BIOL2301 - Week 3 Lecture Slide (May 22 and 24)

Week 3 – Linkage &
Recombination
BIOL2301: Genetics
Teaching team: Sara Good
May 22nd, 2024
Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Midterm exam
Midterm exam will cover material from first class until
end linkage (today or Friday).
I anticipate the exam to take 70 minutes to complete. It
will take place during class time in person. Location
TBA.
Content:
•30 multiple-choice questions (0.5 points/question,
totaling 15 points)
•20 true/false questions (0.5 points/question, totaling
10 points)
•3 short answer questions (5 points/question, totaling
15 points)
•Total of 40 points – midterm is worth 20%
Agenda today
1. Linkage
2. Recombination
3. Eukaryotic Gene Mapping

Linkage
Linked Genes Do Not Assort
Independently
● The independent separation
of alleles results in
recombination, the sorting
of alleles into new
combinations.
● Recombination is the
sorting of alleles into new
combinations.

Linked Genes Do Not Assort
Independently
● In 1903, Walter Sutton
proposed the chromosome
theory of heredity, which
holds that genes are found
on chromosomes.
● Genes located close
together on the same
chromosome are called
linked genes and belong to
the same linkage group.

Linked Genes Segregate Together
While Crossing Over Produces
Recombination Between Them

Notation for Crosses with Linkage
Consider a cross between an individual homozygous for
dominant alleles at two linked loci and another individual
homozygous for recessive alleles at those loci (AA BB ×
aa bb).
For linked genes, it’s necessary to write out the specific

alleles as they are arranged on each of the homologous
chromosomes:
Allele A Allele b
Allele B Allele a

In this notation, each horizontal line represents one of the
two homologous chromosomes. Because they inherit one
chromosome from each parent, the F progeny will have
the following genotype:
Allele A Allele B
Allele a Allele b

Here, the importance of designating the alleles on each
chromosome is clear. One chromosome has the two
dominant alleles A and B, whereas the homologous
chromosome has the two recessive alleles a and b.
The notation can be simplified by drawing only a single

line, and that genes located on the same side of the line
lie on the same chromosome:
Allele A Allele B
Allele a Allele b
Remember that the two alleles at a locus are always
located on different homologous chromosomes and
therefore must lie on opposite sides of the line.
Consequently, we would never write the genotypes as
Allele A Allele a
Allele B Allele b
because it would imply that alleles A and b are allelic (at

the same locus).

Complete Linkage Compared with
Independent Assortment
A geneticist might produce this heterozygous plant by
crossing a variety of tomato that is homozygous for
normal leaves and tall height with a variety that is
homozygous for mottled leaves and dwarf height:
Normal leaves Mottled leaves
P generation
Allele for tall
Allele for dwarf
F1 generation

The geneticist would then use this F heterozygote in a
testcross, crossing it with a plant that is homozygous for
mottled leaves and dwarf height:
Mottled leaves
Normal leaves
Allele for tall Allele for dwarf


● Gametes that contain only original
combinations of alleles that were
present in the parents are
nonrecombinant gametes, or
parental gametes.
● When its gametes pair with the two
types of gametes generated by the
heterozygous parent, two types of
progeny result:
○ half have normal leaves and are
tall, and
○ half have mottled leaves and are
dwarf.
● These progeny display the
original combinations of traits
present in the P generation and
are nonrecombinant progeny,
or parental progeny.
● Gametes with new combinations
of alleles are called
recombinant gametes.
● The progeny with new
combinations of traits formed
from recombinant gametes are
termed recombinant progeny.

Crossing Over Between Linked
Genes
Theory

Crossing Over Between Linked
Genes
Application
Suppose a geneticist carried out this testcross:
Allele for tall
Normal leaves
Mottled leaves
Allele for dwarf
When crossing over takes place between the genes for

leaf type and height, two of the four gametes produced
are recombinants. When there is no crossing over, all
four resulting gametes are non recombinants.

Recombination
Calculating Recombination
Frequency
The percentage of recombinant progeny produced in a
cross is called the recombination frequency (or rate of
recombination), which is calculated as follows:

Coupling and Repulsion
Green thorax Brown puparium
Purple thorax Black puparium
This arrangement, in which wild-type alleles are found

on one chromosome and mutant alleles are found on
the other chromosome, is referred to as the coupling,
or cis configuration.

Green thorax Black puparium
Purple thorax Brown puparium
This arrangement, in which each chromosome contains

one wild-type and one mutant allele, is called the
repulsion, or trans configuration.


Predicting the Outcomes of Crosses
with Linked Genes
● The recombination frequency refers to how often the
alleles in the gametes appear in new combinations,
allowing us to predict the proportions of offspring
phenotypes that will result from a specific cross that
entails linked genes.
● Suppose that we cross a plant that is homozygous for
warty and dull fruit with a plant that is homozygous for
smooth and glossy fruit, and then carry out a testcross
using the F1:
Dull fruit
Warty fruit
Glossy fruit
Smooth fruit
with Linked Genes
Dull fruit
Warty fruit
Glossy fruit
Smooth fruit
● Four types of gametes will be produced by the

heterozygous parent:
○ two types of nonrecombinant gametes, and
○ two types of recombinant gametes

with Linked Genes

with Linked Genes

Testing for Independent Assortment
● Question to ask:
○ Is the inheritance of alleles at one locus independent of
the inheritance of alleles at a second locus?
● To test for independent assortment,

1. calculate the expected probability of each progeny
type, and then
2. use the chi-square goodness-of-fit test.
● A faster method is to test for independence in

genotypes with a chi-square test of independence.

The Chi-Square Test of
Independence
The chi-square test of independence evaluates whether
the segregation of alleles at one locus is independent of the
segregation of alleles at another locus without making any
assumption about the probability of single-locus genotypes.
Sum
Chi-square
obtained

Independence
Determining whether the proportions of progeny with
genotypes at the two loci are independent:
Step 1 Construct a table of the observed numbers of

progeny, somewhat like a Punnett square,
except that we put the genotypes that result from
the segregation of alleles at one locus along the
top and the genotypes that result from
the segregation of alleles at the other locus along
the side

Independence
Step 1

Independence
Step 2 Compute the total for each row, the total for
each column, and the grand total (the sum of all
row totals or the sum of all column totals, which
should be the same).
Step 3 Compute the expected numbers for each

combination of genotypes.

Independence
Step 3 In addition, we use this formula:
Step 4 We now calculate a chi-square value:

Independence
Step 5 To determine the probability associated with the

chi-square value, we need the degrees of
freedom.

Expected
43.46 52.53
47.53 57.46
Chi-square = (63-43.5)^2/43.46 + (33-52.5)^2/52.5 + (47.5-28)^2/47.4) + (77-57.5)^2/57.5
= 30.66
d.f. = (2-1)*(2-1) = 1
Eukaryotic Gene Mapping
Gene Mapping with Recombination
Frequencies
● Chromosome maps calculated by using the genetic
phenomenon of recombination are called genetic
maps.
● Chromosome maps calculated by using physical
distances along the chromosome (often expressed as
numbers of base pairs) are called physical maps.
● Distances on genetic maps are measured in map
units (abbreviated m.u.)
● Map units are also called centiMorgans (cM), in
honor of Thomas Hunt Morgan.

Frequencies
There are two important points on constructing
chromosome maps from recombination frequencies:
1. If genes exhibit 50% recombination, the most that can
be said about them is that they belong to different
linkage groups, either on different chromosomes or far
apart on the same chromosome.
2. A testcross for two genes that are far apart on the
same chromosome tends to underestimate the true
physical distance between them because the cross
does not reveal double crossovers that might take
place between the two genes.

Frequencies

Constructing a Genetic Map with
Two-Point Testcross
A testcross between two genes is called a two-point
testcross, or simply a two-point cross.
Suppose that we carried out a series of two-point crosses
for four genes, a, b, c, and d, and obtained the following
recombination frequencies:

Two-Point Testcross
Genes a and b may either be on different chromosomes
or be very far apart on the same chromosome; we will
place them in different linkage groups with the
understanding that they may or may not be on the same
chromosome:
Gene a
Gene b

Two-Point Testcross
The recombination frequency between a and c is 50%,
indicating that they, too, are in different linkage groups.
The recombination frequency between b and c is 20%, so
these genes are linked and separated by 20 map units:
Gene a
Gene b

Two-Point Testcross
A discrepancy arises because double crossovers
between the two outer genes go undetected, causing an
underestimation of the true map distance. The genetic
map of these genes is now complete:
Gene a
Gene c
Gene b
Gene d
map units

A Three-Point Testcross Can Be
Used to Map Three Linked Genes
Three-point testcross, or three-point cross
● With a three-point cross, the order of the three genes
can be established in a single set of progeny, and
some double crossovers can usually be detected,
providing more accurate map distances.
● When crossing over takes place among three
hypothetical linked genes, they are in the coupling
configuration:
○ all the dominant alleles are on one chromosome, and
○ all the recessive alleles are on the other chromosome

A Three-Point Testcross Can Be
Used to Map Three Linked Genes

Constructing a Genetic Map with a
Three-Point Testcross
● In the three-point testcross, we cross the F
heterozygotes with flies that are homozygous for all
three recessive mutations.
● In many organisms, it makes no difference whether
the heterozygous parent in the testcross is male or
female (provided that the genes are autosomal), but in
Drosophila, no crossing over takes place in males.
● In some three-point crosses, one or more of the
phenotypes may be missing if the number of progeny
is limited.

Determining the Gene Order
Steps in determining gene order in a three-point cross:
1. Identify the nonrecombinant progeny (two most
numerous phenotypes).
2. Identify the double-crossover progeny (two least
3. Compare the phenotypes of double crossover
progeny with the phenotypes of nonrecombinant
progeny. They should be alike in two characteristics
and differ in one.
4. The characteristic that differs between the double
crossover and the nonrecombinant progeny is
encoded by the middle gene.

Three-Point Testcrosses
To examine gene mapping with a
three-point testcross, let’s consider
three recessive mutations in the fruit
fly Drosophila melanogaster.
In this species:
● scarlet eyes (st) are recessive to
wild-type red eyes (st+)
● ebony body color (e) is recessive
to wild-type gray body color (e+),
and
● spineless (ss)—that is, the
presence of small bristles—is
recessive to wild-type normal
bristles (ss+).
Drosophila melanogaster (fruit fly)
wild-type normal bristles
spineless
wild-type red eyes
ebony body color
wild-type gray body color scarlet eyes




Determining the Gene Order
Steps in determining gene order in a three-point cross:
1. Identify the nonrecombinant progeny (two most
2. Identify the double-crossover progeny (two least
3. Compare the phenotypes of double crossover
progeny with the phenotypes of nonrecombinant
progeny. They should be alike in two characteristics
and differ in one.
4. The characteristic that differs between the double
crossover and the nonrecombinant progeny is
encoded by the middle gene.

Effects of Multiple Crossovers
● As the distance between genes increases, more
multiple crossovers are likely, and the discrepancy
between genetic distances (based on recombination
rates) and physical distances increases.
● To correct for this discrepancy, geneticists have
developed mathematical mapping functions, which
relate recombination frequencies to actual physical
distances between genes.

Crossover Interference
● The degree to which one crossover interferes with
additional crossovers in the same region is termed the
interference.
● To calculate the interference, we first determine the
coefficient of coincidence, which is the ratio of observed
double crossovers to expected double crossovers:
● Sometimes a crossover increases the probability of another

crossover taking place nearby, and we see more double-
crossover progeny than expected. In this case, the
coefficient of coincidence is greater than 1 and the
interference is negative.
Gene Mapping and it’s
applications
Frequencies
● Chromosome maps
calculated by using the
genetic phenomenon of
recombination are called
genetic maps.
● Chromosome maps
calculated by using physical
distances along the
chromosome (often
expressed as numbers of
base pairs) are called
physical maps.

Frequencies
● Distances on genetic maps
are measured in map
units (abbreviated m.u.)
● Map units are also called
centiMorgans (cM), in
honor of Thomas Hunt
Morgan.

Application in Meiosis
A single nucleotide strand of one chromosome pairs with the
complementary strand of another, forming heteroduplex
DNA, which is DNA consisting of nucleotide strands from
different sources.

In meiosis, homologous recombination (crossing over)
could theoretically take place before, during, or after DNA
synthesis. Cytological, biochemical, and genetic evidence
indicates that it takes place in prophase I of meiosis,
whereas DNA replication takes place earlier, in interphase.
Thus, crossing over must entail the breaking and rejoining
of chromatids when homologous chromosomes are at the
four-strand stage


Effects of Multiple Crossovers

Practical Applications
Linkage Mapping in Plants
● Plant breeders often use
linkage mapping to identify and
map genes associated with
agriculturally important traits,
such as disease resistance or
yield.
● By analyzing the segregation
patterns of traits in the progeny
and correlating them with
molecular markers, breeders
can map the genomic regions
associated with these traits and
facilitate marker-assisted
selection in breeding programs.
Linkage Mapping in Plants
In rice breeding, researchers might perform test crosses
between different rice varieties to identify genes linked to
traits like drought tolerance.

Medical Genetics: Mapping Disease Genes

Medical Genetics: Mapping Disease
Genes
● In medical genetics, researchers
use gene mapping techniques to
identify genetic variants linked to
inherited diseases.
● By analyzing recombination events
in affected individuals and
correlating them with disease
phenotype, researchers can map
the chromosomal region harboring
the disease gene.
● Combined with pedigree data
Medical Genetics: Mapping
Disease Genes
In familial cases of breast
cancer, researchers may
perform test crosses within
affected families to identify the
inheritance pattern of the
disease-associated alleles.
Again combined with pedigree

data

Genome-wide association studies (GWAS)
● It is now possible to quickly and inexpensively
genotype people for hundreds of thousands or millions
of SNPs.
● Single-nucleotide polymorphisms (SNPs) are
positions in the genome where individuals vary in a
single nucleotide base.
● This genotyping has provided the genetic markers
needed for conducting genome-wide association
studies in which SNP haplotypes of people who have a
particular disease, such as bipolar disorder, are
compared with the haplotypes of healthy people.

Genome-wide association studies
(GWAS)
An alternative approach to mapping
genes is to conduct genome-wide
association studies, looking for
nonrandom associations between the
presence of a trait and alleles at many
different loci scattered across the
genome.

Genome-wide association studies (GWAS)

Population Genetics and Evolutionary Studies
● Population geneticists use recombination and gene
mapping to study patterns of genetic variation within
and between populations.
● By analyzing recombination rates and patterns of
linkage disequilibrium, researchers can infer aspects of
population history, such as demographic events or
selection pressures.

Population Genetics and Evolutionary Studies

References
● Duchenne Muscular Dystrophy (DMD) - Diseases.
(n.d.). Muscular Dystrophy Association. Retrieved May
23, 2024, from https://www.mda.org/disease/duchenne-
muscular-dystrophy
● Chen, Z., Wu, J., Deng, X.W. et al. Establishment and

Advances of Third-Generation Hybrid Rice Technology:
A Review. Rice 16, 56 (2023).
https://doi.org/10.1186/s12284-023-00670-z
● Five ways mapping the human genome has changed

cancer care. (2020, April 24). Cancer Treatment
Centers of America. Retrieved May 23, 2024, from
https://www.cancercenter.com/community/blog/2020/04/
dna-day
Midterm
● May 6 – Overview, chromosomes, eukaryote-prokaryote
● May 8th Sex determination systems, aneuploidies, dosage compensation
● May 10th – Extensions Mendel, Penetrance, expressivity, epistasis, co-
dominance etc.
● May 13th, Using pedigrees to infer mode of inheritance, twin studies,
genetic testing
● May 15th – DNA structure, experiments to show that DNA was the
hereditary material
● May 17th Over genomes – DNA replication
● May 22nd DNA replication continued + linkage
● May 24th – Linkage – three point crosses
See you in room 1RC018
Monday at 10:30 for the midterm

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Week 3 – Linkage &

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

For linked genes, it’s necessary to write out the specific

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

The notation can be simplified by drawing only a single

because it would imply that alleles A and b are allelic (at

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Allele for tall Allele for dwarf

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

When crossing over takes place between the genes for

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Green thorax Brown puparium

Purple thorax Black puparium

This arrangement, in which wild-type alleles are found

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Green thorax Black puparium

Purple thorax Brown puparium

This arrangement, in which each chromosome contains

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

● Four types of gametes will be produced by the

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

● To test for independent assortment,

● A faster method is to test for independence in

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Step 1 Construct a table of the observed numbers of

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Step 3 Compute the expected numbers for each

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Step 3 In addition, we use this formula:

Step 4 We now calculate a chi-square value:

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Step 5 To determine the probability associated with the

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Chi-square = (63-43.5)^2/43.46 + (33-52.5)^2/52.5 + (47.5-28)^2/47.4) + (77-57.5)^2/57.5

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved

Copyright © 2024 Summations Knowledge Inc. All Rights Reserved