Lecture 8 Flashcards
(24 cards)
Define polymorphism
two or more allies of a gene in a population
Define SNPs
single base differences- single nucleotide polymorphism
Define indels
insertion or deletion
What is copy number variation caused by?
large insertion or deletion in one chromosome
Describe DNA sequencing
- Chain-termination – accurate, low throughput 800 bases
- Next generation sequencing – extremely high throughput, 100 bases, small sequences – most popular, good for SNP detection, poor for CNVs
- Single molecule – high error rates and cost, 10,000 bases, how molecules are arranged
How can SNPs be detected?
DNA hybridisation techniques
How different from each other are individuals?
Watsons genome contains 3.3 millions SNPS, approx. 10million common SNPS in humans
Describe indels
analysed using PCR and gel electrophoresis, STRs are multi allelic, used in genetic profiling, less than SNPS
Describe genetic variation regions on phenotypic effects
- Intergenic region: no effect
- Non-coding regions – silent and may affect gene expression
- Protein coding region – effects
Describe base substitutions
silent, neutral (affects sequence but not properties), mis-sense or nonsense(stop codons)
Describe mutations
rare alleles, mutant are useful for genetics, normal allele is termed wild type
Define mendelian disease
mutations of a single gene- rare disease
What mechanisms do cells have to prevent mutation?
- Proofreading DNA polymerase
- Postreplication mistmatch repair
- DNA repair by homologous recombindation
- Cell cycle checkpoints
What are the environmental factors that cause mutations?
radiation and chemical mutagens
Transitions
substituting pyrine for pyrine or pyrimidine for pyrmidine
Transversions
pyrine (2 ring) to pyrimidine (3 ring structure)
What do mutations cause thymines to do?
covalently link to produce a photodimer caused by UV light, photolyase and light can reverse this,
Intercalating agents
insert between base pairs frameshift
Base analogues
incoroporated into DNA in place of normal base, mis pairing
Base modifying agents
covalently modify the DNA causing mis pairning
• Deaminating agents remove amino groups – 5-methylcytosine to thymine
• Hydroxlyating agents add hydroxyl groups
• Aklyating agents add alkyl groups
Alkylating agents
• ENU converts G to A, MMS acts similarly but by addition of a methyl group
What generates STR variation
replication slippage
Describe mutations in coding regions
Mutations in coding regions:
• Mutant genes- non functional or unstable proteins
• Diploid have mostly recessive mutations
Describe temperature sensitive mutations
mutant protein is less stable at non-permissive temperature, very useful for studying essential cell functions eg yeast
