Assuntos
Transformação Celular Neoplásica , Regulação para Baixo , PTEN Fosfo-Hidrolase/metabolismo , Animais , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Humanos , Miosina Tipo V/genética , Miosina Tipo V/metabolismo , Ubiquitina-Proteína Ligases Nedd4 , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Domínios PDZ , PTEN Fosfo-Hidrolase/genética , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Ligação Proteica , Transdução de Sinais/fisiologia , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismoRESUMO
BACKGROUND: With the completion of the whole genome sequence for many organisms, investigations into genomic structure have revealed that gene distribution is variable, and that genes with similar function or expression are located within clusters. This clustering suggests that there are evolutionary constraints that determine genome architecture. However, as most of the evidence for constraints on genome evolution comes from studies on yeast, it is unclear how much of this prior work can be extrapolated to mammalian genomes. Therefore, in this work we wished to examine the constraints on regions of the mammalian genome containing conserved gene clusters. RESULTS: We first identified regions of the mouse genome with microsynteny conservation by comparing gene arrangement in the mouse genome to the human, rat, and dog genomes. We then asked if any particular gene types were found preferentially in conserved regions. We found a significant correlation between conserved microsynteny and the density of mouse orthologs of human disease genes, suggesting that disease genes are clustered in genomic regions of increased microsynteny conservation. CONCLUSION: The correlation between microsynteny conservation and disease gene locations indicates that regions of the mouse genome with microsynteny conservation may contain undiscovered human disease genes. This study not only demonstrates that gene function constrains mammalian genome organization, but also identifies regions of the mouse genome that can be experimentally examined to produce mouse models of human disease.
