在Y染色体上的生殖系和体质变异的遗传调节有助于2型糖尿病
Go Sato1,2,3,4, Yuji Yamamoto5,6, Kyuto Sonehara7,5,8
1Department of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan. gsato@m.u-tokyo.ac.jp.
Nature medicine
|February 23, 2026
概括
Y染色体影响复杂的特征和2型糖尿病 (T2D) 的风险. 失去Y染色体 (LOY) 对跨种族的T2D风险有不同的影响,影响疾病预测.
科学领域:
- 遗传学 遗传学 是一个
- 人类生物学 人类生物学
- 医学科学 医学科学 医学科学
背景情况:
- Y染色体的生物学作用尚未完全理解.
- 性染色体变异,包括Y染色体单双组和Y染色体丧失 (LOY),可能会影响复杂的特征和疾病.
研究的目的:
- 在大型东亚和欧洲男性队伍中系统地描述Y染色体变异 (半组和LOY).
- 研究Y染色体变异与复杂特征的关联,特别是2型糖尿病 (T2D).
- 探索Y染色体变异对T2D风险预测模型的影响.
主要方法:
- 来自日本和英国生物银行的30多万名男性的生殖系Y半组和体质LOY的大规模遗传概况.
- 现象范围的关联扫描以识别特征关联.
- 分析LOY对T2D风险的贡献,与多基因风险得分相关.
- 单细胞分析以调查细胞类型特定的LOY积累.
主要成果:
- 鉴定了复杂特征的男性特异性遗传调节,包括日本单基组D对身高和T2D的类效应.
- 发现LOY在东亚人中增加了T2D风险,但在欧洲人中降低了风险.
- 证明LOY可以补偿东亚T2D发病率中低多基因风险得分.
- 表明,结合性染色体变异可以改善两性T2D风险预测.
- 揭示了细胞类型特定的LOY积累,对胰腺β细胞功能和葡萄糖代谢有潜在的影响.
结论:
- 包括哈普洛组和LOY在内的Y染色体变异在调节复杂特征和T2D风险方面发挥着重要作用.
- LOY对T2D风险的影响是群体特异性的,突出显示了对多样化的遗传研究的需要.
- 将Y染色体变异整合到风险预测模型中可以提高T2D风险评估.
- 对细胞特异性LOY机制的进一步研究是有必要的,以了解其在代谢疾病中的作用.
相关概念视频
The Y Chromosome Determines Maleness
8.6K
The Y chromosome is a sex chromosome found in several vertebrates and mammals, including humans. In addition to 22 pairs of autosomes, the human males have one X chromosome and one Y chromosome. In these organisms, the presence or absence of the Y chromosome determines the development of male traits.
Evolution
Around 300 million years ago, the two sex chromosomes diverged from two identical autosomal chromosomes. Over time, the Y chromosome has lost most of its genes, shrinking in size....
Evolution
Around 300 million years ago, the two sex chromosomes diverged from two identical autosomal chromosomes. Over time, the Y chromosome has lost most of its genes, shrinking in size....
8.6K
X and Y Chromosomes
30.4K
Among mammals, the gender of an organism is determined by the sex chromosomes. Humans have two sex chromosomes, X and Y. Every human diploid cell has 22 pairs of autosomes and one pair of sex chromosomes. A human female has two X chromosomes, while a male has one X chromosome and one Y chromosome.
The germline cells such as egg and sperm cells carry only half the number of chromosomes, i.e., 22 autosomes and one sex chromosome. All eggs have an X chromosome, while sperm cells can carry an X or...
The germline cells such as egg and sperm cells carry only half the number of chromosomes, i.e., 22 autosomes and one sex chromosome. All eggs have an X chromosome, while sperm cells can carry an X or...
30.4K
Diabetes Mellitus: Type 2 and Gestational
5.2K
Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
5.2K
Sex-linked Disorders
109.6K
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.
109.6K
Epigenetic Regulation
34.0K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
34.0K
Epigenetic Regulation
4.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
4.0K


