Institute of Genetics and Physiology, 93 Al-Farabi Ave., Almaty 050060, Kazakhstan.
Al-Farabi Kazakh National University, 71 Al-Farabi Ave., Almaty 050040, Kazakhstan.
Dis Markers. 2022 Sep 26;2022:1509994. doi: 10.1155/2022/1509994. eCollection 2022.
The study of extended pedigrees containing autism spectrum disorder- (ASD-) related broader autism phenotypes (BAP) offers a promising approach to the search for ASD candidate variants. Here, a total of 650,000 genetic markers were tested in four Kazakhstani multiplex families with ASD and BAP to obtain data on mutations (DNMs), common, and rare inherited variants that may contribute to the genetic risk for developing autistic traits. The variants were analyzed in the context of gene networks and pathways. Several previously well-described enriched pathways were identified, including ion channel activity, regulation of synaptic function, and membrane depolarization. Perhaps these pathways are crucial not only for the development of ASD but also for ВАР. The results also point to several additional biological pathways (circadian entrainment, NCAM and BTN family interactions, and interaction between L1 and Ankyrins) and hub genes (CFTR, NOD2, PPP2R2B, and TTR). The obtained results suggest that further exploration of PPI networks combining ASD and BAP risk genes can be used to identify novel or overlooked ASD molecular mechanisms.
对包含自闭症谱系障碍（ASD）相关广泛自闭症表型（BAP）的扩展家系进行研究，为寻找 ASD 候选变异体提供了一种很有前途的方法。在这里，对 4 个哈萨克斯坦的 ASD 和 BAP 多重家庭进行了总计 65 万个遗传标记的测试，以获得与基因突变（DNMs）、常见和罕见的遗传变异相关的数据，这些变异可能会增加自闭症特征的遗传风险。对这些变体进行了基因网络和途径的分析。鉴定出了一些先前描述过的富集途径，包括离子通道活性、突触功能调节和膜去极化。也许这些途径不仅对 ASD 的发展至关重要，对 BAP 也很重要。研究结果还指出了其他几个生物学途径（昼夜节律同步、NCAM 和 BTN 家族相互作用以及 L1 和锚蛋白之间的相互作用）和枢纽基因（CFTR、NOD2、PPP2R2B 和 TTR）。研究结果表明，进一步探索将 ASD 和 BAP 风险基因相结合的 PPI 网络，可用于识别新的或被忽视的 ASD 分子机制。
