论文部分内容阅读
目的 用基因连锁分析方法对一个Ａｌｐｏｒｔ综合征家系的致病基因定位。方法应用聚合酶链反应（ＰＣＲ）方法分别扩增与２号染色体上Ⅳ型胶原α３和α４链基因（ＣＯＭＡ３／ＣＯＬ４Ａ４）连锁的微卫星遗传标记ＣＡ１１、ＰＡＸ３、Ｄ２Ｓ４０１及与Ｘ染色体上Ⅳ型胶原α５链基因（ＣＯＬ４Ａ５）紧密连锁的微卫星遗传标记２Ｂ６。ＤＸＳ１０１，找出家系中与疾病连锁的单体型，并计算出 Ｌｏｄ Ｓｃｏｒｅ值，从而判定是否存在连锁关系。结果基因连锁分析提示这个家系致病基因与 ２号染色体上 ＣＡ１１、ＰＡＸ３。Ｄ２Ｓ４０１一起分离（Ｌｏｄ Ｓｃｏｒｅ＝ ２．１０， θ＝ ０），不与 Ｘ染色体上２Ｂ６及ＤＸＳ１０１一起分离（Ｌｏｄ Ｓｃｏｒｅ＝ ０， θ＝０．５）。结论这个Ａｌｐｏｆｔ综合征家系的致病基因与ＣＯＬ４Ａ３／ＣＯＬ４Ａ４基因连锁。可能因２号染色体上Ⅳ型胶原α３／α４链基因突变致病。
Objective To locate the causative genes of a Alport syndrome pedigree by genetic linkage analysis. Methods The microsatellite markers CA11, PAX3 and D2S401 linked to the α3 and α4 chain genes of type Ⅳ collagen (COMA3 / COL4A4) on chromosome 2 were amplified by polymerase chain reaction (PCR) Microsatellite Genetic Markers 2B6 in which the α5 chain gene (COL4A5) is tightly linked. DXS101, to find haplotypes in the pedigree linked to the disease and calculate the Lod Score to determine if there is a linkage. Results Gene linkage analysis suggested that this pedigree was associated with CA11 and PAX3 on chromosome 2. D2S401 (Lod Score = 2.10, θ = 0), not with 2B6 and DXS101 on the X chromosome (Lod Score = 0, θ = 0.5). Conclusion The causative gene of Alpoft syndrome pedigree is linked to COL4A3 / COL4A4 gene. May be due to chromosome 2 collagen type α3 / α4 chain mutations cause disease.