Foundations 1 Week 5 Flashcards
What is the difference between promotion and progression in tumorigenesis?
Promotion is the process by which cells with a mutation in a critical gene (initiated cells) are induced to proliferate.
Progression is a result of the accumulation of mutations allowing the tumor to invade and metastasize.
Lecture: Carcinogenic Agents
Objective 2: Define initiation, promotion, and progression and explain the importance of these processes in understanding cell transformation and tumorigenesis.
You are a genetic counselor trying to advise a couple on the risk of their second child having Cleft Lip +/- Cleft Palate since their first child was affected. Neither of the parents are affected.
What data could you use to quantify the chance their second child has CL +/- CP?
Use the empiric risk from the same population.
Lecture: Multifactorial Traits
Objective 3: Define empiric risk
A Robertsonian translocation can occur between which of the following chromosomes?
- 11;13
- 9;21
- 15;20
- 14;22
D. 14;22
A Robertsonian translocation can occur between chromosomes 14 and 22.
They can only occur with acrocentric chromosomes (13, 14, 15, 21, 22).
Lecture: Cytogenetics Review
Describe the genetic mechanism by which an individual with Fragile X can be mosaic for the amount of repeats in different cells.
Full expansions are unstable in both meiosis and mitosis. This means that even after the expansion that occurs in (female) meiosis, more can occur during mitosis after fertilization.
Lecture: Trinucleotide Repeat Diseases
Objective 2: Explain the inheritance of Fragile X syndrome, including the role of repeat length in determining phenotype.
What is the mechanism by which UV-B can lead to tumor formation?
UV light causes the formation of pyrimidine dimers in DNA. These are normally removed through Nucleotide Excision Repair, but if they are not, mutations can occur in p53.
Other mechanisms include:
- Formation of free radicals which can damage DNA
- Strand breaks in DNA.
Lecture: Carcinogenic Agents
Objective 4: Describe the role of physical carcinogens UV light, ionizing radiation and asbestos in carcinogenesis.
Other than production of Reactive Oxygen Species (ROS) by immune cells, how can chronic inflammation lead to the progression of cancer?
Chronic exposure to prostaglandins and cytokines can drive proliferation of cancerous cells.
Lecture: Carcinogenic Agents
Objective 5: Describe the role of inflammation in the development and progression of cancer. Identify products of inflammation that may cause DNA mutation, cancer growth and progression.
Multifactorial Trait X is more common in females in the population. You encounter two siblings with the trait. Who is more likely to pass on the trait to offspring: the sister or the brother?
The brother. Since males are less likely to exhibit Multifactorial Trait X, they are then more likely to transmit it.
Lecture: Multifactorial Traits
Objective 4: Describe the relationship between degree of relatedness and incidence of a multifactorial trait.
Unlike the trinucleotide expansions seen in Spinal and Bulbar Muscular Atrophy (SBMA) and Huntington disease, the expansions in Fragile X and Myotonic Dystrophy occur in what type of genomic region?
They occur in noncoding regions of the chromosome.
Lecture: Trinucleotide Repeat Diseases
Objective 3: List the genomic locations where trinucleotide repeats may occur.
The increase of CAG repeats in an exon leads to the expansion of what type of tract? Name a disorder which is caused by this type of expansion.
Increased CAG repeats lead to expansion of polyglutamine tracts. An example of one of these disorders is Spinal and Bulbar Muscular Atrophy (SBMA). The resulting gene product is toxic to neurons.
Lecture: Trinucleotide Repeat Disorders
Objective 4: Describe the typical mechanism whereby expansion of polyglutamine tracts cause disease.
You see a 24yo patient who cannot unclench his hand after forming a fist, and you diagnose him with Myotonic Dystrophy.
With the genetic mechanism of the disease in mind, what age range would you expect his affected parent to have begun exhibiting signs and symptoms of the disorder?
The affected parent likely experienced symptoms after age 24.
Myotonic Dystrophy is caused by the expansion of CTG repeats in the DMPK gene. This disorder exhibits anticipation, where offspring who inherit longer repeats will exhibit signs of the disorder at a younger age. Symptoms will frequently be more severe as well.
Lecture: Trinucleotide Repeat Disorders
Objective 5: Define genetic anticipation and explain how it can occur.
