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相关概念视频

Genetic Screens02:46

Genetic Screens

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Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
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Background and Environment Affect Phenotype02:27

Background and Environment Affect Phenotype

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Although the genetic makeup of an organism plays a major role in determining the phenotype, there are also several environmental factors, such as temperature, oxygen availability, presence of mutagens, that can alter an organism’s phenotype.
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
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Evolutionary Relationships through Genome Comparisons02:54

Evolutionary Relationships through Genome Comparisons

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Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...
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Human Genetics01:28

Human Genetics

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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...
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In-vitro Mutagenesis01:16

In-vitro Mutagenesis

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To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
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Genomics02:02

Genomics

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Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
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相关实验视频

Updated: May 27, 2025

In Vivo Modeling of the Morbid Human Genome using Danio rerio
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将定向进化与机器学习相结合,可以准确地预测基因型到表型.

Alexander J Howard1, Ellen Y Rim1, Oscar D Garrett1

  • 1Department of Plant Pathology and the Genome Center, University of California, Davis, CA, 95616, USA.

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概括

研究人员开发了一种使用定向进化和蛋白质语言建模的新方法,以了解大米免疫受体变体. 这种方法通过分析序列变异及其对蛋白质功能的影响来确定新的抗米疾病基因.

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相关实验视频

Last Updated: May 27, 2025

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科学领域:

  • 植物科学 植物科学
  • 分子生物学分子生物学
  • 生物信息学是一种生物信息学.

背景情况:

  • 了解遗传变异和可观察的特征 (表型效应) 之间的关系对于有效利用大型基因组数据集至关重要.
  • 像Pik-1这样的水免疫受体在植物对病原体的防御中起着至关重要的作用,但它们的自然变体通常会逃避检测特定的真菌因子.

研究的目的:

  • 开发和应用一种结合定向进化和蛋白质语言建模的新方法,以表征大米免疫受体Pik-1的自然存在变体.
  • 设计Pik-1变种,能够识别现有的Pik-1等位基因不针对的真菌蛋白 (Avr-PikC和Avr-PikF).
  • 通过分析3000米基因组项目数据集中的序列变异来识别和验证大米中疾病耐药性的新来源.

主要方法:

  • 使用高通量定向进化来设计Pik-1受体以结合和识别真菌蛋白Avr-PikC和Avr-PikF.
  • 微调了一种蛋白质语言模型,使用定向进化数据来建立序列变异和联结能力之间的相关性.
  • 利用受过训练的蛋白质语言模型来分析来自3000米基因组项目数据集的Pik-1变体.

主要成果:

  • 成功设计了Pik-1变体,可以结合和识别真菌蛋白质Avr-PikC和Avr-PikF,这些蛋白质通常不会被当前的Pik-1等位基因识别.
  • 蛋白质语言模型有效地将序列变异与改变的连接体结合行为相关联.
  • 从3000米基因组项目中确定了两种Pik-1变异,它们对Avr-PikC具有很高的结合亲和力,通过体外分析证实了比野生型Pik-1更好的结合对象.

结论:

  • 定向进化和蛋白质语言建模的结合方法是描述蛋白质变异及其功能影响的强大工具.
  • 这种以机器学习为驱动的策略成功地识别了具有增强联体结合能力的新型大米免疫受体变体,代表了对疾病耐药性的有希望来源.
  • 该方法对探索其他感兴趣的蛋白质的表型变异具有重大潜力,有助于作物改进和理解蛋白质演变.