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BioSci 97: Lecture 16
Linked Genes & Mapping II
Famous Thomas Morgan’s fly room at Columbia, 1914
© 2016-2024 Kvon, Warrior, Lee, Cinquin
Learning Objectives
• Use a chi-squared test to determine whether genes
are linked
• Understand why recombination frequency is good
approximation of map distance
• Articulate why recombination frequencies cannot be
simply added
• Explain why physical distance and map distance are
not necessarily proportional to each other
• Know how to order three genes on a map using two-
point cross data
Test cross is used to to measure
recombination frequency
Gamete
formation
Test cross:
Cross to an individual with a
homozygous recessive genotype
Recombination frequency is a measure
of how linked are two genes
Recombination frequency
(10.7% in this case)
# of flies with non-parental genotypes
Recomb. frequency = Frequency of recomb. alleles
Gamete
formation
Cross
What is the maximum recombination
frequency?
If genes are very far apart on the same
chromosome, at what frequency will they
recombine?
A.25%
B. 50%
C. 100%
D. No limit
What is the maximum recombination
frequency?
If genes are very far apart on the same
chromosome, at what frequency will they
recombine?
A.25%
B. 50%
C. 100%
D. No limit
What is the maximum recombination
frequency?
If genes are very far apart on the same
chromosome, at what frequency will they
recombine?
A.25%
B. 50%
C. 100%
D. No limit
•Crossovers occurs in the 4-strand stage of meiosis I, and involve only two of the
four chromatids.
•Thus any single crossover event creates two recombinant (non parental)
chromatids, while leaving the other two in the parental configuration.
Recombination frequency is a measure
of how linked are two genes
Recombination frequency
is low
(10.7% in this case)
You can detect genetic linkage
using a chi-squared test
(Obs-
Phenotype Observed Expected
Exp)2/Exp
vg+, pr +
vg pr
vg+ pr
vg pr+
286 284 213 217 Total
Independent assortment is my _____ hypothesis.
You can detect genetic linkage
using a chi-squared test
(Obs-
Phenotype Observed Expected
Exp)2/Exp
vg+, pr + 286 250 5.184
vg pr 284 250 4.624
vg+ pr 213 250 5.476
vg pr+ 217 250 4.356
286 284 213 217 Total 1000 1000 19.640
Independent assortment is my _____ hypothesis.
Based on the chi-square value of 19.6
can you reject your null hypothesis?
A. Yes, the genes are likely linked
B. No, we cannot reject the null hypothesis
df = (number of genotypes) - 1
Based on the chi-square value of 19.6
can you reject your null hypothesis?
A. Yes, the genes are likely linked
B. No, we cannot reject the null hypothesis
df = 4-1
19.6 > 16.27
A chi-squared test can be completed by
following five simple steps:
A. Identify hypotheses (null versus alternative)
B. Construct a table of frequencies (observed versus
expected)
C. Apply the chi-squared formula
D. Determine the degree of freedom (df)
E. Identify the p value (should be <0.05)
The probability of crossing over
between two genes (or loci) is
roughly proportional to their distance
apart on the chromosome.
Genetic Linkage Mapping
is based on recombination
frequency between genes
Alfred H. Sturtevant
“The linear arrangement of
sex-linked factors in
Drosophila, as shown by their
mode of association”
J. Exp. Zool., 1913
Work done while he was an undergraduate
In T.H. Morgan’s lab (UROP)
Which of the following do you expect to
show the relationship between distance and
recombination frequency?
A B
recombination recombination
frequency frequency
C distance D distance
recombination recombination
frequency frequency
distance distance
Which of the following do you expect to
show the relationship between distance and
recombination frequency?
A
recombination
frequency
distance
The centiMorgan is a measure of the distance between two linked
genes. It is based on the idea that recombination frequency is
roughly proportional to actual physical distance.
1% recombination
=
1 centiMorgan (cM)
=
1 map unit (m.u.)
~
1 million base pairs (Mbp)
Can Recombination Frequency
be used to map genes?
Recombination frequency
between vg and pr alleles is
10.7% = 10.7 centiMorgans
(cM)
Definition of linkage
Linked genes
exhibit less than 50%
recombination
(that is, they are less than
50 cM apart)
(Human Chrm 9 is ~ 200 cM)
1 2 3 4 5
19 20 21 22 X Y
Chrm 1
Chrm 7
w
z
50
cM { y
x
x and y are
x and z are
x and w are
x and v are
w, x, y and z are
3 linked genes: A, B, and C
How to map them relatively to each other?
A B C
A C B
B A C
?
3 linked genes: A, B, and C
How to map them relatively to each other?
A B C
AB BC
AC
Measure pairwise recombination frequencies
using test cross
3 linked genes: A, B, and C
AB/ab x ab/ab: 39% AB 11% Ab 11% aB 39% ab
AC/ac x ac/ac: 42% AC 8% Ac 8% aC 42% ac
BC/bc x bc/bc: 46% BC 4% Bc 4% bC 46% bc
Map: which gene is in the middle?
A B A C = C A B
B A B C = D B A
C B C A = A C B
22 cM
A B
16 cM
A C
8 cM
B C
Map: which gene is in the middle?
A B A C = C A B
B A B C = D B A
C B C A = A C B
22 cM
A B
16 cM
A C
8 cM
B C
A 16 cM C 8 cM B
22 cM
A B ?
Why don’t the numbers add up?
In a genetic mapping experiment, double
crossovers between two loci can affect the
calculated genetic distance. How do double
crossovers impact the observed genetic distance
between these loci?
A. They increase the observed genetic distance.
B. They decrease the observed genetic distance.
C. They have no effect on the observed genetic
distance.
D. They cause the observed genetic distance to be equal
to the physical distance.
Double-crossovers cause
an under-estimation of the
distance between two loci.
Double-crossovers cause
an under-estimation of the
distance between two loci.
#𝑅𝑒𝑐𝑜𝑚𝑏
Rec Freq =
#𝑅𝑒𝑐𝑜𝑚𝑏+#𝑃𝑎𝑟𝑒𝑛𝑡
In a genetic mapping experiment, double
crossovers between two loci can affect the
calculated genetic distance. How do double
crossovers impact the observed genetic distance
between these loci?
A. They increase the observed genetic distance.
B. They decrease the observed genetic distance.
C. They have no effect on the observed genetic
distance.
D. They cause the observed genetic distance to be equal
to the physical distance.
A simplification we’ve
made
• Assumed that crossovers are equally likely to
occur all along the chromosome
• Reality: recombination hotspots and cold spots
PM
GM
Recombination frequency can be
affected by biological factors
“Hot spots” and “cold
spots”
• Sex
• Temperature
