相关实验视频
Updated: Jun 30, 2026

08:36
Separation of Mouse Embryonic Facial Ectoderm and Mesenchyme
Published on: April 12, 2013
对基因与性别相互作用的全基因组研究确定了口腔裂的风险
Kelsey Robinson1, Randy Parrish1,2, Wasiu Lanre Adeyemo3
1Department of Human Genetics, Emory University, Atlanta, GA, 30322, USA.
Human genetics
|October 3, 2024
概括
口腔裂 (CP) 显示了性别特异性风险,特别是在女性中,这些风险在组合分析中被忽略了. 基因LTBP1被确定为女性CP的关键遗传风险因素.
科学领域:
- 遗传学 是一个遗传学.
- 发展生物学 发展生物学
- 出生缺陷的研究研究研究.
背景情况:
- 结构性出生缺陷影响3-4%的活产,经常表现出性别偏差的流行.
- 耳脸裂 (OFCs),包括带有或没有口腔裂 (CL/P) 和仅口腔裂 (CP) 的口唇裂,是常见的面缺陷.
- 虽然CL/P表现出已知的性别特异性风险,但CP的风险仍然被低估.
研究的目的:
- 使用全基因组关联研究 (GWAS) 调查口腔裂 (CP) 的性别特异性遗传风险.
- 为了确定与CP相关的基因对性别 (G×S) 相互作用.
- 探索LTBP1作为CP候选风险基因的作用,特别是在女性中.
主要方法:
- 在基于三组的队列上进行了性别分层的GWAS,随后进行了全基因组G×S相互作用测试.
- 确定了重要的G×S相互作用位点,重点关注LTBP1.1的顶部发现.
- 在性别分层分析中评估了基因调节的LTBP1表达和CP表型之间的关联.
主要成果:
- 发现了13个基位与CP的显著G×S相互作用,其中LTBP1显示了最强的关联 (p=1.93×10−6).
- LTBP1在面发育中起作用,在老鼠和人类中观察到性别之间的差异性表达.
- 在女性试验者 (p=0.0013) 中发现LTBP1表达和CP之间的显著关联,但在男性中没有.
结论:
- 肌肉疾病表现出显著的性别特异性遗传风险,这些风险在综合性分析中被掩盖.
- 已确定LTBP1为CP的新型候选风险基因,对女性有显著影响.
- 这些发现强调了性别分层方法在理解出生缺陷的遗传结构方面的重要性.
相关概念视频
Pleiotropy
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,...
X-linked Traits
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
Sex-linked Disorders
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.
The Ratio of X Chromosome to Autosomes
In most organisms, sex is determined by the ratio of X and Y chromosomes. However, in some organisms, such as Drosophila and C.elegans, sex is determined by the ratio of the number of X chromosomes to the number of sets of autosomes. The Y chromosome in Drosophila is active but does not determine sex. It contains genes responsible for the production of sperms in adult flies.
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female Drosophila...
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female Drosophila...
Sex Linked Disorders
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.
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...

