Molecular Mapping

1
Molecular Mapping
2
Terminology

• Gene a particular sequence of nucleotides along
  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)

3
Terminology

• Allele one of two or more alternate forms of a
  gene occupying the same locus on a particular
  chromosome or linkage structure and differing
  from other alleles of that locus at one or more
  sites. (Johannsen, 1909).

4
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.

5
Terminology

• 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 product of exchange of
  alleles from parental types as a result of
  crossing-over.

6
Terminology

• Phenotype the observable properties of an
  organism, produced by the interaction between the
  organisms genotype and the environment.
  (Johannsen, 1909)

7
Terminology

• Genotype the genetic constitution in respect to
  the alleles at one or a few genetic loci under
  observation. (Johannsen, 1909)

AA Aa aa
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Recombinant
Parental Type
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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

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

15
Double cross-overs

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

16
Double cross-overs
If cross-overs are equally likely along the
chromosome and closer genes have few cross-overs,
then the likelihood of two crossovers close to
one another would be small. So,
mapping algorithms can order genes by minimizing
the number of double cross-overs.
17
Mapping Maize at UMC

• Genetic mapping is based on DNA fingerprint data
  of offspring from two parents which differ in
  their appearance.
• Similar fingerprint data for two gene indicates
  they are physically close together on a
  chromosome.

18
Scoring your gel

• Each parent A and B have different size DNA
  fragments.
• Progeny are either
• A (homozygous parent A)
• H (heterozygous)
• B (homozygous parent B)
• Can also use a if missing or not clear.

19
Molecular mapping
Digest DNA
Electrophorese
Hybridize with probe
-
Southern
blot

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Scoring data
A B H H A B A H
21
Recombination and Mapping

• Assume that 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
  very far apart.

22
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
• Few recombinants close together

23
How Maximum Likelihood Works

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

24

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