Lecture 34 - Genomic Imprinting and Cancer Flashcards
Mention two types of genes involved in cancer.
- Oncogenes (Activation of proto-oncogenes)
- Tumour suppressor gene
Mention two ways in which oncogene can be activated.
- Amplification
- Chromosomal Rearrangement (Translocation to Active Region)
A dysfunctional Tumour Suppressor Gene (TSG) must require both allele copies to be ________. This effect is called _______.
non-functional, recessive effect
Loss or Mutation of TSG can occur via: ______ (3)
deletion, mutation, epigenetic effect
Mention the role of proto-oncogenes and tumour suppressor genes.
Proto-oncogenes: genes that stimulate cell proliferation
TSG: genes that keep proliferation in check
Explain Knudson’s “two hot” Model for TGS.
Knudson suggested that multiple “hits” to DNA were necessary to cause cancer. In the case of the TSG, a mutation in both alleles is required to deactivate the gene.
Provide an explanation on differences between cases of inherited and sporadic retinoblastoma in the context of Knudson’s hypothesis.
In inherited retinoblastoma, one of the TSG allele is already deactivated. The first mutation was inherited in the DNA, and any second mutation would then rapidly lead to cancer. In non-inherited retinoblastoma, two “hits” had to take place before a tumor could develop.
Because of this fact, inherited retinoblastoma occurs at a younger age than the sporadic disease since it takes more time to accumulate two mutations. In addition, the children with inherited retinoblastoma often developed the tumor in both eyes, suggesting an underlying predisposition (such as a inheritable trait rather than a random mutation). q
Define the concept of genetic imprinting.
Genetic imprinting refers to a epigenetic phenomenon that causes genes to be expressed differently depending of maternal/paternal origin. This difference is a result of methylation of cytosine of the gene promoter.
Explain why genetic imprinting must be reversible.
If genetic imprinting were irreversible, than an individual will always have a 50% chance of inheriting a chromosome with paternal or maternal imprinting regardless of sex. Since, we know that all gametes of an individual have the same imprinting, during gametogenesis a mechanism of wiping the parental imprinting and imposing a new methylation pattern must exist.
Explain the concept of linkage analysis in humans.
Some genes do not assort independently. The presence of one gene in the genome maybe LINKED to another. For example, the gene expressing the disease nail patella is linked to the gene for the ABO blood group. From pedigree analysis, one allele of the blood group gene then can be associated to the nail patella allele.
Explain how variations in gene alleles can be inferred through the linkage and usage of molecular markers.
Restriction enzymes cut DNA at specific sites. These sites can be CLOSE to the genes of interest. Different alleles may lead to different recognition sites, leading to RFLP. Hence, linkage between the molecular marker (recognition sequence –> RFLP sequence) and a certain allele of a gene can be inferred.
Mention an evidence backing genomic imprinting.
- Deletion of the same part of chromosome 15 of paternal and maternal origin results in two different phenotype. (Deletion in maternal -> Angelmann Syndrome, paternal–> Prader-Willi Syndrome)
Explain the concept of UPD (Uniparental disomy).
Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome from one parent and no copy from the other parent.
Mention both mechanisms resulting in UPD. Differ between them.
- Isodisomy: happens as a result of non-disjunction in meiosis II
- Heterodisomy: happens as a result of non-disjunction of meiosis I
