Dissecting the genetics of human high myopia: a molecular biologic approach.
Dissecting the genetics of human high myopia: a molecular biologic approach.
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发表时间：
2004
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通讯作者：
T. Young
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作者：
T. Young
尽管有大量的实验性近视动物研究证明了各种眼组织的生化因子变化，以及有限的利用药理学药物阻止眼轴伸长的人类研究，但我们对驱动近视发展的基本生理学知之甚少。确定近视易感性的相关基因将提供对近视发生的基本分子理解，并可能导致定向生理（即药理学，基因治疗）干预。本研究的目的是描述18p11.31染色体常染色体显性高度近视-2位点（MYP2）内选定基因的定位候选基因筛选结果。方法编制MYP2收缩间隔的物理图谱，并使用互补DNA文库筛选、微阵列匹配和逆转录技术在眼组织中进行基因表达研究，以帮助优先筛选基因选择。TGIF、EMLIN-2、MLCB和CLUL1基因在来自不相关对照的DNA样本以及来自原始7个MYP2家系的高度近视受影响和未受影响的家庭成员中进行筛选。所有候选基因均通过直接碱基对序列分析筛选。结果在7个家族中均未发现与近视相关的基因序列改变（多态性）。发现了新的单核苷酸多态性。结论候选基因TGIF、EMLIN-2、MLCB和CLUL1与myp2相关性高度近视无相关性。通过碱基序列筛选发现的碱基变化多态性被提交到互联网数据库。其他也在这个区间内的基因目前正在进行突变筛选。
PURPOSE Despite the plethora of experimental myopia animal studies that demonstrate biochemical factor changes in various eye tissues, and limited human studies utilizing pharmacologic agents to thwart axial elongation, we have little knowledge of the basic physiology that drives myopic development. Identifying the implicated genes for myopia susceptibility will provide a fundamental molecular understanding of how myopia occurs and may lead to directed physiologic (ie, pharmacologic, gene therapy) interventions. The purpose of this proposal is to describe the results of positional candidate gene screening of selected genes within the autosomal dominant high-grade myopia-2 locus (MYP2) on chromosome 18p11.31. METHODS A physical map of a contracted MYP2 interval was compiled, and gene expression studies in ocular tissues using complementary DNA library screens, microarray matches, and reverse-transcription techniques aided in prioritizing gene selection for screening. The TGIF, EMLIN-2, MLCB, and CLUL1 genes were screened in DNA samples from unrelated controls and in high-myopia affected and unaffected family members from the original seven MYP2 pedigrees. All candidate genes were screened by direct base pair sequence analysis. RESULTS Consistent segregation of a gene sequence alteration (polymorphism) with myopia was not demonstrated in any of the seven families. Novel single nucleotide polymorphisms were found. CONCLUSION The positional candidate genes TGIF, EMLIN-2, MLCB, and CLUL1 are not associated with MYP2-linked high-grade myopia. Base change polymorphisms discovered with base sequence screening of these genes were submitted to an Internet database. Other genes that also map within the interval are currently undergoing mutation screening.