Linkage analysis of HLA and candidate genes for celiac disease in a North American family-based study

BACKGROUND: Celiac disease has a strong genetic association with HLA. However, this association only explains approximately half of the sibling risk for celiac disease. Therefore, other genes must be involved in susceptibility to celiac disease. We tested for linkage to genes or loci that could play a role in pathogenesis of celiac disease. METHODS: DNA samples, from members of 62 families with a minimum of two cases of celiac disease, were genotyped at HLA and at 13 candidate gene regions, including CD4, CTLA4, four T-cell receptor regions, and 7 insulin-dependent diabetes regions. Two-point and multipoint heterogeneity LOD (HLOD) scores were examined. RESULTS: The highest two-point and multipoint HLOD scores were obtained in the HLA region, with a two-point HLOD of 3.1 and a multipoint HLOD of 5.0. For the candidate genes, we found no evidence for linkage. CONCLUSIONS: Our significant evidence of linkage to HLA replicates the known linkage and association of HLA with CD. In our families, likely candidate genes did not explain the susceptibility to celiac disease

Coeliac disease and Down syndrome: associations not due to genetic linkage on chromosome 21.

BACKGROUND: Individuals with Down syndrome have an increased prevalence of coeliac disease (CD). The HLA region accounts for only 30% of the heritability of CD, and segregation analyses have suggested the involvement of at least one other non-HLA gene. Distribution of known HLA susceptibility types in Down syndrome and normal populations are similar and do not explain the difference in disease frequency. This study tests the hypothesis that the association between these disorders is due to a susceptibility gene for coeliac disease being present on chromosome 21. METHODS: We studied 21 families multiply affected with CD, none of whom had Down syndrome. The typing information of six microsatellite markers across chromosome 21 was used to test likage. RESULTS: Negative results form lod score and model-free linkage analysis were obtained, providing no support for genetic linkage of coeliac disease to chromosome 21 in this population. CONCLUSIONS: The high prevalence of coeliac disease in Down syndrome is not due to an increased copy number of a polymorphic susceptibility gene on chromosome 21

Robotic system for magnetic resonance guided focused ultrasound ablation of abdominal cancer

Background A prototype robotic system that uses magnetic resonance guided focused ultrasound (MRgFUS) technology is presented. It features three degrees of freedom (DOF) and is intended for thermal ablation of abdominal cancer. Methods The device is equipped with three identical transducers being offset between them, thus focussing at different depths in tissue. The efficacy and safety of the system in ablating rabbit liver and kidney was assessed, both in laboratory and magnetic resonance imaging (MRI) conditions. Results Despite these organs' challenging location, in situ coagulative necrosis of a tissue area was achieved. Heating of abdominal organs in rabbit was successfully monitored with MR thermometry. Conclusions The MRgFUS system was proven successful in creating lesions in the abdominal area of rabbits. The outcomes of the study are promising for future translation of the technology to the clinic