黑色素受体1A变体作为异常性骨质疏松症的遗传原因
Brygida Bisikirska1, Rossella Labella1, Alvaro Cuesta-Dominguez1
1Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY 10032, USA.
Science translational medicine
|October 16, 2024
概括
黑激素受体1A (MTNR1A) 基因中的遗传变异与异常性骨质疏松症 (IOP) 有关. 一种特定的MTNR1A变体导致骨质细胞功能障碍,导致骨质量低和内脏压力增加的风险,特别是在亚什肯纳兹犹太人的个人中.
科学领域:
- 遗传学 遗传学 是一个
- 骨生物学 骨生物学 骨生物学
- 内分泌学 在内分泌学.
背景情况:
- 异常性骨质疏松症 (IOP) 是一种罕见的,早期发病的疾病,原因不明.
- 患者往往有骨折和家族骨质疏松症的病史,这表明遗传因素.
- 黑色素受体1A (MTNR1A) 变异已与IOP有关.
研究的目的:
- 调查MTNR1A变异在异常性骨质疏松症的发病过程中的作用.
- 为了确定一个特定的MTNR1A变体 (rs374152717) 对骨生理学的功能影响.
主要方法:
- 在IOP队列中进行全外体序列测序,以识别MTNR1A变异.
- 为人类的rs374152717变体生成一个小鼠模型.
- 使用人体细胞进行体外研究,以评估蛋白质功能和信号通路.
主要成果:
- 在IOP患者中确定了致病性MTNR1A变异,在阿什肯纳兹犹太人的患病率更高.
- 在小鼠中的rs374152717变体重复了IOP的低骨质量表型.
- 在人体细胞中,该变异导致一种非功能MTNR1A蛋白,导致骨质细胞衰老和骨周转受损害.
结论:
- MTNR1A突变代表了异常性骨质疏松症的遗传原因.
- rs374152717变体是一种功能丧失的等位基因,通过诱导骨质细胞衰老,为IOP做出贡献.
- 增加MTNR1A变种的流行率表明IOP的风险更高,特别是在特定人群中.
更多相关视频
09:37A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
8.2K
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
33.7K
相关概念视频
02:19Circadian Rhythms and Gene Regulation
4.0K
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.0K
01:29Bone Disorders
3.4K
Aging and its effect on bone remodeling is the most common cause of bone disorders. In young and healthy people, bone deposition and resorption happen at an equal rate to maintain optimal bone health.
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
3.4K
01:17Sedatives and Hypnotics Drugs: Miscellaneous Agents
149
Sedatives and hypnotics encompass a wide range of substances, each with its unique mechanism of action, uses, and potential adverse effects.
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
149
01:31Translation
141.6K
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
141.6K
01:28Human Genetics
539
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...
539
01:19Management of Insomnia
234
The sleep cycle, an integral part of human health, consists of several stages with distinct characteristics and functions. It begins with a transition from wakefulness to sleep, known as the light sleep phase, followed by the restorative deep sleep phase, essential for physical recovery and growth. The cycle concludes with the Rapid Eye Movement (REM) phase, characterized by high brain activity and vivid dreaming. Insomnia, a prevalent sleep disorder, involves difficulty falling asleep, staying...
234