L17 - genetics Flashcards
true or false
many renal diseases are inherited even when they only occur in one family member
true
many apparently sporadic diseases are genetic
true or false
affected family members DNA is more useful tha unaffected when checking for mutation
false
equally useful
Describe Scalp-ear-nipple syndrome?
ectodermal dysplasia
rare AD
renal abnormalities
potentially due to missense mutations in KCTD1 transcription factor
An AD disease wilth mutations in TFAP2A causing branchial and periauricular skin defects is….
branchio-oculo-facial syndrome
What does TFAP2 control?
expression of keratin, collagen - explains skull defect, thinned membrane and astigamatism
What is a missense mutation?
where one AA is replaced by another
- can build up in ER and cause ER stress
What is a nonsense mutation?
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.
Describe the CRISPR technique
used to target and correct mutation
cuts out the mutationa dn provides a template of normal DNA that can be copied
- desig ss DNA oligonucleotides
- Anneal ss oligos to generate ds oligo
- dilute to working concentration
- clone to nuclease vector
- transform e.coli cells and select for expression
- Analyse transformants for insert by sequencing
- Prepare purified plasmid DNA and transfect patient fibroblasts
True or false
you need a monoclonal population of cells for the CRISPR technique
true
True or false
the mutations tha cause disease are often difference between each family which makes gene editing labourious and not as good
true
also risks of transfected cells
Future treatments for genetic dieases will..
be a cocktail of treatments
directed against underlying mutation
True of false
humans have much less non-coding sequences than other animals
false
much more
Mitochondrial DNA mutations often affect ___
muscles
increase mutations with ageing
about _% of RNA is messenger RNA
3%
the rest is ribosomal RNA
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
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
why is it important to do pedigree analysis?
to give genetic counselling to family members
identify novel genes for inherited disease
There are at least _ different genes involved in colour blindness
18
How is intelligence inherited?
5 themes of intelligence - 3 on X chromosome
No transmission from father to son
controversial but generally true
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
true
What is imprinting?
when the maternal or paternal chromosomal region behave differently
e.g prader willi syndrome
What has an increased risk with IVF and why?
Beckwith Wiedeman and angelman syndromes
loss of methylation of maternal chromosomes
What is locus heterogeneity/
mutations in different genes causing the same disease
what is allelic heterogeneity?
different mutations in a gene causing different diseases
What is copy number variation and where is it important?
variation in the number of copies of gene or DNA sequence
probably important in autism and schizophrenia
What are genome-wide association studies?
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
85% of disease causing mutations are in ____ which make up _% of the genome
exomes - 1% of the genome
true or false
genes for many rare diseases are still unknowm
true
What is gene discovery based on?
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
Name some drugs where prospective genotyping/phenotyping may be useful
antidepressants
Warfarin
Perhexiline
Proton pump inhibitors
Why test for mutations/
Diagnosis
genotype-phenotype correlations and predicting clinical outcome
treatments will be tailored to mutation type
