性差异有助于神经发育障碍患者的表型多样性
Tania Cuppens1, Julie Shatto2, Loïc Mangnier1
1Centre de Recherche du CHU de Québec-Université Laval, Département de Médecine Moléculaire de L'Université Laval, Québec, QC, Canada.
Frontiers in pediatrics
|August 23, 2023
概括
全球发育迟缓 (GDD) 的男性和女性表现出不同的表型和遗传变异. 虽然许多GDD基因重叠,但女性在某些基因中表现出更高的突变负载,突出了GDD的性别特异性差异.
科学领域:
- 遗传学 是一个遗传学.
- 发育生物学 发展生物学
- 神经科学是一个神经科学.
背景情况:
- 全球发育迟缓 (GDD) 影响所有年龄和性别的人.
- 了解GDD的性别差异对于准确的诊断和治疗至关重要.
- 以前的研究还没有完全阐明GDD的性别特异性表型和基因型变异.
研究的目的:
- 研究GDD个体的表型和基因型的性别特异性差异.
- 为了确定GDD的男性和女性之间的基因表达和通路的变异.
- 探索共发生的条件,如自闭症,对GDD的影响.
主要方法:
- 利用解密发育障碍 (DDD) 数据集,分析了65,888名患有GDD的个人.
- 对表型信息,基因型和基因表达特征进行基于性别的比较.
- 进行基因网络分析,分子功能的丰富,并对患有并发性自闭症的个体进行分析.
主要成果:
- 确定了显著的性别特异性表型差异,自闭症和大脑症在男性中更常见,而小脑症和刻板印象在女性中更常见.
- 在GDD基因与性别之间的致病变体之间发现了大量的重叠 (66%),X链接基因流行率略有差异.
- 观察到女性对GDD基因的突变负载较高,具有对功能丧失 (pLI) 的高不耐受性,以及伴随性自闭症患者的明显模式.
结论:
- 患有GDD的男性和女性表现出明显不同的表型和独特的遗传变异.
- 患有GDD的女性可能会容忍特定基因中更高的功能丧失突变负载.
- 包括自闭症等相关疾病在内的全面的表型化对于理解GDD的基因组基础至关重要.
相关概念视频
01:43Sex-linked Disorders
102.4K
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
102.4K
01:28Human Genetics
611
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
611
01:33Pleiotropy
40.6K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.6K
02:27Background and Environment Affect Phenotype
6.6K
Although the genetic makeup of an organism plays a major role in determining the phenotype, there are also several environmental factors, such as temperature, oxygen availability, presence of mutagens, that can alter an organism’s phenotype.
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
6.6K
01:35Pedigree Analysis
84.5K
Overview
84.5K
01:19X-linked Traits
55.0K
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
55.0K