genetic testing and single base variation

Question 1

how does PCR work

Answer 1

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

Question 2

Mutation:

Answer 2

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

Question 3

Polymorphisms

Answer 3

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

-Does not cause disease in its own right, but may predispose to common disease

Question 4

Penetrance:

Answer 4

the likelihood of having a 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 for any one mutation is low

Question 7

what is a missense mutation

Answer 7

• Point mutations that cause a change to a single amino acid
• Usually caused by substitutions
• Most likely mutation to directly activate an oncogene
  
  • Other mutations tend to inactivate the gene

Question 8

what happens in a mutation that results in the change to amino acid sequence

Answer 8

• Mutation may change protein sequence which may alter protein function
• Mutation may result in a premature stop codon

Question 9

describe insertion/ deletion mutation

Answer 9

• Causes a complete change to the entire amino acid sequence after the mutation site
• In frame - insertion/deletion of a multiple of 3 bases
• Out of frame - results in a frame shift

Question 10

Promotor and splice site sequence changes

Answer 10

Stop transcription or cause abnormal splicing

Question 11

Whole exome sequencing

Answer 11

Sequences exome - all the exons (vs. whole genome sequencing – introns and exons)

Question 12

describe genetic filtering

Answer 12

On average approx. 3 000 000 polymorphisms are detected when sequencing the entire genome in a person

To identify the pathogenic variant, the list of variants is filtered to remove those that are unlikely to be disease causing

Question 13

what does FISH use

Answer 13

fluorescent probes that bind only to parts of a nucleic acid sequence with a high degree of sequence complementarity

Question 14

why is FISH often used

Answer 14

for finding specific features in DNA for use in genetic counselling

Question 15

what is aCHG and describe it

Answer 15

a 1st line chromosome test
- Large scale - 3 million BPs
- Detects missing/duplicated pieces of chromosome
- Find polymorphisms
- Does not detect balanced rearrangements