Weiss Scott T, Raby Benjamin A
Channing Laboratory, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R83-9. doi: 10.1093/hmg/ddh080. Epub 2004 Feb 5.
The use of positional cloning for the identification of complex trait susceptibility genes has gained momentum with the completion of the human genome project. The approach involves the collection of well-phenotyped cohorts (either family-based or case-control designs), the generation of high-density single-nucleotide polymorphism linkage disequilibrium maps, and the application of powerful statistical methods to localize narrow regions of genetic association with disease. In 2003, two novel genes relating to asthma were identified using this approach, PHF11 and DPP10, neither of which had previously been implicated in the pathobiology of either asthma or allergy. In addition, further support for ADAM33 (the first asthma susceptibility gene identified by positional cloning) as an asthma gene was presented, although with mixed results. These discoveries open new avenues for research in asthma and allergy, and highlight the power (and limitations) of positional cloning for the identification of asthma genes, and complex trait genes in general.
随着人类基因组计划的完成，利用定位克隆技术鉴定复杂性状易感基因的研究得到了进一步发展。该方法包括收集表型明确的队列（基于家系或病例对照设计），构建高密度单核苷酸多态性连锁不平衡图谱，并应用强大的统计方法定位与疾病相关的狭窄基因区域。2003年，通过该方法鉴定出两个与哮喘相关的新基因，即PHF11和DPP10，此前这两个基因均未被认为与哮喘或过敏的病理生物学有关。此外，尽管结果不一，但有更多证据支持ADAM33（首个通过定位克隆鉴定出的哮喘易感基因）是哮喘相关基因。这些发现为哮喘和过敏研究开辟了新途径，并凸显了定位克隆技术在鉴定哮喘基因及一般复杂性状基因方面的作用（及其局限性）。
