BACKGROUND Many studies have demonstrated a robust statistical overlap between genes whose transcripts are reported as Fragile X Mental Retardation Protein (Fmrp)-binding targets and genes implicated in various psychiatric disorders, including autism. However, it is not clear how to interpret this overlap as the Fmrp protein itself is not considered to be central to all instances of these conditions. FINDINGS We tested whether Fmrp binding may be a proxy for some other features of these transcripts. Reviewing recent literature on the cross-linking and immunoprecipitation (CLIP)-derived targets of Fmrp in the brain, and the literature on identifying genes thought to mediate autism and other psychiatric disorders, reveals that both appear to be disproportionately made up of highly brain-expressed genes. This suggests a parsimonious explanation-that the overlap between Fmrp targets and neuropsychiatric candidate genes might be secondary to simple features such as transcript length and robust expression in the brain. Indeed, reanalyzing Fmrp high-throughput sequencing of RNAs isolated by CLIP (HITS-CLIP) data suggests that approximately 60% of CLIP tag depth can be predicted by gene expression, coding sequence length, and transcript length. Furthermore, there is a statistically significant overlap between autism candidate genes and random samples of long, highly brain-expressed genes, whether they are Fmrp targets or not. CONCLUSIONS Comparison of known Fmrp-binding targets to candidate gene lists should be informed by both of these features.

中文翻译：

---

Fmrp 目标与否：长的、高度大脑表达的基因往往与自闭症和大脑疾病有关。

背景许多研究已经证明，其转录本被报告为脆性X智力迟钝蛋白（Fmrp）结合靶标的基因与涉及各种精神疾病（包括自闭症）的基因之间存在强大的统计重叠。然而，目前尚不清楚如何解释这种重叠，因为 Fmrp 蛋白本身并不被认为是这些情况的所有情况的核心。结果 我们测试了 Fmrp 结合是否可以代表这些转录本的一些其他特征。回顾最近关于大脑中 Fmrp 的交联和免疫沉淀 (CLIP) 衍生靶标的文献，以及关于识别被认为介导自闭症和其他精神疾病的基因的文献，发现两者似乎不成比例地由高度脑-表达的基因。这提出了一种简洁的解释——Fmrp 靶点和神经精神候选基因之间的重叠可能是次要的，因为简单的特征，如转录长度和大脑中的稳健表达。事实上，重新分析通过 CLIP (HITS-CLIP) 分离的 RNA 的 Fmrp 高通量测序数据表明，大约 60% 的 CLIP 标签深度可以通过基因表达、编码序列长度和转录本长度来预测。此外，自闭症候选基因和大脑高度表达的长基因的随机样本之间存在统计上显着的重叠，无论它们是否是 Fmrp 目标。结论 已知 Fmrp 结合靶标与候选基因列表的比较应根据这两个特征来进行。