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Cystic Fibrosis Disease Modifiers: Complex Genetics Defines the Phenotypic Diversity in a Monogenic Disease
Annual Review of Genomics and Human Genetics ( IF 7.7 ) Pub Date : 2018-08-31 00:00:00 , DOI: 10.1146/annurev-genom-083117-021329
Wanda K. O'Neal 1 , Michael R. Knowles 1
Affiliation  

In many respects, genetic studies in cystic fibrosis (CF) serve as a paradigm for a human Mendelian genetic success story. From recognition of the condition as a heritable pathological entity to implementation of personalized treatments based on genetic findings, this multistep pathway of progress has focused on the genetic underpinnings of CF clinical disease. Along this path was the recognition that not all CFTR gene mutations produce the same disease and the recognition of the complex, multifactorial nature of CF genotype–phenotype relationships. The non-CFTR genetic components (gene modifiers) that contribute to variation in phenotype are the focus of this review. A multifaceted approach involving candidate gene studies, genome-wide association studies, and gene expression studies has revealed significant gene modifiers for multiple CF phenotypes. The bold challenges for the future are to integrate the findings into our understanding of CF pathogenesis and to use the knowledge to develop novel therapies.

中文翻译:


囊性纤维化疾病修饰因子:复杂遗传学定义单基因疾病的表型多样性

在许多方面,囊性纤维化(CF)的遗传学研究都是人类孟德尔遗传学成功故事的典范。从将病情识别为可遗传的病理实体,到根据遗传学发现实施个性化治疗,这种多步骤的进展途径一直侧重于CF临床疾病的遗传基础。沿着这条道路,人们认识到并非所有的CFTR基因突变都会产生相同的疾病,并且认识到CF基因型与表型之间关系的复杂性,多因素性。非CFTR导致表型变异的遗传成分(基因修饰子)是本文的重点。涉及候选基因研究,全基因组关联研究和基因表达研究的多方面方法揭示了多种CF表型的重要基因修饰子。未来的大胆挑战是将研究结果整合到我们对CF发病机理的理解中,并利用这些知识来开发新颖的疗法。

更新日期:2018-08-31
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