Genetic Variation Flashcards
Phylogenetic Tree
show evolutionary distance between species and even within species
Reasons the Mouse is a Good Model for Human Studies
~40% of genome is perfectly aligned, ~80% of mouse genes have a single human counterpart, mutation rat is twice as high in mouse genome
ortholog
gene differs in sequence but its main function is conserved across species
homolog
protein sequence identical
Outgroup
the least related to the other species in a phylogenetic tree (think wolves in a dog breeds tree)
How much of the genetic sequence is shared between humans and chimpanzees?
99.8%
What three factors resulted in humans and chimps being different?
- Protein evolution (small (0.2%), critical changes)
- Gene regulation
- Less is more
Does a species become more or less genetically diverse over time?
MORE genetically diverse (assuming random mating and stable population)
Bottleneck
a way to reduce genetic diversity (for example, creating breeds) (eliminates some alleles in some breeds)
Is there more genetic diversity within a breed or between breeds?
BETWEEN breeds
How can you reintroduce genetic diversity to a population?
cross-breeding
Comparing Humans?
can be done at individual or population level; 1 million variants are unique to each population, but still shared within the population
How many base pairs in the human genome?
~3 billion
Recombination vs Mutation
Recombination is a result of variability that is ALREADY PRESENT in the population.
Mutations introduce NEW VARIABILITY to the population.
Types of Variants/Mutations (3)
- Sequence Variants
- Structural Variants
- Chromosomal Abnomalities
Trisomy 21
extra chromosome 21, results in Down’s Syndrome
Chromosomal Fusion
part of one chromosome ran away from home to join another chromosome
Reciprocal Translocation
“The Holiday” - two chromatids swapped homes
Single Nuclotide Polymorphism (SNPs), aka point mutation
single base pair change
Minor Allele Frequency
how often does the less common allele [of a SNP] occur within a population
>5-10% MAF = common variant
<1% MAF = rare variant
Are the majority of SNPs non-functional?
yes
Synonymous SNP
has no effect (non-functional, silent)
Non-Synonymous SNP
results in direct change to normal gene product, possibly via change of AA, loss/gain of start or stop codon, or changing a splicing site
Can SNPs have indirect effects?
potentially, through change in regulatory sequences (like in a promoter region)
Nonsense mutation
SNP results in a STOP codon
Missense
results in a different nucleotide, can be conservative (same type of AA) or nonconservative
INDEL
structural variant; insertions/deletions of 1-10k bases within a sequence (INDEL because they commonly happen together one respective chromosomes but don’t have to)
In-Frame Mutation
an effect of INDEL that occurs in multiples of three, therefore just shifting the codons and all other AA remain unchanged
Frame Shift
INDEL in anything other than a multiple of 3, resulting in changed AAs and typically a premature stop codon
Effect of INDEL on product?
altered protein product or no product at all
Copy Number Variant
structural variant; deletion or duplication of segments of DNA much larger than an INDEL (1-3kb), can affect the entire gene, problem due to mispairing in areas of repeat sequence
CNV in Mice?
olfactory genes! so they can smell hella good
Effect of CNV
can be postive, neutral, or negative
What % of mutations are sequence variants/SNPs?
~80%
What % of genetic mutations are structural variants?
~20%
Types of Structural Variants
INDEL
Copy Number Variants
Inversions
Inversion
entire segment of chromosome gets flipped around; recombination can no longer occur in this region; gene expression and phenotype can be normal as long as the inversion isn’t part ofthe gene or regulatory elements
What structural variation can be used to trac speciation?
inversions (ex: rats and mice)
Effects of Inversions
if located within a gene or regulatory region:
frequently lethal or sterility
but also tobianos color in horses (and other phenotypic changes)
trait
measurable/observable characteristic
very generalized
phenotype
observed category of a trait
ex: if the trait is coat color, the phenotype is red
Qualitative trait
few measured categories
ex: all or nothing disease, coat color
Quantitative trait
trait with continuous scale
ex: speed, weight
Sequencing
determine exact order of base pairs in a segment of DNA
Markers/SNP Chips
common variants within a genome that can be specifically assayed instead of sequencing the entire genome
Haplotypes
ordered genotyped bases; can look at variation over a larger scale
Linkage Analysis
look at haplotypes that are shared by affected individuals that are not shared by unaffected individuals to idenify region(s) that contain variants associated with a trait/disease
Genome Wide Association Analysis (GWAS)
calculating the statistical association of marker frequency with the phenotype of innterest by using markers/SNP chips that have already been identified
