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A strong major gene effect in the isolated, hyperendemic Prata Colony indicates enrichment of genetic risk factors, suggesting a population particularly suitable for leprosy gene identification studies.

A supplemental appendix to this article is published electronically only at http://jdr.sagepub.com/supplemental. AbSTRACT Despite recent advances revealing genetic factors influencing caries susceptibility, questions regarding the model of inheritance involved are yet to be addressed. We conducted a Complex Segregation Analysis on decayed teeth in a sample of homogenous, isolated families recruited from the Brazilian Amazon. A dominant, major gene effect controlling resistance to phenotype was detected. The frequency of the resistance allele "A" was 0.63; mean numbers of decayed teeth were 1.53 and 9.53 for genotypes AA/AB and BB, respectively. These results represent a step toward a description of the exact nature of the genetic risk factors controlling human susceptibility to caries.

Celiac disease (CD) is characterized by a striking expansion of gamma delta T cells in the intestine. These cells interact with MICA, a cell surface protein encoded by a major histocompatibility complex gene. We investigated whether MICA gene polymorphism could contribute to susceptibility to CD. DNA typing for HLA-DR, DQA1, DQB1, TNF-308, TNFa, TNFb and a triplet repeat polymorphism in the transmembrane region of the MICA gene were carried out. We performed case-control stratified association studies and transmission disequilibrium tests. Our results indicate that although there is no primary association between MICA polymorphism and CD, there is, in addition to HLA-DQ, a second susceptibility locus on the 8.1 ancestral haplotype in strong linkage disequilibrium with MICA A5.1 allele.

Idiopathic achalasia is a motility disorder of the esophagus whose etiology is unknown. An association between HLA genes and susceptibility to achalasia which suggests a possible immunogenetic mechanism has been reported recently. This study was designed to examine the HLA class II association in a large group of achalasia patients further and to investigate the distribution of TNFa and TNFb microsatellites in these patients. The study population, all Spanish, white and unrelated, consisted of 115 consecutive patients and 339 healthy controls. All of the patients had been diagnosed with primary achalasia of the esophagus with manometric, radiographic and endoscopic studies. All studies were performed on DNA samples after locus-specific amplification with the polymerase chain reaction: HLA-DRB1, DQA1 and DQB1 were typed by dot-blot hybridization and the size of the TNFa and TNFb microsatellites was measured using a semiautomatic method. The broad allele HLA-DQ1 was seen to be weakly associated with achalasia. The TNFa11 allele and the DRB1*1501-DQA1*0102-DQB1*0602 haplotype were reduced in achalasia patients but the stratified analyses showed that this was true only when both were present in the same individual. These results confirm the association between achalasia and HLA-DQ1 allele and suggest that TNFa11 is a marker for a protective allele for the disease, present on the B7-DRB1*1501 (7.1) ancestral haplotype in our population.

Selective IgA deficiency (IgAD) is the most common form of primary immunodeficiency. Its association with genes within the major histocompatibility complex (MHC) has been repeatedly reported. Recently the susceptibility gene has been located in the class III region, around the tumor necrosis factor (TNF) cluster. In this study we have examined IgAD association with TNF-alpha gene promoter polymorphisms and TNFa and b microsatellites. No significant association was found with the former polymorphisms and the observed associations with TNFa2 allele and haplotypes TNFa2b1 and TNFa2b3 were proven to be secondary to their occurrence on the B14-DR1 and B8-DR3 haplotypes, previously reported to be associated with susceptibility to IgAD. However, a primary negative (protective) association was found between the TNFa10 allele and IgAD.

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