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BIO1A03 Test 3 Reminder

Test 3 will take place in-person, on Wednesday November 27, 2023
from 7:00-8:30pm

• Test 3 will evaluate all of Themes 4 and 5 (including Reviews and Applied Lectures, along
with all Supplementary Information for these Themes and Modules)
• Additional details on Avenue

Test format
• 90 minutes in duration
• 30 multiple choice, and 10 marks worth of short answer questions
• Bring an HB pencil, eraser, blue or black ink pen, and your McMaster student card
• A practice test is available on Avenue.
• Dr. da Silva’s office hours for test 3 will be posted later this week
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BIOLOGY 1A03
Cellular and Molecular Biology

Theme 5
Module 3 & 4 Review
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Module 3

Linkage and linkage maps

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Genes are in a linear sequence on a chromosome
X Chromosome size: 155,000,000
base pairs, ~1,100 genes
Unreplicated
chromosome

(Mitosis)
Replicated
Remember that a chromosome
is a DNA molecule wound
around proteins.
• They are only ever
condensed like this during
mitosis or meiosis
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Two copies of the X-chromosome (females)
Homologous pair of X-chromosomes in a female: We inherit different versions
X chromosome from her mother (or alleles) of the same genes
D CB

d cb
X chromosome from her father

Each chromosome carries the same genes, but perhaps different

alleles (versions of a gene). Let’s represent possible alleles:
Genes: Alleles
Dystrophin D and d
HPRT1 H and h Capital letter are dominant alleles
Colour-blindness CB and cb Small letters are recessive alleles
Haemophilia HM and hm
Sometimes we can track the different alleles that are6
inherited through a family tree (or pedigree)
Prince Albert
X-linked inheritance of
hemophilia: a case study
Queen Victoria
Inherited the recessive
version (allele) of the
hemophilia gene from one
of her parents

IMPORTANT NOTE:
Sometimes carriers are
How to interpret a pedigree: represented by a dot in
• circles represent females the shape (you might see
• squares represent males this in another kind of
• a line between a male pedigree we will see later
and a female represents a on) , and affected
mating couple individuals will just have
• 2 lines between a male their shape filled in, or
and female means that fully shaded
the male and female
mating couple are related
 How do we pass on our alleles? 7

Mapping out the segregation of chromosomes

Prince Albert Queen Victoria
Her genotype is HM/hm

hm HM

His genotype is HM/ Y We can calculate mathematical likelihoods:

hm HM
HM HM ….these likelihoods
HM
are seen less in human
HM pedigrees, but can be
seen in model
organisms with lots of
hm offspring
HM (eg. Drosophila)
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Some good practice questions!
Prince Albert Queen Victoria

Questions: X-linked inheritance of

1. What sex genotype is hemophilia in the
Edward VII? modern British monarchy
2. Was Diana affected? was genetically wiped
Why/why not? out with the marriage of
3. Is there a chance that Philip Queen Elizabeth II and
has passed on the affected Phillip.
allele? Why/why not?
Why?
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Segregation of chromosomes = segregation of alleles
What if we follow
the alleles of 2
genes on the X d D Mother’s genotype:
chromosome? D CB / d cb
cb CB

What is the likelihood

that one of the
D daughters is a carrier?

CB

Father’s
genotype:
D CB / Y
 Is inheritance that simple? What about 10

recombination that takes place during meiosis?

Tetrad
Mendel did not observe Prophase I
recombinant versions of genotypes The likelihood of crossing
in his dihybrid crosses (eg. Seed over, increases with Sites of
shape and seed colour) distance between genes crossing
• He was lucky! Because he was over
looking at genes on completely
Metaphase I Spindle
different chromosomes

• Remember, recombination only Metaphase II

occurs between homologous

chromosomes during prophase I Gametes

Recombinant chromosomes
What recombination between non-sister chromatids
11

looks like during prophase I

Recombination occurs
anytime you are making
germ (egg or sperm) cells End result: the
haploid germ cells,
have the potential to
have one of the 2
non-recombined X
chromosomes (the
paternal or maternal
chromosomes), or
one of the 2
recombinant
chromosomes that
are produced as a
result of crossing
over
Singular: chiasma
Plural: chiasmata
 Crossing over takes place between double-stranded12
non-sister chromatids
During gamete (Egg and sperm cell) formation, crossing over happens in prophase I:

Condensed
chromosomes are
DOUBLE STRANDED!

Outer chromatids that are not crossed over stay

in their paternal or maternal form. The ones that
crossed over are called recombinant or
recombined chromosomes.
 Recombination frequency depends on the 13

distance between genes

Recombination occurs between chromatids on opposite,
paired homologues = non-sister chromatids

Scenario A:
2 genes are far apart

Scenario B:
2 genes are
very close together
• Alleles of these
genes are more
likely to be
inherited together
in parental form
(linked)
 What are the possible egg genotypes if: 14

no recombination?
D CB These are
D CB replicated X
chromosomes
d cb at start of
d cb Meiosis I

Mother’s genotype (remember, she has two X-chromosomes!):

D CB / d cb
If there is no recombination between the chromosomes that carry genes D and
CB during meiosis I that occurs during egg formation:

Genotype is D CB because alleles are always together = linked

Or d cb because alleles are always together = linked
 What are the possible egg genotypes if: 15

always have recombination?

D CB
D CB

d cb
d cb
If there is always recombination between the chromosomes that carry genes D and
CB during meiosis I that occurs during egg formation:

D and CB alleles are separated = unlinked

d and cb alleles are separated = unlinked
Still produce eggs with But also have eggs with
Maternal/parental genotype: recombinant genotype:
D CB or d cb D cb or d CB
We can often see recombination take place when we
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observe family pedigrees

Recombination of chromatids results in genetic recombination of alleles.

Colour-blindness Parental carrier genotype:

Hemophilia
CB HM
Look at allele
transmission through
cb hm
these 4 generations
2 recombinant genotypes:
Why do we see the
genotypes we see in CB hm / Y
Generation IV?
cb HM / Y

Be comfortable with being able to identify

inherited genotypes and possible recombinant
genotypes that emerge in a family pedigree…
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This principle allows researchers to create maps
The probability of a crossover occurring within a region will increase
with the increasing size of the region

or
The distance between two genes is proportional to the
frequency of genetic recombination events

So…where may you more likely see a crossover event in the

genes listed below?
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Linkage
Linkage: physical proximity along a chromosome that makes recombination less likely

Linked genes sit close together on a chromosome, so that two alleles on one
chromosome more likely to be inherited together

Association: increased probability of seeing alleles of two genes or two

markers together due to linkage
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Allele genotype of linked genes
Let’s look at an example using 3 gene loci on a
pair of X chromosomes:
• Genes B and C are closer together
• Gene A is far from both genes B and C

Assuming linkage between genes B and C, the

expected genotypes of genes B and C in the
A A a resulting eggs by the end of meiosis II would be:
a

B c and b C : there is association, linkage

B b
B b b this would be parental or maternal genotype
C
because no recombination occurred
c c C C
*Note: locus means location
loci plural way of saying location
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What recombination does:

Assuming no linkage between genes A and B,

the expected genotypes for genes A and B in the
resulting eggs by the end of meiosis II would be:
A A a a

B b B b
c C c C
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What recombination does:
Remember! The outer non-sister chromatids DO NOT cross over!!!

Assuming no linkage between genes A and B, the

expected genotypes for genes A and B in the resulting
eggs by the end of meiosis II would be:
A A a a
A B , A b , a B , a b : no linkage,
B b B
no association
b
c C c C Which are parental and which are recombinant?
 Frequency of recombination 22

helps us create gene maps

Remember that you are not looking at one meiotic
division, but across many .
Observed genotypes:
B c and b C : 90% of the time (parental genotype)
B C and b c : 10% of the time
(recombinant genotype)
A B and a b : 55% of the time (parental genotype)
A A a a A b and a B : 45% of the time
Map: (recombinant genotype)
B b B b
A

C
ne

ne

ne
c C c C
Ge

Ge

Ge
B and C show lower frequency of recombination, closer together
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Recombination frequency can tell us “map” distance
Linkage maps were first
created in fruit flies: Mother Father
A b/a B x A B/Y

Male offspring:
A b/Y Parental 45%
10% of offspring are
aB/Y Parental 45%
recombinants= 10 map units
AB/Y Recombinant 5%
Map distance between gene
A and B is 10 map units
ab/Y Recombinant 5%
(these are arbitrary units)
We now know that 1 map
Gene A Gene B unit = ~ 1 million base pairs
Map:
10 map units
Alfred Sturtevant and Thomas Hunt Morgan
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How far apart are genes A, B and C?
Remember that you are not looking at one meiotic
division, but across many .
Observed genotypes:
B c and b C : 90% of the time (parental genotype)
B C and b c : 10% of the time
(recombinant genotype)
A B and a b : 55% of the time (parental genotype)
A A a a A b and a B : 45% of the time
Map: (recombinant genotype)
B b B b
A

C
ne

ne

ne
c C c C
Ge

Ge

Ge
45 map units 10 map units

B and C show lower frequency of recombination, closer together

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Linkage: Not just for genes
Map: molecular markers
(eg. SNPs that are associated or not with a gene)

May see linkage between Gene A and Marker 4

May see linkage between Gene A and Marker 3

But see no linkage between Gene A and Marker 8

 Mapping techniques can be 26

applied to all chromosomes

We used the X-chromosome
as a model, but these
techniques can be used for all
chromosomes.

To map genes today:

-we can sequence the DNA...
This matches well with
relative distances you get
using recombination
frequencies for linkage
mapping
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Tomorrow’s applied lecture…

Theme 5 Applied Lecture #2

“Innovative Science Using Cell and Molecular Biology”