Genetic Testing and Single Base Variation 🗸

Question 1

Mutation

Answer 1

any heritable change in the human genome which causes a genetic disorder

Question 2

polymorphism

Answer 2

any variation in the human genome which has a population frequency of >1%

Question 3

Do polymorphisms cause disease?

Answer 3

no, but may predispose to common ones

Question 4

Penetrance

Answer 4

the likelihood of having disease if you have a gene mutation

Question 5

Classical genetic disease (mendelian disorders)

Answer 5

one mutation sufficient to cause disease (high penetrance, small environmental contribution)

Question 6

Multifactorial disease

Answer 6

multiple polymorphisms cause a risk of disease (penetrance of one mutation is low)

Question 7

Gene analysis uses…

Answer 7

aCGH
FISH
PCR
Whole exome sequencing
Genetic filtering

Question 8

aCGH

Answer 8

1st line chromosome test, large scale
detects missing/duplicated pieces of chromosome
finds polymorphisms
doesnt detect balanced rearrangements

Question 9

FISH

Answer 9

uses fluorescent probes that bind only to parts of a nucleic acid sequence with a high degree of sequence complementarity
often used for finding specific features in DNA for use in genetic counselling

Question 10

PCR

Answer 10

can select one small piece of human genome from a patient and amplify it
pieces can be selected to find mutations

Question 11

Whole exome sequencing

Answer 11

sequences exome = all the exons

Question 12

Genetic filtering

Answer 12

approx 3 million polymorphism are detected
remove the unlikely ones first to identify the pathogenic variant

Question 13

Four types of mutation

Answer 13

missense
changes in amino acid sequence
insertion/deletion
promotor and splice site sequence changes

Question 14

missense mutations

Answer 14

change in a single amino acid
usually caused by substitutions
most likely mutation to activate an oncogene (others tend just to inactivate the gene itself)

Question 15

changes to amino acid sequences

Answer 15

mutation may change protein sequence which can alter protein function
mutation may result in premature stop codon

Question 16

insertion/deletion

Answer 16

causes complete change to entire amino acid sequence after the mutation
can be in or out of frame

Question 17

in frame insertion/deletion

Answer 17

changes multiples of 3, not so bad

Question 18

out of frame insertion/deletion

Answer 18

results in frame shift

Question 19

promotor and splice site sequence changes

Answer 19

stop transcription or cause abnormal splicing

Question 20

meaning of g.

Answer 20

genomic build
g.123[G>A];[=]

Question 21

meaning of c.

Answer 21

RNA as if DNA
c.125[C>G];[=]

Question 22

meaning of p.

Answer 22

protein
p.Pro172Arg

Question 23

meaning of >

Answer 23

substitution

Question 24

meaning of ins/del

Answer 24

insertion/deletion
c.76insG

Question 25

+blank

Answer 25

within intron