Weber B, Hedrick A, Andrew S, Riess O, Collins C, Kowbel D, Hayden M R
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Am J Hum Genet. 1992 Feb;50(2):382-93.
The defect causing Huntington disease (HD) has been mapped to 4p16.3, distal to the DNA marker D4S10. Subsequently, additional polymorphic markers closer to the HD gene have been isolated, which has led to the establishment of predictive testing programs for individuals at risk for HD. Approximately 17% of persons presenting to the Canadian collaborative study for predictive testing for HD have not received any modification of risk, in part because of limited informativeness of currently available DNA markers. Therefore, more highly polymorphic DNA markers are needed, which will further increase the accuracy and availability of predictive testing, specifically for families with complex or incomplete pedigree structures. In addition, new markers are urgently needed in order to refine the breakpoints in the few known recombinant HD chromosomes, which could allow a more accurate localization of the HD gene within 4p16.3 and, therefore, accelerate the cloning of the disease gene. In this study we present the identification and characterization of nine new polymorphic DNA markers, including three markers which detect highly informative multiallelic VNTR-like polymorphisms with PIC values of up to .84. These markers have been isolated from a cloned region of DNA which has been previously mapped approximately 1,000 kb from the 4p telomere.
导致亨廷顿舞蹈病（HD）的缺陷基因已被定位于4p16.3，位于DNA标记D4S10的远端。随后，又分离出了一些更靠近HD基因的多态性标记，这使得针对有HD风险的个体建立了预测性检测项目。在参与加拿大HD预测性检测合作研究的人群中，约17%的人并未因检测而改变其风险评估，部分原因是目前可用的DNA标记信息量有限。因此，需要更多高度多态的DNA标记，这将进一步提高预测性检测的准确性和可用性，特别是对于那些系谱结构复杂或不完整的家庭。此外，迫切需要新的标记来完善少数已知重组HD染色体上的断点，这将有助于更精确地将HD基因定位在4p16.3内，从而加速疾病基因的克隆。在本研究中，我们展示了9个新的多态性DNA标记的鉴定和特征，其中包括3个能检测到信息高度丰富的多等位基因VNTR样多态性的标记，其PIC值高达0.84。这些标记是从一个DNA克隆区域中分离出来的，该区域先前已被定位在距离4p端粒约1000 kb处。
