导航ALS遗传迷宫:MAPT杂型的作用
Ivan Tourtourikov1,2, Kristiyan Dabchev2,3, Tihomir Todorov2
1Department of Medical Chemistry and Biochemistry, Medical University of Sofia, 1431 Sofia, Bulgaria.
Genes
|November 25, 2023
概括
一个特定的MAPT基因单基因型 (H1b) 几乎使得患有偶发性肌缩侧面硬化症 (ALS) 的风险增加了一倍. 这一发现突显了MAPT遗传变异在ALS风险中的作用.
科学领域:
- 神经遗传学 神经遗传学
- 分子生物学分子生物学
- 神经学 神经学
背景情况:
- 肌缩侧面硬化症 (ALS) 呈现出显著的临床和生物异质性.
- 相当一部分的ALS患者也表现出前性痴呆 (FTD) 频谱症状.
- 微管相关蛋白 (MAPT) 基因,特别是H1亚型,与神经退行性疾病有关.
研究的目的:
- 为了描述MAPT基因H1亚型的风险亚型.
- 研究这些亚型作为疾病发病年龄的风险因素和修饰因子在零星ALS (sALS) 的作用.
- 探索特定的MAPT类型与sALS风险和发病之间的相关性.
主要方法:
- 100名保加利亚零星ALS患者的基因定型针对特定的MAPT变异 (rs1467967,rs242557,rs1800547,rs3785883,rs2471738,rs7521).
- 使用Haploview 4.2和SHEsisPlus重建哈普型频率,以1000个基因组项目数据作为控制.
- 基因型-表型相关性分析,重点关注疾病发病年龄和疾病发展风险.
主要成果:
- 个别的MAPT变异对ALS发病年龄没有显著影响.
- 在特定的GGAGCA单元型 (H1b) 和发展sALS的风险之间发现了显著的相关性.
- 与其他H1亚型相比,患有H1b亚型的人患sALS的风险增加了近两倍.
结论:
- 在MAPT基因中的H1b单元型与散发性ALS的风险增加有关.
- 在MAPT位点的精细转录调节可能会影响ALS易感性.
- 对MAPT单元型变异的进一步研究可以完善对ALS病变和风险分层的理解.
更多相关视频
06:33Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis
Published on: June 9, 2018
7.7K
07:26High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment
Published on: July 18, 2017
11.9K
相关概念视频
01:11Genome-wide Association Studies-GWAS
13.5K
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...
13.5K
01:42Microtubule Associated Proteins (MAPs)
4.3K
Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
4.3K
01:49Multiple Allele Traits
34.3K
The Concept of Multiple Allelism
34.3K
02:17Microtubule Instability
5.1K
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
5.1K
01:19Allosteric Proteins-ATCase
5.8K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.8K
02:41Lethal Alleles
15.5K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
15.5K