在CELSR3中双基变异与中枢神经系统和尿路异常有关
Jil D Stegmann1,2, Jeshurun C Kalanithy3,4, Gabriel C Dworschak3,4,5
1Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, 53127, Germany. jil.stegmann@uni-bonn.de.
NPJ genomic medicine
|March 1, 2024
概括
CELSR3中的双变体,平面细胞极性蛋白质,导致中枢神经系统和脏和尿路的先天性异常 (CAKUT). 这些发现强调了CELSR3在发育中的关键胚胎作用.
科学领域:
- 遗传学 是一个遗传学.
- 发育生物学 发展生物学
- 人类病理生理学 人类病理生理学
背景情况:
- CELSR3编码了一个平面细胞极性蛋白质,对组织发育至关重要.
- 在人类发育障碍中,CELSR3的遗传变异已被涉及到.
研究的目的:
- 通过分析具有双基变异的个体来研究CELSR3在人类发育中的作用.
- 阐明与CELSR3变体相关的表型谱.
- 探索已识别的CELSR3变异对蛋白质结构和胚胎发育的功能影响.
主要方法:
- 对11个具有双等位基因CELSR3变异的家族进行遗传分析.
- 临床评估受影响的个体,记录中枢神经系统 (CNS) 和脏和尿路的先天性异常 (CAKUT).
- 计算型蛋白质结构模拟.
- 在人类胚胎组织中进行免疫定位研究.
- 斑马鱼 Celsr3 击倒和救援实验.
主要成果:
- 来自11个家族的12个个体呈现出双基CELSR3变体.
- 现型谱包括中枢神经系统异常 (7/12),中枢神经系统和CAKUT联合 (3/12),以及仅CAKUT (2/12).
- 蛋白质结构模拟表明了影响透率和表型的变异位置.
- 在胚胎尿路中观察到CELSR3的表达;斑马鱼实验证实了其在中枢神经系统和尿路形成中的作用.
结论:
- 双等位基CELSR3变体与多种中枢神经系统和CAKUT表型相关.
- 在中枢神经系统和泌尿道的胚胎发育过程中,CELSR3起着至关重要的作用.
- 了解CELSR3的功能,可以了解发育异常的遗传基础.
相关概念视频
02:26Comparing Copy Number Variations and SNPs
17.7K
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
17.7K
02:02Cis-regulatory Sequences
9.9K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
9.9K
01:33Pleiotropy
40.4K
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,...
40.4K
01:30Neurulation
41.9K
Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the...
41.9K
02:30Histone Variants at the Centromere
4.3K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
4.3K