Biomedical subjects

J I Rotter

Publications and source records attributed to J I Rotter.

184 records · Page 11Linked to original sources

PubMedDate not supplied

The genetic background of inflammatory bowel disease.

Available evidence indicates that genetic factors are essential in providing the susceptibility to the majority of the various forms of inflammatory bowel disease occurring in man. It is also clear that the genetic susceptibility to these diseases is complex, and that more than one gene may predispose (the concept of multilocus/oligogenic inheritance), and likely in different etiologic combinations (the concept of genetic heterogeneity). Paradigms are now available that should lead to the identification of a number of these predisposing genes. These paradigms include the candidate gene approach, systematic genome wide scans, and mouse human synteny. While genome wide scans are currently limited to multiplex family linkage studies, both candidate genes and mouse human synteny can be approached in either linkage or association paradigms. Eventually whole genome association studies will be available as well. Identification of inflammatory bowel disease predisposing genes should lead to their incorporation in studies of natural history, investigation of environmental risk factors, and especially utilization of genetic markers in clinical trials. This will allow us to identify the best therapy available for the individual patient based on their unique genetic constitution. With advances in molecular technology, the search for genes influencing traits and diseases with a complex genetic background, such as the inflammatory bowel diseases, has become a realistic task. Although exogenous or infectious agents may contribute to the pathogenesis or may trigger the onset of disease, and the immune system almost certainly mediates the tissue damage, it is clear from available data that genetic factors determine the susceptibility of a given individual to inflammatory bowel disease (reviewed below). Thus, genetic studies are essential for the delineation of the basic etiologies of the various forms of inflammatory bowel disease and thus can aid in the development of radically new and specific therapies. In this review, we will discuss the importance and complexity of genetic factors in inflammatory bowel disease, methods and problems in the genetic dissection of complex traits, and future directions of genetic studies in inflammatory bowel disease.

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PubMedDate not supplied

Restriction fragment length polymorphism (RFLP) heterogeneity of HLA-DQ beta genes associated with DNA fragment identical to the DR1-beta DNA structure.

Restriction fragment length polymorphism (RFLP) analyses of DR1 positive peripheral blood leukocytes DNA was carried out. The Taq I digested DNA was hybridized with cDNA probes for HLA-DR and -DQ beta genes. The DR probe detected fragments commonly observed in the DR1 specificity, whereas a new DQ-beta fragment was detected in some DR1 haplotypes when the DQ-beta probe was used. This fragment had an RFLP pattern identical to the DQ-beta fragment typically associated with most DR2 and some DRw6 specificities.

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PubMedDate not supplied

Application of synthetic oligonucleotides to detect DQ beta genes transmission within insulin-dependent diabetes families.

Class II antigen genes encoded by the major histocompatibility complex region (HLA-D region) in man play an important role in susceptibility to insulin dependent diabetes mellitus (IDDM). Evidence suggests that the DQ subregion within the HLA-D region is more directly responsible for susceptibility to IDDM. Therefore, we designed a synthetic oligonucleotide specific for the DQ beta gene to further the understanding of the disease association with HLA-D region genes at the molecular level. Restriction fragment length polymorphism (RFLP) analysis was carried out using DNA isolated from nine families, each including at least two affected siblings (a total of 37 siblings). The segregation pattern of hybridizing fragments showed that: (1) for each of the DR2, DR3, and DR4 specificities, two different alleles can be identified by the DQ beta probe; (2) a 1.9 kb-Taq 1 fragment with the DR4 specificity and a 6.0 kb-Taq-1 fragment within the DR2 specificity tend to cosegregate with IDDM; (3) there was no preferential segregation of the two alleles detected within the DR3 specificity (one allele identified by a 4.7 kb-Taq 1 fragment is quite common among individuals with the DR3 specificity). The results from this study add to the evidence that certain DQ alleles appear to be more directly associated with the diabetogenic gene (or genes) in certain DR specificities.

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PubMedDate not supplied

The genetic basis of systemic lupus erythematosus.

Although cumulative evidence suggests that a genetic predisposition plays a major role in the development of systemic lupus erythematosus (SLE), the susceptibility genes are mostly unknown. The difficulty in identifying susceptibility genes is due in part to the inherent nature of this polygenic complex disease and the diverse genetic backgrounds of human populations. Murine SLE models that have homogenous genetic backgrounds are less complex for genetic dissection. Genome-wide linkage studies of murine SLE have mapped the position of a number of susceptibility loci. Recently, several of these major murine loci have been shown to link to different clinical and laboratory features of lupus-like phenotypes. In addition, evidence for additional genetic contributions via interaction between murine loci has been reported. In human SLE, many polymorphic genes (which have potential roles in SLE, as suggested by their known functions) have been associated with SLE or SLE subsets by population-based case-control or within-case studies. Because more compelling genetic evidence includes linkage analysis, our group has used the identified murine susceptibility loci as a guide and conducted linkage analysis of genetic markers located within a specific, possibly syntenic human chromosomal region. Evidence for linkage of a chromosome 1q41-42 region was observed in SLE-affected sibling pairs from multiple ethnic groups. This article summarizes recent developments and outlines possible future directions in delineating the genetic basis of SLE.

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