Trigger 9: Phenotypes and genetic variants

Question 1

children with DD

Answer 1

do not develop normally

Question 2

DDs can be syndromic

Answer 2

a set of medical signs and symptoms that are correlated with each other and often with a disease

Question 3

DDs can also be

Answer 3

nonsyndromic

Question 4

many phenotypes are

Answer 4

noticeable from birth

Question 5

noticeable phenotypes

Answer 5

• abnormal growth
• deformities
• intellectual disabilities

Question 6

abnormal growth

Answer 6

of body or specific part

Question 7

deformities

Answer 7

birth defects e.g. cleft lip, extra fingers etcs

Question 8

intellectual disabilities

Answer 8

• problems learning

- behavioural problems

Question 9

most common phenotype associated with DD

Answer 9

intellectual disability and seizures

Question 10

other common phenotypes

Answer 10

congenital heart defects
ASD
hearing impairment
oral cleft
scoliosis
visual impairment
polydactyly

Question 11

abnormal phenotypes can be produced by a

Answer 11

single gene mutation or mutations in over 500 genes

Question 12

cystic fibrosis is caused by

Answer 12

a single gene defect (Cl- channel)

Question 13

intellectual disability occurs as a result of

Answer 13

mutations in over 500 genes

Question 14

how many genes linked to DD

Answer 14

1,500

Question 15

a gene

Answer 15

made up of DNA are the basically physical and functional unit of herdity

Question 16

exotic regions account ofr

Answer 16

1-2% of the genome

Question 17

exome

Answer 17

protein coding regions

Question 18

mutations which occur within exonic regions

Answer 18

substitution

indels

Question 19

substitution (3)

Answer 19

silence

missense (non-synonymous)

nonsense (premature stop)

Question 20

indels

Answer 20

insertions/ deletions- often cause frameshift

Question 21

what often causes frameshift

Answer 21

idels- which changes the amino acid

Question 22

intronic regions

Answer 22

non-coding

Question 23

non coding regions affect

Answer 23

the rate of transcript and translation

Question 24

intronic regions are found

Answer 24

between genes or exons

Question 25

intronic mutations do not

Answer 25

affect the protein diretly

Question 26

intronic mutations can

Answer 26

effect the regulation of transcription or splicing

Question 27

copy number variant

Answer 27

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

Question 28

multiexon/multigene

Answer 28

structural variant can affect multiple genes e.g. CV

Question 29

DNA is transcribed to

Answer 29

pre-mRNA

Question 30

pre-mNA is

Answer 30

spliced to form mRNA

Question 31

mRNA is translated to form

Answer 31

the protein

Question 32

name two disease mechanisms which cause DD phenotypes

Answer 32

1) reduced or loss or function

2) increase or gain of function

Question 33

reduced or loss of function

Answer 33

• reduce or zero functioning proteins

- often protein-truncating variants resulting in nonsense-mediated decay (NMD)

Question 34

Increase or gain of function

Answer 34

• increased amount of protein

- new function of protein (e.g. toxicity)