Understanding genetics of aging: Canis familiaris model

描述（由申请人提供）：本研究的长期目标是建立犬类作为人类衰老的模型，这将有助于阐明与衰老相关的机制，原因有几个。在物种内部，有一个自然多样的寿命范围，从中取样。与人类相比，寿命很短，这将允许对年轻群体进行分析，而不会对寿命缩短做出未经证实的估计。由于缺乏种内异质性，家犬对遗传研究特别有用，这是一个经常混淆人类连锁分析的问题。很有可能，通过使用具有相似表型（如果不是相同表型）但贡献基因较少的模型，可以更容易地解剖人类的异质现象。为此，我们建议鉴定和绘制与人类衰老有关的犬类同源基因位点，特别是人类4号染色体上标记D4S 1564区域内的基因（Puca, 2001）。犬类同源物的识别将允许它们在综合犬类链接-辐射混合地图上定位。FISH分析将完成绘制工作，并有助于破译目前缺乏的关于人类4号染色体与犬类遗传图谱同源区域的数据，以及定义进化断点。最后，利用犬寡核苷酸微阵列芯片的基因表达谱的开发将允许延长寿命的狗与自然寿命较短的狗之间的基因表达比较。

DESCRIPTION (provided by applicant): The long-term objective of this research is to establish the canine as a model of human aging, which would be useful for the elucidation of mechanisms associated with aging for several reasons. Within the species, there is a naturally diverse range of life span from which to sample. Compared to the human, life span is short which will allow analysis of a young cohort without making unconfirmed estimates of reduced life span. Canis familiaris is particularly useful for genetic studies due to a lack of intrabreed heterogeneity, which is a problem often confounding linkage analyses in the human. It is quite possible that heterogeneous phenomena in the human can be more easily dissected by utilizing a model with similar, if not identical phenotype, yet fewer contributing genes. To this end, we propose the identification and genetic mapping of the canine orthologs of loci implicated in human aging, specifically genes within the region of marker D4S 1564 on human chromosome 4 (Puca, 2001). Identification of canine orthologs will allow their positioning on the integrated canine linkage-radiation hybrid map. FISH analysis will complete the mapping efforts and help to decipher the current paucity of data concerning homologous regions of human chromosome 4 to the Canine genetic map as well as define evolutionary breakpoints. Lastly, development of gene expression profiles utilizing canine oligo microarray chips will allow gene expression comparisons between dogs living extended lives verses those having naturally short life spans.