Assuntos
Cromossomos Humanos X/genética , Variações do Número de Cópias de DNA/genética , Fator VIII/genética , Hemofilia A/epidemiologia , Hemofilia A/genética , Íntrons/genética , Europa (Continente)/epidemiologia , Feminino , Estudos de Associação Genética , Marcadores Genéticos/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Hemofilia A/diagnóstico , Humanos , Masculino , PrevalênciaRESUMO
We established a radiation hybrid (RH) map of several genes and anonymous markers in the lower half of rat chromosome 2, a chromosome region that contains quantitative trait loci (QTLs) for blood pressure, diabetes and inflammatory response. Two of the newly localized genes (Crh and Il6r) encode proteins involved in the regulation of inflammatory and immune events. Our data show that they reside within regions that were genetically defined as QTLs controlling the inflammatory response. These genes are thus both functional and positional candidates.
Assuntos
Hormônio Liberador da Corticotropina/genética , Inflamação/genética , Característica Quantitativa Herdável , Mapeamento de Híbridos Radioativos , Receptores de Interleucina-6/genética , Animais , Genes , Marcadores Genéticos , Hibridização in Situ Fluorescente , Escore Lod , Ratos , SoftwareRESUMO
The rat strain COP is resistant to spontaneous and carcinogen-induced mammary cancer, whereas the strain WF is susceptible. Using genetic linkage analysis of (WF x COP) F1 x WF backcrosses, LC Hsu, LA Shepel and co-workers showed that a region at the centromeric end of Chromosome (Chr) 2 (2q1) segregates with the sensitivity to mammary cancer development. The responsible locus was named Mcs1 (for mammary cancer susceptibility 1). We have developed the chromosome map of the 2q1 region by localizing 18 genes, 4 ESTs, and several anonymous markers, using radiation hybrids and fluorescence in situ hybridization. The region containing Mcs1 was delineated to 2q12-q14. Five of the genes (Mef2c, Map1b, Ccnh, Rasa, Rasgrf2) were assigned to this region and were shown to be expressed in the rat mammary glands, while three possible functional candidate genes, Pi3kr1, Rad17, and Naip, were excluded from the critical region. Since cyclin H, encoded by Ccnh, plays an important role in the control of the cell cycle and since the proteins encoded by Rasa and Rasgrf2 control the activity of the RAS oncoprotein, the corresponding genes appeared as both functional and positional Mcs1 candidates. RT-PCR experiments on RNA extracted from mammary glands of the two rat strains (COP, WF) was done. No amino acid sequence difference was found between the two strains. These results argue against the hypothesis that any of these three genes is Mcs1.
Assuntos
Neoplasias Mamárias Experimentais/genética , Animais , Sequência de Bases , DNA Complementar , Etiquetas de Sequências Expressas , Humanos , Imunidade Inata/genética , Camundongos , Dados de Sequência Molecular , Mutagênese , RatosRESUMO
The centromeric region of rat chromosome 2 (2q1) harbors unidentified quantitative trait loci of genes that control tumor growth or development. To improve the mapping of this chromosome region, we microdissected it and generated 10 new microsatellite markers, which we included in the linkage map and/or radiation hybrid map of 2q1, together with other known markers, including four genes: Pcsk1 (protein convertase 1), Dhfr (dihydrofolate reductase), Ndub13 (NADH ubiquinone oxidoreductase subunit b13), and Ccnb1 (cyclin B1). To generate anchor points between the different maps, the gene Ndub13 and the microsatellite markers D2Ulb25 and D2Mit1 were also localized cytogenetically. The radiation map generated in region 2q1 extends its centromeric end of about 150 cR.
