week 1 reading

Question 1

define substitutions mutation

Answer 1

replacement of a single nucleotide by another (very common)

Question 2

what is meant by the term transition?

Answer 2

Substitution mutation involving replacement by the same type of nucleotide - pyrimidine for a pyrimidine (C for T) or a purine for a purine (A for G)

Question 3

what is meant by the term transversion?

Answer 3

substitution of a pyrimidine by a purine or vice versa

Question 4

What is more frequent transitions of transverions?

Answer 4

transitions due to hotspots of CpG dinucleotides into a T

Question 5

deletions

Answer 5

involves loss of one or more nucleotides

Question 6

what can be the result of a deletion mutation?

Answer 6

• if this occurs in a coding sequence and involves one, two or more nucleotides that are not a multiple of three, the reading frame ill be disrupted

Question 7

what can be the cause of large deletions?

Answer 7

unequal crossover between repeat sequences

Question 8

insertions

Answer 8

involves addition of one or more nucleotides to a gene

Question 9

what can be the consequences of insertions?

Answer 9

• if it occurs in a coding sequence and involves one, two, more nucleotides that are not a multiple of three, it will disrupt the reading frame

Question 10

what can be the cause of a large insertion?

Answer 10

unequal crossover or insertions of transposable elements

Question 11

define dynamic mutations

Answer 11

• triple repeat expansion (insertion) that make the sequence more unstable as it expands in size
• take place over number of generations within a family

Question 12

what might be the reason for triplet repeat expansions?

Answer 12

• unequal crossover or unequal sister chromatid exchange in non-replicating DNA
• slipped-strand misfiring and polymerase slippage in replication DNA

Question 13

eg. expansion (insertions) in relation to huntingtons

Answer 13

• expansion of CAG repeat in doing region of HTT gene and some SCA genes result in a protein with an elongated polyglutamine tract that forms toxic aggregates within certain cells

Question 14

What other subdivisions for mutations are there?

Answer 14

according to the effect on polypeptide sequence of the encoding protein - synonymous or non-synonymous

Question 15

synonymous/ silent mutations

Answer 15

• if it doesn’t alter polypeptide product of the gene
• eg. single base pair substitution, particularly if it occurs in the third position of a codon will often result in other triplet coding for same amino acid with no alteration in properties of resulting protein

Question 16

non-synonymous mutations

Answer 16

• mutation leading to an alteration in encoded polypeptide
• less frequent
• likely to result in abnormal function, associated with disease or lethality

Question 17

describe the three main ways in which non-synonymous mutations can occur

Answer 17

• missense
• nonsense
• frameshift

Question 18

missense mutation

Answer 18

single-base pair substitution resulting in coding for a different amino acid and synthesis of an altered protein

Question 19

non-conservative substitution

Answer 19

altered porbtein

Question 20

conservative substitution

Answer 20

no functional effect

Question 21

nonsense

Answer 21

substitution leading to generation of one of the stop codons will result in premature termination of translation of a peptide chain - most times shortened chain unable to retain normal biological activity

Question 22

what happens to faulty mRNA transcripts containing premature termination codons due to a nonsense mutation?

Answer 22

degraded by the process of nonsense-mediated decay

Question 23

frameshift

Answer 23

mutation involving insertion or deletion of nucleotides that are not. multiple of three, it will disrupt the reading frame -> frameshift

Question 24

most common consequence of frameshift mutations

Answer 24

• result in premature stop codon downstream to the mutation
  may lead to expression of truncated protein, unless the mRNA is degraded by nonsense-mediated decay

Question 25

What could be the effect of mutations in non-coding DNA ? eg. promoter sequence, enhancers

Answer 25

affects level of gene expression (mutations in miRNA or siRNA binding sites within UTRs can also result in disease)

Question 26

splicing mutations

Answer 26

mutations of highly conserve splice donor (GT) and splice acceptor (AG) sites result in aberrant splicing

Question 27

what is the result of splicing mutations?

Answer 27

- loss of coding sequence (exon skipping) or retention of intronic sequence -> may lead to frameshift mutations

Question 28

What are the functional effects of mutations on the protein?

Answer 28

- loss of function mutations - gain of function mutations - dominant negative mutations

Question 29

loss of function mutation

Answer 29

- phenotypic effect - can result in either reduced activity (hypomorph) or complete loss of gene product (null allele/ amorph)

Question 30

loss of function mutations involving enzymes are inherited in what way?

Answer 30

autosomal/ X-linked recessive, because data;ytic activity of product of the normal allele is more than adequate to carry out the reactions of most metabolic pathways

Question 31

Haploinsufficiency

Answer 31

- loss of function mutations in the heterozygous state - half-normal levels of gene product results in phenotypic effects - homozygous mutations result in more severe phenotypic effects - eg. familial hypercholesterolemia

Question 32

gain of function mutations

Answer 32

- increased level of gene expression or development of a new function of the gene product - eg. point mutations or increased gene dosage - Charcot-marie-tooth disease - more severe in homozygous state

Question 33

dominant-negative mutations

Answer 33

- mutant gene in heterozygous state results in loss of protein activity or function as a consequence of a mutant gene product interfering with the function of the normal gene product of the corresponding allele

Question 34

where are dominant-negative mutations most common in?

Answer 34

- in proteins that are dimers or multimers eg. mutations in genes encoding structural proteins such as collagens can lead to osteogenesis imperfecta

Question 35

Define DNA

Answer 35

basic template that provides blueprint for the formation and maintenance of an organism - DNA - chromosome - genes

Question 36

define chromosomes

Answer 36

factors that distinguish one species form another and enable transmission of genetic information form one generation to the next - vehicle that facilitate reproduction and maintenance of a species

Question 37

cytogenetics

Answer 37

study of chromosomes and cell division

Question 38

How many chromosomes in humans?

Answer 38

46, abnormalities disrupts development and growth

Question 39

centromere

Answer 39

- joins sister chromatids, consists of several hundred kilobases of repetitive DNA, responsible for movement of chromosomes at cell division

Question 40

p arm

Answer 40

short

Question 41

q arm

Answer 41

long

Question 42

telomere

Answer 42

tip of each chromosome arm - shortening part of aging process

Question 43

role of telomeres

Answer 43

- sealing ends of chromosomes and maintaining structural integrity - highly conserve through evolution

Question 44

telomerase

Answer 44

- enzyme that replaces the 5' end of the long strand during DNA replication which otherwise becomes progressively shorter until a critical length was reached when the cell could no longer divide and thus became senescent

Question 45

telomeres relation to cancer

Answer 45

- increased activity leads to prolonged cell survival off tumour cells

Question 46

morphological classification of chromosomes

Answer 46

- metacentric - Acrocentric - submetacentric

Question 47

metacentric

Answer 47

centromere located centrally

Question 48

acrocentric

Answer 48

centromere located terminally - formation of satellites instead of p arms

Question 49

submetacentric

Answer 49

centromere is an intermediate position

Question 50

satellites

Answer 50

in acrocentric chromosomes, stalk-like appendages, form nucleolus of resting interphase cell, contain multiple repeat copies of genes for ribosomal RNA