Variation & Disease Flashcards
Give 2 reasons as to why variants cause disease.
May cause change in sequence of gene product resulting in either gain/loss of function.
Mutations may result in change in the amount of product made.
Define and give an example of missense.
A genetic alteration where a single BP substitution which produced an amino acid that is different from the original. (E.g sickle cell mutation in HBB gene, an A -> T sub)
Define and give an example of nonsense.
A change in DNA that causes a protein to terminate or end its translation earlier than expected. (E.g. PAX3 mutation of G -> A which creates a stop codon)
Define and give an example of frameshift.
Any downstream change that removes nucleotides that are not a multiple of three will cause a frameshift. Severe frameshifts cause Duchenne muscular dystrophy. Frame-neutrals cause Becker muscular dystrophy.
(The code usually hits premature termination, NMD)
Define and give an example of splicing mutation.
Mutations affecting the GT or AG recognition sequences always affects splicing. (E.g. SMN1 and SMN2 both encode for phenylalanine but the TTC change prevents correct splicing)
Define and give an example of variation in short tandem repeats.
Variations in short tandem repeats are mostly found in non-coding regions and occasionally pathogenic (if located near promoters or splice sites). Additionally, Variations in short tandem repeats in coding regions are not polymorphic and can arise through an error and be pathogenic and stable in a family line. (E.g. polyalanine runs in certain proteins that cause diseases; Synpolydactly 1)
Define and give an example of dynamic mutation.
Dynamics mutations are short tandem repeats that, above a certain size, become unstable & increase number of repeats. (E.g. Huntington’s Disease is an example of dynamic mutations, since it shows a high number of repeat expansion in polyglutamine diseases, renders the RNA transcripts toxic)
What are the 2 types of general genetic mutations, give examples. (Sex)
Autosomal and anomalies; DOWN SYNDROME, Patau syndrome, edwards syndrome
Sex chromosomes anomalies; Turner syndrome, 47 XYY syndrome
Define gene dosage.
It’s the number of copies of a gene in a genome and is related to the amount of gene product the cell is Abe to express.
What causes changes in gene dosage, examples?
Insertions and deletions affect gene dosage and have a severe phenotype effect. (E.g. severe phenotypes accosted with trisomies like DS genes; DSCR1 and DYRK1A)
(Every gene has an appropriate gene dosage which is regulated by expression)
Define microdeletions and give examples.
Micro-deletions are essentially chromosomal deletions that are too small to be detected through microscope.
Microdeletion syndromes are characterized by several delayed development. (E.g. WAGR Syndrome, the combination of wilms’ tumor and absent iris)
Describe/explain the cytogenetic of Down syndrome. Why is it important to establish a precise cytogenetic cause of DS?
The extra chromosomes is maternal 90% of the time, with 75% of cases due to meiosis 1 errors.
Paternal origin has equal frequencies in meiosis 1 and 2 errors.
Translocation occurs in 33% of cases. Mosaics are rare.
It’s important to establish a precise cause is to prevent or plan against a recurrence risk for future generations within the family.
What are the types of genes that may mutate to cause cancer?
Suppressors genes, p53, ONCOGENES
Explain oncogenic function mutations.
Oncogenic mutations in tumor cells are gain of function mutations which create forms that are excessively or inappropriately active.
List and outline the 3 ways activation in cancer may occur.
Amplification; many cancer cells contain multiple copes of structurally normal oncogenes.
Point mutation; specific point mutations in oncogenes can lead to enhanced expression.
Translocation.
