Genetic Variation Flashcards
Mutation
Changes in DNA sequence, basis of all variation
Types of single-gene mutations
Base-pair substitution, insertions and deletions, duplications, control and structural types, unusual types
Silent mutation
Change in one base pair, third position, no change in the amino acid, can be detected in DNA or RNA but not in protein
Missense mutation
Change in one base pair, changes codon from one amino acid to another
Nonsense mutation
Change in one base pair, becomes stop codon, truncates protein
Insertion and deletion
Bases added to or removed from a sequence, large ones can disrupt more than one gene, small ones can change sequence
Frameshift mutation
Special insertion/deletion, number is not a multiple of 3, changes the “reading frame”, completely different amino acid sequence, premature truncation likely
Mutations in non-coding DNA
Mutations can occur in any DNA sequence, may affect mRNA expression instead of protein sequence- promotors, enhancers, silencers, may affect mRNA processing and protein sequence
Duplications
Large regions, whole genes are duplicated, sometimes gene function
Transposons
Mobile genetic elements, can insert in or near gene and alter expression
Expanded repeats
Trinucleotides, run of one amino acid, number increases, too many disrupt function
Effects of mutation
Loss of function mutations- protein has no activity
Gain of function mutations- protein has new or greater activity
Hemoglobin mutations
Structural- change protein (sickle cell anemia- glutamate 6 to valine)
Control of expression- thalassemias, hereditary persistence of fetal hemoglobin
Thalassemias
Defect in production of alpha- or beta-globin, tetramers form due to excess of other subunit, damage to RBCs by precipitation, shorten lifespan of RBCs, cause anemia, splenomegaly
Molecular causes of mutation
Ionizing radiation, nonionizing radiation, chemicals
Ionizing radiation
Creates reactive radicals, react with bases, cause double-stranded breaks
Nonionizing radiation
Shift electrons, cause reactions (pyrimidine dimers from UV)
Chemicals
Base analogs insert, react, change, deamination reactions convert C to U
Rate of mutation
Influenced by size of the gene, age at reproduction, “hot spots”
DNA repair
Major role is to prevent mutation, some repairs require determining which base is changed, some mutations affect more than one base
Xeroderma pigmentosum
Defect in nucleotide excision repair, cannot repair pyrimidine dimers, UV causes mutations in skin cells, several related disorders of DNA repair
Blood groups
Natural variation, ABO system, A and B are antigens, O lacks antigens, co-dominant, antibodies are present to antigen not present in the cell, Rh + or -
Hardy-Weinberg rule
Randomly mating population, large numbers, can estimate frequency of gene variants
Gene frequency in population
Important to know risk of two carriers reproducing, high gene frequency in a population increases the chance of carriers reproducing, increases frequency of homozygotes for that gene
