The ciliopathies: a transitional model into systems biology of human genetic disease

被引:109
作者
Davis, Erica E.
Katsanis, Nicholas [1 ]
机构
[1] Duke Univ, Med Ctr, Dept Pediat, Ctr Human Dis Modeling, Durham, NC 27710 USA
基金
美国国家卫生研究院;
关键词
BARDET-BIEDL-SYNDROME; LEBER CONGENITAL AMAUROSIS; RIB-POLYDACTYLY SYNDROME; MECKEL-GRUBER-SYNDROME; INTRAFLAGELLAR TRANSPORT PROTEIN; ASPHYXIATING THORACIC DYSTROPHY; POLYCYSTIC KIDNEY-DISEASE; CAUSE JOUBERT-SYNDROME; HUMAN OBESITY SYNDROME; PLANAR CELL POLARITY;
D O I
10.1016/j.gde.2012.04.006
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The last decade has witnessed an explosion in the identification of genes, mutations in which appear sufficient to cause clinical phenotypes in humans. This is especially true for disorders of ciliary dysfunction in which an excess of 50 causal loci are now known; this discovery was driven partly by an improved understanding of the protein composition of the cilium and the co-occurrence of clinical phenotypes associated with ciliary dysfunction. Despite this progress, the fundamental challenge of predicting phenotype and or clinical progression based on single locus information remains unsolved. Here, we explore how the combinatorial knowledge of allele quality and quantity, an improved understanding of the biological composition of the primary cilium, and the expanded appreciation of the subcellular roles of this organelle can be synthesized to generate improved models that can explain both causality but also variable penetrance and expressivity.
引用
收藏
页码:290 / 303
页数:14
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