Human bZIP transcription factor gene NRL: Structure, genomic sequence, and fine linkage mapping at 14q11.2 and negative mutation analysis in patients with retinal degeneration
Human bZIP transcription factor gene NRL: Structure, genomic sequence, and fine linkage mapping at 14q11.2 and negative mutation analysis in patients with retinal degeneration
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DOI：
10.1006/geno.1997.4964
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发表时间：
1997-10-15
期刊：
影响因子：
4.4
通讯作者：
Swaroop, A
中科院分区：
文献类型：
--
作者：
Farjo, Q;Jackson, A;Swaroop, A
NRL基因编码一种进化上保守的基本基序-亮氨酸拉链转录因子，该转录因子与调节光受体特异性基因视紫红质的表达有关。NRL在胚胎发育期间在有丝分裂后神经元细胞和晶状体中表达，但在成人中表现出视网膜特异性表达模式。为了了解NRL表达的调控并研究其可能与视网膜病变的关系，我们确定了人类NRL基因的完整序列，在含有NRL的cosmid中鉴定了一个多态性（CA）(n)重复序列（与D14S64相同），并通过连锁分析确定了其位置。由于常染色体隐性视网膜色素变性（arRP）的基因座与14q11的标记相关联，并且由于视紫红质突变可导致唇裂，我们对来自一组代表遗传性视网膜变性独立家族的患者的NRL基因和视紫红质- NRL反应元件的基因组PCR产物进行了测序。分析没有显示这组患者中有任何致病突变。这些研究为描述在不同神经细胞类型中调控NRL表达的DNA序列元件提供了基础，并有助于分析NRL作为影响视觉功能的遗传性疾病/综合征的候选基因。(C) 1997学术出版社。
The NRL gene encodes an evolutionarily conserved basic motif-leucine zipper transcription factor that is implicated in regulating the expression of the photoreceptor-specific gene rhodopsin. NRL is expressed in postmitotic neuronal cells and in lens during embryonic development, but exhibits a retina-specific pattern of expression in the adult. To understand regulation of NRL expression and to investigate its possible involvement in retinopathies, we have determined the complete sequence of the human NRL gene, identified a polymorphic (CA)(n) repeat (identical to D14S64) within the NRL-containing cosmid, and refined its location by linkage analysis. Since a locus for autosomal recessive retinitis pigmentosa (arRP) has been linked to markers at 14q11 and since mutations in rhodopsin can lead to lip, we sequenced genomic PCR products of the NRL gene and of the rhodopsin-Nrl response element from a panel of patients representing independent families with inherited retinal degeneration. The analysis did not reveal any causative mutations in this group of patients. These investigations provide the basis for delineating the DNA sequence elements that regulate NRL expression in distinct neuronal cell types and should assist in the analysis of NRL as a candidate gene for inherited diseases/syndromes affecting visual function. (C) 1997 Academic Press.