Mod 9 - effects of DNA mutations Flashcards
why are mutations important?
- important for evolution
- important for diversity of organisms
what is a point mutation?
when one base is replaced with another
- transition - purine-> purine (e.g. A to G)
- transversion - purine->pyrimidine or vice versa (e.g. C to G)
what is an insertion mutation?
insertion of one or more base pairs into the sequence (frameshift)
what is a deletion mutation?
deletion of one or more base pairs from the sequence (frameshift)
what is an inversion mutation?
when two or more bases are excised from the original sequence and reinserted in the opposite orientation
what is a synonymous mutation?
a mutation that has no effect on the amino acid sequence (e.g. silent point mutation)
what is a non-synonymous mutation?
a mutation that changes the amino acid sequence (aka missense mutation)
what is a nonsense mutation?
a mutation that changes an amino acid to a stop codon (cuts the amino acid sequence short)
what is a readthrough mutation?
a mutation that changes a stop codon to a codon for an amino acid (amino acid is much longer)
what is a frameshift?
when a mutation changes the reading frame - all codons downstream of mutations are altered
what is suppressive mutation?
when a second mutation restores the amino acid, despite the nucleotide sequence still being altered
what is a monogenic disorder?
an inherited disease caused by a defect in individual genes ( e.g. cystic fibrosis)
what gene does cystic fibrosis affect?
cystic fibrosis transmembrane regulator gene (chromosome 7)
what happens as a result of cystic fibrosis?
causes a dysfunction of the salt + water balance - leads to thick mucous + excessive loss of salt in sweat
what are some features of cystic fibrosis?
- loss-of-function - is recessive
- people can be carriers - carry only one allele of the gene
F508del - gets rid of Phe (508th amino acid) - doesn’t cause a frameshift as one whole nucleotide is deleted
G542X - nonsense mutation - changes a glycine to a stop codon
G511D - missense mutation - changes a glycine to aspartic acid
how is CF treated?
Orkambi - made of Ivacaftor + Lumacaftor
what does Lumacaftor do?
improves conformational stability of F508del - helps CFTR protein to move to cell surface
what does Ivacaftor do?
CFTR potentiator - helps it to function better - facilitates increased chloride ion treatment
what does it mean to be a diploid organism?
- to have 2 copies of each chromosome + 2 copies of each gene
e.g. peas have 14 chromsomes = 2 sets of seven
what is haploinsufficiency?
- when in certain genes, both copies must be functional
- a mutation in just one gene will cause disease (kind of like a dominant disease)
e.g. algaille syndrome
how can being a carrier give a predisposition to disease?
retinoblastoma
- sporadic retinoblastoma is rare - involves both copies of a gene becoming inactivated
- familial retinoblastoma is less rare - has only one functional copy of a gene to begin with, so is less rare when that gene becomes inactive
what is trisomy?
- having three copies of a chromosome
- e.g. down syndrome - caused by having 3 copies of chromosome 21
what is monosomy?
- when 1 chromosome is missing
- e.g. monosomy 7 - involves one copy of chromosome 7 being missing - leads to high risk of leukemia
what is a chromosome translocation?
- when part of one chromosome becomes attached to another chromosome
what is the Philadelphia chromosome?
- involves a translocation on chromosome 22
- loss of control region to control an ABL gene - gene is switched on all the time - cell division is uncontrolled
