Monoallelic expression of the human FOXP2 speech gene
Monoallelic expression of the human FOXP2 speech gene
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DOI：
10.1073/pnas.1411270111
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发表时间：
2015-06-02
影响因子：
11.1
通讯作者：
Chess, Andrew
中科院分区：
文献类型：
--
作者：
Adegbola, Abidemi A.;Cox, Gerald F.;Chess, Andrew
最近的描述广泛随机单等位基因表达（RMAE）的基因分布在整个常染色体基因组表明，有更多的基因常染色体上的RMAE比X染色体上的基因的数量，其中X-失活决定RMAE的X-连锁基因。经历RMAE的几个常染色体基因已经独立地与人类孟德尔疾病有关。因此，解析这些基因的等位基因特异性表达与疾病之间的关系是有意义的。人类叉头盒P2基因FOXP 2的突变导致发育性言语运动障碍，并伴有严重的言语和语言缺陷。在这里，我们表明，人类FOXP 2基因经历RMAE。研究一个个体与发展性言语运动障碍，我们确定了一个缺失3 Mb远离FOXP 2基因，影响FOXP 2基因表达的顺式。总之，这些数据表明了有趣的可能性，即RMAE影响FOXP 2突变观察到的单倍不足表型。
The recent descriptions of widespread random monoallelic expression (RMAE) of genes distributed throughout the autosomal genome indicate that there are more genes subject to RMAE on autosomes than the number of genes on the X chromosome where X-inactivation dictates RMAE of X-linked genes. Several of the autosomal genes that undergo RMAE have independently been implicated in human Mendelian disorders. Thus, parsing the relationship between allele-specific expression of these genes and disease is of interest. Mutations in the human forkhead box P2 gene, FOXP2, cause developmental verbal dyspraxia with profound speech and language deficits. Here, we show that the human FOXP2 gene undergoes RMAE. Studying an individual with developmental verbal dyspraxia, we identify a deletion 3 Mb away from the FOXP2 gene, which impacts FOXP2 gene expression in cis. Together these data suggest the intriguing possibility that RMAE impacts the haploinsufficiency phenotypes observed for FOXP2 mutations.