Biomedical subjects

D M Shubitowski

Publications and source records attributed to D M Shubitowski.

3 recordsLinked to original sources

PubMed2002

The complement factor 5a receptor gene maps to murine chromosome 7.

Complement factor 5a (C5a) promotes local inflammation and is a potent chemoattractant for neutrophils and macrophages. We had an interest in C5a and its receptor, C5r1, because we previously identified C5a as a positional candidate gene for the quantitative trait locus Abhr2, which determines allergen-induced bronchial hyperresponsiveness in our murine model of asthma. To study the significance of C5r1 in our asthma model we first had to determine its genomic map location in mice. Genomic sequence surrounding murine C5r1 was analyzed for polymorphisms and two variable microsatellites were identified. These microsatellites were genotyped in A/J x (C3H/HeJ x A/J)F1 backcross mice (n = 355) and mapped in a panel of 164 markers spaced at approximately 10 cM intervals throughout the genome. Multipoint linkage analysis placed C5r1 on murine chromosome 7, 3.9 cM from the top of the linkage group. This map location has been previously identified as containing an additional quantitative trait locus for allergen-induced airway hyperresponsiveness, Abhr3, in this population of mice.

Animals↗

PubMed2001

Polymorphism identification within 50 equine gene-specific sequence tagged sites.

The continued discovery of polymorphisms in the equine genome will be important for future studies using genomic screens and fine mapping for the identification of disease genes. Segments of 50 equine genes were examined for variability in 10 different horse breeds using a pool-and-sequence method. We identified 11 single nucleotide polymorphisms (SNPs) in 9380 bp of sequenced exon, and 25 SNPs, six microsatellites, and one insertion/deletion in 16961 bp of sequenced intron. Of all genes studied 52% contained at least one polymorphism, and polymorphisms were found at an overall rate of 1/613 bp. Several of the putative SNPs were tested and verified by restriction enzyme analysis using natural restriction sites or ones created by primer mutagenesis. The lowest allele frequency for a SNP detected in pooled samples was 10%. Three of the SNPs verified in the diverse horse pool were further tested in six breed-specific horse pools and were found to be reasonably variable within breeds. The pool-and-sequence method allows identification of polymorphisms in horse populations and will be a valuable tool for future disease gene and comparative mapping in horses.

Animals↗

PubMed2000

Quantitative trait loci controlling allergen-induced airway hyperresponsiveness in inbred mice.

Identification of the genetic loci underlying asthma in humans has been hampered by variability in clinical phenotype, uncontrolled environmental influences, and genetic heterogeneity. To circumvent these complications, the genetic regulation of asthma-associated phenotypes was studied in a murine model. We characterized the strain distribution patterns for the asthma-related phenotypes airway hyperresponsiveness (AHR), lung eosinophils, and ovalbumin (OVA)-specific serum immunoglobulin (Ig) E induced by allergen exposure protocols in A/J, AKR/J, BALB/cJ, C3H/HeJ, and C57BL/6J inbred strains and in (C3H/HeJ x A/J)F1 mice. Expression of AHR differed between strains and was sometimes discordant with lung eosinophils or serum IgE. Furthermore, we identified two distinct quantitative trait loci (QTL) for susceptibility to allergen-induced AHR, Abhr1 (allergen-induced bronchial hyperresponsiveness) (lod = 4. 2) and Abhr2 (lod = 3.7), on chromosome 2 in backcross progeny from A/J and C3H/HeJ mice. In addition, a QTL on chromosome 7 was suggestive of linkage to this trait. These QTL differ from those we have previously found to control noninflammatory AHR in the same crosses. Elucidation of the genes underlying these QTL will facilitate the identification of biochemical pathways regulating AHR in animal models of asthma and may provide insights into the pathogenesis of human disease.

Allergens↗