Comstock Kenine E, Lingaas Frode, Kirkness Ewen F, Hitte Christophe, Thomas Rachael, Breen Matthew, Galibert Francis, Ostrander Elaine A
Clinical and Human Biology Divisions, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave., D4-100, P.O. Box 19024, Seattle, Washington 98109-1024, USA.
Mamm Genome. 2004 Jul;15(7):544-51. doi: 10.1007/s00335-004-2365-5.
A high-density map of the region of canine Chromosome 5 (CFA5) surrounding the evolutionary breakpoint between human Chromosomes 1p32 and 17pll was constructed by integrating a radiation hybrid map including 41 microsatellites, 10 BACs, and 59 genes and a linkage map including 18 markers. A collection of canine genomic survey sequences providing 1.5x coverage was used to identify dog orthologs of human genes, proving instrumental in the development of this map. Of particular interest is the canine BHD gene, within which we have previously described a single nucleotide polymorphism associated with Hereditary Multifocal Renal Cystadenocarcinoma and Nodular Dermatofibrosis (RCND) in German Shepherd dogs. The corresponding region of the human genome is particularly gene rich, containing genes involved in development, metabolism, and cancer that are likely to be of interest in future mapping studies. This current mapping effort on CFA5 expands the degree to which initial findings of linkage in canine families can be followed by successful positional cloning efforts and increases the value of the human genome sequence for defining candidate genes. Moreover, this study demonstrates the utility of genomic survey sequences when combined with accurate genome maps for rapid mapping of disease susceptibility loci.
通过整合一个包含41个微卫星、10个细菌人工染色体（BAC）和59个基因的辐射杂种图谱以及一个包含18个标记的连锁图谱，构建了犬5号染色体（CFA5）上围绕人类1号染色体p32和17号染色体p11进化断点区域的高密度图谱。利用一组提供1.5倍覆盖率的犬基因组调查序列来鉴定人类基因的犬直系同源基因，这对该图谱的构建起到了重要作用。特别值得关注的是犬BHD基因，我们之前在德国牧羊犬中描述了该基因内一个与遗传性多灶性肾囊肿腺癌和结节性皮肤纤维瘤病（RCND）相关的单核苷酸多态性。人类基因组的相应区域基因特别丰富，包含参与发育、代谢和癌症的基因，这些基因可能在未来的定位研究中受到关注。目前对CFA5的这项定位工作扩大了在犬类家族中连锁的初步发现随后通过成功的位置克隆工作得以跟进的程度，并增加了人类基因组序列在定义候选基因方面的价值。此外，这项研究证明了基因组调查序列与精确的基因组图谱相结合在快速定位疾病易感位点方面的实用性。
