Leegwater Peter A, van Hagen Marjan A, van Oost Bernard A
Department of Veterinary Medicine of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO Box 80154, 3508 TD Utrecht, The Netherlands.
J Hered. 2007;98(5):549-52. doi: 10.1093/jhered/esm022. Epub 2007 Jun 4.
New techniques allow fast genotyping of large numbers of single-nucleotide polymorphisms (SNPs) of the genome. These techniques are used to map disorders with complex inheritance patterns and require large study groups. Linkage analysis of monogenetic traits exploits close family relationships between relatively small numbers of cases and controls. Linkage studies are typically performed with a set of microsatellite markers spaced at 10 cM. We were interested to test whether SNP typing could be applied in genome-wide linkage analysis because of the speed of the procedure. White spotting in Boxer dogs was chosen as a model because it is a semidominant trait, allowing the assignment of locus genotypes to each phenotyped dog. A set of just more than 1500 SNPs were typed in 5 families with heterozygous parents and offspring that included 11 white, 6 brown, and 19 spotted dogs. Multipoint linkage analysis was performed and a LOD score of 12.1 was obtained on canine chromosome 20. The CFA20 region was the only region with a positive LOD score. The gene MITF, coding for a transcription factor implicated in Waardenburg syndrome in humans, is located in the region close to a SNP that is in apparent linkage disequilibrium with the white spotting locus. Thus, MITF is a likely candidate for involvement in white spotting in boxers. We conclude that SNPs, spaced at an average distance of 1.6 Mb, are highly informative in linkage analysis of monogenic traits and are a powerful alternative to microsatellite markers.
新技术可实现对基因组中大量单核苷酸多态性（SNP）的快速基因分型。这些技术用于绘制具有复杂遗传模式的疾病图谱，且需要大型研究群体。单基因性状的连锁分析利用相对少量病例与对照之间的紧密家族关系。连锁研究通常使用间距为10厘摩（cM）的一组微卫星标记进行。由于该方法速度快，我们有兴趣测试SNP分型是否可应用于全基因组连锁分析。拳师犬的白斑被选作模型，因为它是一种半显性性状，可据此为每只表型犬确定基因座基因型。在5个家族中对1500多个SNP进行了分型，这些家族的亲代杂合且有后代，其中包括11只白色犬、6只棕色犬和19只花斑犬。进行了多点连锁分析，在犬20号染色体上获得了12.1的对数优势（LOD）分数。CFA20区域是唯一具有正LOD分数的区域。编码与人类瓦登伯革氏综合征相关转录因子的MITF基因位于与白斑基因座存在明显连锁不平衡的一个SNP附近区域。因此，MITF很可能是参与拳师犬白斑形成的候选基因。我们得出结论，平均间距为1.6兆碱基（Mb）的SNP在单基因性状的连锁分析中具有高度信息性，是微卫星标记的有力替代物。
