title: Variants within protectin (CD59) and CD44 genes linked to an inherited haplotype in a family with coeliac disease.
abstract: Coeliac disease (CD) is an autoimmune disorder characterised by inflammation, villous atrophy and hyperplasia of the small intestinal mucosa that affects genetically susceptible individuals. A genome-wide scan was performed in 17 family members with high incidence of CD. Highest nonparametric linkage (NPL) and logarithm of odds (LOD) scores were of 6.21 (P = 0.0107) and 2.57, respectively, to a region on chromosome 11p13-12. Following fine mapping, NPL and LOD scores did not change, but the linkage interval on chromosome 11 was narrowed to a region that is approximately 50.94 cM from pTer. Two inherited haplotypes on chromosomes 11p13-12 and 9q21 were observed in all affected members but not in the majority of clinically normal individuals. Sequencing of genes at region 11p13-12 showed a number of sequence variants, two of which were linked with the inherited haplotype. One of these variants in the CD59 gene was found at a very low frequency in the population and could possibly affect pre-messenger RNA splicing. This study is of particular importance for the identification of novel genes that might be responsible for CD other than human leukocyte antigen.
authors.affiliation: Laboratory of Molecular Genetics, Department of Physiology and Biochemistry, University of Malta, Msida, Malta.
authors.forename: C
authors.initials: C
authors.lastname: Vidal
authors.forename: J
authors.initials: J
authors.lastname: Borg
authors.forename: A
authors.initials: A
authors.lastname: Xuereb-Anastasi
authors.forename: C A
authors.initials: CA
authors.lastname: Scerri
mesh_terms: D001483:Base Sequence; D018957:CD59 Antigens / Q000235:genetics*; D002446:Celiac Disease / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D012326:RNA Splicing
chemical_list: C497483:CD44 protein, human; D018957:CD59 Antigens; D018960:Hyaluronan Receptors; C051590:CD59 protein, human