Transcript Ch. 7 (part 2)

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
(2 out of 13 offspring)
2/13= 0.154 recombination frequency
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”
• Deletion mapping
• Somatic Cell hybridization
• In Situ Hybridization
• DNA Sequencing
DELETION MAPPING
(this has been used to map Muscular Dystrophy gene to X chromosome
50% have mutation
all have normal phenotype
Deletion Mapping
• Can also be done with homozygous recessive
Crossed with
• Homozygous wt+ but with deletion(s)
Offspring will be:
B+
Deletion area a
b
B+
a
b
aB+
a
b
We now know this deletion includes the locus that
is within the region deleted for A+ but not for B+
You can perform this
a panel of deletions.
Mutations
del
a
1
m
2
m
3
+
4
+
5
+
6
+
a
b
+
+
m
+
+
m
c
m
+
m
m
+
+
d
+
+
m
m
m
m
e
+
+
m
m
m
+
f
m
+
+
+
+
+
d
c
etc.
chromosome
deletion 1
deletion 2
deletion 3
deletion 4
deletion 5
deletion 6
f?
a f? c
e
d
b
SOMATIC CELL HYBRIDIZATION
+ Human somatic cell
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!
In Situ Hybridization
detects genes on chromsomes
DNA SEQUENCING
More to come with our
molecular discussions
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.
The End