Sampson J R, Yates J R, Pirrit L A, Fleury P, Winship I, Beighton P, Connor J M
University Department of Medical Genetics, Duncan Guthrie Institute, Glasgow.
J Med Genet. 1989 Aug;26(8):511-6. doi: 10.1136/jmg.26.8.511.
The question of genetic heterogeneity in tuberous sclerosis (TSC) was addressed by genetic linkage studies in eight affected families using nine polymorphic markers (EFD126.3, MCT136, ABO, ABL, AK1, and MCOA12 from distal 9q, and PBGD, MCT128.1, and 1CJ52.208M from distal 11q). The data as a whole supported a TSC locus on distal 9q, the peak lod score on multipoint analysis being 3.77 at 6 cM proximal to the Abelson oncogene locus (ABL). However, analysis of two point lod scores using the HOMOG programs showed significant evidence for genetic heterogeneity (p = 0.01), linkage to ABL being unlikely in one family. After exclusion of the unlinked family, multipoint analysis gave a peak lod score of 6.1 in the vicinity of ABL. The family unlinked to ABL showed no recombinants with two chromosome 11 probes, but was too small to provide significant evidence for linkage. Genetic heterogeneity in TSC will complicate efforts to clone the causative genes and severely limit the use of linked probes for carrier detection and prenatal diagnosis.
通过对八个患病家庭进行基因连锁研究，使用九个多态性标记（来自9号染色体长臂远端的EFD126.3、MCT136、ABO、ABL、AK1和MCOA12，以及来自11号染色体长臂远端的PBGD、MCT128.1和1CJ52.208M），探讨了结节性硬化症（TSC）的基因异质性问题。总体数据支持9号染色体长臂远端存在一个TSC基因座，多点分析的最高连锁值在距阿贝尔森癌基因座（ABL）近端6厘摩处为3.77。然而，使用HOMOG程序进行的两点连锁值分析显示出基因异质性的显著证据（p = 0.01），在一个家庭中与ABL连锁的可能性不大。排除不连锁的家庭后，多点分析在ABL附近给出的最高连锁值为6.1。与ABL不连锁的家庭与两个11号染色体探针未出现重组，但该家庭规模太小，无法提供连锁的显著证据。TSC中的基因异质性将使克隆致病基因的努力变得复杂，并严重限制用于携带者检测和产前诊断的连锁探针的使用。
