Mod 9 - effects of DNA mutations

Question 1

why are mutations important?

Answer 1

• important for evolution
• important for diversity of organisms

Question 2

what is a point mutation?

Answer 2

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)

Question 3

what is an insertion mutation?

Answer 3

insertion of one or more base pairs into the sequence (frameshift)

Question 4

what is a deletion mutation?

Answer 4

deletion of one or more base pairs from the sequence (frameshift)

Question 5

what is an inversion mutation?

Answer 5

when two or more bases are excised from the original sequence and reinserted in the opposite orientation

Question 6

what is a synonymous mutation?

Answer 6

a mutation that has no effect on the amino acid sequence (e.g. silent point mutation)

Question 7

what is a non-synonymous mutation?

Answer 7

a mutation that changes the amino acid sequence (aka missense mutation)

Question 8

what is a nonsense mutation?

Answer 8

a mutation that changes an amino acid to a stop codon (cuts the amino acid sequence short)

Question 9

what is a readthrough mutation?

Answer 9

a mutation that changes a stop codon to a codon for an amino acid (amino acid is much longer)

Question 10

what is a frameshift?

Answer 10

when a mutation changes the reading frame - all codons downstream of mutations are altered

Question 11

what is suppressive mutation?

Answer 11

when a second mutation restores the amino acid, despite the nucleotide sequence still being altered

Question 12

what is a monogenic disorder?

Answer 12

an inherited disease caused by a defect in individual genes ( e.g. cystic fibrosis)

Question 13

what gene does cystic fibrosis affect?

Answer 13

cystic fibrosis transmembrane regulator gene (chromosome 7)

Question 14

what happens as a result of cystic fibrosis?

Answer 14

causes a dysfunction of the salt + water balance - leads to thick mucous + excessive loss of salt in sweat

Question 15

what are some features of cystic fibrosis?

Answer 15

• 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

Question 16

how is CF treated?

Answer 16

Orkambi - made of Ivacaftor + Lumacaftor

Question 17

what does Lumacaftor do?

Answer 17

improves conformational stability of F508del - helps CFTR protein to move to cell surface

Question 18

what does Ivacaftor do?

Answer 18

CFTR potentiator - helps it to function better - facilitates increased chloride ion treatment

Question 19

what does it mean to be a diploid organism?

Answer 19

• to have 2 copies of each chromosome + 2 copies of each gene
  e.g. peas have 14 chromsomes = 2 sets of seven

Question 20

what is haploinsufficiency?

Answer 20

• 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

Question 21

how can being a carrier give a predisposition to disease?

Answer 21

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

Question 22

what is trisomy?

Answer 22

• having three copies of a chromosome
• e.g. down syndrome - caused by having 3 copies of chromosome 21

Question 23

what is monosomy?

Answer 23

• when 1 chromosome is missing
• e.g. monosomy 7 - involves one copy of chromosome 7 being missing - leads to high risk of leukemia

Question 24

what is a chromosome translocation?

Answer 24

• when part of one chromosome becomes attached to another chromosome

Question 25

what is the Philadelphia chromosome?

Answer 25

• 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