Introduction

to
Gene Linkage and Recombination

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 Three genes on the X chromosome

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 Linkage, recombination, and mapping of
genes on chromosomes
Genes linked together
on the same
chromosome

Linked genes may

become separated by

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 Detecting linkage by recombination
Syntenic genes – genes located on the same chromosome
Two X-linked genes in Drosophila with recessive alleles
• w+ (red eyes) and w (white eyes)
• y+ (brown body) and y (yellow body)

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 Cross for detecting linkage

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 Detecting linkage

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 Detecting linkage
Compare allele
configurations in F2 to P
generation
Deviation from

segregation in F2
indicates the genes are

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 Parental Cross: AaBb X aabb
Among the progeny what percentage of each genotype would
you expect based on independent assortment?

Possible Genotype # Progeny

AaBb

Aabb

aaBb

Aabb
Chromosome A B

Cross: AB/ab X ab/ab

Among the progeny what percentage of each genotype would
you expect in this linked case without crossing over?

Possible Genotype % Progeny

AaBb

Aabb

aaBb

aabb
Chromosome A B

Cross: Ab/aB X ab/ab

Among the progeny what percentage of each genotype would
you expect in this linked case without crossing over?

Possible Genotype % Progeny

AaBb

Aabb

aaBb

aabb
 Designation of “parental” and
“recombinant” relate to past history

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 When genes are linked, the expected
9:3:3:1 ratio of genotypes is altered

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 Testing autosomal genes linkage is more
accurate and easier with a testcross

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 Recombination
and
Recombination frequencies

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 Evidence that recombination results from reciprocal
exchanges between homologous chromosomes

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 Why is there recombination?
• Recombination increases genetic diversity in a
species, but there is conflicting evidence for
this improving evolutionary outcomes (fitness)
• Main role maybe to prevent nondisjunction
events

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 Recombination in Meiosis I

a: © Dr. Paula Cohen & Dr. Miguel Angel Brieño-Enríquez, The Cohen Lab, Center for
Reproductive Genomics, Cornell University, Ithaca, NY; b: © Dr. Paula Cohen & Dr. Kim
Holloway, The Cohen Lab, Center for Reproductive Genomics, Cornell University, Ithaca, NY
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 Recombination helps ensure proper
chromosome segregation during meiosis I
If recombination did not occur nondisjunction during
meiosis I would happen frequently.
Synaptonemal complexes pair homologous
chromosomes, but they disappear during prophase I.
Chromosomes are still attached at chiasmata by
cohesin.
Molecular details of recombination in Chapter 6

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 Recombination frequency

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 Recombination frequencies are a
measure of distance between two genes
1 % RF = 1 map unit (m.u.) = 1 centiMorgan (cM)

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 Recombination frequencies are a measure of distance
between two genes

A white-eyed (w) yellow bodied (y) female is crossed to a red-eyed,

brown-bodied male. The F1 females (red-eyed, brown-bodied) are
crossed to males and the F2 male phenotypes are scored. How
many of a 1000 progeny would you expect to be red-eyed, yellow
bodied?

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 recombination frequency = 50% for
genes that independently assort

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 Recombination frequencies between two
genes never exceed 50%
Just as the RF of unlinked genes
is 50% due to independent
assortment.
The RF of linked genes cannot
exceed 50%
• Meioses without crossovers
produce only parental
chromosomes.
• Single and double crossovers
produce a 1 to 1 parental to
recombinant chromosome ratio
on average.

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 Gene Mapping Along a Chromosome

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 Mapping genes by comparisons
of two-point crosses

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 Mapping genes by comparisons
of two-point crosses

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 Limitations of two point crosses

Difficult to determine gene order if two genes

are close together
Actual distances between genes do not
always add up
Pairwise crosses are time and labor
consuming

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 Three point crosses provide faster and
more accurate mapping

Testcross of triply-heterozygous F1

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 Testcross of triply-heterozygous F1
Example 5.13 from book

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 results of a three-point cross

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 Looking at genes vg-b linkage

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 Looking at genes vg-pr linkage

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 Looking at genes pr-b linkage

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 Genetic map deduced from three-point
cross

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 Inferring the location of crossover event #1

Examine numbers of progeny

Compare configuration of alleles at two genes at a
time to parental configuration

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 Inferring the location of crossover events

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 Analyzing the results of a three-point
cross
Testcross progeny have four sets of reciprocal pairs of genotypes
• Most frequent pair has parental configuration of alleles
• Least frequent pair results from double crossovers
• Examination of double crossover class reveals which gene is in the
middle

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 Still a discrepancy in map distances

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 Accounting for double crossovers

Remember the results from the 2 point cross

Jump to long description

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 Double cross overs (DCO) account for the
difference in map distances

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 Correction for double crossovers

This calculation isn’t accurate because it fails

to account for double crossovers

Correct calculation that accounts for double crossovers

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 Interference: The number of double
crossovers may be less than expected
Chromosomal interference – occurrence of crossover
in one portion of a chromosome interferes with
crossover in an adjacent part of the chromosome
Not uniform between chromosomes or within a
chromosome
Compare observed and expected frequencies of
double crossovers (DCO)

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 Calculation of interference in the three-
point cross in
Expected probability of double crossovers is the
product of the single crossover frequencies in each
interval
• Probability of single crossover between vg and pr is
0.123 (12.3 m.u.)
• Probability of single crossover between pr and b is 0.064
(6.4 m.u.)
If interference 0, crossovers in adjacent regions
occur independently of each other
If interference 1, no double crossovers occur

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 Calculation of interference in the three-
point cross in Figure 5.13 #2
Expected probability of double crossovers

Observed proportion of double crossovers

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 Drosophila melanogaster has four
linkage groups

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 Drosophila melanogaster has four
linkage groups
When many genes per chromosome have been mapped, a
linkage group is synonymous with a chromosome

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 Genetic maps correlate with physical
reality
Order of genes revealed by
genetic mapping corresponds to
the actual order of genes along
the chromosome
Actual physical distance (amount
of DNA) does not always show
direct correspondence to genetic
distance
• Double, triple, and more
crossovers
• 50% limit on observable
recombination frequency
• Recombination hotspots

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Deviations from 1 to 1 to 1 to 1 ratios —
chance events or linkage?
 Chi square test and evidence of linkage

Chi square test measures “goodness of fit”

between observed and expected values
Null hypothesis – observed values are no different
from expected values
• In linkage studies, the null hypothesis is no linkage
• If genes are not linked, expect 1 to 1 to 1 to 1 ratio in F2
progeny
• Chi-square test can reject the null hypothesis, but it
cannot prove a hypothesis

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 Information used for the chi-square test

Use data from breeding experiment

• Total number of progeny
• How many classes of progeny

• Number of offspring observed in each class

Calculate number of offspring expected in
each class if there is no linkage (1 to 1 to 1 to
1 segregation)

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 Mitotic recombination
and
genetic mosaics

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 Mitotic recombination can produce
genetic mosaics
1.Rare occurrence
2.Can be observed in yeast and multicellular organisms

3.Have major repercussions to human health

C. Stern (1936), inferred existence of mitotic
recombination from observations of “twin spots” in
Drosophila
• Patches of somatic tissue that have different genotypes

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 Twin spots are a form of genetic mosaicism

Double heterozygous Drosophila females y sn+/y+ sn

• yellow (y) mutant – yellow body
• wildtype (y+) – brown body
• singed (sn) mutant – short and curled bristles
• wildtype (sn+) – long and straight bristles

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 Mitotic recombination results in twin
spots

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