Lecture 4i: Genetic Interactions with Regulatory Genes

Introduction

• Focus on genetic interactions involving regulatory genes.
• Simplified model using two genes: STOP and GO.
• Analysis of mutations in embryonic and adult cells.

Gene Function in Normal Cells

Embryonic Cells

• STOP Gene: Not expressed.
• GO Gene: Active; produces protein stimulating cell growth.

Adult Cells

• STOP Gene: Active; produces protein that turns off the GO Gene.
• GO Gene: Not expressed, preventing cell growth.

Impact of Mutations

Single Knockout Mutation of STOP Gene

• Embryonic Cells: Little to no effect due to recessive nature.
• Adult Cells: One functional copy suffices; no expected phenotype change.

Single Mutation in GO Gene

• Embryonic Cells: Growth likely normal unless protein deficit slows growth.
• Adult Cells: No effect since GO Gene is off.

Promoter Mutations

STOP Gene Mutation

• Embryonic Cells: Constitutive activity prevents GO Gene expression; cell won't grow and may die.
• Adult Cells: No effect due to existing high STOP protein levels.

GO Gene Mutation

• Embryonic Cells: No phenotype change.
• Adult Cells: Causes growth despite STOP protein presence, akin to cancer cells.

Dual Mutations: Inherited and Somatic

• Inherited knockout of one STOP allele + somatic knockout of the other can lead to uncontrolled cell growth (cancer behavior).
• Similar scenarios with the GO Gene do not result in growth due to the gene being off.

Complexity of Genetic Regulations

• Real-world genetic interactions are far more complex.
• Diagrams illustrate complexity in embryonic stem cells and blood cell production networks.
• Many genes and interactions regulate transcription and cell behavior.

Conclusion

• Explored regulatory mutations in a simple model.
• Set the foundation for understanding how somatic mutations cause cancer.
• Next lecture will delve into the inheritance of cancer risk.