van Geel M, van Deutekom J C, van Staalduinen A, Lemmers R J, Dickson M C, Hofker M H, Padberg G W, Hewitt J E, de Jong P J, Frants R R
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA.
Cytogenet Cell Genet. 2000;88(3-4):316-21. doi: 10.1159/000015518.
The human beta-tubulin supergene family consists of several isotypes with many associated pseudogenes. Here we report the identification of yet another beta-tubulin sequence designated TUBB4Q. This tubulin maps 80 kb proximal to the facioscapulohumeral muscular dystrophy (FSHD1) associated D4Z4 repeats on chromosome 4q35. The genomic structure contains four exons encoding a putative protein of 434 amino acids. The TUBB4Q nucleotide and protein sequence show 87% and 86% homology to beta2-tubulin, respectively. Although the genomic structure shows all functional aspects of a genuine gene, no transcript could be detected. TUBB4Q-related sequences were identified on multiple chromosomes. Since these sequences mutually exhibit a high nucleotide sequence homology, they presumably belong to a novel subfamily of beta-tubulin genes. Although the chromosome 4q35 tubulin-member probably represents a pseudogene, ectopic expression due to a postulated position effect variegation (PEV), makes TUBB4Q an ideal dominant-negative candidate gene for FSHD1.
人类β-微管蛋白超基因家族由几种同型异构体和许多相关假基因组成。在此，我们报告鉴定出另一种β-微管蛋白序列，命名为TUBB4Q。该微管蛋白定位于4号染色体4q35上与面肩肱型肌营养不良（FSHD1）相关的D4Z4重复序列近端80 kb处。基因组结构包含四个外显子，编码一个由434个氨基酸组成的假定蛋白质。TUBB4Q核苷酸序列和蛋白质序列与β2-微管蛋白的同源性分别为87%和86%。尽管基因组结构显示出一个真正基因的所有功能特征，但未检测到转录本。在多条染色体上鉴定出了与TUBB4Q相关的序列。由于这些序列相互之间表现出高度的核苷酸序列同源性，它们可能属于β-微管蛋白基因的一个新亚家族。尽管4号染色体4q35上的微管蛋白成员可能代表一个假基因，但由于假定的位置效应斑驳（PEV）导致的异位表达，使TUBB4Q成为FSHD1理想的显性负性候选基因。
