Trigger 9: Major classes of genetic variants

Question 1

single nucleotide variants relates to

Answer 1

changes in single nucleotides

Question 2

insertion/ deletion (indels)

Answer 2

occurs when nucleotides are detected or inserted

Question 3

copy number variation

Answer 3

Number of copies of a particular gene varies from one individual to the next

• A type of structural variation e.g. duplication or deletion of genes
• Affects a considerable number of base pairs

Question 4

chromosomal aneuploidies

Answer 4

presence of an abnormal number of chromosomes in a cell

Question 5

mutation mechanism for aneuploidies

Answer 5

non-disjunction (NDJ)

Question 6

NDJ

Answer 6

non-disjunction

Question 7

NDJ

Answer 7

Failure of homologous chromosomes to separate equally into daughter cells during mitosis/ meiosis

Question 8

majority of variants occur within

Answer 8

intronic regions

Question 9

intronic

Answer 9

between genes or between exons, therefore do not affect protein directly.
–>Can affect regulation of transcription or splicing

Question 10

majority of disease causing variants

Answer 10

found in exotic regions

Question 11

exotic silent variants

Answer 11

synonymous

Question 12

missense variation

Answer 12

-changes amino acid (non synonymous)

Question 13

nonsense variant

Answer 13

results in a premature STOP

Question 14

frameshift variants

Answer 14

-alters reading frame (indwells)

Question 15

multiexon

Answer 15

structural variant can affect multiple genes e.g. copy number)

Question 16

a genetic diagnosis in DD is useful for

Answer 16

• helps inform future reproductive decisions
• informs prognosis
• informs management

Question 17

diagnosis of DD is not

Answer 17

particularly useful in enabling treatment

Question 18

NGLY1

Answer 18

autosomal recessive N-glycanase 1 deficiency

Question 19

NGLY1 causes

Answer 19

an impaired ability to deglycosylate protein–> cells accumulate misfiled glycoproteins

Question 20

physical and neurological symptoms of NGLY1

Answer 20

lack of tears
developmental delay
movement disorder
elevated enzymes