Biomedical subjects

R W Doerge

Publications and source records attributed to R W Doerge.

6 recordsLinked to original sources

PubMed1998

Autoimmune orchitis, epididymitis, and vasitis are immunogenetically distinct lesions.

Experimental allergic orchitis (EAO), the principle animal model of noninfectious testicular inflammatory disease, is a genetically determined phenotype. Classical EAO, induced by inoculation with testicular homogenate and the appropriate adjuvants, is characterized by inflammatory infiltrates in the testis (orchitis), epididymis (epididymitis), and vas deferens (vasitis). In this study, the genetic control of susceptibility and resistance to these three lesions was analyzed in the mouse. The results obtained with independent inbred strains and H2 congenic mice show that the genetic control of all three lesions is complex and involves both H2 and non-H2-linked genes. Whole-genome exclusion mapping was performed on a backcross population segregating for all three phenotypes. Permutation-derived thresholds provided experimentwise, chromosomewise, comparisonwise, and marker-specific chromosomewise thresholds for declaration of significant regions linked to marker loci. Unique loci were identified on chromosome 8 for orchitis, chromosome 16 for epididymitis, and chromosome 1 for vasitis and have been designated as Orch6, Epd1, and Vas1, respectively. These results show that autoimmune orchitis, epididymitis, and vasitis are immunogenetically distinct lesions.

Animals↗

PubMed1997

Evidence that Tmevd2 and eae3 may represent either a common locus or members of a gene complex controlling susceptibility to immunologically mediated demyelination in mice.

Theiler's murine encephalomyelitis virus (TMEV)-induced demyelination and experimental allergic encephalomyelitis are the principal immunologically mediated, genetically controlled models of multiple sclerosis. Previous studies using different mapping techniques identified susceptibility loci for both diseases on chromosomes 3, 6, and 17. To more precisely map these TMEV and experimental allergic encephalomyelitis loci relative to each other, linkage analysis using microsatellite markers and a (BALB/cByJ x DBA/2J) x BALB/cByJ backcross population segregating for TMEV-induced disease was conducted. Comparisonwise and chromosomewise critical values based on permutation theory were estimated for each chromosome. Evidence for linkage to markers on chromosome 17 was not seen. Chromosomewise linkage (p = 0.13) was detected with D6 Mit36 and D6 Mit149 (marker-specific chromosomewise p values = 0.02) at 40.4 cM on chromosome 6. Chromosomewise linkage (p < 0.01) (marker-specific chromosomewise p value = 0.0) and comparisonwise linkage (p < < 0.0001) to D3 Mit156 at 33.9 cM on chromosome 3 were observed along with chromosomewise linkage (p < 0.05) and comparisonwise linkage (p < < 0.0001) to D3 Mit29, D3 Mit311, D3 Mit28, and D3 Mit11 from 33.9 to 37.2 cM, respectively. Significant linkage to D3 Mit156 places Tmevd2 1.1 cM proximal of D3 Mit101 (35 cM), the maximally linked marker to the eae3 susceptibility gene. Maximum likelihood estimates conducted by multilocus linkage analysis localized Tmevd2 within a 95% confidence interval bordered by D3 Mit29 and D3 Mit10, at 33.9 and 37.2 cM, respectively. Taken together these results suggest that Tmevd2 and eae3 may represent either a single, common susceptibility gene or members of a gene complex involved in central nervous system immunopathology.

Animals↗

PubMed1996

Permutation tests for multiple loci affecting a quantitative character.

The problem of detecting minor quantitative trait loci (QTL) responsible for genetic variation not explained by major QTL is of importance in the complete dissection of quantitative characters. Two extensions of the permutation-based method for estimating empirical threshold values are presented. These methods, the conditional empirical threshold (CET) and the residual empirical threshold (RET), yield critical values that can be used to construct tests for the presence of minor QTL effects while accounting for effects of known major QTL. The CET provides a completely nonparametric test through conditioning on markers linked to major QTL. It allows for general nonadditive interactions among QTL, but its practical application is restricted to regions of the genome that are unlinked to the major QTL. The RET assumes a structural model for the effect of major QTL, and a threshold is constructed using residuals from this structural model. The search space for minor QTL is unrestricted, and RET-based tests may be more powerful than the CET-based test when the structural model is approximately true.

Alleles↗

PubMed1995

QTL mapping in rice.

In the past 10 years, interest in applying the tools of molecular genetics to the problem of increasing world rice production has resulted in the generation of two highly saturated, molecular linkage maps of rice, and the localization of numerous genes and quantitative trait loci (QTLs). Primary studies have identified QTLs associated with disease resistance, abiotic stress tolerance and yield potential of rice in a range of ecosystems. The ability to identify, manipulate and potentially clone individual genes involved in quantitatively inherited characters, combined with the demonstrated conservation of numerous linkage blocks among members of the grass family, emphasizes the contribution of map-based genetic analyses both to applied and to basic crop research.

Chromosome Mapping↗

PubMed1994

Empirical threshold values for quantitative trait mapping.

The detection of genes that control quantitative characters is a problem of great interest to the genetic mapping community. Methods for locating these quantitative trait loci (QTL) relative to maps of genetic markers are now widely used. This paper addresses an issue common to all QTL mapping methods, that of determining an appropriate threshold value for declaring significant QTL effects. An empirical method is described, based on the concept of a permutation test, for estimating threshold values that are tailored to the experimental data at hand. The method is demonstrated using two real data sets derived from F(2) and recombinant inbred plant populations. An example using simulated data from a backcross design illustrates the effect of marker density on threshold values.

Chromosome Mapping↗

PubMedDate not supplied

Testing for linkage: phase known/unknown.

It has been well established in human genetics that when one is testing for linkage between two loci, the significance test must be one-sided for the purpose of reflecting the theoretical limits placed on the estimated recombination fraction. However, the issue becomes obscure when phase-known/-unknown data are considered. This paper presents the subtle difference in hypotheses for testing linkage between two loci when data from which one estimates recombination fractions is phase known or phase unknown. It is shown that a one-sided significance test is appropriate for phase-known data, while a two-sided significance test is correct for phase-unknown data.

Alleles↗