Biomedical subjects

O Nerman

Publications and source records attributed to O Nerman.

4 recordsLinked to original sources

PubMed2001

Rat-mouse and rat-human comparative maps based on gene homology and high-resolution zoo-FISH.

The laboratory rat, Rattus norvegicus, and the laboratory mouse, Mus musculus, are key animal models in biomedical research. A deeper understanding of the genetic interrelationsships between Homo sapiens and these two rodent species is desirable for extending the usefulness of the animal models. We present comprehensive rat-human and rat-mouse comparative maps, based on 1090 gene homology assignments available for rat genes. Radiation hybrid, FISH, and zoo-FISH mapping data have been integrated to produce comparative maps that are estimated to comprise 83-100% of the conserved regions between rat and mouse and 66-82% of the conserved regions between rat and human. The rat-mouse zoo-FISH analysis, supported by data for individual genes, revealed nine previously undetected conserved regions compared to earlier reports. Since there is almost complete genome coverage in the rat-mouse comparative map, we conclude that it is feasible to make accurate predictions of gene positions in the rat based on gene locations in the mouse.

Animals↗

PubMed2001

Genome-wide linkage analysis of Scandinavian affected sib-pairs supports presence of susceptibility loci for celiac disease on chromosomes 5 and 11.

Celiac disease (CD) is a common chronic inflammatory disorder of the small intestine with a multifactorial aetiology. HLA is a well-known risk factor, but other genetic factors also influence disease susceptibility. To identify the genes involved in this disorder, we performed a genome-wide scan on 106 well-defined Swedish and Norwegian families with at least two affected siblings. We investigated familial segregation of 398 microsatellite markers, and utilised non-parametric linkage analysis. The strongest linkage with disease was found to the HLA locus (6p) (P<0.000006). There were eight regions besides HLA with a point wise P value below 0.05. Among these eight regions were 11q and 5q, both of which have been suggested in several linkage studies of independent celiac disease families. We also performed a stratification analysis of families according to their HLA genotypes. This resulted in significant differences on chromosome 2q. These results indicate that 11q, 5q and possibly also 2q are true susceptibility regions in CD.

Adolescent↗

PubMed2000

The CTLA4/CD28 gene region on chromosome 2q33 confers susceptibility to celiac disease in a way possibly distinct from that of type 1 diabetes and other chronic inflammatory disorders.

The effect of the gene region on chromosome 2q33 containing the CD28 and the cytotoxic T-lymphocyte associated (CTLA4) genes has been investigated in several diseases with chronic inflammatory nature. In addition to celiac disease (CD), type I diabetes, Grave's disease, rheumatoid arthritis and multiple sclerosis have all demonstrated associations to the A/G single nucleotide polymorphism (SNP) in exon 1, position +49 of the CTLA4 gene. The purpose of this study was to investigate this gene region in a genetically homogeneous population consisting of 107 Swedish and Norwegian families with CD using genetic association and linkage methods. We found a significant association with preferential transmission of the A-allele of the exon 1 +49 polymorphism by using the transmission disequilibrium test (TDT). Suggestive linkage of this region to CD was moreover demonstrated by non-parametric linkage (NPL) analysis giving a NPL-score of 2.1. These data strongly indicates that the CTLA4 region is a susceptibility region in CD. Interestingly, of the several chronic inflammatory diseases that exhibit associations to the CTLA4 +49 A/G dimorphism, CD appears to be the only disease associated to the A allele. This suggests that the +49 alleles of the CTLA4 gene are in linkage disequilibrium with two distinct disease predisposing alleles with separate effects. The peculiar association found in the gut disorder CD may possibly relate to the fact that the gastrointestinal immune system, in contrast to the rest of the immune system, aims to establish tolerance to foreign proteins.

Abatacept↗

PubMed1999

A parametric estimation procedure for relapse time distributions.

In a relapse clinical trial patients who have recovered from some recurrent disease (e.g., ulcer or cancer) are examined at a number of predetermined times. A relapse can be detected either at one of these planned inspections or at a spontaneous visit initiated by the patient because of symptoms. In the first case the observations of the time to relapse, X, is interval-censored by two predetermined time-points. In the second case the upper endpoint of the interval is an observation of the time to symptoms, Y. To model the progression of the disease we use a partially observable Markov process. This approach results in a bivariate phase-type distribution for the joint distribution of (X, Y). It is a flexible model which contains several natural distributions for X, and allows the conditional distributions of the marginals to smoothly depend on each other. To estimate the distributions involved we develop an EM-algorithm. The estimation procedure is evaluated and compared with a non-parametric method in a couple of example based on simulated data.

Algorithms↗