Chapter 12- Gene Mutations

Question 1

Variant DNA

Answer 1

DNA that is different from reference DNA

Question 2

Minor Allele Frequency

Answer 2

Percentage of population with variant allele

Question 3

Polymorphism

Answer 3

Allele with MAF over 1%, considered normal variation

Question 4

Mutation

Answer 4

Allele with MAF under 1%

Question 5

Single Nucleotide Variants
Single Nucleotide Polymorphisms (SNPs)

Answer 5

Change of one base pair
Most frequent genetic variation 90%

Question 6

Insertions and Deletions (Indels)

Answer 6

Removal or addition of 1+ base pairs
Causes reading frame to shift
Insertion- Replicating strand slips
Deletion- Template stand slips
Unequal crossing over

Question 7

Copy number variants

Answer 7

Large DNA segments that are present in different number than reference genome
Commonly entire genes

Question 8

Repeat variants

Answer 8

Interspersed and Tandem repeats

Question 9

Transition point mutation

Answer 9

Purine to purine
Pyrimidine to pyrimidine

Question 10

Transversion point mutation

Answer 10

Purine to pyrimidine

Question 11

Missense Mutation

Answer 11

Changes one amino acid to another
Conservative- Similar properties
Non-conservative- Different properties

Question 12

Nonsense mutation

Answer 12

New codon is a stop codon
Premature end to translation

Question 13

Silent mutation

Answer 13

Encodes for the same amino acid

Question 14

Splice Site mutation

Answer 14

Mutation alters intron splicing

Question 15

Gain-of-function

Answer 15

Mutation causes excess or novel protein production

Question 16

Loss of function

Answer 16

Mutation causes reduced or absent protein production

Question 17

Heterozygote

Answer 17

1 gene copy is effected

Question 18

Homozygote

Answer 18

Both gene copies are mutated

Question 19

Haploinsufficiency

Answer 19

Partial protein production by 1 gene copy is insufficient

Question 20

Dominant Negative

Answer 20

Mutation causes protein that interferes with normal protein function

Question 21

Variations in Normal Genome

Answer 21

5-10 million SNPs
75 new base pair mutations from parents
3-7 copy number variants
200-250 shifts in reading frame
100 premature stops

Question 22

Spontaneous mutations

Answer 22

Result from errors in DNA replication or chemical instability, de novo

Question 23

Tautomer

Answer 23

Unstable bases in alternating forms
Cause mispairing during replication

Question 24

Effects of repeat sequences

Answer 24

Cause self-pairing during replication and formation of hairpin loop, causing DNA polymerase to skip section of DNA

Question 25

Deamination

Answer 25

Cytosine spontaneously deaminates to uracil
Methylated cytosine becomes thymine

Question 26

Transposable Insertion

Answer 26

Insertion can occur into gene coding sequence, inactivating or promoting genes

Question 27

Intercalating Agents

Answer 27

Chemicals wedge between base pairs and cause distortions, unwinding, deletions, and frameshift mutations

Question 28

UV Light

Answer 28

Cause pyrimidine dimers

Question 29

Base Excision Repair

Answer 29

Modified bases, uracil misincorporation, and oxidative damage
Glycosylase cuts defective base
Endonuclease cuts DNA
DNA polymerase and ligase repair DNA

Question 30

Nucleotide Excision Repair

Answer 30

Repair wide variety of DNA damage, including pyrimidine dimers

Question 31

Mismatch Repair

Answer 31

Enzyme detests nucleotide bulk with misincorporation
Repair microsatellites

Question 32

Allelic Disease

Answer 32

Different phenotypes caused by mutations in the same gene

Question 33

Xeroderma Pigmentosum

Answer 33

Mutation in nucleotide excision repair gene (XPA, XPB, or XPF)
Autosomal recessive
Cannot repair DNA damage caused by UV light
Cause multiple skin cancers and premature death

Question 34

Hereditary Non-polyposis colorectal Cancer (HNPCC)
Lynch syndrome

Answer 34

Inactivation of MMR genes in germline or de novo
Autosomal dominant
Increase risk of many cancers and colorectal
Appears at younger age without polyp stage

Question 35

Beta Globin Gene

Answer 35

Epsilon- Embryonic globin
Gamma- Fetal globin
Delta- HbA2
Beta- Adult globin

Question 36

Alpha Globin Genes

Answer 36

Zeta- Embryonic globin
Alpha- Fetal and adult globin
2 copies on each parental genome

Question 37

Types of hemoglobin

Answer 37

Embryonic- HbE- 2 epsilon, 2 zeta
Fetal- HbF- 2 gamma, 2 alpha
Adult- HbA- 2 alpha, 2 beta

Question 38

Sickle Cell Disease (SCD)

Answer 38

Caused by Glu6Val missense mutation in beta chain
RBCs aggregate and polymerize, blocking blood flow
Hemolytic anemia, damage to organs, repeated infections
Autosomal recessive
Heterozygotes carry malaria resistance

Question 39

Thalassemia

Answer 39

Imbalance in globin gene production

Question 40

Beta Thalassemia

Answer 40

Reduced synthesis of beta globin
Mutation in the HBB genes, many mutations cause dysfunction
Excess alpha chains precipitate and damage RBCs
Iron overload damages liver, pancreas, and heart
Protective against malaria

Question 41

Allelic Heterogeneity

Answer 41

Many mutations in gene cause similar dysfunction