Linkage, Recombination and Eukaryotic Mapping

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Linkage, Recombination and Eukaryotic Mapping
Part 2
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Outline

• Gene mapping in Humans
• Pedigrees and linkage
• Physical Chromosome mapping

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Nail-Patella Syndrome

• Autosomal dominant abnormal fingernails and
  absent (underdeveloped kneecaps)
• ABO blood type alleles linkage

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(2 out of 13 offspring)
2/13 0.154 recombination frequency
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Physical Chromosome Mapping

• Provides us alternative methods for gene mapping
  that do not rely on rates of crossing over to
  determine gene location

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Methods that are considered physical mapping of
the chromosome

• Deletion mapping
• Somatic Cell hybridization
• In Situ Hybridization
• DNA Sequencing

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DELETION MAPPING (this has been used to map
Muscular Dystrophy gene to X chromosome
50 have mutation
all have normal phenotype
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Deletion Mapping

• Can also be done with homozygous recessive
• Homozygous wt but with deletion(s)

Crossed with
Offspring will be
Deletion area
a b
a b
aB
B
B
a b
We now know this deletion includes the locus that
is within the region deleted for A but not for B
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You can perform this a panel of deletions.
Mutations del a b c d e
f 1 m m m 2 m 3 m m m m 4
m m m 5 m m 6 m m
d
a
c
etc.
f? a f? c e d b
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SOMATIC CELL HYBRIDIZATION
Human somatic cell
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You set up a panel of these hybrid cells that
include a random selection of human chromosomes
Look for which cell lines produce the product AND
which chromosomes are present.
Bingo! You can determine which gene is
associated with which chromosome!
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In Situ Hybridizationdetects genes on chromsomes
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DNA SEQUENCING
More to come with our molecular discussions
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Practice Physical Mapping

• Questions 4, 5, 26 and 27 at the back of chapter
  7 to try out your skills at deletion analysis and
  somatic-cell hybridization.
• I will post the answer for question 26 (others
  are in the book).
• Does not have to be handed injust to practice to
  see if it all makes sense.

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The End