Mapping Basics

1
Mapping Basics

• MUPGRET Workshop
• June 18, 2004

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Randomly Intermated
P1 x P2
?
F1
? SELF

• F2
• 2 3 4 5 6 7
• One seed from each used for next generation
• Recombination.
• After recombination self to create line.

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Randomly Intermated.

• Very high resolution.
• Accumulates recombination events across
  generations and fixes them.
• Excellent for fine mapping
• Only homozygous genotypes.

4
Population Size

• Dependent on type of population
• Generally 200-300 individuals
• If doing trait analysis, the number of
  individuals determines the maximum number of QTL
  you can find.
• Two samples from the same population will produce
  different maps because they sample different
  gametes.

5
Genetic Mapping Basics

• Gene a particular sequence of nucleotides among
  a molecule of DNA which represents a functional
  unit of inheritance. (Johannsen, 1909)
• Locus the position of a gene on a chromosome or
  a genetic map. (Morgan, Sturtevant, Muller, and
  Bridges, 1915)

6
More terminology

• Linkage the association in inheritance of
  certain genes and their associated phenotypes due
  to their being localized in the same chromosome.
  (Morgan, 1910)
• Linked two genes showing less than 50
  recombination.

7
More terms

• Recombination Any process which gives rise to
  cells or individuals (recombinants) associating
  the alleles of two or more genes in new ways.
  (Bridges and Morgan, 1923)
• Recombinants are the end products of exchange of
  alleles from parental types as a result of
  crossing-over.

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Terminology

• Phenotype the observable properties of an
  organism, produced by the interaction between the
  organisms genotype and the environment
  (Johannsen, 1909).
• Genotype the genetic constitution in respect to
  the alleles at one or a few genetic loci under
  observation. (Johannsen, 1909).

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Recombination
Recombinant
Parental
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Recombination and Mapping

• Assume the frequency of crossing-over is equal
  along the chromosome.
• Two genes that are very close to one another will
  have a lower likelihood of having a cross-over
  between them than two genes that are far apart.

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Recombination and Mapping

• So, we can determine the relative distance
  between genes by counting the number of
  recombinant genotypes for each pair of genes.
• Lots of recombinants far apart
• Fewer recombinants close together

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Two Point Analysis

• Parental Types
• Tall, Green
• 42
• Short, White
• 39
• 81

• Recombinant Types
• Tall, White
• 7
• Short, Green
• 12
• 19

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Map Units

• 1 map unit is equal to 1 recombination.
• Map units are also called centimorgans after
  geneticist Thomas Hunt Morgan who won the Nobel
  Prize for discovering how chromosomes govern
  inheritance.

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Challenge

• How do we merge the information about each pair
  of genes together into one common framework?
• How do we order the genes relative to one another?

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Three-Point Analysis

• Single cross-over

A
B
C
a
b
c
Double cross-over
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Double cross-overs and Map Distance

• If we only look at the outer markers A and C on
  the previous slide, we will underestimate the
  true distance between them because we have not
  accounted for the double cross-overs.

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Three-Point Analysis

• Distance Singles 2 Doubles
• Total
• If cross-overs are equally likely along the
  chromosome and closer genes have few cross-overs,
  then the likelihood of two cross-overs close to
  one another would be small.

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Double cross-overs

• So mapping algorithms can order genes by
  minimizing the number of double cross-overs.

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Maximum Likelihood Method

• Gives an estimate of the distances and the
  relative orders of the loci which would maximize
  the probability that the observed data would have
  occurred.

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How Maximum Likelihood Works

• BHBBAHBHHBHHBHB umc157
• HHBBABBHHBBBBAB umc76
• BHBBABHAHHBHBAB asg45
• BHBBABBAHHBHBAB zb4
• BHBBHBHAHHBHBAB csu3

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• BHBBAHBHHBHHBHB umc157
• BHBBABHAHHBHBAB asg45
• HHBBABBHHBBBBAB umc76
• BHBBABBAHHBHBAB zb4
• BHBBHBHAHHBHBAB csu3

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MapMaker

• Mapping program that uses maximum likelihood
  method.
• Initially calculates what is linked (lt 50
  recombination).

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MapMaker

• Works one linkage group at a time.
• Randomly picks two genes with the group and
  calculates the distance between them.
• Adds another gene from the group and determines
  the correct placement by using maximum likelihood
  to minimize the double cross-overs.

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MapMaker

• Does this by calculating a LOD value for the
  placement of the gene in each of the intervals.
• Accepts the placement with the highest LOD value.
• Can be used for molecular markers or for trait
  data.

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LOD

• Log likelihood.
• LOD log 10 (Probability that the observed data
  would have occurred /probability that the gene is
  unlinked).