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ASSOCIATION MAPPING
T. Nivethitha , GPB
4 Cycles of intermating and selection – 15 years
Extensive phenotyping and value judgement
Association Mapping &
Advantages
 ‟Association genetics‟ or
‟association studies,” or
‟linkage disequilibrium
mapping”
 Tool to resolve complex
trait variation down to the
sequence level by exploiting
historical and evolutionary
recombination events at the
population level.
 Natural population surveyed
to determine MTA using LD.
Approaches
• On the basis of distance between two loci
• By analyzing linkage disequilibrium between marker and target gene in natural
population.
 LD refers to nonrandom association of alleles at different loci.
 LD can occur between more distant sites or sites located in different chromosomes
 LD is difference between the observed gametic frequencies of haplotypes and the
expected gametic haplotype frequencies under linkage equilibrium .
D = PAB − PAPB = (PAB.Pab − PAb.PaB)
…A..T.. 2
…A..C.. 2
…G..T.. 2
…G..C.. 2
…A..T.. 4
…A..C.. 0
…G..T.. 4
…G..C.. 0
Linkage Equilibrium
Linkage disequilibrium
 Significantly differs
from expected 1:1:1:1
ratio
Estimation of LD
AB - 4/8 = 0.5
ab - 3/8 = 0.375
aB - 1/8 = 0.125
Frequencies
Lewontin, 1964
D = PAB-PA.PB
= 0.5-0.5*0.625 = 0.1875
Again if we calculate for “Ab”
D = PAb -PA.Pb
= 0.0-0.5*0.375 = -0.1875
D = PAB.Pab - PAb.PaB
= 0.5*0.375 – 0*0.125
= 0.1875
 Standardised estimates
D’ and r2
• LD mapping detects and locates quantitative trait loci (QTL) by the strength of the
correlation between a trait and a marker.
• Offers greater precision in QTL location than family-based linkage analysis
• More efficient marker-assisted selection, facilitate gene discovery.
• Does not require family or pedigree information , can be applied to a range of
experimental and non experimental populations.
• Care must be taken during analysis to control for the increased rate of false
positive results arising.
(Mackay and Powell, 2007)
Mapping Populations
Advantages of Natural population
 Any panmictic population.
 Samples from natural
/breeding and synthetic
population
 Random sample or core set
of germplasm .
 Superior QTL from elite
germplasm directly used for
MAS.
NAM  First developed in Maize, Common
founder – B73.
 Higher power than AM panel, the
controlled crosses for NAM
minimize population structure and
familial relatedness.
 Frequency of rare alleles increases.
 Uses both historical LD and
recombinant LD.
 BC NAM & DH NAM – also
developed.
MAGIC
 Population development includes
many rounds of recombination .
 - QTL precision & Resolution
 Can be used directly or indirectly for
varietal development.
 Common Wheat and Rice.
Approaches-GWAS
Population Structure
Relatedness
 IBS (Identical By State)-Two
individual carrying the same
allele but not from common
ancestry.
 IBD (Identical By Descend)-
Two individual carrying the
same allele and they have a
common ancestry
Procedure
Association mapping
Association mapping

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Association mapping

  • 2. 4 Cycles of intermating and selection – 15 years Extensive phenotyping and value judgement
  • 3. Association Mapping & Advantages  ‟Association genetics‟ or ‟association studies,” or ‟linkage disequilibrium mapping”  Tool to resolve complex trait variation down to the sequence level by exploiting historical and evolutionary recombination events at the population level.  Natural population surveyed to determine MTA using LD.
  • 4. Approaches • On the basis of distance between two loci • By analyzing linkage disequilibrium between marker and target gene in natural population.  LD refers to nonrandom association of alleles at different loci.  LD can occur between more distant sites or sites located in different chromosomes  LD is difference between the observed gametic frequencies of haplotypes and the expected gametic haplotype frequencies under linkage equilibrium . D = PAB − PAPB = (PAB.Pab − PAb.PaB)
  • 5. …A..T.. 2 …A..C.. 2 …G..T.. 2 …G..C.. 2 …A..T.. 4 …A..C.. 0 …G..T.. 4 …G..C.. 0 Linkage Equilibrium Linkage disequilibrium  Significantly differs from expected 1:1:1:1 ratio
  • 6. Estimation of LD AB - 4/8 = 0.5 ab - 3/8 = 0.375 aB - 1/8 = 0.125 Frequencies Lewontin, 1964 D = PAB-PA.PB = 0.5-0.5*0.625 = 0.1875 Again if we calculate for “Ab” D = PAb -PA.Pb = 0.0-0.5*0.375 = -0.1875 D = PAB.Pab - PAb.PaB = 0.5*0.375 – 0*0.125 = 0.1875  Standardised estimates D’ and r2
  • 7. • LD mapping detects and locates quantitative trait loci (QTL) by the strength of the correlation between a trait and a marker. • Offers greater precision in QTL location than family-based linkage analysis • More efficient marker-assisted selection, facilitate gene discovery. • Does not require family or pedigree information , can be applied to a range of experimental and non experimental populations. • Care must be taken during analysis to control for the increased rate of false positive results arising. (Mackay and Powell, 2007)
  • 9. Advantages of Natural population  Any panmictic population.  Samples from natural /breeding and synthetic population  Random sample or core set of germplasm .  Superior QTL from elite germplasm directly used for MAS.
  • 10. NAM  First developed in Maize, Common founder – B73.  Higher power than AM panel, the controlled crosses for NAM minimize population structure and familial relatedness.  Frequency of rare alleles increases.  Uses both historical LD and recombinant LD.  BC NAM & DH NAM – also developed.
  • 11. MAGIC  Population development includes many rounds of recombination .  - QTL precision & Resolution  Can be used directly or indirectly for varietal development.  Common Wheat and Rice.
  • 13. Population Structure Relatedness  IBS (Identical By State)-Two individual carrying the same allele but not from common ancestry.  IBD (Identical By Descend)- Two individual carrying the same allele and they have a common ancestry