Modifier genes in Mendelian disorders: the example of cystic fibrosis.
Modifier genes in Mendelian disorders: the example of cystic fibrosis.
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DOI：
10.1111/j.1749-6632.2010.05879.x
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发表时间：
2010-12
影响因子：
5.2
通讯作者：
Cutting GR
中科院分区：
文献类型：
--
作者：
Cutting GR
在过去的三十年里，科学家们在识别导致一系列疾病的基因及其变异方面取得了巨大的成功。虽然这些遗传变异的鉴定使我们了解了疾病的病因基础，但我们对改变疾病严重程度的因素的理解仍然存在很大差距。单基因疾病提供了一个机会来确定修饰，因为它们具有统一的病因，受影响个体的详细表型和家族聚类。囊性纤维化（CF）是较常见的缩短寿命的隐性疾病之一，在临床特征和生存率方面表现出广泛的可变性。在阐明遗传和非遗传因素对CF的贡献方面取得了相当大的进展。CF的基因CFTR的等位基因变异与该疾病的某些方面相关。然而，肺功能、新生儿肠梗阻、糖尿病和人体测量显示出强大的独立于CFTR的遗传控制，候选基因研究揭示了这些性状的遗传修饰因子。全基因组技术的应用为鉴定CF的遗传特征和并发症的新遗传变异带来了巨大的希望。由于已知遗传修饰因子可以改变疾病的进程，它们的蛋白质产物成为治疗干预的直接目标。
In the past three decades, scientists have had immense success in identifying genes and their variants that contribute to an array of diseases. While the identification of such genetic variants has informed our knowledge of the etiologic bases of diseases, there continues to be a substantial gap in our understanding of the factors that modify disease severity. Monogenic diseases provide an opportunity to identify modifiers as they have uniform etiology, detailed phenotyping of affected individuals, and familial clustering. Cystic fibrosis (CF) is among the more common life-shortening recessive disorders that displays wide variability in clinical features and survival. Considerable progress has been made in elucidating the contribution of genetic and nongenetic factors to CF. Allelic variation in CFTR, the gene responsible for CF, correlates with some aspects of the disease. However, lung function, neonatal intestinal obstruction, diabetes, and anthropometry display strong genetic control independent of CFTR, and candidate gene studies have revealed genetic modifiers underlying these traits. The application of genome-wide techniques holds great promise for the identification of novel genetic variants responsible for the heritable features and complications of CF. Since the genetic modifiers are known to alter the course of disease, their protein products become immediate targets for therapeutic intervention.
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影响因子：
3.1
作者：
Corvol, Harriet;Boelle, Pierre-Yves;Clement, Annick
通讯作者：
Clement, Annick
影响因子：
10
作者：
Arkwright, PD;Laurie, S;Hutchinson, IV
通讯作者：
Hutchinson, IV
影响因子：
29.4
作者：
Bronsveld, I;Mekus, F;Veeze, HJ
通讯作者：
Veeze, HJ
DOI：
10.1164/rccm.200204-364oc
发表时间：
2003-02-01
影响因子：
24.7
作者：
Arkwright, PD;Pravica, V;Hutchinson, IV
通讯作者：
Hutchinson, IV
影响因子：
8.2
作者：
Blackman, S. M.;Hsu, S.;Ritter, S. E.;Naughton, K. M.;Wright, F. A.;Drumm, M. L.;Knowles, M. R.;Cutting, G. R.
通讯作者：
Cutting, G. R.