genome variation Flashcards
(39 cards)
what is karyotyping?
process of sorting chromosomes into their matched pairs
important technique for investigating chromosomal disorders
what are macro level differences in the genome
generally associated with disease
- aneuploidy
- translocations
what are micro/molecular level differences in the genome
sometimes associated with disease
- point mutation
- deletion
ie coding variants such as hair, height
what is exome
where the coding genes are found (about 2% of the genome)
what does polymorphic mean
position on the genome that varies between individuals (a variant)
what is a reference sequence
a consensus (general agreement) that tells us what we expect to see in the genome - used to determine whether there are any genetic variants (polymorphisms)
what are the three main causes for variations
- single nucleotide polymorphism (SNPs)
- microsatellites
- copy number variants
what is SNP?
substitution of a single nucleotide at a specific position in the genome
high in frequency, happens in 1 in every 300 nucleotides
bi allelic
What does it mean to be biallelic?
2 possible alleles
What does triallelic mean
3 possible alleles
If there are >3 possible alleles what term do we use to describe the genotype?
multiallelic
What is the major allele?
the most common allele for a given SNP
What is the minor allele?
the less common allele for a SNP
What is the minor allele frequency (MAF)?
frequency at which the second most common allele occurs in a given population
how are SNPs formed?
during mismatch repair system during DNA replication (mitosis)
Although there are mismatch repair mechanisms which should correct these mistakes, some don’t get corrected and we end up with a SNP
Where are SNPs found?
Majority not in exome bc exome has strong selective pressure to not incorporate mutations which lead to detriment in people
Where in a gene may an SNP be found and what is the impact?
No amino acid change (synonymous) Amino acid change (non-synonymous/missense) Stop codon (nonsense) Splice sit UTR (gene expression)
promoter - affects protein expression
what is the only way for SNPs to disappear?
if they have a deleterious effect or population annihilation
otherwise, SNPs never disappear
What is a missense point mutation?
A point mutation where a single nucleotide change results in a codon that codes for a different amino acid
> type of nonsynonymous substitution
an example of a disease associated with missense mutation
Sicke cell anaemia
codon GAG -> GTG
Glu -> Val
Beneficial in places where malaria is rife (heterozygote advantage)
How do we define a polymorphism?/ when is SNV described to be a mutation or polymorphism?
polymorphism = If minor allele freqy >1% mutation = MAF is <1%
rare polymorphism = MAF 1-5%
Common polymorphism: MAF >5%
Outline the features of a variant
All variants start off from a mutation and are rare
- Evoly forces affect whether or not a variant remains rare
- Rare variant may be damaging and/or recent
what are SNV/Ps called when proven to be pathogenic?
point mutations
Summarise SNVs
Millions in genome
A position in genome at which the base can vary
Can be anywhere in the genome (genic or non-genic)
May do nothing, may affect a trait, may be associated with disorder
Generally bi-allelic
Due to mutation and mismatch repair
These are base substitutions
When pathogenic, may call point mutations
