meeting 20 pt 1 11/17

Overview of Genomic Imprinting and Gene Expression

Definition: A genetic phenomenon where only one allele of a gene is expressed while the other allele is silenced.
Importance: Impacts gene expression and has implications in genetics and development.

Each cell contains two copies of DNA:
- One copy inherited from the mother (maternal allele).
- One copy inherited from the father (paternal allele).
Typically, both alleles can be expressed, allowing for protein production from both copies.

In certain genes, expression is restricted to either the maternal or paternal allele.
- Example: If the paternal gene is imprinted, it will not be expressed, shutting down that gene's ability to produce protein.
- Only the maternal gene will result in protein expression.
Consequences of Mutations:
- If a mutation occurs in the paternal allele (mutant copy), the phenotype or disease can manifest despite having a healthy maternal allele due to imprinting.

In germ cells:
- Female mice produce eggs, while male mice produce sperm.
- Information undergoes a reset process in the germline where imprints are re-established in the next generation.
- This ensures that gene expression patterns can change across generations.
Imprinting Patterns:
- Generally, only the paternal chromosome is imprinted in the germline of female offspring, leaving maternal alleles to be potentially expressed.

Regulatory Sequences and Insulators:
- A regulatory sequence can modulate whether gene expression occurs through mechanisms involving barrier proteins.
- Example: A barrier protein may prevent communication between a regulatory element and the gene, affecting overall expression patterns.
Role of DNA Methylation:
- DNA methylation functions as a key regulatory mechanism influencing gene expression and silencing specific gene copies.
- Methylation may lead to the activation of secondary start sites for mRNA production, depending on whether a region is imprinted or not.

Example of Start Sites in mRNA Generation:
- When an imprint is not present, a secondary start site may become accessible, resulting in altered mRNA production.
Promoter Functionality:
- The presence or absence of imprinting can determine which promoter is accessed by transcription machinery, leading to the expression of different protein products based on regulatory elements.
Regulatory Output:
- Factors present and modifications (like methylation) can influence whether a certain promoter is active, affecting which mRNA is generated based on imprinting status.

In females, random X chromosome inactivation occurs early in development:
- Each female cell will express one X chromosome while silencing the other, leading to mosaicism in X-linked traits.
- This silencing occurs via a complex involving RNA elements such as short interfering RNAs (siRNAs).

siRNAs functionality:
- A single-stranded RNA is incorporated into a protein complex that seeks out complementary RNA strands.
- When binding occurs, the target mRNA is cleaved, preventing translation and effectively silencing the gene product.
Clinical Relevance:
- Research on RNA applications includes therapeutic strategies to shut down harmful protein expression, such as those causing blindness.
- This might involve regular injections to introduce therapeutic RNA targeting problematic genes, although it is noted that such treatments typically have transient efficacy and require frequent administration.

Clarification can be sought on the specifics of gene imprinting, expression mechanisms, and role of regulatory elements in altering gene transcription.