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目的研究强直性肌营养不良症(MD)是否存在致病新位点及可能的致病新位点的位置。方法以中国上海地区一个较大的MD家系的31名成员为研究对象, 抽取血样后首先进行MD1及MD2位点PCR扩增,并PAGE电泳检测;对该家系的部分成员血样进行MD1位点克隆和测序检测,在MD1和MD2位点未显示异常之后,采用全基因组扫描技术为平台的连锁分析方法,计算LOD值,以判定某些可能与MD连锁的基因位点。结果该家系31名成员的血样MD1及MD2位点未显示寡核苷酸串的异常扩增;并经参数型连锁分析,其MD1及MD2位点两侧微卫星标记的LOD值均小于0.3,在D1S484、D2S486、D5S641、D5S471、D5S436、D6S434、D12S79、D14S70、D14S292位点得到的LOD值分别为1.9393(θ=0.0)、1.2857(θ=0.1)、1.1064(θ=0.1)、1.4488(θ=0.0)、1.1298(θ=0.1)、1.6851(θ=0.0)、1.3882(θ=0.1)、1.1212(θ=0.1)、1.7720(θ=0.0)。提示这些标记可能与MD存在连锁关系。结论强直性肌营养不良症(MD)极可能存在致病新位点,并且致病新位点可能存在于以上微卫星标记处。
Objective To investigate whether there is a new pathogenicity site and possible new pathogenic sites in myotonic dystrophy (MD). METHODS: Thirty-one members of a large MD family in Shanghai, China, were selected for the study. After blood samples were taken, MD1 and MD2 loci were first amplified by PCR and detected by PAGE electrophoresis. Some members of this pedigree were cloned for MD1 locus And sequencing. After the MD1 and MD2 sites showed no abnormalities, genome-wide scanning technique was used as a platform for linkage analysis to calculate the LOD value to determine some possible loci linked to MD. Results The MD1 and MD2 loci in 31 blood samples of this pedigree did not show the abnormal amplification of oligonucleotide strands. The LOD values of microsatellite markers on both sides of MD1 and MD2 loci were both less than 0.3 by parametric linkage analysis. The LOD values obtained at sites D1S484, D2S486, D5S641, D5S471, D5S436, D6S434, D12S79, D14S70 and D14S292 were 1.9393 (θ = 0.0), 1.2857 (θ = 0.1), 1.1064 (θ = 0.1), 1.4488 = 0.0), 1.1298 (θ = 0.1), 1.6851 (θ = 0.0), 1.3882 (θ = 0.1), 1.1212 (θ = 0.1), 1.7720 (θ = 0.0). Suggesting that these markers may be linked to MD. Conclusion Myotonic dystrophy (MD) is likely to have a new pathogenicity, and new pathogenic sites may exist in the above microsatellite markers.