L17 - genetics

Question 1

true or false

many renal diseases are inherited even when they only occur in one family member

Answer 1

true

many apparently sporadic diseases are genetic

Question 2

true or false

affected family members DNA is more useful tha unaffected when checking for mutation

Answer 2

false

equally useful

Question 3

Describe Scalp-ear-nipple syndrome?

Answer 3

ectodermal dysplasia

rare AD

renal abnormalities

potentially due to missense mutations in KCTD1 transcription factor

Question 4

An AD disease wilth mutations in TFAP2A causing branchial and periauricular skin defects is….

Answer 4

branchio-oculo-facial syndrome

Question 5

What does TFAP2 control?

Answer 5

expression of keratin, collagen - explains skull defect, thinned membrane and astigamatism

Question 6

What is a missense mutation?

Answer 6

where one AA is replaced by another

• can build up in ER and cause ER stress

Question 7

What is a nonsense mutation?

Answer 7

is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in a truncated, incomplete, and usually nonfunctional protein product.

Question 8

Describe the CRISPR technique

Answer 8

used to target and correct mutation

cuts out the mutationa dn provides a template of normal DNA that can be copied

1. desig ss DNA oligonucleotides
2. Anneal ss oligos to generate ds oligo
3. dilute to working concentration
4. clone to nuclease vector
5. transform e.coli cells and select for expression
6. Analyse transformants for insert by sequencing
7. Prepare purified plasmid DNA and transfect patient fibroblasts

Question 9

True or false

you need a monoclonal population of cells for the CRISPR technique

Answer 9

true

Question 10

True or false

the mutations tha cause disease are often difference between each family which makes gene editing labourious and not as good

Answer 10

true

also risks of transfected cells

Question 11

Future treatments for genetic dieases will..

Answer 11

be a cocktail of treatments

directed against underlying mutation

Question 12

True of false

humans have much less non-coding sequences than other animals

Answer 12

false

much more

Question 13

Mitochondrial DNA mutations often affect ___

Answer 13

muscles

increase mutations with ageing

Question 14

about _% of RNA is messenger RNA

Answer 14

3%

the rest is ribosomal RNA

Question 15

Often families too ____to work out the inheritance pattern of disease. Families may not know of other _____ family members - take alot of ___ to ask around

Answer 15

Often families too small to work out the inheritance pattern of disease. Families may not know of other affected family members - take alot of time to ask around

Question 16

why is it important to do pedigree analysis?

Answer 16

to give genetic counselling to family members

identify novel genes for inherited disease

Question 17

There are at least _ different genes involved in colour blindness

Answer 17

18

Question 18

How is intelligence inherited?

Answer 18

5 themes of intelligence - 3 on X chromosome

No transmission from father to son

controversial but generally true

Question 19

true or false

There are at least 8000 inherited diseases. Sometimes mutations in the same gene can cause different mutations. Most of us have 5 significant mutations

Answer 19

true

Question 20

What is imprinting?

Answer 20

when the maternal or paternal chromosomal region behave differently

e.g prader willi syndrome

Question 21

What has an increased risk with IVF and why?

Answer 21

Beckwith Wiedeman and angelman syndromes

loss of methylation of maternal chromosomes

Question 22

What is locus heterogeneity/

Answer 22

mutations in different genes causing the same disease

Question 23

what is allelic heterogeneity?

Answer 23

different mutations in a gene causing different diseases

Question 24

What is copy number variation and where is it important?

Answer 24

variation in the number of copies of gene or DNA sequence

probably important in autism and schizophrenia

Question 25

What are genome-wide association studies?

Answer 25

large studies that identify multiple variants each with small effect on risk of diseases

risk of false-positives tho - need to confirm with independent populations

Question 26

85% of disease causing mutations are in ____ which make up _% of the genome

Answer 26

exomes - 1% of the genome

Question 27

true or false

genes for many rare diseases are still unknowm

Answer 27

true

Question 28

What is gene discovery based on?

Answer 28

shared haplotypes (a group of genes within an organism that was inherited together from a single parent.)

uses multiple bioinfromatics steps

pathogenic varient then identified

confirm by demonstrating variants in other families with same condition

Question 29

Name some drugs where prospective genotyping/phenotyping may be useful

Answer 29

antidepressants
Warfarin
Perhexiline
Proton pump inhibitors

Question 30

Why test for mutations/

Answer 30

Diagnosis

genotype-phenotype correlations and predicting clinical outcome

treatments will be tailored to mutation type