Causes and effects of haploinsufficiency
Causes and effects of haploinsufficiency
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DOI：
10.1111/brv.12527
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发表时间：
2019-10-01
影响因子：
10
通讯作者：
Veitia, Reiner A.
中科院分区：
文献类型：
--
作者：
Johnson, Adam F.;Nguyen, Ha T.;Veitia, Reiner A.
单倍不足是遗传显性的一种形式，是许多人类遗传性疾病的潜在机制，其中致病基因对改变的剂量敏感。本文综述了单倍不足，剂量敏感性和遗传优势，其共同的主题是基因型和表型之间存在的非线性关系之间的关系知之甚少。我们从理论和实验模型的角度提出了一个最新的单倍不足的基础。我们还讨论了人类的条件所造成的单倍不足，包括发育综合征和癌症。这些条件的遗传机制和治疗进展的理解之间的联系也进行了描述。
Haploinsufficiency is a form of genetic dominance and is the underlying mechanism of numerous human inherited conditions in which the causal genes are sensitive to altered dosage. This review examines the poorly understood relationships between haploinsufficiency, dosage sensitivity and genetic dominance, whose common theme is the existence of nonlinear relationships between genotype and phenotype. We present an up-to-date account of the bases of haploinsufficiency from the perspective of theoretical and experimental models. We also discuss human conditions caused by haploinsufficiency, including developmental syndromes and cancer. Connections between the understanding of these conditions' genetic mechanisms and advances in treatments are also described.