Gene Mutations and Pathogenesis

These flashcards cover key concepts related to gene mutations, pathogenesis, and their implications in genetic diseases.

What are the main types of mutations?

Missense, Insertion & Deletion, Silent, Splice Site, Nonsense, Dynamic.

What is Fragile X syndrome associated with?

CGG repeats in the FMR1 gene.

How many CGG repeats are considered unstable in Fragile X syndrome?

More than 200 CGG repeats.

What type of gene mutation is associated with Huntington disease?

CAG repeat expansion in the HTT gene.

What is the role of the gene HTT?

Codes for huntingtin.

What is a characteristic of dynamic mutations?

They can expand over time due to tandem repeats.

What is haploinsufficiency?

When a single gene copy does not produce enough gene product for normal function.

What generally suggests a mutation has a dominant effect?

If it causes haploinsufficiency, leading to disease with only one functional gene copy.

What syndrome is caused by loss of function in the PAX3 gene?

Waardenburg syndrome.

What is the typical mutation type in Waardenburg syndrome?

Loss of function mutations.

What is an example of a disease that demonstrates anticipation?

Fragile X syndrome.

What happens in anticipation?

A disease manifests earlier and/or increases in severity with successive generations.

What is the importance of protein dosage in disease manifestation?

Disease manifestation can depend on the amount of normal active product; dominant mutations need >50%, recessive mutations need <<50%.

What is a common mechanism for gain of function mutations?

Overexpression of genes.

What disease is linked to overexpression of PMP22?

Charcot-Marie-Tooth disease type 1A.

What causes chronic myeloid leukemia?

A translocation between chromosomes 9 and 22 resulting in BCR-ABL fusion gene.

What type of mutations primarily lead to monogenic diseases?

Loss of function mutations.

What type of mutation causes sickle cell anemia?

A missense mutation in the HBB gene.

What happens to collagen type I in osteogenesis imperfecta?

Mutations in collagen genes lead to improper assembly and function.

What defines a dominant negative mutation?

A mutation that leads to a stable but inactive protein.

What is the phenotype severity for COL1A1 null alleles?

Mild-moderate bone fragility, normal stature.

How do environmental factors relate to genetic diseases?

They can interact with genetic variants to influence disease risk.

What is the difference between monogenic, polygenic, and multifactorial genetic diseases?

Monogenic involves one gene, polygenic involves multiple genes, and multifactorial includes genetics and environment.

How do genetic variants contribute to polygenic diseases?

They combine to reach a threshold above which disease may manifest.

What are common consequences of mutated proteins?

Aggregation or misfolding that can cause disease.

What disease is linked to mutations in the COL1A2 gene?

Osteogenesis imperfecta.

Which part of the collagen protein is crucial for its assembly and function?

The triple helix structure.

What is a hallmark of gain of function mutations in oncogenes?

Acquisition of new functions or increased activity.

What is a mutation that causes a gene to function improperly by altering signaling responses?

Gain of function mutation.

What can happen with allelic heterogeneity in Waardenburg syndrome?

Different mutations in the PAX3 gene can cause the same disease phenotype.

What clinical significance does anticipation have for genetic counseling?

It indicates potential risks for severity and onset age in future generations.

What do expansions of short tandem repeats lead to?

They can result in dynamic mutations that are unstable.

What is the relationship between the CAG repeat length and age of onset in Huntington's disease?

Longer CAG lengths are associated with earlier age of motor onset.

Which domain of collagen mutations is often associated with severe disease outcomes?

Mutations in C-terminal domains.

What type of genetic variants can modify the effect of pathogenic gene mutations?

Risk variants.

What can be inferred about dominant negative mutations and protein interactions?

They can disrupt normal protein dimerization and function.

Which protein aggregation is linked with mutant HBB protein?

Sickle cell anemia.

What are the potential impacts of gain of function mutations in gene regulation?

Overexpression of harmful genes or functions.

Why are mutations in signaling genes significant in cancer?

They can lead to uncontrolled cell growth.

What evidence suggests a genetic component in multifactorial diseases?

Familial recurrence risk observed in affected individuals.

What is an important characteristic of splice site mutations?

They can lead to incorrect protein formation due to improper RNA splicing.

What is the primary growth factor for evolutionary conservation of gene function?

The importance of normal protein function for survival.

How do CAG repeats in Huntington disease demonstrate dynamic mutation behavior?

CAG repeats can expand during DNA replication, causing instability.

What cellular response can protein misfolding induce?

Protein aggregation leading to apoptosis.

Why is early diagnosis critical in disorders with anticipation?

To manage symptoms proactively and address family planning concerns.

What technique can detect repeat expansions in genes?

PCR (Polymerase Chain Reaction) combined with gel electrophoresis.

How does the number of normal gene products relate to dominant and recessive mutations?

Dominant mutations often require less than 50% of normal product for disease; recessive mutations require even less.

What is the function of FMR1 in the context of Fragile X syndrome?

It regulates neuronal growth and synaptic plasticity.

What distinguishes gain of function mutations from loss of function mutations?

Gain of function mutations result in increased activity or novel functions.

What practical implications does understanding gene dosage effects have in medicine?

It informs treatment options and genetic counseling strategies.

How do mutations in collagen genes impact the structure of connective tissue?

They disrupt normal protein assembly and lead to structural deficiencies.

What is an example of a chimeric gene resulting from a genetic alteration?

The BCR-ABL fusion gene in chronic myeloid leukemia.

What is the significance of studying genotype/phenotype correlations in clinical genetics?

To better understand disease mechanisms and potential outcomes based on specific mutations.