Clinical Genetics and Children

Question 1

what is DNA comprised of

Answer 1

2 strands bound in an antiparallel form

sugar back bone - 2-deoxyribose

Question 2

how many base pairs are there in the genome

Answer 2

3 million

Question 3

how many polymorphisms are there per genome

Answer 3

3 million

Question 4

what is a balanced polymorphism

Answer 4

the same amount of material is still present but in different orders

Question 5

what is an unbalanced polymorphism

Answer 5

different amount of material eg. extra or missing bases

Question 6

what are the 2 main approaches to genetic testing

Answer 6

array genomic hybridisation (chromosome test)

Next generation sequencing

Question 7

what does an array allow you to look at

Answer 7

looks for sub-microscopic deletions or duplications of chromosome material

can only detect unbalanced polymorphisms

compare control DNA to that of your patient to see if there’s the same amount in each. If theres half as much - deletion, if theres 50% more - duplication

Question 8

what is the first line test for looking at chromosomes

Answer 8

Array

Question 9

what does Next generation sequencing do

Answer 9

sequences whole genome - you only need to analyse the specific bits you want

v expensive, but sequencing more is more effective

Question 10

disadvantages to next generation sequencing

Answer 10

• big data files
• identification of many polymorphisms however only one is causative
• data interpretation is complex

Question 11

what is considered to be a normal genome

Answer 11

the commonest form of gene sequence

Question 12

what percentage of the gene actually codes for things

Answer 12

2% are exons (code for things)

Question 13

what can you compare an unusual polymorphism to

Answer 13

NOMAD data base - lets you see if its come up before so if its present in the general population its probably harmless

Question 14

how to tell if a genetic change matches a disease

Answer 14

• it is in a gene which matches the phenotype
• it has an effect on gene function
• it is evolutionarily conserved bit of gene
• it is de-novo in child if only child is effected OR present in other family members with the same condition

Question 15

what us a premature stop mutation

Answer 15

early stop to a gene sequence

Question 16

what is a missence mutation

Answer 16

one base in the genetic sequence is changed

Question 17

what is an insertion mutation

Answer 17

an extra base is added to the genetic sequence moving them all down

Question 18

what is a deletion mutation out of frame

Answer 18

one base is deleted so everything moves down one

Question 19

what is a deletion mutation in frame

Answer 19

one whole codon is deleted

Question 20

what is a triplet expansion mutation

Answer 20

repetition of a codon

Question 21

what is the presentation of Kabuki Makeup Syndrome

Answer 21

speech delay 
cleft palate 
Unusual eyes and eyebrows 
Tendency to drool 
short 2nd phalanges of 5th finger

Question 22

what gene is mutated in kabuki makeup syndrome

Answer 22

MLL2

Question 23

What increases the number of de-novo mutations in a child

Answer 23

the paternal age (older fathers - more mutations)