FOXP2:: novel exons, splice variants, and CAG repeat length stability
FOXP2:: novel exons, splice variants, and CAG repeat length stability
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DOI：
10.1007/s00439-002-0768-5
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发表时间：
2002-08-01
期刊：
影响因子：
5.3
通讯作者：
Margolis, RL
中科院分区：
文献类型：
--
作者：
Bruce, HA;Margolis, RL
FOXP2是一种含有多聚谷氨酰胺区、锌指基序和叉头DNA结合结构域的转录因子。FOXP2基因位于7q31。叉头结构域（外显子14）的错义突变和平衡的相互易位t（5; 7）（q22; q31.2）与外显子3b和4之间的断点最近已与言语和语言障碍（SPCH 1）。FOXP2在这种神经发育障碍中的作用表明，FOXP2的突变可能导致其他神经精神疾病。为了开始研究这种可能性，我们检测了FOXP 2的基因组结构和CAG/CAA重复区。我们在142名进行性运动障碍患者中检测到FOXP2 CAG/CAA重复序列的多态性很小，没有扩增。我们发现了交替剪接变体和六个以前未检测到的外显子的证据：三个5 '非翻译外显子（s1，s2，s3），外显子2和3之间的两个额外的非翻译外显子（2a和2b），外显子4和5之间的翻译外显子（4a），以及外显子10（10+）的较长版本，包含一个交替终止密码子并产生截短蛋白（FOYP2-S）。我们的研究结果表明，FOXP2跨越至少603 kb的基因组DNA，超过以前定义的区域的两倍，并提供证据的启动子区侧翼外显子S1。这种额外的FOXP2外显子和剪接变异体的证明应该有助于理解FOXP2的功能和寻找额外的FOXP2突变。
FOXP2 is a transcription factor containing a polyglutamine tract, a zinc-finger motif, and a forkhead DNA-binding domain. The FOXP2 gene is located on 7q31. A missense mutation in the forkhead domain (exon 14) and a balanced reciprocal translocation t(5;7)(q22;q31.2) with a breakpoint between exons 3b and 4 have recently been associated with a speech and language disorder (SPCH1). The role of FOXP2 in this neurodevelopmental disorder suggests that mutations in FOXP2 could cause other neuropsychiatric disorders. To begin investigation of this possibility, we examined the genomic structure and CAG/CAA repeat region of FOXP2. We detected little polymorphism and no expansions in the FOXP2 CAG/CAA repeat in 142 individuals with progressive movement disorders. We found evidence of alternate splice variants and six previously undetected exons: three 5' untranslated exons (s1, s2, s3), two additional untranslated exons (2a and 2b) between exons 2 and 3, a translated exon (4a) between exons 4 and 5, and a longer version of exon 10 (10+) that contains an alternate stop codon and produces a truncated protein (FOYP2-S). Our results suggest that FOXP2 spans at least 603 kb of genomic DNA, more than twice the previously defined region, and provide evidence of a promoter region flanking exon s1. This demonstration of additional FOXP2 exons and splice variants should facilitate understanding of FOXP2 function and the search for additional FOXP2 mutations.