Genetics Semester 4 Flashcards
Philadelphia chromosome related disorder - type of inheritance?
No inheritance type, it occurs sporadically
Philadelphia chromosome related disorder - mechanism?
Translocation between chromosome 9 and 22 leading to fusion between ABL on ch.9 and BCR och ch.22.
Philadelphia chromosome related disorder - gain or loss of function?
Gain of function
Philadelphia chromosome related disorder - incidence?
1:100,000
Pathogenesis of Philadelphia chromosome related disorder?
Abnormal tyrosine kinase activity, which is cytoplasmic and nuclear protein needed for control of differentiation, division, adhesion and stress response.
Philadelphia chromosome related disorder, what does abnormal tyrosine kinase lead to?
Leads to uncontrolled growth and division of white blood cells.
Philadelphia chromosome related disorder, how many cases lead to chronic myelogenous leukemia?
90%
Philadelphia chromosome related disorder, how many cases lead to adult acute lymphoblastic leukemia?
25-30%
Philadelphia chromosome related disorder, how many cases lead to childhood acute lymphoblastic leukemia?
2-10%
Philadelphia chromosome related disorder, age of onset?
Later in adulthood, around age of 40-60.
Philadelphia chromosome related disorder, male to female ratio?
More common in males.
Symptoms of Philadelphia chromosome related disorder?
Development of fatigue
Malaise
Weight loss
Splenomegaly
Pancytopenia - anemia, thrombocytopenia and leukopenia
Philadelphia chromosome related disorder, treatment?
Inhibit BCR-ABL tyrosine kinase by binding to active binding site.
Examples: Imatinib/masitinib/nilotinib
Retinoblastoma - type of inheritance?
Autosomal dominant
Retinoblastoma - de novo mutations occurrence?
20-30%
Retinoblastoma - incidence?
1:15,000 - 1:20,000
Retinoblastoma - mechanism?
Mutation of tumor suppressor gene (RB1) on chromosome 13.
Retinoblastoma - what is RB1 gene responsible for?
Produces retinoblastoma protein pRB which controls cell cycle and prevents excessive cell growth.
Retinoblastoma - mutations can be caused due?
Point mutations, deletion, hypermethylation of promotor region.
Retinoblastoma - what does pRB do normally?
Binds to transcription factor complex E2F and surpasses transcription of genes needed for cell cycle progression to S phase.
Retinoblastoma - what is RB1 involved in?
Checkpoint in cell cycle, differentiation and apoptosis of genes. So mutation of RB1 can lead to increased proliferation of cells.
Retinoblastoma - locus or allelic heterogeneity?
Allelic
Retinoblastoma - what is two hit theory?
In hereditary retinoblastoma – one mutated copy if the RB1 gene in all cells including germ cells. They then get a second somatic mutation in the remaining normal copy in the retinal cell leading to tumor.
In sporadic retinoblastoma – both copies of the RB1 get the mutation independently.
Retinoblastoma - penetrance?
Incomplete penetrance
Retinoblastoma - pathogenesis in case of sporadic retinoblastoma?
Sporadic retinoblastoma usually occurs unilaterally (on eye) and late onset.
Retinoblastoma - pathogenesis in case of heriditary retinoblastoma?
Hereditary retinoblastoma usually occurs bilaterally (both eyes) and could be associated with other malignancies.
Retinoblastoma - when does intraocular malignancies usually manifest?
During childhood
Retinoblastoma - main symptoms?
Leukocoria - When light is shined on pupil it is rather white than red.
Strabismus: misalignment of eyes.
Loss of vision
Painful red eye
Retinal detachment
Lynch syndrome - type of inheritance?
Autosomal dominant
Lynch syndrome is also known as?
Heriditary non-polyposis colorectal cancer (HNPCC)
Lynch syndrome - mechanism?
Mutations of MSH2, MLH1, MSH6 gene.
MSH2 accounts for 60% of cases
MLH1 accounts for 30%
Lynch syndrome - what are the genes normally responsible for?
They are known as DNA mismatch repair genes (MMR), that correct errors during DNA replication (correct mismatched bases or insertions/deletions).
Lynch syndrome - loss or gain of function?
Loss of function