Trigger 9: Phenotypes and genetic variants Flashcards
children with DD
do not develop normally
DDs can be syndromic
a set of medical signs and symptoms that are correlated with each other and often with a disease
DDs can also be
nonsyndromic
many phenotypes are
noticeable from birth
noticeable phenotypes
- abnormal growth
- deformities
- intellectual disabilities
abnormal growth
of body or specific part
deformities
birth defects e.g. cleft lip, extra fingers etcs
intellectual disabilities
- problems learning
- behavioural problems
most common phenotype associated with DD
intellectual disability and seizures
other common phenotypes
congenital heart defects ASD hearing impairment oral cleft scoliosis visual impairment polydactyly
abnormal phenotypes can be produced by a
single gene mutation or mutations in over 500 genes
cystic fibrosis is caused by
a single gene defect (Cl- channel)
intellectual disability occurs as a result of
mutations in over 500 genes
how many genes linked to DD
1,500
a gene
made up of DNA are the basically physical and functional unit of herdity
exotic regions account ofr
1-2% of the genome
exome
protein coding regions
mutations which occur within exonic regions
substitution
indels
substitution (3)
silence
missense (non-synonymous)
nonsense (premature stop)
indels
insertions/ deletions- often cause frameshift
what often causes frameshift
idels- which changes the amino acid
intronic regions
non-coding
non coding regions affect
the rate of transcript and translation
intronic regions are found
between genes or exons
intronic mutations do not
affect the protein diretly
intronic mutations can
effect the regulation of transcription or splicing
copy number variant
number of copies of a particular gene varies from one individual to the next
–>large duplication in exon, gene or even larger caused by a spicing defect
multiexon/multigene
structural variant can affect multiple genes e.g. CV
DNA is transcribed to
pre-mRNA
pre-mNA is
spliced to form mRNA
mRNA is translated to form
the protein
name two disease mechanisms which cause DD phenotypes
1) reduced or loss or function
2) increase or gain of function
reduced or loss of function
- reduce or zero functioning proteins
- often protein-truncating variants resulting in nonsense-mediated decay (NMD)
Increase or gain of function
- increased amount of protein
- new function of protein (e.g. toxicity)
