Topic 16: Adaptive Variation Flashcards
What are putatively neutral genetic markers?
These are microsatellites, and other DNA non-coding regions that have no effect on phenotype
They are useful for studying demographic processes (changes in effective population size, dispersal), and for social structure (parentage and relatedness)
How are discrete traits inherited? How do we study them?
Usually inherited in a Mendelian fashion and are controlled by a single gene.
Can study them through controlled crosses.
Most traits show a continuous range of variation, why is this?
They are governed by many genes, each of small effect and each following the Mendelian rules of inheritance.
Hard to study genetic variation for quantitative traits when there are so many genes
What is quantitative genetics? What is variance?
Quantitative genetics describes populations using trait means, variances, and co-variances among traits and relatives.
Variance is dispersion around the mean:
- individual observations usually differ from the mean
-deviation is distance from the mean
-variance is average squared deviation
Covariance is the product of deviation from the mean for two measures
What is VA, VD and VI?
VA= additive genetic variation, measurement of the phenotypic variance among individuals that is due to directly inherited genetic effects
VD: non-additive source of genetic variation due to dominance
VI: non-additive source of genetic variation due to epistasis
What is VA responsible for in terms of phenotype?
THe component of genetic variance that causes the resemblance between parents and offspring, and also responds to natural selection and therefore allows adaptation to happen
How is Va often expressed?
As a fraction of the phenotypic variance, known as heritability (narrow sense heritability) h^2
Phenotypic variance among relatives allows estimating of VA in a number of ways. What are some ways to estimate heritability?
Can be estimated as the slope of the offspring value on the average parental value, and the steeper the slope the higher the higher the VA
Can be estimated in natural populations if parentage is known and traits are measured in a large sample
How do you determine narrow sense heritability (h^2)?
The slope of the line of best fit on a graph containing average phenotype of parents and average height of offspring, is used to directly measure the heritability of a trait.
Slope is narrow sense heritability.
What else can heritability and additive genetics variance be estimated from?
Single parent regression, full sib/ half sib ANOVA, controlled crosses, selection experiments, more complex tests than ANOVA and regression
What are some difficulties in estimating VA?
Large sample size needed for compared to most population genetic data
Good pedigree information is needed and often requires genetic markers
Phenotypic data is often harder to collect than genetic data
Parameters (heritability and variance) are population and trait specific
Extremely difficult to separate environmental and maternal effects from genetic effects
What genetic architecture?
When you find out how much genetic variation there is for a particular trait but you do not know how many genes influence that trait, their relative importance, or how they influence that trait
What are the two options for genetic dissection of complex traits?
Quantitative trait loci mapping
Association genetics (candidate genes and genome-wide association studies)
What are the four steps in QTL?
- Define underlying population sample (families, controlled crosses, multigenerational pedigree where trait of interest is variable and segregating)
- Collect genetic data from markers of known chromosomal location (type each individual at a panel of markers that are mapped in the species of interest)
- Measure phenotypes
- Test for association (test for relationships between genotypes along chromosomes and phenotype)
What is a linkage map?
An ordered array of genetic markers places at regular intervals along chromosomes.
Typically first generation maps have 250-300 markers, or one marker every 10 CM
What is one centimorgan equal too?
it is equal to a 1% chance that a marker at one genetic locus on a chromosome will be seperated from a marker at a second locus due to crossing over in a single generation
Used to identify regions of chromosomes that have genes which affect trait variation
Alleles at genes that affect trait variation will co-segregate with linked marker alleles
This generates a statistical correlation between marker alleles near the gene and trait variation
What does QTL refer to?
A chromosomal region that affects trait variation
What are advantages of QTL?
Few markers needed (100s) to cover the genome because it relies on meiosis and physical linkage to create associations between markers and genetic variants that influence traits along wide chromosomal regions
What are disadvantages of QTL?
Low resolution (wide QTL intervals), like assigning heritability to large regions of the chromosomes
Requires a pedigree or controlled crosses in which the trait and markers are segregating
Requires a genetic map (know markers)
What are candidate genes?
Genes that have known function usually in a model organism, that can be hypothesized to have a similar function in another organism.
“Shortcut” to target a few genes that are likely to play a role in trait variation instead of searching across entire genome
You sequence the candidate gene in a new taxon, and look for polymorphic regions that can be used as markers and tested for association (SNPS)
What is an example of a candidate gene in beach mice?
Melanocortin-1 receptor plays a role in melanin biosynthesis, good candidate gene for controlling coat colour polymorphisms, identified a SNP causing a single amino acid change in MCR-1 in beach mice therefore lighter coat
This is a large effect locus, with a quantitative trait nucleotide contributing to variation in fitness
What are pitfalls of the candidate gene hypothesis?
Not always easy to identify likely candidates (genes/pathway may be unknown, or many genes in a pathway contribute to a phenotype)
Polymorphisms outside of the coding region may relate to function (expression, regulation, dosage, or other post-transcriptional modification may contribute)
What is involved in association mapping? What does it rely on?
Involves detecting statistical associations between markers and phenotypes using a large sample of unrelated individuals. Relies on linkage disequilibrium between markers, and functional genes generating statistical associations
Associations extend over short distances, much denser coverage is needed compared to linkage mapping
What is the general procedure for a GWAS study?
Score individuals for phenotype
Genotype them at thousands or millions of markers
Mathematically test for association between phenotype and genotype for each marker to obtain p-values (chi-square or regression)
