亚洲人群中的外体序列测定确定了影响帕金森病风险的低频率和罕见编码变异
Elaine Gy Chew1, Zhehao Liu2,3, Zheng Li3
1Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore.
Nature aging
|November 21, 2024
概括
GBA1和SMPD1中的罕见遗传变异与帕金森病 (PD) 风险有关. 这项研究使用全外因组测序来识别这些关联,为PD病变发生提供了新的见解.
科学领域:
- 遗传学 是一个遗传学.
- 神经学 神经学
- 基因组学就是基因组学.
背景情况:
- 帕金森病 (PD) 是一种进展性神经退行性疾病,全球发病率不断增加.
- 了解PD的遗传基础对于开发有效的治疗方法至关重要.
- 罕见的遗传变异可能为PD病变发生提供新的见解.
研究的目的:
- 调查罕见的蛋白质改变变异在帕金森病易感性中的作用.
- 在亚洲人群中确定与PD风险的新型遗传关联.
主要方法:
- 在4,298例PD病例和5,512例亚裔对照中进行了全外体序列测序.
- 用基因测试来评估变体与PD风险的关联.
- 在体外测试被用来功能性地表征已识别的变异.
主要成果:
- 基因GBA1和SMPD1与PD风险有显著的关联,在一个独立的队列中复制.
- 酶活性降低的SMPD1变体 (<44%活性) 显示出与PD最强的关联 (OR=2.24,P=1.25×10−15).
- 在SMPD1中发现的亚洲特异变异p.Pro332Arg在80.5%的SMPD1携带者中被发现 (OR=2.16,P=4.47×10−8).
结论:
- 在GBA1和SMPD1的罕见变体有助于帕金森病的风险.
- 变异的功能性特征,特别是影响SMPD1酶活性的变异,对于理解PD至关重要.
- 在不同种群中对外体序列测序对于发现与PD等复杂疾病相关的罕见变异非常有价值.
更多相关视频
05:51A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
25.8K
11:35Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay EMSA and DNA-affinity Precipitation Assay DAPA
Published on: August 21, 2016
12.9K
相关概念视频
02:26Comparing Copy Number Variations and SNPs
17.3K
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%...
17.3K
01:05Single Nucleotide Polymorphisms-SNPs
14.0K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
14.0K
01:11Genome-wide Association Studies-GWAS
12.5K
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...
12.5K
01:28Human Genetics
535
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...
535
01:37Neural Regulation
39.1K
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
39.1K
01:43Incomplete Dominance
21.6K
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.
21.6K