Age of diagnosis-based linkage analysis in type 1 diabetes

Genetic linkage studies of type 1 diabetes have produced a number of conflicting results, suggesting a high degree of locus heterogeneity in this disease. Approaches which model such heterogeneity will increase the power to fine map susceptibility loci. Here, using data from a genome scan of 356 affected sib pairs with type 1 diabetes, we performed heterogeneity analysis based on similarity of age at diagnosis of the sib pairs. We observed linkage to the region on chromosome 4p16.3 in sib pairs both diagnosed over the age of 10 years, whilst there was no evidence for linkage in sib pairs diagnosed before age 10 years. In contrast the sib pairs diagnosed before the age of 10 years demonstrated linkage to IDDM10, on chromosome 10p. Age of diagnosis-based heterogeneity analyses in complex diseases may be particularly helpful in mapping some susceptibility loci.     

Sex of affected sibpairs and genetic linkage to type 1 diabetes

A mouse model of diabetes shows gender dimorphism in the cumulative incidence of diabetes. Based on this, evidence for genetic linkage to IDDM13 on chromosome arm 2q was reported to be greater in type 1 diabetes families where there was a predominance of affected female offspring compared with families with a predominance of affected male offspring. Our objective was to investigate whether the sex of affected offspring affects evidence for linkage to susceptibility loci. Data from a genome scan of 356 affected sibpair families with type 1 diabetes were analysed to determine if there is differential evidence for linkage in families with affected children of a particular sex. At markers on chromosomes 3, 5, 7, 9, 11, and 19, we found a number of regions where the evidence for linkage is greater in families with affected sibpairs of a particular sex. Thus, evidence for linkage in families with affected sibpairs of the same gender suggests the presence of additional susceptibility loci. Several biological explanations are possible for these findings, including X and Y linkage, effects of sex hormones on gene expression, and quasi-linkage between sex chromosomes and autosomes.     

The autoantigenic response to rabbit cytochrome c

In this report we describe the production and characterization of autoantibody responses to rabbit cytochrome c (cyt c) in rabbits immunized with either the native monomeric or polymerized form of rabbit cyt c. Fine-specificity analyses of the response indicated that the majority of the response was to the evolutionarily conserved amino-terminal region of the molecule. The relative affinity of the autoantibody interaction with rabbit cyt c was assessed by a solid-phase assay and was found to be lower than that observed for rabbit anti-horse cyt c antibody populations. These findings are consistent with the prediction that low-affinity self-reactive B cells may escape tolerance induction.     

Analysis and gene assignment of mRNAs of a paramyxovirus, simian virus 5

Polypeptides synthesized by the paramyxovirus SV5 in infected CV-1 cells were readily identified when the host cell was treated with actinomycin D. The unglycosylated forms of HN and Fo synthesized in infected cells in the presence of tunicamycin and HN and Fo synthesized in vitro were identified by immunoprecipitation with specific antibodies. Separation of SV5-specific poly(A)-containing RNAs on methyl-mercury agarose gels and in vitro translation of fractions, indicated that the viral polypeptides were translated from individual mRNAs except P (Mr approximately 44K) and the nonstructural polypeptide V (Mr approximately 24K) for which the mRNAs could not be separated. cDNA copies of SV5-specific mRNAs were synthesized and cloned in plasmid pBR322. Clones to NP, P + V, M, F, and HN were identified by hybrid-arrest and hybrid-selection translation of SV5 mRNAs. Tryptic peptide mapping of polypeptides P and V indicated that the peptides of V were a subset of those of P. Hybridization of cDNA probes to infected cell mRNAs separated on agarose gels permitted identification of the NP, P + V, M, F, and HN mRNAs and presumptive polycistronic mRNAs. The sizes and sequence homologies of these polycistronic mRNAs were used to derive a likely gene order on the SV5 50 S genome RNA.     

Measuring changes in self-concept: a qualitative evaluation of outcome questionnaires in people having acupuncture for their chronic health problems

Background  

Changes in self-concept are an important potential outcome for many interventions for people with long-term conditions. This study sought to identify and evaluate outcome questionnaires suitable for quantifying changes in self-concept in people with long-term conditions, in the context of treatment with acupuncture and Chinese medicine.     

Exclusion of the alpha 1(II) cartilage collagen gene as the mutant locus in type IA osteogenesis imperfecta.

Using two restriction site polymorphisms within the structural gene coding for human type II collagen we have examined the segregation of this gene in three pedigrees with dominantly inherited osteogenesis imperfecta (Sillence type IA). We have demonstrated that the gene does not segregate with clinical expression of the disease and cannot, therefore, contain the mutation responsible for osteogenesis imperfecta in these families.