DIA1R Is an X-Linked Gene Related to Deleted In Autism-1
DIA1R Is an X-Linked Gene Related to Deleted In Autism-1
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DOI：
10.1371/journal.pone.0014534
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发表时间：
2011-01-17
期刊：
影响因子：
3.7
通讯作者：
Bishop, Naomi E.
中科院分区：
文献类型：
--
作者：
Aziz, Azhari;Harrop, Sean P.;Bishop, Naomi E.
背景：自闭症谱系障碍(ASD)是一种常见的疾病，由三个核心功能领域的缺陷诊断：社交技能、沟通、行为和/或兴趣。精神发育迟缓经常伴随着最严重的自闭症形式，而总体自闭症在男性中更常见。大多数自闭症都有遗传起源，最近在自闭症病因学中涉及的一个基因是自闭症中删除-1(DIA1)基因。方法/主要发现：我们利用生物信息学的方法，发现了一个与DIA1密切相关的人类基因，我们称之为DIA1R(DIA1-Related)。DIA1是常染色体(3号染色体，位置3q24)，而DIA1R定位在X染色体的Xp11.3位置，可以逃脱X失活。基因产物大小相似，DIA1编码430个残基，DIA1R编码433个残基。在氨基酸水平上，DIA1和DIA1R总体上有62%的相似性(28%相同)，都编码针对分泌途径的信号肽。结论：研究发现DIA1R基因的点突变与X-连锁精神发育迟滞(XLMR)相关，DIA1R缺失与具有ASD样特征的综合征和/或XLMR相关。综上所述，这些结果支持这样一种模型，即DIA1和DIA1R基因产物通过细胞分泌途径调节分子交通或影响分泌因子的功能，而功能缺陷会导致具有ASD样症状和/或智力低下的疾病。
Background: Autism spectrum disorders (ASDs) are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1) gene.Methodology/Principal Findings: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related). While DIA1 is autosomal (chromosome 3, position 3q24), DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62% similar overall (28% identical), and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue.Conclusions/Significance: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-like symptoms and/or mental retardation.