6. Normal Genetic Variation Flashcards
What can reduce diversity
Genetic bottlenecks
What is a genetic bottleneck caused by
Speciation, migration, environment, disease
Reduction in population
What promotes diversity
Mutation
What is a mutagen
Agents that cause mutations eg, physical/ chemical
How can UV light cause melanoma
Too much UV light = causes pyrimidine dimers to form = abnormalities in subsequent replication
In what way do alkylating agents cause mutation
Transfer methyl/ ethyl to backbone phosphate = causes G to T
How many base pairs do we all have
3 x 10^9
What percent of human genome differs between people
0.1%
6 x 10^6 different base pairs
Which genetic testing technique can show frequency of mutations
WGS
What happens to the rate of germ line mutations with paternal age
Increases
Where is a germ line mutation present
Egg or sperm = heritable = all cells affected in offspring
Are somatic mutations inheritable and where do they occur
In non germ line tissues
Cannot be inherited
What are the two types of origins of genetic variation and give examples fir each
- exogenous (eg, radiation, chemicals, mostly somatic)
- endogenous ( segregation/aneuploidys , recombination/trasnoclations, DNA replication errors, inadequate DNA repair
What types of mutations dont alter teh DNA content
- Single nucleotide replacements
- balanced translocations/ inversions
What percentage of our DNA is poorly conserved
90%
Small DNA changes don’t always result in an obvious effect on phenotype
What is a SNP
Single nucleotide polymorphism = if a single nucleotide variation occurs in more than 1 % of population
What is the most common SNP
C —> T
Indel meaning
Insertion or deletion of one or more nucleotides
What is a CNV
Large indels
Changes in copy number of sequences greater than 100 in length
Are silent variations of SNPs more common
Yes
What is minor allele frequency- MAF
The frequency of the less common variant in a population (of a SNP)
What % of all human genome variation do SNPs make up
90%
What is a diallelic SNP
When the base can change to one other base eg:
C —> T
What is a triallleic SNP
When the base can change to two other bases eg,
C—> A or T
What are Intronic/ intergenic variants
- Variants that occur between genes/ exons
- dont affect protein directly
Why can intronic variantions still be bad
Can affect the regulation of transcription/ splicing
What are three types of coding ‘extronic’ variants
- missense = nonsynmous = a.a change
- nonsense = stop= change of a.a to stop codon = leads to truncation of protein
- silent = synonymous = codon for a.a is changed but some same a.a still coded for, eg: GGC = Glycine and GGU = Glycine
Which type of mutation leads to truncation of protein
Nonsense
Which type of protein leads to the same amino acid being coded for
Silent
What are SSRs
Simple repeat sequences/ micro satellites = repeated region of DNA = occur at thousands of locations on the gene
- unstable, prone to replication slippage
What is genetic anticipation
When the repeat length of variant in a gene can increase in meiosis so the longer sequence is passed onto child = earlier onset in child
What is microsatelltie DNA
A tract of repetitive DNA motifs are repeated, about 5 to 50 times
Give 3 examples of a disease which is subject to genetic anticipation
Huntington’s disease
Fragile X syndrome
Spinocerebellar ataxia = progressive, degenerative involving loss of full control of bodily movements
What does the CNV map show
Documents teh extent and characteristics of CNV among healthy populations
Which regions of a chromosome show a particularly high rate of CNV variation
- pericentromeric (near/ on each side of the centromere)
- subtelomeric (segments of DNA between telomeric caps and chromatin)
Which genes are the least affected by CNVs
Genes that are associated with disease
How many genes can be comepletly removed from the genome without producing apparent phenotypic consequences
More than 100
Give an example of cells where CNVs are enriched n why
In cells involved in immune response - need to be diverse to respond to different pathogens etc
What a percentage of teh human genome isn’t functionally restrained n generally permissive of variation
90%
What are deleterious mutations eliminated by
Natural selection
Eg, mutations that compromise early dev/ neonatal health wont persist in population
What is postive selection of CNVs
When a beneficial adaptation spreads
What does teh human AMY1A gene code for n how is it an example of postive selection of CNVs
- codes for salivary amylase which hydrolyses starch
- people in populations with high starch diets have more copies of this AMY1A gene = spread as human diets became increasingly rich in insoluble starch
What % of human genetic variation is found within populations
85 to 90%
What % of human genetic variation is found between populations
Only 10 to 15%
