Quantitative Genetics Flashcards
what are complex traits?
traits that are controlled by multiple genes
- you have to measure these traits rather than categorise
when does variation follow a normal distribution?
- multiple loci are evolved
- each locus has about equal effect size
- each locus acts independently
what is a quantitative trait locus?
a locus (section of DNA) which correlates with variation of a quantitative trait in the phenotype of a population or organisms
what is QTL mapping?
uses the populations derived from bi-parental crosses to identify QTL
what is GWAS?
use populations of diverse (not closely related) individuals to identify QTL
what do both QTL mapping and GWAS use?
use nearby markers (eg SNP markers) to map QTL
what happens when the marker is closer?
the closer the marker the more often its co-inherited with the QTL, looking to find markers closest to the gene of interest
what is the process of QTL mapping?
- begins with bi-parental cross between parents of different phenotype
- F1 will be identical
what happens in an F1 x F1 in QTL mapping?
- recombination will occur during meiosis
- reshuffles genes in the games
- phenotypes segregate at F2
what happens when the parents and F2 are genotyped in QTL mapping?
- can identify which sections of the chromosome have been inherited from each parent
- can see what phenotypes they have
- can find associations between phenotype and section of DNA inherited
- sections that correlate with the phenotype = QTL
what are the advantages of F2 and BC (F1 x Parent) populations?
quick and simple
good for preliminary mapping
what are the disadvantages of F2 and BC (F1 x Parent) populations?
a single individual represents each genotype
replications overtime/space can’t be carried out
low resolution
what are recombinant inbred lines?
selfing F2 populations through more generations
what are the advantages of recombinant inbred lines?
- very homozygous - can fix the alleles
- dont have a single individual, there are populations of individuals of each genotype
- immortal, can get large populates and breed to get more of the same genotype
what are the disadvantages of recombinant inbred lines?
time consuming to produce, there are more generations
what is advanced backcross population?
several rounds of backcrossing and selfing
what are the advantages of advanced backcross population?
- useful for simultaneous QTL analysis
- breeding QTL into elite lines
- can be use to produce near isogenic lines (NILs) for additional analysis
what are near isogenic lines?
nearly identical apart from small sections of DNA from one of the parents
what are the disadvantages of advanced backcross population?
time consuming
how can we identify QTL?
- single marker analysis
- interval mapping (IM)
- composite interval mapping
what is single marker analysis?
- looks at every marker-trait combination (t test or ANOVA)
- simple and quick but low precision
what is interval mapping (IM)?
- uses information from pairs of consecutive markers to estimate the likelihood of a QTL being between them
- expect if you have a marker either side of a mutation then both of those markers are more likely to be inherited then those further apart
- more powerful and gives a slight more precise QTL location
what is composite interval mapping?
- tests for QTL using IM but simultaneously controls for variance
- tries to estimate the effect that each individual locus has on the trait
- allows you to separate two regions that are close together
- most accurate but statistically complicated and requires more computational power
what are the limitations of QTL studies?
- resolution is often to low to identify candidate genes without further fine mapping
- can be time consuming to build populations
- QTL detection limited to the genetic variation between the two parents
- not always possible to build a population
how can you carry out a QTL study without building a population?
- existing families can be studied
- there are constraints on population size and experimental design
- limits statistical power
what is GWAS?
identifies markers (usually SNPs) that are significantly associated with a trait of interest across a diversity panel of individuals - don't want them to be closely related
how does GWAS work?
- phenotype the indiduals and look for genome wide SNP phenotypes
- identify SNP alleles associated phenotype
- each of the marker is normally presented according to its position in the genom
- find not only signle marker but multiple markers
- forms peaks
why do you get multiple markers?
because there are markers of linkage disequilibrium
what does QTL analysis rely on?
linkage - the physical state of being linked due to the chromosomal organisation of the genome
what is linkage disequilibrium?
refers to the presence of statistical association between allelic variants, is this marker statistically associated with his marker
- the degree of non-random association of alleles at two or more loci
whats linkage disequilibriums role in GWAS?
determines the resolution of mapping
what is long distance LD?
- mapping the centimorgan (cM) distance
- markers across a large amount of chromosome
- low resolution
what is short distance LD?
- mapping at the base pair (gene) distance
- get to a candidate gene more easily
when are alleles in perfect LD?
- if alleles are always seen together in a population
what is linkage equilibrium?
- if all combinations of alleles are seen at a random in a population
- recombination breaks down allele combinations over time
- more distant loci will be broken down more quickly
when does LD decay?
decays with distance between markers
markers can be co-inherited even if they’re far away
what are the major factors of LD?
- recombination rates
- population size
- inbreeding
- mutation rate
- selection
- population structure
what are recombination rates in LD?
- changes arrangement of haploytypes
- creates new haplotypes
what is population size in LD?
- LD may increase in small populations as haplotypes are lost through genetic drift
- rapid population growth reduces drift and LD
what is inbreeding in LD?
- decay of LD is reduced in selfing populations
what are mutation rates in LD?
- rapidly mutatin loci may show low LD even in the absence of recombination
what is selection in LD?
- fixation of beneficial alleles through positive selection, get regions of inflated LD
what is population structure in LD?
- population stratification may shape patterns of LD across population
how can population structure effect data?
- can cause false positives or type 1 errors in association analysis
- some individuals will be more closely realted than others
- are markers really associated with the causative gene or are they just common in some populations
how can we correct from population structure?
principle component analysis (PCA) - estimates how the individuals are related from their SNPs
how would design a GWAS experiment to optimise analysis?
- maximise resolution (diverse panel of accession and plenty of accessions)
- saturate with markers (dependent on extnet of LD and size of genome, SNP clips/next generational sequencing)
- control false positives (use linear models that incorporate population structure)
