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In-vitro Mutagenesis

In-vitro Mutagenesis

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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Related Experiment Video

Updated: Feb 27, 2026

In Vivo Modeling of the Morbid Human Genome using Danio rerio

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Published on: August 24, 2013

GWAS signals revisited using human knockouts.

Sateesh Maddirevula¹, Fatema AlZahrani¹, Shams Anazi¹

¹Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Genetics in Medicine : Official Journal of the American College of Medical Genetics

|June 23, 2017

Summary

Researchers identified natural human gene knockouts in Saudi Arabia, revealing new insights into complex traits and improving the interpretation of genome-wide association studies (GWAS). This study highlights the clinical relevance of genetic variations.

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Last Updated: Feb 27, 2026

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Selection-dependent and Independent Generation of CRISPR/Cas9-mediated Gene Knockouts in Mammalian Cells

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Published on: June 16, 2017

Area of Science:

Human Genetics
Genomics
Medical Research

Background:

Genome-wide association studies (GWAS) identify genetic variants associated with complex traits.
Interpreting GWAS signals often relies on proximity to genes, which can be challenging.
Naturally occurring human gene knockouts offer a direct way to study gene function and clinical relevance.

Purpose of the Study:

To identify novel knockout events in genes previously highlighted by GWAS.
To leverage the unique population structure of Saudi Arabia for genetic discovery.
To assess the clinical phenotypes associated with natural gene knockouts identified through GWAS.

Main Methods:

Utilized combined autozygome and exome analysis in the Saudi Arabian population.
Identified homozygous truncating mutations in genes previously linked to human disease via GWAS.
Characterized the phenotypes of individuals with these identified gene knockouts.

Main Results:

Reported five families with homozygous truncating mutations in GWAS-implicated genes (TRAF3IP2, FRMD3, RSRC1, BTBD9, PXDNL).
Observed phenotypes in these natural knockouts varied, sometimes aligning with, and sometimes diverging from, GWAS-reported associations.
Demonstrated the utility of human knockouts in understanding gene function beyond GWAS correlations.

Conclusions:

Human knockouts are valuable for the medical annotation of the human genome.
This study expands the role of naturally occurring gene knockouts in interpreting GWAS findings for complex traits.
The findings underscore the importance of studying complete loss-of-function mutations in understanding genetic determinants of health.