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Genetic analysis workshop IV: summary for coeliac disease.


Two groups analyzed the pedigrees with CD using two different approaches. Louis et al (1986, referred to as Louis) first analyzed the haplotype information to determine which HLA antigens were significantly associated with CD. Subsequently, they used the antigen genotype frequencies among patients (AGFAP) method (Thomson, 1983) to determine the mode of inheritance of the HLA-linked susceptibility gene and to determine the number of possible alleles at that locus. Sherman et al (1986, referred to as Sherman) used the method of MacLean et al (1984) which combines segregation, linkage and association information to define the susceptibility locus. The model assumed that the phenotype of an individual was the result of independent contributions of a genetic component and random environment. The genetic contribution was partitioned into two components: the effect due to the major gene which is linked to HLA and the effect due to the modifier which is not linked to HLA. The modifier was included to absorb additional family resemblance such as polygenes or environmental factors. Both groups analyzed the Liverpool data of Ellis et al (1981) separately. The data of Tiwari et al (1984) was analyzed as one data set by Sherman whereas Louis used a subset of these data, first analyzing the 30 BLG French families and subsequently combining the 13 probands from the BET French families. Both groups used similar association information to define the segregation of the HLA-linked susceptibility gene. Louis found that the haplotype A1-B8 was significantly associated with CD in the Liverpool data and that the DR3 and DR7 specificities were significantly associated in the French data.(ABSTRACT TRUNCATED AT 250 WORDS).

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