Identification of novel genes involved in congenital hypothyroidism using serial analysis of gene expression
Identification of novel genes involved in congenital hypothyroidism using serial analysis of gene expression
复制标题
DOI：
10.1159/000074509
复制
发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Moreno, JC
中科院分区：
文献类型：
--
作者：
Moreno, JC
先天性甲状腺功能减退症（CH）的部分分子基础已被阐明，在垂体和甲状腺特异性基因的各种亚型的甲状腺功能减退症患者的分子缺陷的鉴定。到目前为止，已确定的遗传缺陷只能解释一小部分甲状腺功能减退症病例。因此，需要新的研究策略，以分离更多的组织特异性基因参与的发病机制CH目前被认为是'特发性'从分子的角度来看。我们对人甲状腺组织进行了基因表达的系列分析，并开发了一种计算减法来识别组织特异性基因。其结果是确定了三个优先在甲状腺中表达的基因。第一个编码甲状腺氧化酶（THOX 2）系统的一部分。我们将THOX 2基因突变与特发性一过性和永久性CH病例联系起来。第二个转录本DEHAL 1编码负责甲状腺中碘循环的蛋白质，代表CH特定亚型的候选基因。第三个转录本编码NM 41，一种目前正在研究的蛋白质，显示出胱氨酸结蛋白质家族的特征，通常参与早期发育。版权所有（C）2003 S. Karger AG，巴塞尔。
Part of the molecular basis of congenital hypothyroidism ( CH) has been elucidated by the identification of molecular defects in pituitary- and thyroid-specific genes in patients with various subtypes of hypothyroidism. So far identified genetic defects only explain a small proportion of cases of hypothyroidism. Thus novel research strategies are required to isolate more tissue-specific genes involved in the pathogenesis of CH at present considered 'idiopathic' from a molecular perspective. We applied serial analysis of gene expression to human thyroid tissue and developed a computational substraction method to identify tissue-specific genes. The result has been the identification of three genes preferentially expressed in the thyroid gland. The first one encodes part of the thyroid oxidase (THOX2) system. We linked mutations in the THOX2 gene with idiopathic cases of transient and permanent CH. The second transcript identified, DEHAL1, encodes the protein responsible for the recycling of iodine in the thyroid gland and represents the candidate gene for a specific subtype of CH. The third one encodes NM41, a protein currently under investigation which shows features characteristic of the cystine-knot family of proteins, typically involved in early development. Copyright (C) 2003 S. Karger AG, Basel.