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Linkage, Recombination and Eukaryotic Mapping. Part 2. Outline. Gene mapping in Humans Pedigrees and linkage Physical Chromosome mapping. Nail-Patella Syndrome. Autosomal dominant: abnormal fingernails and absent (underdeveloped kneecaps) ABO blood type alleles linkage.

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Presentation Transcript
outline
Outline
  • Gene mapping in Humans
    • Pedigrees and linkage
  • Physical Chromosome mapping
nail patella syndrome
Nail-Patella Syndrome
  • Autosomal dominant: abnormal fingernails and absent (underdeveloped kneecaps)
  • ABO blood type alleles linkage
slide4

(2 out of 13 offspring)

2/13= 0.154 recombination frequency

physical chromosome mapping
Physical Chromosome Mapping
  • Provides us alternative methods for gene mapping that do not rely on rates of crossing over to determine gene location
methods that are considered physical mapping of the chromosome
Methods that are considered “physical mapping of the chromosome”
  • Deletion mapping
  • Somatic Cell hybridization
  • In Situ Hybridization
  • DNA Sequencing
slide7

DELETION MAPPING

(this has been used to map Muscular Dystrophy gene to X chromosome

50% have mutation all have normal phenotype

deletion mapping
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+

slide9

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

slide10

SOMATIC CELL HYBRIDIZATION

+ Human somatic cell

slide11

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!

slide13

DNA SEQUENCING

More to come with our molecular discussions

practice physical mapping
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 in—just to practice to see if it all makes sense.