Chapter 12- Gene Mutations Flashcards
Variant DNA
DNA that is different from reference DNA
Minor Allele Frequency
Percentage of population with variant allele
Polymorphism
Allele with MAF over 1%, considered normal variation
Mutation
Allele with MAF under 1%
Single Nucleotide Variants
Single Nucleotide Polymorphisms (SNPs)
Change of one base pair
Most frequent genetic variation 90%
Insertions and Deletions (Indels)
Removal or addition of 1+ base pairs
Causes reading frame to shift
Insertion- Replicating strand slips
Deletion- Template stand slips
Unequal crossing over
Copy number variants
Large DNA segments that are present in different number than reference genome
Commonly entire genes
Repeat variants
Interspersed and Tandem repeats
Transition point mutation
Purine to purine
Pyrimidine to pyrimidine
Transversion point mutation
Purine to pyrimidine
Missense Mutation
Changes one amino acid to another
Conservative- Similar properties
Non-conservative- Different properties
Nonsense mutation
New codon is a stop codon
Premature end to translation
Silent mutation
Encodes for the same amino acid
Splice Site mutation
Mutation alters intron splicing
Gain-of-function
Mutation causes excess or novel protein production
Loss of function
Mutation causes reduced or absent protein production
Heterozygote
1 gene copy is effected
Homozygote
Both gene copies are mutated
Haploinsufficiency
Partial protein production by 1 gene copy is insufficient
Dominant Negative
Mutation causes protein that interferes with normal protein function
Variations in Normal Genome
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
Spontaneous mutations
Result from errors in DNA replication or chemical instability, de novo
Tautomer
Unstable bases in alternating forms
Cause mispairing during replication
Effects of repeat sequences
Cause self-pairing during replication and formation of hairpin loop, causing DNA polymerase to skip section of DNA
Deamination
Cytosine spontaneously deaminates to uracil
Methylated cytosine becomes thymine
Transposable Insertion
Insertion can occur into gene coding sequence, inactivating or promoting genes
Intercalating Agents
Chemicals wedge between base pairs and cause distortions, unwinding, deletions, and frameshift mutations
UV Light
Cause pyrimidine dimers
Base Excision Repair
Modified bases, uracil misincorporation, and oxidative damage
Glycosylase cuts defective base
Endonuclease cuts DNA
DNA polymerase and ligase repair DNA
Nucleotide Excision Repair
Repair wide variety of DNA damage, including pyrimidine dimers
Mismatch Repair
Enzyme detests nucleotide bulk with misincorporation
Repair microsatellites
Allelic Disease
Different phenotypes caused by mutations in the same gene
Xeroderma Pigmentosum
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
Hereditary Non-polyposis colorectal Cancer (HNPCC)
Lynch syndrome
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
Beta Globin Gene
Epsilon- Embryonic globin
Gamma- Fetal globin
Delta- HbA2
Beta- Adult globin
Alpha Globin Genes
Zeta- Embryonic globin
Alpha- Fetal and adult globin
2 copies on each parental genome
Types of hemoglobin
Embryonic- HbE- 2 epsilon, 2 zeta
Fetal- HbF- 2 gamma, 2 alpha
Adult- HbA- 2 alpha, 2 beta
Sickle Cell Disease (SCD)
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
Thalassemia
Imbalance in globin gene production
Beta Thalassemia
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
Allelic Heterogeneity
Many mutations in gene cause similar dysfunction
