Cheng Jack C Y, Tang Nelson L S, Yeung Hiu-Yan, Miller Nancy
Department of Orthopaedics and Traumatology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
Clin Orthop Relat Res. 2007 Sep;462:38-44. doi: 10.1097/BLO.0b013e3180d09dcc.
Although the exact etiology of adolescent idiopathic scoliosis is still undefined, genetic factors play an important role. Some patients have familial genetic disease that appears to have an autosomal dominant pattern. Linkage studies of these families revealed multiple potential genetic loci that may predispose individuals to the condition. Additional genetic analysis is required to identify the disease-predisposition genes of the loci found in the linkage studies. The initial localization of potential critical loci through large family-based population studies now needs fine mapping by association studies using high-density polymorphic markers (single nucleotide polymorphisms or SNPs). These markers are now available as a result of the Human Genome Project, International HapMap Project, and other genetic diversity projects. The application of this emerging data in a large association study of affected individuals and controls is integral for the identification of putative genes. With these complementary approaches, we will be able to progress with mutational analysis of hopefully a small set of candidate genes in the near future. In this commentary, we illustrate what is possible in the genomic era, and indicate what we should expect from genetic studies in adolescent idiopathic scoliosis, a complex trait disease.
尽管青少年特发性脊柱侧弯的确切病因仍不明确，但遗传因素起着重要作用。一些患者患有呈现常染色体显性模式的家族遗传病。对这些家族的连锁研究揭示了多个可能使个体易患该病的潜在基因位点。需要进一步的基因分析来确定连锁研究中发现的基因位点的疾病易感基因。通过基于大家庭的群体研究对潜在关键基因位点进行初步定位后，现在需要利用高密度多态性标记（单核苷酸多态性或SNP）通过关联研究进行精细定位。由于人类基因组计划、国际人类基因组单体型图计划及其他遗传多样性项目，现在已有这些标记。在对受影响个体和对照进行的大型关联研究中应用这些新出现的数据对于鉴定推定基因不可或缺。通过这些互补方法，我们有望在不久的将来对一小部分候选基因进行突变分析。在本评论中，我们阐述了基因组时代可能实现的目标，并指出了我们对青少年特发性脊柱侧弯这一复杂性状疾病的遗传研究的期望。
