Using Xenopus to discover new genes involved in branchiootorenal spectrum disorders.
Using Xenopus to discover new genes involved in branchiootorenal spectrum disorders.
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使用xenopus发现涉及分支植物谱系障碍的新基因。
DOI：
10.1016/j.cbpc.2015.06.007
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发表时间：
2015-12
期刊：
影响因子：
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通讯作者：
Pignoni F
中科院分区：
文献类型：
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作者：
Moody SA;Neilson KM;Kenyon KL;Alfandari D;Pignoni F
先天性听力损失是一个重要的临床问题，因为如果没有早期干预，受影响的儿童无法正确地获得语言，因此难以发展社交技能。虽然美国的大多数新生儿都接受了听力缺陷的筛查，但产前基因筛查可以更早地诊断出听力缺陷。识别相关突变基因的遗传筛查也可以警告与听力无关的器官的潜在先天性缺陷。我们将讨论努力确定新的候选基因的基础上Branchiootorenal谱系障碍，其中受影响的儿童有听力障碍，也有肾缺陷的风险。SIX1和EYA 1两个基因的突变在大约一半的受试患者中被发现。为了发现新的候选基因，我们使用了水生动物模型，非洲爪蟾，以确定在耳和肾脏发育过程中的Six1的发育遗传途径的一部分的基因。我们已经确定了大量潜在的Six1转录靶点和候选辅因子蛋白，它们在发育过程中在正确的时间和正确的组织中表达，与Six1相互作用。我们讨论了使用该系统的优势，在人类先天性听力损失综合征的基因发现。
Congenital hearing loss is an important clinical problem because, without early intervention, affected children do not properly acquire language and consequently have difficulties developing social skills. Although most newborns in the US are screened for hearing deficits, even earlier diagnosis can be made with prenatal genetic screening. Genetic screening that identifies the relevant mutated gene can also warn about potential congenital defects in organs not related to hearing. We will discuss efforts to identify new candidate genes that underlie the Branchiootorenal spectrum disorders in which affected children have hearing deficits and are also at risk for kidney defects. Mutations in two genes, SIX1 and EYA1, have been identified in about half of the patients tested. To uncover new candidate genes, we have used the aquatic animal model, Xenopus laevis, to identify genes that are part of the developmental genetic pathway of Six1 during otic and kidney development. We have already identified a large number of potential Six1 transcriptional targets and candidate co-factor proteins that are expressed at the right time and in the correct tissues to interact with Six1 during development. We discuss the advantages of using this system for gene discovery in a human congenital hearing loss syndrome.