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Genes and Genomes II > Quantitative Genetics > Flashcards

Quantitative Genetics Flashcards

1
Q

what are complex traits?

A

traits that are controlled by multiple genes

- you have to measure these traits rather than categorise

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2
Q

when does variation follow a normal distribution?

A
  • multiple loci are evolved
  • each locus has about equal effect size
  • each locus acts independently
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3
Q

what is a quantitative trait locus?

A

a locus (section of DNA) which correlates with variation of a quantitative trait in the phenotype of a population or organisms

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4
Q

what is QTL mapping?

A

uses the populations derived from bi-parental crosses to identify QTL

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5
Q

what is GWAS?

A

use populations of diverse (not closely related) individuals to identify QTL

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6
Q

what do both QTL mapping and GWAS use?

A

use nearby markers (eg SNP markers) to map QTL

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7
Q

what happens when the marker is closer?

A

the closer the marker the more often its co-inherited with the QTL, looking to find markers closest to the gene of interest

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8
Q

what is the process of QTL mapping?

A
  • begins with bi-parental cross between parents of different phenotype
  • F1 will be identical
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9
Q

what happens in an F1 x F1 in QTL mapping?

A
  • recombination will occur during meiosis
  • reshuffles genes in the games
  • phenotypes segregate at F2
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10
Q

what happens when the parents and F2 are genotyped in QTL mapping?

A
  • 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
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11
Q

what are the advantages of F2 and BC (F1 x Parent) populations?

A

quick and simple

good for preliminary mapping

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12
Q

what are the disadvantages of F2 and BC (F1 x Parent) populations?

A

a single individual represents each genotype
replications overtime/space can’t be carried out
low resolution

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13
Q

what are recombinant inbred lines?

A

selfing F2 populations through more generations

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14
Q

what are the advantages of recombinant inbred lines?

A
  • 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
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15
Q

what are the disadvantages of recombinant inbred lines?

A

time consuming to produce, there are more generations

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16
Q

what is advanced backcross population?

A

several rounds of backcrossing and selfing

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17
Q

what are the advantages of advanced backcross population?

A
  • useful for simultaneous QTL analysis
  • breeding QTL into elite lines
  • can be use to produce near isogenic lines (NILs) for additional analysis
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18
Q

what are near isogenic lines?

A

nearly identical apart from small sections of DNA from one of the parents

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19
Q

what are the disadvantages of advanced backcross population?

A

time consuming

20
Q

how can we identify QTL?

A
  • single marker analysis
  • interval mapping (IM)
  • composite interval mapping
21
Q

what is single marker analysis?

A
  • looks at every marker-trait combination (t test or ANOVA)

- simple and quick but low precision

22
Q

what is interval mapping (IM)?

A
  • 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
23
Q

what is composite interval mapping?

A
  • 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
24
Q

what are the limitations of QTL studies?

A
  • 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
25
Q

how can you carry out a QTL study without building a population?

A
  • existing families can be studied
  • there are constraints on population size and experimental design
  • limits statistical power
26
Q

what is GWAS?

A 
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
27
Q

how does GWAS work?

A
  • 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
28
Q

why do you get multiple markers?

A

because there are markers of linkage disequilibrium

29
Q

what does QTL analysis rely on?

A

linkage - the physical state of being linked due to the chromosomal organisation of the genome

30
Q

what is linkage disequilibrium?

A

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

31
Q

whats linkage disequilibriums role in GWAS?

A

determines the resolution of mapping

32
Q

what is long distance LD?

A
  • mapping the centimorgan (cM) distance
  • markers across a large amount of chromosome
  • low resolution
33
Q

what is short distance LD?

A
  • mapping at the base pair (gene) distance

- get to a candidate gene more easily

34
Q

when are alleles in perfect LD?

A
  • if alleles are always seen together in a population
35
Q

what is linkage equilibrium?

A
  • 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
36
Q

when does LD decay?

A

decays with distance between markers

markers can be co-inherited even if they’re far away

37
Q

what are the major factors of LD?

A
  • recombination rates
  • population size
  • inbreeding
  • mutation rate
  • selection
  • population structure
38
Q

what are recombination rates in LD?

A
  • changes arrangement of haploytypes

- creates new haplotypes

39
Q

what is population size in LD?

A
  • LD may increase in small populations as haplotypes are lost through genetic drift
  • rapid population growth reduces drift and LD
40
Q

what is inbreeding in LD?

A
  • decay of LD is reduced in selfing populations
41
Q

what are mutation rates in LD?

A
  • rapidly mutatin loci may show low LD even in the absence of recombination
42
Q

what is selection in LD?

A
  • fixation of beneficial alleles through positive selection, get regions of inflated LD
43
Q

what is population structure in LD?

A
  • population stratification may shape patterns of LD across population
44
Q

how can population structure effect data?

A
  • 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
45
Q

how can we correct from population structure?

A

principle component analysis (PCA) - estimates how the individuals are related from their SNPs

46
Q

how would design a GWAS experiment to optimise analysis?

A
  1. maximise resolution (diverse panel of accession and plenty of accessions)
  2. saturate with markers (dependent on extnet of LD and size of genome, SNP clips/next generational sequencing)
  3. control false positives (use linear models that incorporate population structure)

Genes and Genomes II (8 decks)

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