全基因组关联研究确定了新的乳腺癌易感点
Douglas F Easton1, Karen A Pooley, Alison M Dunning
1CR-UK Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. d.easton@srl.cam.ac.uk
Nature
|May 29, 2007
概括
研究人员使用一项大型全基因组关联研究确定了与乳腺癌风险相关的五个新的遗传位置. 这一发现有助于解释已知的基因之外的家族性乳腺癌的遗传基础.
科学领域:
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
- 流行病学 流行病学
背景情况:
- 乳腺癌显示出家族聚合,这表明对易感性的遗传成分.
- 目前已发现的易感基因解释了不到25%的家族乳腺癌风险.
- 剩余的遗传变异可能涉及具有中等风险效应的变异.
研究的目的:
- 为了确定乳腺癌的额外遗传易感性等位基因.
- 调查导致乳腺癌遗传性的常见变异.
主要方法:
- 进行了两阶段的全基因组关联研究 (GWAS),涉及数千例病例和对照.
- 利用227,876个单核酸多态 (SNP) 来归因常见变体.
- 在22个独立研究中对30个有前途的SNP进行了第三阶段确认.
主要成果:
- 确定了五个与乳腺癌风险显著相关的新型独立位点 (P < 10^-7).
- 四个位置含有可信的候选基因:FGFR2,TNRC9,MAP3K1和LSP1.1.
- 该研究发现了比预期更重要的SNP,这表明该方法的有效性.
结论:
- 这些发现扩大了对乳腺癌遗传易感性的理解.
- 这种GWAS方法有效地发现了额外的常见乳腺癌风险等位基因.
- 鉴定出来的基因为进一步研究乳腺癌病因提供了潜在的目标.
相关概念视频
Genome-wide Association Studies-GWAS
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...
Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
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Such genes that act...
Single Nucleotide Polymorphisms-SNPs
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,...
lncRNA - Long Non-coding RNAs
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...
