: the pericentromeric region on chromosome 16 (IBD1) and chromosome 12q (IBD2). As with other complex diseases, the subsequent support for these localizations has been variable. In this article, we report the results of an international collaborative effort to investigate these putative localization by pooling of data sets that do not individually provide convincing evidence for linkage to these regions. Our results, generated by the genotyping and analysis of 12 microsatellite markers in 613 families, provide unequivocal replication of linkage for a common human disease: a Crohn disease susceptibility locus on chromosome 16 (maximum LOD score 5.79). Despite failure to replicate the previous evidence for linkage on chromosome 12, the results described herein indicate the need to further investigate the potential role of this locus in susceptibility to ulcerative colitis. This report provides a convincing example of the collaborative approach necessary to obtain the sample numbers required to achieve statistical power in studies of complex human traits. |
| Databáze: | OpenAIRE |
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