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Related Concept Videos

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
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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,...
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Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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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.
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A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
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Back to the future with phenotypic screening.

Marguerite Prior1, Chandramouli Chiruta, Antonio Currais

  • 1Cellular Neurobiology Laboratory, The Salk Institute for Biological Studies , La Jolla, California 92037-1002, United States.

ACS Chemical Neuroscience
|June 6, 2014
PubMed
Summary
This summary is machine-generated.

Current drug discovery for neurodegenerative diseases fails because it targets single causes. A new approach using phenotypic screening for aging brain biology is needed to find effective treatments.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Aging Research

Background:

  • No disease-modifying drugs exist for age-related neurodegenerative diseases or stroke.
  • Current drug development often fails due to a limited understanding of disease complexity.

Purpose of the Study:

  • To propose a shift in drug discovery strategy for neurodegenerative diseases.
  • To advocate for phenotypic screening that reflects aging brain biology.

Main Methods:

  • Critique of single-target drug discovery approaches.
  • Argument for phenotypic screening assays relevant to aging.

Main Results:

  • Current single-target strategies are unlikely to yield effective treatments.
  • Phenotypic screening offers a more promising avenue for drug development.

Conclusions:

  • Drug discovery for neurodegeneration must move beyond single targets.
  • Focusing on the aging brain's complex biology through phenotypic screening will yield safer, more effective drugs.