Young Andrea C, Kirkness Ewen F, Breen Matthew
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
Chromosome Res. 2008;16(8):1193-202. doi: 10.1007/s10577-008-1268-9. Epub 2008 Nov 16.
The domestic dog continues to represent an influential model organism for comparative biomedical research owing to the numerous genetic and pathophysiological similarities shared between human and dog diseases. The combined availability of a high-quality genome assembly and a 1 Mb-resolution genome-assembly integrated bacterial artificial chromosome (BAC) panel now provides the essential resources to combine cytogenetic and computational analyses to determine the precise locations of chromosome breakpoint regions within aberrant karyotypes. In this study we demonstrate the synergy of using a such a combined in-situ/in-silico approach to define chromosome breakpoints using the naturally occurring breakpoint present on all canine X chromosomes--the pseudoautosomal breakpoint (PAB). In so doing we have further characterized the canine pseudoautosomal region (PAR) to extend approximately 6.6 Mb from the telomeric end of CFA Xp and established that the canine PAB is contained within a 2 kb region. Our characterization of the canine PAR allowed for the comparative study of gene content across previously defined mammalian PARs and indicates that the canine PAB is contained with the gene Shroom2. The future application of the approach demonstrated in this study will prove useful when seeking to identify the genomic sequences surrounding recurrent chromosome breakpoints present in canine cancers.
由于人类疾病和犬类疾病之间存在众多遗传和病理生理相似性，家犬仍然是比较生物医学研究中一种具有影响力的模式生物。高质量基因组组装和1 Mb分辨率的基因组组装整合细菌人工染色体（BAC）文库的联合可用性，现在提供了必要的资源，可将细胞遗传学和计算分析相结合，以确定异常核型中染色体断点区域的精确位置。在本研究中，我们展示了使用这种原位/计算机相结合的方法来定义染色体断点的协同作用，该方法利用了所有犬类X染色体上天然存在的断点——假常染色体断点（PAB）。通过这样做，我们进一步对犬类假常染色体区域（PAR）进行了表征，该区域从CFA Xp的端粒末端延伸约6.6 Mb，并确定犬类PAB包含在一个2 kb的区域内。我们对犬类PAR的表征使得能够对先前定义的哺乳动物PAR中的基因内容进行比较研究，并表明犬类PAB包含在Shroom2基因内。当试图鉴定犬类癌症中存在的复发性染色体断点周围的基因组序列时，本研究中展示的方法的未来应用将被证明是有用的。
