Mutation types, and effects

Question 1

Mutations of DNA are broadly divisible into _____ mutations with gain or loss of genetic material, and _____ mutations with alteration of the genetic code but no overall gain or loss of genetic material.

Answer 1

length; point

Question 2

Length mutations include _____, _____, and _____.

Answer 2

deletions

duplications

insertions

trinucleotide repeat amplifications.

Question 3

Larger deletions can arise from chromosomal breakage, as a result of a parental chromosome ____ or from _____ between homologous gene sequences or flanking repeat sequences.

Answer 3

rearrangement

unequal crossing - over

Question 4

Small deletions (often 1 – 5 nucleotides) commonly result from _____, and this is favoured by the presence of _____ of two bases or more and by ____ of the same nucleotide.

Answer 4

slipped mispairing

direct repeats

runs

Question 5

The spontaneous rate of chromosomal breakage is markedly increased by _____ and by some _____.

Answer 5

ionizing radiation

mutagenic chemicals

Question 6

Unequal crossing - over is especially likely to occur in areas with _____ of similar sequence. This is exemplified by studies on the genes responsible for _____.

Answer 6

duplicated genes

colour vision

Question 7

There are three separate genes for each of the cone pigments blue, on _____ chromosome, red and green, near the tip of the long arm of the _____ chromosome.

Answer 7

7

X

Question 8

There is a _____ red gene on each X chromosome and _____ copies of the green genes. The red and green genes have _____ percent sequence homology, and unequal crossing - over in this area can result in loss of gene function for one type or hybrid genes that produce pigments of altered function

Answer 8

single

one to three

96%

Question 9

Large deletions remove many adjacent genes and results in _____. These should be suspected if, for instance, a boy has several X - linked disorders or if a patient with a single - gene disorder has an unexplained mental handicap and/ or unexplained congenital malformations.

Answer 9

contiguous gene disorders

Question 10

Removal of all of a gene directly prevents transcription from that allele but smaller deletions that are not exactly 3 (or a multiple of 3) bp in length can be equally serious by altering the reading frame. This mutation is called?

Answer 10

Frameshift mutation

Question 11

Large deletions are particularly common in what diseases:

Answer 11

Duchenne muscular dystrophy
α – thalassaemia
steroid sulphatase deficiency
Di George
Prader – Willi
Angelman
Williams
Smith – Magenis syndromes

Question 12

Duplications of a chromosomal region can also disrupt the reading frame. In addition, in some patients with single – gene disorders, the gene has been disrupted by insertion of a _____ from a distant site or by a _____ (often one nucleotide) after _____.

Answer 12

repeat element

short insertion

slipped mispairing

Question 13

Another mechanism of length mutation is _____ whereby one allele is converted to another. This may occur at meiosis during the process of _____.

Answer 13

gene conversion; recombination

Question 14

When gene conversion occurs, the product lacks one of the original sections of chromosome and this results in a _____ allele ratio for the involved region in contrast to the expected _____ ratio.

Answer 14

3:1; 2:2

Question 15

About _____ percent of the genome is composed of tandem repeats, which are mostly stably inherited.

Answer 15

10%

Question 16

Most trinucleotide repeats are stably inherited, but some of these trinucleotide repeats become unstable if longer than a critical number of repeat elements and, if associated with a gene, this can result in a _____.

Answer 16

single – gene disorder

Question 17

In diseases associated with trinucleotide repeats, the instability of long repeats means that different members of the same family can show different repeat lengths and corresponding clinical variation in disease severity. This exemplified by _____.

Answer 17

myotonic dystrophy type 1

Question 18

The CTG repeat normally occurs 5 – 35 times, but in patients affected by myotonic dystrophy there is an expansion ranging from _____ to _____.

Answer 18

50 to over 1000 repeats

Question 19

There are now over _____ known disorders that have been found to be associated with expansion of a trinucleotide repeat. The mechanism of expansion can involve ______ or ______.

Answer 19

20; unequal recombination; DNA polymerase slippage

Question 20

CAG trinucleotide repeat expansions that encode polyglutamine stretches is associated with what
diseases?

Answer 20

Huntington disease (a cause of dementia); spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7 and 17.

Question 21

Some congenital malformation syndrome scan result from shorter expansions of a _____ repeat that encodes an alanine tract, usually within transcription factor genes.

Answer 21

GCG trinucleotide

Question 22

Some congenital malformation syndrome scan result from shorter expansions of a GCG trinucleotide repeat that encodes an ______, usually within transcription factor genes.

Answer 22

alanine tract

Question 23

Some congenital malformation syndrome can result from shorter expansions of a GCG trinucleotide repeat that encodes an alanine tract, usually within ______.

Answer 23

transcription factor genes

Question 24

_____ repeat expansions that encode polyglutamine stretches is associated with Huntington disease (a cause of dementia) and spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7 and 17.

Answer 24

CAG

Question 25

CAG repeat expansions that encode _____ stretches is associated with Huntington disease (a cause of dementia) and spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7 and 17.

Answer 25

polyglutamine

Question 26

An ______ repeat is responsible for SCA - 10

Answer 26

intronic pentanucleotide

Question 27

An intronic pentanucleotide repeat is responsible for ______.

Answer 27

SCA-10

Question 28

An enormous expansion of an intronic _____ (up to 11,000 units) in the ZNF9 gene causes myotonic dystrophy type 2.

Answer 28

tetranucleotide repeat

Question 29

An enormous expansion of an intronic tetranucleotide repeat (up to 11,000 units) in the _____ causes myotonic dystrophy type 2.

Answer 29

ZNF9 gene

Question 30

An enormous expansion of an intronic tetranucleotide repeat (up to 11,000 units) in the ZNF9 gene causes ______.

Answer 30

myotonic dystrophy type 2

Question 31

A repeat of 12 bp just upstream of the _____ causes an autosomal recessive progressive myoclonic epilepsy

Answer 31

CSTB gene

Question 32

A repeat of 12 bp just upstream of the CSTB gene causes an ______.

Answer 32

autosomal recessive progressive myoclonic epilepsy

Question 33

An expansion of an _____ bp repeat is associated with Usher syndrome type 1C (a genetic cause of deafness and visual loss)

Answer 33

intronic 45

Question 34

An expansion of an intronic 45 bp repeat is associated with _____, a genetic cause of deafness and visual loss.

Answer 34

Usher syndrome type 1C

Question 35

In a _____ mutation, a single nucleotide base is replaced by a different nucleotide base, termed _____ if the change is purine to purine or pyrimidine to pyrimidine, i.e. A ↔ G, or T ↔ C, or _____ if purine to pyrimidine or vice versa, i.e. G ↔ C or A ↔ T.

Answer 35

point; transitions; transversions

Question 36

This leads, in 25% of instances, to no change in the amino acid encoded for that triplet, i.e. _____ mutations, due to _____ of the code

Answer 36

silent; degeneracy

Question 37

How many percent of all point mutations lead to no change in the amino acid encoded?

Answer 37

25%

Question 38

70% of cases of point mutation lead to the substitution of a different amino acid. This mutation is called ______.

Answer 38

missense mutation

Question 39

How many percent of point mutations lead to the substitution of a different amino acid?

Answer 39

70%

Question 40

5% of cases of point mutation lead to the production of a termination codon. This mutation is called _____.

Answer 40

nonsense mutation

Question 41

_____ are a common type of human mutation and their frequency reflects the fidelity of DNA replication and the efficiency of subsequent error - correction mechanisms.

Answer 41

Single nucleotide substitutions

Question 42

The frequency of single nucleotide substitutions reflect the _____ of DNA replication and the efficiency of subsequent _____ mechanisms.

Answer 42

fidelity; error-correction

Question 43

What is mutation rate during DNA replication?

Answer 43

1 in every 10^9 to 10^10

Question 44

The rate of mutation is markedly increased by exposure to mutagenic chemicals in proportion to the _____ and the _____.

Answer 44

concentration of the chemical; duration of exposure

Question 45

What are example of mutagenic chemicals?

Answer 45

deamination of hydroxylamine; alkylation by nitrogen mustard

Question 46

Ultraviolet (UV) light can also cause mutations including _____ in which pairs of adjacent pyrimidine bases become linked.

Answer 46

pyrimidine dimers

Question 47

T/F. Defense mechanisms exist to identify and repair such damage and patients w/ inherited deficiencies of key components of these pathways rapidly accumulate mutations and develop premature cancer.

Answer 47

T

Question 48

A deficiency in the _____ pathway, w/c normally corrects UV - induced pyrimidine dimers, can result in the cancer - predisposing condition xeroderma pigmentosum.

Answer 48

nucleotide excision repair

Question 49

A deficiency in the nucleotide excision repair pathway, w/c normally corrects _____, can result in the cancer - predisposing condition xeroderma pigmentosum.

Answer 49

UV - induced pyrimidine dimers

Question 50

A deficiency in the nucleotide excision repair pathway, w/c normally corrects UV - induced pyrimidine dimers, can result in the cancer - predisposing condition, _____.

Answer 50

xeroderma pigmentosum

Question 51

Another example is the more recently identified ____, an autosomal recessive condition that results from a deficiency of a DNA glycosylase that normally (by base excision repair) removes adenines that have been misincorporated into DNA

Answer 51

MutYH - associated polyposis of the bowel

Question 52

Another example is the more recently identified MutYH - associated polyposis of the bowel, an autosomal recessive condition that results from a deficiency of a _____ that normally (by base excision repair) removes adenines that have been misincorporated into DNA.

Answer 52

DNA glycosylase

Question 53

Another example is the more recently identified MutYH - associated polyposis of the bowel, an autosomal recessive condition that results from a deficiency of a DNA glycosylase that normally (by base excision repair) removes _____ that have been misincorporated into DNA

Answer 53

adenines

Question 54

Misincorporation of adenines can occur as a result of pairing with an _____, a stable product of oxidative DNA damage.

Answer 54

8 - oxoG residue

Question 55

A separate multistep _____ process is involved in error correction at the time of DNA replication.

Answer 55

DNA mismatch repair

Question 56

Deamination of cytosine produces _____, which is recognized & removed by the base excision repair pathway

Answer 56

uracil

Question 57

Deamination of cytosine produces uracil, which is recognized & removed by the base ______.

Answer 57

excision repair pathway

Question 58

Cytosine, when it occurs in conjunction with guanine as a 5 ′ - CpG- 3 ′ dinucleotides, is generally methylated at the _____ and deamination of methylated cytosine results in thymine.

Answer 58

5 ′ position

Question 59

Cytosine, when it occurs in conjunction with guanine as a 5 ′ - CpG- 3 ′ dinucleotides, is generally methylated at the 5 ′ position and deamination of methylated cytosine results in ______. In turn, this substitution of C by T results in substitution of _____ on the complementary strand and neither of these changes can be recognized by the repair mechanisms. This results in an overall tendency to lose ____ and an overrepresentation of _____ transitions amongst point mutations (they account for 35 – 50% of all point mutations).

Answer 59

thymine; G by A; CpG; C to T

Question 60

Nonmethylated cytosine residues are spared from deamination and hence CpG dinucleotides have a relatively high frequency in non - methylated CpG islands, w/c are associated w/ the ____ of many genes.

Answer 60

5 ′ ends

Question 61

These C to T transitions most commonly occur in _____ & this might reflect the heavy methylation of sperm DNA compared w/ oocyte DNA, w/c tends to be undermethylated.

Answer 61

male germ cells (w/ a sevenfold higher frequency than in females)