LINKAGE ANALYSES OF CHROMOSOME-6 LOCI, INCLUDING HLA, IN FAMILIAL AGGREGATIONS OF CROHN DISEASE

Segregation analyses of familial aggregations of Crohn disease have pr ovided consistent results pointing to the involvement of a predisposin g gene with a recessive mode of inheritance. Although extensively inve stigated, the role played by human leucocyte antigen (HLA) genes in th is inflammatory bowel disease remains elusive and the major histocompa tibility complex is a candidate region for the mapping of the Crohn di sease susceptibility gene. A total of 25 families with multiple cases of Crohn disease was genotyped for HLA DRB1 and for 16 highly polymorp hic loci evenly distributed on chromosome 6. The data were subjected t o linkage analysis using the lod score method. Neither individual nor combined led scores for any family and for any locus tested reached va lues suggesting linkage or genetic heterogeneity. The Crohn disease pr edisposing locus was excluded from the whole chromosome 6 with lod sco res less than -2. It was excluded from the major histocompatibility co mplex and from 91% of the chromosome 6 genetic map with lod scores les s than -4. The major recessive gene involved in genetic predisposition to Crohn disease does not reside on the major histocompatibility comp lex nor on any locus mapping to chromosome 6. (C) 1994 Wiley-Liss, Inc .