Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Corniche Road, Dammam, Saudi Arabia.
Department of Biololgy, College of Science, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Mol Biol Rep. 2020 Oct;47(10):7623-7632. doi: 10.1007/s11033-020-05832-6. Epub 2020 Sep 29.
Autism is heterogeneous multifactorial neurodevelopmental and neuropsychiatric disorder with repetitive and limited behaviors as well as communication deficits. Prevalence of autism in males is predominant than females, but their genetic association is unclear. The study was performed to investigate Y-chromosome haplotypes, significant risk variants and susceptibility genes associated with autistic Saudi young males with autism. Exome genotyping microarray analysis was performed in Saudi young boys with autism (cases, n = 47) and without autism and other genetic or neurodevelopmental disorders (control, n = 43) to identify the functional exonic risk variations among 243,345 exonic variations. The most significant single nucleotide polymorphisms (SNPs) of protein coding associated with autism in Saudi young boys were studied for functional enrichment. Y-chromosome haplotyping analysis of 6 SNPs such as rs1865680, rs2032624, rs2032658, rs2032631, rs9786153 and rs13447352 uncovered the most significant protective (ACGACA p = 2.94 × 10) among the controls and the high risk Y-haplotype (GAAGTC p = 6.85 × 10) among autistic boys. Exome association study revealed 6 susceptible genes, MCC, AUTS2, VSX1, SETBP1, CNTN3, and PCDH11Y that were known for autistic disorder. The significant predisposed genes with functional variants of Y-chromomere are strongly connected with spermatogenic failure (p = 8.02 × 10), azoospermia (p = 6.32 × 10), partial chromosome Y deletion (p = 7.66 × 10), HDMs demethylate histones pathway (p = 3.55 × 10) and immune system diseases (p = 4.11 × 10). Y-haplotypes and highly significant pathogenic exonic variants in MCC, AUTS2, VSX1, SETBP1, CNTN3 and PCDH11Y genes are more influential genetic factors for developing autism in boys of Arab origin.
自闭症是一种异质性多因素神经发育和神经精神障碍，具有重复和有限的行为以及沟通障碍。自闭症在男性中的患病率高于女性，但他们的遗传关联尚不清楚。本研究旨在调查与沙特自闭症男性青年相关的 Y 染色体单倍型、显著风险变异和易感基因。对患有自闭症的沙特青年男性（病例，n=47）和无自闭症及其他遗传或神经发育障碍的男性（对照，n=43）进行外显子组基因分型微阵列分析，以鉴定 243345 个外显子变异中的功能外显子风险变异。对与沙特自闭症青年男性相关的最显著的单核苷酸多态性（SNP）进行了蛋白编码相关的功能富集研究。对 rs1865680、rs2032624、rs2032658、rs2032631、rs9786153 和 rs13447352 等 6 个单核苷酸多态性的 Y 染色体单倍型分析显示，在对照组中最显著的保护性单倍型（ACGACA，p=2.94×10）和自闭症男孩中高风险 Y 单倍型（GAAGTC，p=6.85×10）。外显子关联研究发现了 6 个易感基因，即 MCC、AUTS2、VSX1、SETBP1、CNTN3 和 PCDH11Y，这些基因与自闭症有关。具有 Y 染色体功能变异的显著易感基因与精子发生失败（p=8.02×10）、无精子症（p=6.32×10）、部分染色体 Y 缺失（p=7.66×10）、HDMs 去甲基化组蛋白途径（p=3.55×10）和免疫系统疾病（p=4.11×10）密切相关。MCC、AUTS2、VSX1、SETBP1、CNTN3 和 PCDH11Y 基因中的 Y 单倍型和高度显著的致病性外显子变异是导致阿拉伯裔男孩自闭症的更具影响力的遗传因素。
