Mutational Mechanisms and Disease Flashcards
What are 4 causes of disease due to mutations?
- loss of function
- gain of function
- novel property
- ectopic or heterochromic expression
what occurs to the protein with loss of function?
decreased amount of protein
what occurs to the protein with gain of function?
increased amount of protein
what occurs in heterochromic expression?
gene is expressed at the wrong time
what is the most common genetic mechanism leading to human disease?
loss of function mutation
what is the major loss of function mutation in Duchenne Muscular Dystrophy?
frameshift deletions
What is the major reduction of function in Becker Muscular dystrophy?
in-frame deletions
How does Hereditary neuropathy with liability to pressure palsies form and what type of mutation is it?
deletion of PmP22 gene
loss of function mutation
what is the genetic linkage of HNPP (Hereditary neuropathy with liability to pressure palsies)?
autosomal dominant
what are allelic disorders?
refer to conditions that are genetically related (due to the same gene most commonly)
how are HNPP and CMT1A allelic disorders?
different mutations in the same gene lead to different phenotypes
what occurs with ectopic expression?
gene is expressed in the wrong place
what occurs in hemoglobin kempsey?
locks hemoglobin in high affinity state thus reducing oxygen delivery to tissues
what is the most common way loss of function mutations are inherited to become abnormal phenotypes?
autosomal recessive because need 2 defective genes to display full phenotype
what are the causes of duschenne muscular dystrophy?
stop codon, frameshift, or deletion of multiple exons
what causes alpha-thalassemia or beta-thalassemia?
deletion of alpha globin or beta globin gene respectively thus reduction in protein causing disease
what causes turner syndrome?
loss of entire chromosome (X)
what causes hereditary retinoblastoma?
somatic mutation leading to loss of tumor suppressor protein (2nd hit)
what is the novel phenotype of osteogenesis imperfecta I?
blue sclera
what type of mutation causes osteogenesis imperfecta type I?
premature termination codons (nonsense or frameshift) in COL1A1
what is a novel property mutation?
mutation that confer a novel property on a protein without necessarily altering normal functions
what are the 2 diseases covered in class that have novel property mutations?
- sickle cell anemia
2. Huntington disease
what is the mechanism of ectopic or heterochronic expression mutations?
mutations that later regulatory regions of a gene and alter either the timing (heterochronic) or location (ectopic) of expression.
what are 2 disease examples of ectopic or heterochronic mutations?
- cancer
2. hereditary persistence of fetal hemoglobin
what causes unstable repeat expansions?
slipped mispairing during DNA replication
replicating strand detatches inappropriately and then DNA pol replicates a region in the middle of the gene
what is the relationship between repeats and severity of disease?
more repeats leads to more severe disease
what process explains genetic anticipation?
tri/tetra nucleotide repeat number expansions occurring from parent to offspring
