一个完整的框架,用于功能剖析的变量表达性在遗传性疾病的综合框架.
Jiawan Sun1, Serena Noss1, Deepro Banerjee1
1Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802.
medRxiv : the preprint server for health sciences
|August 8, 2025
概括
遗传背景变异影响神经发育的16p12.1删除效应. 这项研究揭示了遗传结构如何影响疾病结果的变化,并确定了关键的调节基因.
科学领域:
- 遗传学和基因组学 在
- 发展生物学 发展生物学
- 系统生物学 系统生物学
背景情况:
- 遗传变异往往导致不同的表型结果,但基本的生物机制尚未得到充分理解.
- 16p12.1删除可以作为研究遗传疾病中可变表达性的模型.
研究的目的:
- 开发一个研究基因架构如何促进表型变异的研究框架.
- 阐明16p12.1删除综合征中驱动变量表达性的分子机制.
主要方法:
- 使用诱导多能干细胞 (iPSC) 模型,这些模型来自具有16p12.1删除的家族.
- 使用CRISPR编辑的细胞系来建模16p12.1删除和二次遗传变异.
- 进行了细胞分析,CRISPR激活实验和整合性监管分析.
主要成果:
- 16p12.1删除和背景遗传变异共同影响了染色质可访问性和神经发育基因表达.
- 鉴定了特定家族的细胞表型,包括改变的神经发生和祖细胞增殖,与头部大小的变化有关.
- 证明CRISPR激活16p12.1基因可以通过调节TGF-β和PI3K-AKT通路来可变地挽救细胞缺陷.
- 发现转录因子FOXG1和JUN是这些遗传效应的关键媒介.
结论:
- 建立了一个功能框架来剖析表型变异性的遗传基础.
- 突出了删除,二次变异和基因调节之间的相互作用,以确定疾病的结果.
- 提供了有关神经发育变异性所涉及的分子通路和调节枢纽的见解.
相关概念视频
01:43Sex-linked Disorders
103.0K
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.
103.0K
01:09Epistasis Analysis
5.2K
Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The...
5.2K
01:33Pleiotropy
41.1K
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,...
41.1K
01:11Genome-wide Association Studies-GWAS
14.2K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
14.2K
01:43Incomplete Dominance
25.4K
Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
25.4K
01:28Human Genetics
722
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...
722