RESUMO
Fifty-five novel rat microsatellite markers were isolated from libraries specific for rat chromosomes (Chrs) 1, 2, and 7. The markers were mapped in three backcross rat populations. Thirty of these markers mapped to Chrs 1, 2, or 7, while the other 25 mapped to other chromosomes. New markers for two genes, liver-specific transporter gene (Livtr) and insulin-responsive glucose transporter (Glut4), were also mapped to rat Chrs 9 and 10, respectively. Three provisionally assigned markers from previous studies were also confirmed. Detailed methodologies for the generation and enrichment of clones containing repeat sequences and for the isolation of chromosome-specific markers are presented, since they represent unique combinations and modifications of previous protocols. Such methods and the newly presented markers should be useful for both specific and general mapping studies in the rat.
Assuntos
Mapeamento Cromossômico , Biblioteca Gênica , Repetições de Microssatélites , Proteínas Musculares , Ratos Endogâmicos/genética , Animais , Sequência de Bases , Proteínas de Transporte/genética , Cruzamentos Genéticos , Feminino , Ligação Genética , Marcadores Genéticos , Transportador de Glucose Tipo 4 , Fígado/metabolismo , Masculino , Dados de Sequência Molecular , Proteínas de Transporte de Monossacarídeos/genética , Reação em Cadeia da Polimerase , Ratos , Ratos Endogâmicos F344/genética , Ratos Endogâmicos WF/genética , Ratos Endogâmicos WKY/genéticaRESUMO
We have used a rat model of induced mammary carcinomas in an effort to identify breast cancer susceptibility genes. Using genetic crosses between the carcinoma-resistant Copenhagen (COP) and carcinoma-sensitive Wistar-Furth rats, we have confirmed the identification of the Mcs1 locus that modulates tumor number. We have now also identified two additional loci, Mcs2 and Mcs3. These three loci map to chromosomes 2, 7, and 1, respectively, and interact additively to suppress mammary carcinoma development in the COP strain. They are responsible for a major portion of the tumor-resistant phenotype of the COP rat. No loss of heterozygosity was observed surrounding the three loci. A fourth COP locus, Mcs4, has also been identified on chromosome 8 and acts in contrast to increase the number of carcinomas. These results show that mammary carcinoma susceptibility in the COP rat is a polygenic trait. Interestingly, a polymorphism in the human genomic region homologous to the rat Mcs4 region is associated with an increased breast cancer risk in African-American women. The isolation of the Mcs genes may help elucidate novel mechanisms of carcinogenesis, provide information important for human breast cancer risk estimation, and also provide unique drug discovery targets for breast cancer prevention.
Assuntos
Neoplasias Mamárias Animais/genética , Alelos , Animais , Cruzamentos Genéticos , Modelos Animais de Doenças , Feminino , Dosagem de Genes , Ligação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Perda de Heterozigosidade , Ratos , Ratos Endogâmicos WFRESUMO
We have mapped 11 novel, anonymous genetic markers to rat chromosome 2. The rat ceruloplasmin gene (Cp) had been previously mapped to chromosomes 2 and 7q11-->q13 by two different methods. To resolve the assignment and to localize the Cp gene on the rat genetic linkage map, we used linkage analysis to confirm that rat Cp lies on chromosome 2.