Mutation & Inherited Disease Flashcards
What are base substitutions?
Replacement of a single base
What are deletions?
When one or more nucleotides are eliminated
What are insertions?
When one or more nucleotides are inserted into a sequence
What are endogenous mutations?
Mutations that occur as errors of replication or DNA repair
DNA is vulnerable to spontaneous damage from what?
Exposure to reactive metabolites or ionizing radiation.
Mutations occur in our somatic cells and gremlins. Which of these two give it the potential of being passed on to offspring?
Mutations in germline.
What are polymorphisms?
Existence of two or more variants (alleles sequence variants) at significant frequencies in the population
Any sequent variant present at a frequency greater than 1% in a population is called?
Polymorphism
Any non pathogenic sequent variant, regardless of frequency is a
polymorphism
What does the term heterozygosity describe?
Percentage difference between allelic sequences. (different versions of a gene)
What is the mean heterozygosity of the human genome?
0.08%
What type of polymorphism classifies a change in a single nucleotide?
Single nucleotide polymorphism.
Most SNPs are substitutions be a different
nucleotide
Where do most SNPs occur?
In non-coding DNA like introns nd intergenic sequences
What are synonymous/silent substitutions?
This is when base change results in a a new codon but specifies the same amino acid
Silent substitutions usually occur at?
the wobble position (3rd base)
Base substitutions that result in a different amino acid are called?
Missense mutations
What is the difference between conservative and non-conservative missense mutations?
Conservative shows replacement with a chemically similar amino acid while non-conservative shows replacement with a dissimilar amino acid.
A base substitution that results into a stop codon is called
nonsense mutation
What is the result of a nonsense mutation?
A truncated protein which is either dysfunctional or nonfunctional
What mutations are a result of an insertion or deletion in coding DNA that is not a multiple of three?
Frame shift mutations
What is the result of frame shift mutations?
They change the translational reading frame, causing a rearrangement of the codons that are read during translation, different amino acid, premature stop codon introduced.
What is penetrance?
This is the frequency of expression of disease phenotype in individuals with a gene mutation
What is the difference between completed and incomplete penetrance?
In complete penetrance, the disease phenotype is expressed in every individual with the mutated gene, while in incomplete penetrance, individuals may have mutated gene bu do not express disease traits.
Complete penetrance is associated with
recessive, dominant or co-dominant disease
Incomplete penetrance is associated with
dominant inherited diseases
Give some examples of complete penetrance
Neurofibromatosis type I, achondroplasia
Give some examples of incomplete penetrance
familial breast cancer, retinoblastoma
What is variable expressivity?
When one mutation causes a range of different disease traits
What is an example of variable expressivity?
Marfan’s syndrome
What is Marfan’s syndrome?
Autosomal dominant disease, mutation in collagen formation
What do single gene disorders involve?
Affect structure and function of different types of proteins resulting in a variety of diseases.
What are lysosomes?
Cellular organelles which degrade endocytosed particles or cellular waste produced by intracellular turnover using special enzymes that work in an acidic environment.
Degradation of endocytosed particles is
heterography
Degradation of cellular waste produced by intracellular turnover is
autography
Lysosomal storage disorders result from
mutations in lysosomal enzymes
What is the accumulated product in Tay Sachs disease?
Spingolipids
What is the accumulated product in Niemann-pick disease?
Sulfatides
What is the accumulated product in Gaucher’s disease?
glucoserobosides
What is hemochromatosis?
a condition that causes over absorption of iron from food
What causes cystic fibrosis?
Loss of function of a chloride channel, CFTR
What causes hemochromatosis?
Mutation in the HFE gene
What are trinucleotide repeats?
Specific short tandem repeats that are a repeated sequence of three nucleotides.
What are the three trinucleotide repeats diseases?
Friedreich’s ataxia
Fragile X syndrome
Huntington disease
GAA is repeated on chromosome 9 causing lack of muscle cordination and heart problems
Friedreich’s ataxia . 6-29 (N) 200-900 (A)
CGG is repeated many times at fragile ends of X-chromosome arms leading to excess protein formation and mental retardation in males
Fragile X syndrome 6-54 (N) 50-1500 (A)
CAG repeats many times on chromosome 4 leading to neurodegenerative disease
Huntington disease. 9-37 (N) 37-121 (A)
The differential activation of genes depending on the parent rom which they are inherited is called
genomic imprinting
Angelman syndrome
Deletion on maternal chromosome 15 given by the mother, severe congenital mental retardation, unusual facial appearance, muscular abnormalities, controlled laughter sometimes.
Prader-Willi syndrome
When there is no inheritance of the genes on chromosome 15 from the father, insatiable appetite, mental retardation, lack of sexual development.
