Mutations and single gene defects Flashcards
mutation definition
a heritable alteration or change in the genetic material, usually pathogenic
polymorphism definition
a non-pathogenic alteration in DNA which may alter protein function but is not usually deleterious
2 main categories of mutations
point mutations and indwells (insertions and deletions)
2 main types of point mutation
transition- purine to purine or pyrimidine to pyrimidine
transversion- purine to pyrimidine or vise versa
3 different results of a point mutation
synonymous- does not change the amino acid sequence due to the redundancy of the genetic code
missense- replacement of one amino acid by another
nonsense- codon specifying an amino acid replaced by a stop codon, premature termination code
notation to show that arginine replaced histone at residue 117
R117H
stop codon notation
X
What do indels result in?
frameshift mutations and premature termination codons if indeed is not an exact multiple of 3
two main non-coding regions to worry about
splice sites for intron removal and mRNA regulatory regions of genes
explain effects of mutation in splice site
can result in intron retention, mRNA remains in the nucleus and is not translated, exon skipping
if from is maintained and the number of nucleotides in a skipped exon are a multiple of 3, a truncated protein is formed
if frame is not maintained then frameshift occurs and a premature stop codon is formed and the RNA degraded
explain effects of mutation in mRNA regulatory region
insertion can adversely affect transcription which can be blocked
3 main effects of mutations
loss of function, gain of function or haploinsufficiency
explain loss of function mutations + examples
mutation affects the level of normal mRNA or produces a gene product with reduced or no function
frameshift, nonsense, mutations in regulatory elements such as promotors or enhancers, mutations in critical domain
dominant negative effect definition
recessive mutant polypeptide has lost its own function and interferes with the polypeptide of the normal allele
gain of function definition
mutation results in a new protein that has gained a function and interferes with others or becomes over expressed
haploinsufficiency definition
dominant loss of function, with one copy of the mutant gene which results in 50% of normal signalling, however the cell is unable to tolerate this
example of a haploinsufficient condition
Waardenburg syndrome type 1, hearing loss, pigment abnormalities
example of gain of function mutation explained
achondroplasia- short limbs, yet normal sized head, body and intelligence
Gly380Arg mutation in FGFR3 gene which results in the receptor signalling in the absence of ligand which inhibits bone growth by inhibiting chondrocyte proliferation and differentiation and therefore preventing endochondral bone growth
Triplet repeat definition
a trinucleotide repeat sequence that can become unstable during replication, leading to expansion
anticipation definition
a genetic phenomenon where expansion is progressive down the generations, leading to more easy onset disease in offspring than their parents
cause of triplet repeat expansion
strand slippage during replication
2 examples of triplet repeat disease + TRIPLET
Huntington’s - CAG in exon 1 of chromosome 4q16, Huntingtin gene
Myotonic dystrophy 1 CTG repeat in the 3- untranslated region of the dystrophia myotonic protein kinase gene on chromosome 3q
number of repeats and age of onset Huntington’s
more than 35 repeats is likely pathological
more than 60 repeats leads to onset before the age of 25
Huntington’s pathology
degeneration of neurones in the basal ganglia and cortical regions of the brain, resulting in an unsteady gait, jerky involuntary movements and later progressive dementia
myotonic dystrophy 1 pathology
myotonia means the hyper excitability of muscles, which leads to shaking hands, person cannot let go and cardiac arrhythmias
chorea definition
ringing hands
conditions where there is a failure or imprinting + gene
prayer-willi syndrome, failure of paternally inherited SNPRN gene
Angelman syndrome, failure of maternally inherited UBE3A
three ways of getting Prader Willi
inherit two chromosome 15s from mother
mutation in father’s SNRPN gene
methylation abnormality, upstream of CpG sequence which switches the gene off
