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Table of Contents

Chapter 1 - Introduction to Genetics

1.1 What is Genetics?

1.2 History of Genetics

1.3 Branches of Genetics

Chapter 2 - DNA, RNA and Chromosome

2.1 The DNA

2.2 The RNA

2.3 The Chromosome

2.4 Types of Chromosome

Chapter 3 – Reproductive System

3.1 The Reproductive System

3.2 Human Fertilization

Chapter 4 – Cell Cycle

4.1 Mitosis

4.2 Stages of Mitosis

4.3 Meiosis

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Chapter 5 – Fundamentals of Genetics
5.1 Mendel’s Experiment
5.2 Punnet Square
5.3 Pedigree

Chapter 6 – Matter of Sex

6.1 Sexual Development

6.2 Traits Inherited on the Sex Chromosomes

6.3 Sex-Limited and Sex-Influenced Traits

6.4 X Inactivation

6.5 Genomic Imprinting

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 Chapter 1—Introduction to Genetics

1.1 What is Genetics?

Genetics is a study of genes, genetic variation, and heredity in

living organisms. It is a field of biology that studies how traits
are passed from parents to their offspring. ‘’Genetikos’’ means
genitive derives from nemesis means origin.
1.2 BRANCHES OF GENETICS
1. Transmission genetics
 Classical or Mendelian genetics
2. Molecular genetics
-chromosomes DNA, regulation of gene expression
-recombinant DNA, Biotechnology, bioinformatics,
genomics, proteomics.
3. Population, evolutionary genetics
 Allelic frequencies in populations
 Effects of migration
 Study relatedness taxa via DNA and protein analysis.
4. Quantitative genetics
-effects of many genes

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 Chapter 2 — DNA, RNA and
Chromosome
2.1 The DNA
What is DNA?
DNA, or deoxyribonucleic acid, is the hereditary material in
humans and almost all other organisms. Nearly every cell in a
person’s body has the same DNA. Most DNA is located in the
cell nucleus (where it is called nuclear DNA), but a small
amount of DNA can also be found in the mitochondria (where it
is that convert the energy from food into a form that cells can
use.
The information in DNA is stored as a code made up of four
chemical bases: adenine (A), guanine (G), cytosine (C), and
thymine (T). Human DNA consists of about 3 billion bases, and
more than 99 percent of those bases are the same in all people.
The order, or sequence, of these bases determines the
information available for building and maintaining an organism,
similar to the way in which letters of the alphabet appear in a
certain order to form words and sentences.

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2.2 The RNA

What is RNA?
Ribonucleic acid, or RNA is one of the three major biological
macromolecules that are essential for all known forms of life
(along with DNA and proteins). A central tenet of molecular
biology states that the flow of genetic information in a cell is from
DNA through RNA to proteins: “DNA makes RNA makes
protein”. Proteins are the workhorses of the cell; they play leading
roles in the cell as enzymes, as structural components, and in cell
signaling, to name just a few. DNA(deoxyribonucleic acid) is
considered the “blueprint” of the cell; it carries all of the genetic
information required for the cell to grow, to take in nutrients, and
to propagate. RNA–in this role–is the “DNA photocopy” of the cell.
When the cell needs to produce a certain protein, it activates the
protein’s gene–the portion of DNA that codes for that protein–and
produces multiple copies of that piece of DNA in the form of
messenger RNA, or mRNA. The multiple copies of mRNA are
then used to translate the genetic code into protein through the
action of the cell’s protein manufacturing machinery,
the ribosomes. Thus, RNA expands the quantity of a given protein
that can be made at one time from one given gene, and it
provides an important control point for regulating when and how
much protein gets made.

The discovery of DNA

How was DNA first discovered and who discovered it? Read on to
find out...

It is a common misconception that James Watson and Francis

Crick discovered DNA? in the 1950s. In reality, DNA was
discovered decades before. It was by following the work of the

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pioneers before them that James and Francis were able to come
to their ground-breaking conclusion about the structure of DNA in
1953.

The story of the discovery of DNA begins in the 1800s…

The molecule of life

The molecule now known as DNA was first identified in the 1860s
by a Swiss chemist called Johann Friedrich Miescher. Johann set
out to research the key components of white blood cells?, part of
our body’s immune system. The main source of these cells? was
pus-coated bandages collected from a nearby medical clinic.

“Johann called this mysterious substance ‘nuclein’. Unbeknown to

him, Johann had discovered the molecular basis of all life – DNA.

Swiss chemist, Friedrich Miescher

Johann was convinced of the
importance of nucleic and came very
close to uncovering its elusive role,
despite the simple tools and methods
available to him. However, he lacked
the skills to communicate and promote
what he had found to the wider
scientific community. Ever the perfectionist, he hesitated for long
periods of time between experiments before he published his
results in 1874. Before then he primarily discussed his findings in
private letters to his friends. As a result, it was many decades
before Johann Friedrich Miescher’s discovery was fully
appreciated by the scientific community.

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 German biochemist, Albrecht
Kossel.

In 1881 Albrecht identified nucleic

as a nucleic acid and provided its
present chemical name,
deoxyribonucleic acid (DNA). He
also isolated the
five nucleotide? bases that are the
building blocks of DNA
and RNA?: adenine (A), cytosine
(C), guanine (G), thymine (T) and
uracil (U).This work was rewarded in 1910 when he received the
Nobel Prize in Physiology or Medicine.

2.3 The chromosome

Chromosome is discover by Walther Flemming. In the middle of

the nineteenth century, Walther Flemming, an anatomist from
Germany, discovered a fibrous structure within the nucleus of
cells. He named this structure ‘chromatin’, but what he had
actually discovered is what we now know as chromosomes?. By
observing this chromatin, Walther correctly worked out how
chromosomes separate during cell division, also known
as mitosis?.

Chromosomes are long strands of DNA, or deoxyribonucleic

acid. DNA -- the material that holds genes -- is considered the
building block of the human body. The term "chromosome"
comes from the Greek word for color, which is “chroma,” and the
Greek word for body, which is “soma.” Chromosomes are
threadlike structures that scientists stain using colorful dyes
when performing research.

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2.4 Types of Chromosome

Four Major Types of Chromosomes

Metacentric Chromosomes
Metacentric chromosomes have the centromere in the center,
such that both sections are of equal length. Human
chromosome 1 and 3 are metacentric.

Submetacentric Chromosomes
Submetacentric chromosomes have the centromere slightly
offset from the center leading to a slight asymmetry in the
length of the two sections. Human chromosomes 4 through 12
are submetacentric.

Acrocentric Chromosomes
Acrocentric chromosomes have a centromere which is
severely offset from the center leading to one very long and one
very short section. Human chromosomes 13,15, 21, and 22 are
acrocentric.

Telocentric Chromosomes
Telocentric chromosomes have the centromere at the very end
of the chromosome. Humans do not possess telocentric
chromosomes but they are found in other species such as mice

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CHAPTER 3 — Reproductive system
The human reproductive system
This page has been written to help with the basic understanding
of the human reproductive system to help clarify issues that may
cause infertility and the potential procedures the Fertility Centre
may utilise to aid conception.
The female reproductive system
The reproductive system, fertilization and menstrual cycle.
The diagram below shows the major components of the female
reproductive system. The vagina which leads to the cervix (neck
of the womb), the uterus (womb) and the fallopian tubes (the site
of fertilization) which lead to the ovaries.

When a woman ovulates (releases an egg) the egg is picked up

by the end of the fallopian tube (the fimbria) and sits inside the
tube awaiting fertilization.

When a man and a woman have intercourse sperm are

deposited at the neck of the womb where they swim into the
mucus. The sperm then swim up into the womb and eventually
into the fallopian tubes where they meet the egg. When one

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sperm binds with the egg, fertilization takes place. The genetic
information (DNA) which the sperm and egg both carry join
together and the fertilized egg (now known as a zygote) begins to
divide to form an embryo which is the beginning of life.

The embryo then travels down the fallopian tube for 3-4 days
and into the womb (uterus). When it reaches the womb it attaches
to the lining (endometrium). This is called implantation. The
embryo receives all its nutrients (food) from the mother through
the lining of the womb.

The menstrual cycle

If fertilization does not occur, the corpus luteum (what is left of
the follicle) degenerates (gets smaller) and stops producing
progesterone. This means that the lining of the womb is no longer
being stimulated and begins to come away from the wall of the
womb. This causes some bleeding and the result is the menstrual
period. This happens about every 28 days in most women but can
vary considerably; it is commonly referred to as ‘coming on’ or
‘having a period’. The usual range of normal menstrual cycles is
21 to 35 days.
The first day of a period is usually referred to during treatment as
day one of the cycle. An average woman ovulates about 14 days
after the start of her last period. It is important that women realize
they are only able to conceive (get pregnant) for two or three days
around the time of ovulation (the release of the egg). Except when
certain drug combinations are used for Intra Uterine Insemination
(IUI), Donor Intra-Uterine Insemination (DIUI), In-Vitro Fertilisation
(IVF) & Intra-Cytoplasm in Sperm Injection Treatment (ICSI)

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The male reproductive cycle
Men start to produce sperm at
puberty and most continue to
do
so for their entire life. Sperm
are produced in specialized
areas of the testicle known as
‘seminiferous tubules’, taking
about 8 weeks to reach
maturity. When they are
mature they are released and
transported to the ‘epididymis’
where they are further matured prior to being ejaculated during
intercourse.
At the time of ejaculation, the sperm are transported through the
‘vas deferens’ and fluid is added to the sperm from various
glands, including the prostate and seminal vesicles during their
journey. This mixture of secretions is known as semen.
The human sperm’s only function is to transport the man’s
genetic information (DNA) through the female reproductive tract to
the egg. Once the sperm reaches the egg in the fallopian tube (of
the 150 million or so that are ejaculated only a few dozen
complete the journey) it penetrates the egg by releasing enzymes
and fertilizes the egg, creating a zygote.

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Human Fertilization:
Definition
Human fertilization is the union or joining of the egg and the
sperm, resulting in a fertilized egg, otherwise known as a zygote.
But the process of human fertilization is very complicated and
comprised of many steps and components necessary to achieve
the ultimate result of human life. Read on to learn how such small
things work together to make a fertilized egg.

Process
The process of human fertilization is a complicated one, but the
egg and sperm will unite in the long run. Although technical in
nature, you could also look at it as a journey to find the perfect
match. The egg will sit waiting for one sperm out of up to 150
million that begin the race, and it will merge with that sperm to
create human life. While the egg waits, the sperm race and
compete to be the first to penetrate the egg. When the one sperm
and egg finally meet, electricity fills the air. Seriously, electric
signals are released. Although the details may not be so romantic,
remember that it is the journey that counts.
Human fertilization begins with a woman's menstrual cycle. This
cycle prepares a woman's body for fertilization. About half way
through this cycle, the woman's body is ready to begin the
process of human fertilization. It is at this point that an egg cell is
released, or ovulated, into the Fallopian tube. Inside this
Fallopian tube, fertilization will take place.

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 Human Egg Cell Diagram
During intercourse, a man can ejaculate, or release semen into
a women's vagina. There are up to 150 million sperm in the
semen in a single ejaculation. The sperm travel to the Fallopian
tube to meet the egg; however, the sperm have some big
challenges ahead to complete this journey. For instance, the
sperm have to complete this journey within 12-48 hours of the egg
being ovulated, or else they will die.
About 85% of the sperm are not properly structured for travel.
This leaves only about 15% of the sperm to complete the journey
to the egg. The remaining sperm will follow chemical signals given
by the vagina and cervix, the opening of the uterus. The
chemical signals will guide the sperm through the cervical mucus
and up the lining of the uterus. The uterus is also known as
the womb and is where the baby will develop after fertilization.
Only about 1,000 sperm are left. After the sperm make it through
the uterus, they face the challenge of picking the correct Fallopian
tube. There are two Fallopian tubes, and only one contains the
egg. The sperm that choose the correct Fallopian tube will finally
reach the egg.

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 Chapter 4 — The cell Cycle
The cell cycle is an ordered series of events involving cell
growth and cell division that produces two new daughter cells.
Cells on the path to cell division proceed through a series of
precisely timed and carefully regulated stages of growth, DNA
replication, and division that produce two genetically identical
cells. The cell cycle has two major phases: interphase and the
mitotic phase During interphase, the cell grows and DNA is
replicated. During the mitotic phase, the replicated DNA and
cytoplasmic contents are separated and the cell divides. Watch
this video about the cell cycle:

Interphase

During interphase, the cell undergoes normal processes while

also preparing for cell division. For a cell to move from interphase
to the mitotic phase, many internal and external conditions must
be met. The three stages of interphase are called G1, S, and G2.

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G1 Phase

The first stage of interphase is called the G1 phase, or first gap,

because little change is visible. However, during the G1 stage, the
cell is quite active at the biochemical level. The cell is
accumulating the building blocks of chromosomal DNA and the
associated proteins, as well as accumulating enough energy
reserves to complete the task of replicating each chromosome in
the nucleus.
S Phase

Throughout interphase, nuclear DNA remains in a semi-

condensed chromatin configuration. In the S phase (synthesis
phase), DNA replication results in the formation of two identical
copies of each chromosome—sister chromatids—that are firmly
attached at the centromere region. At this stage, each
chromosome is made of two sister chromatids and is a duplicated
chromosome. The centrosome is duplicated during the S phase.
The two centrosomes will give rise to the mitotic spindle, the
apparatus that orchestrates the movement of chromosomes
during mitosis. The centrosome consists of a pair of rod-
like centrioles at right angles to each other. Centrioles help
organize cell division. Centrioles are not present in the
centrosomes of many eukaryotic species, such as plants and
most fungi.
G2 Phase

In the G2 phase, or second gap, the cell replenishes its energy

stores and synthesizes the proteins necessary for chromosome
manipulation. Some cell organelles are duplicated, and the
cytoskeleton is dismantled to provide resources for the mitotic
spindle. There may be additional cell growth during G2. The final
preparations for the mitotic phase must be completed before the
cell is able to enter the first stage of mitosis.

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The Mitotic Phase

To make two daughter cells, the contents of the nucleus and the
cytoplasm must be divided. The mitotic phase is a multistep
process during which the duplicated chromosomes are aligned,
separated, and moved to opposite poles of the cell, and then the
cell is divided into two new identical daughter cells.

4.1 Mitosis
Mitosis is divided into a series of phases—prophase,
prometaphase, metaphase, anaphase, and telophase—that result
in the division of the cell nucleus.

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4.2 Stages of mitosis

During prophase, the “first phase,” several events must occur to

provide access to the chromosomes in the nucleus. The nuclear
envelope starts to break into small vesicles, and the Golgi
apparatus and endoplasmic reticulum fragment and disperse to
the periphery of the cell. The nucleolus disappears. The
centrosomes begin to move to opposite poles of the cell. The
microtubules that form the basis of the mitotic spindle extend
between the centrosomes, pushing them farther apart as the
microtubule fibers lengthen. The sister chromatids begin to coil
more tightly and become visible under a light microscope.

During prometaphase, many processes that were begun in

prophase continue to advance and culminate in the formation of a
connection between the chromosomes and cytoskeleton. The
remnants of the nuclear envelope disappear. The mitotic spindle
continues to develop as more microtubules assemble and stretch
across the length of the former nuclear area. Chromosomes
become more condensed and visually discrete. Each sister
chromatid attaches to spindle microtubules at the centromere via
a protein complex called the kinetochore.

During metaphase, all of the chromosomes are aligned in a

plane called the metaphase plate, or the equatorial plane,
midway between the two poles of the cell. The sister chromatids
are still tightly attached to each other. At this time, the
chromosomes are maximally condensed.

During anaphase, the sister chromatids at the equatorial plane

are split apart at the centromere. Each chromatid, now called a
chromosome, is pulled rapidly toward the centrosome to which its
microtubule was attached. The cell becomes visibly elongated as
the non-kinetochore microtubules slide against each other at the
metaphase plate where they overlap.

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 During telophase, all of the events that set up the duplicated
chromosomes for mitosis during the first three phases are
reversed. The chromosomes reach the opposite poles and begin
to decondense (unravel). The mitotic spindles are broken down
into monomers that will be used to assemble cytoskeleton
components for each daughter cell. Nuclear envelopes form
around chromosomes.

Cytokinesis

Cytokinesis is the second part of the mitotic phase during which

cell division is completed by the physical separation of the
cytoplasmic components into two daughter cells. Although the
stages of mitosis are similar for most eukaryotes, the process of
cytokinesis is quite different for eukaryotes that have cell walls,
such as plant cells.
In cells such as animal cells
that lack cell walls, cytokinesis
begins following the onset of
anaphase. A contractile ring
composed of actin filaments
forms just inside the plasma
membrane at the former
metaphase plate. The actin
filaments pull the equator of the
cell inward, forming a fissure. This fissure, or “crack,” is called
the cleavage furrow. The furrow deepens as the actin ring
contracts, and eventually the membrane and cell are cleaved in
two.

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The G1 Checkpoint

The G1 checkpoint determines whether all conditions are

favorable for cell division to proceed. The G1 checkpoint, also
called the restriction point, is the point at which the cell irreversibly
commits to the cell-division process. In addition to adequate
reserves and cell size, there is a check for damage to the
genomic DNA at the G1 checkpoint. A cell that does not meet all
the requirements will not be released into the S phase.
The G2 Checkpoint

The G2 checkpoint bars the entry to the mitotic phase if certain

conditions are not met. As in the G1 checkpoint, cell size and
protein reserves are assessed. However, the most important role
of the G2 checkpoint is to ensure that all of the chromosomes
have been replicated and that the replicated DNA is not damaged.
The M Checkpoint

The M checkpoint occurs near the end of the metaphase stage

of mitosis. The M checkpoint is also known as the spindle
checkpoint because it determines if all the sister chromatids are
correctly attached to the spindle microtubules. Because the
separation of the sister chromatids during anaphase is an
irreversible step, the cycle will not proceed until the kinetochores
of each pair of sister chromatids are firmly anchored to spindle
fibers arising from opposite poles of the cell.

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4.3 Meiosis

The nuclear division that forms haploid cells, which is called

meiosis , is related to mitosis. As you have learned, mitosis is part
of a cell reproduction cycle that results in identical daughter nuclei
that are also genetically identical to the original parent nucleus. In
mitosis, both the parent and the daughter nuclei contain the same
number of chromosome sets—diploid for most plants and
animals. meiosis employs many of the same mechanisms as
mitosis. However, the starting nucleus is always diploid and the
nuclei that result at the end of a meiotic cell division are haploid.
To achieve the reduction in chromosome
number, meiosis consists of one round of chromosome
duplication and two rounds of nuclear division. Because the
events that occur during each of the division stages are
analogous to the events of mitosis, the same stage names are
assigned. However, because there are two rounds of division, the
stages are designated with a “I” or “II.” Thus, meiosis I is the first
round of meiotic division and consists of prophase I,
prometaphase I, and so on. Meiosis I reduces the number of
chromosome sets from two to one. The genetic information is also
mixed during this division to create unique recombinant
chromosomes. Meiosis II, in which the second round of meiotic
division takes place in a way that is similar to mitosis, includes
prophase II, prometaphase II, and so on.

Interphase

Meiosis is preceded by an interphase consisting of the G1, S,

and G2 phases, which are nearly identical to the phases
preceding mitosis. The G1 phase is the first phase of interphase
and is focused on cell growth. In the S phase, the DNA of the
chromosomes is replicated. Finally, in the G2 phase, the cell
undergoes the final preparations for meiosis.

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During DNA duplication of the S phase, each chromosome
becomes composed of two identical copies (called sister
chromatids) that are held together at the centromere until they are
pulled apart during meiosis II. In an animal cell, the centrosomes
that organize the microtubules of the meiotic spindle also
replicate. This prepares the cell for the first meiotic phase.

Meiosis I
Early in prophase I, the chromosomes can be seen clearly
microscopically. As the nuclear envelope begins to break down,
the proteins associated with homologous chromosomes bring the
pair close to each other. The tight pairing of the homologous
chromosomes is called synapsis. In synapsis, the genes on the
chromatids of the homologous chromosomes are precisely
aligned with each other. An exchange of chromosome segments
between non-sister homologous chromatids occurs and is
called crossing over. This process is revealed visually after the
exchange as chiasmata (singular = chiasma).

The crossover events are the first source of genetic variation

produced by meiosis. A single crossover event between
homologous non-sister chromatids leads to a reciprocal exchange
of equivalent DNA between a maternal chromosome and a
paternal chromosome. Now, when that sister chromatid is moved
into a gamete, it will carry some DNA from one parent of the
individual and some DNA from the other parent.
The recombinant sister chromatid has a combination of maternal
and paternal genes that did not exist before the crossover.

To summarize the genetic consequences of meiosis I: the

maternal and paternal genes are recombined by crossover events
occurring on each homologous pair during prophase I; in addition,
the random assortment of tetrads at metaphase produces a
unique combination of maternal and paternal chromosomes that
will make their way into the gametes.
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 In anaphase I, the spindle fibers pull the linked chromosomes
apart. The sister chromatids remain tightly bound together at the
centromere. It is the chiasma connections that are broken in
anaphase I as the fibers attached to the fused kinetochores pull
the homologous chromosomes apart.

In telophase I, the separated chromosomes arrive at opposite

poles. The remainder of the typical telophase events may or may
not occur depending on the species. In some organisms, the
chromosomes decondense and nuclear envelopes form around
the chromatids in telophase I.

Cytokinesis, the physical separation of the cytoplasmic

components into two daughter cells, occurs without reformation of
the nuclei in other organisms. In nearly all species, cytokinesis
separates the cell contents by either a cleavage furrow (in
animals and some fungi), or a cell plate that will ultimately lead to
formation of cell walls that separate the two daughter cells (in

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plants). At each pole, there is just one member of each pair of the
homologous chromosomes, so only one full set of the
chromosomes is present. This is why the cells are considered
haploid—there is only one chromosome set, even though there
are duplicate copies of the set because each homolog still
consists of two sister chromatids that are still attached to each
other. However, although the sister chromatids were once
duplicates of the same chromosome, they are no longer identical
at this stage because of crossovers.

Meiosis II
In meiosis II, the connected sister chromatids remaining in the
haploid cells from meiosis I will be split to form four haploid cells.
In some species, cells enter a brief interphase, or interkinesis,
that lacks an S phase, before entering meiosis II. Chromosomes
are not duplicated during interkinesis. The two cells produced
in meiosis I go through the events of meiosis II in synchrony.
Overall, meiosis II resembles the mitotic division of a haploid cell.

In prophase II, if the chromosomes decondensed in telophase I,

they condense again. If nuclear envelopes were formed, they
fragment into vesicles. The centrosomes duplicated during
interkinesis move away from each other toward opposite poles,
and new spindles are formed. In prometaphase II, the nuclear
envelopes are completely broken down, and the spindle is fully
formed. Each sister chromatid forms an individual kinetochore
that attaches to microtubules from opposite poles. In metaphase
II, the sister chromatids are maximally condensed and aligned at
the center of the cell. In anaphase II, the sister chromatids are
pulled apart by the spindle fibers and move toward opposite
poles.

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 In telophase II, the chromosomes arrive at opposite poles and
begin to decondense. Nuclear envelopes form around the
chromosomes. Cytokinesis separates the two cells into four
genetically unique haploid cells. At this point, the nuclei in the
newly produced cells are both haploid and have only one copy of
the single set of chromosomes. The cells produced are
genetically unique because of the random assortment of paternal
and maternal homologs and because of the recombination of
maternal and paternal segments of chromosomes—with their sets
of genes—that occurs during crossover.

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26
 CHAPTER 5 — Fundamentals of
Genetics
5.1 Mendel’s Experiment

Johann Gregor Mendel (1822–1884) was a lifelong learner,

teacher, scientist, and man of faith. As a young adult, he joined
the Augustinian Abbey of St. Thomas in Brno in what is now the
Czech Republic. Supported by the monastery, he taught physics,
botany, and natural science courses at the secondary and
university levels. In 1856, he began a decade-long research
pursuit involving inheritance patterns in honeybees and plants,
ultimately settling on pea plants as his primary model system (a
system with convenient characteristics that is used to study a
specific biological phenomenon to gain understanding to be
applied to other systems). In 1865, Mendel presented the results
of his experiments with nearly 30,000 pea plants to the local
natural history society. He demonstrated that traits are transmitted

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faithfully from parents to offspring in specific patterns. In 1866, he
published his work, Experiments in Plant Hybridization,1 in the
proceedings of the Natural History Society of Brünn.
Mendel’s Crosses

Mendel’s seminal work was accomplished using the garden

pea, Pisum sativum, to study inheritance. This species naturally
self-fertilizes, meaning that pollen encounters ova within the same
flower. The flower petals remain sealed tightly until pollination is
completed to prevent the pollination of other plants. The result is
highly inbred, or “true-breeding,” pea plants. These are plants that
always produce offspring that look like the parent. By
experimenting with true-breeding pea plants, Mendel avoided the
appearance of unexpected traits in offspring that might occur if
the plants were not true breeding. The garden pea also grows to
maturity within one season, meaning that several generations
could be evaluated over a relatively short time. Finally, large
quantities of garden peas could be cultivated simultaneously,
allowing Mendel to conclude that his results did not come about
simply by chance.

Plants used in first-generation crosses were called P, or parental

generation, plants. Mendel collected the seeds produced by the P
plants that resulted from each cross and grew them the following
season. These offspring were called the F1, or the first filial (filial =
daughter or son), generation. Once Mendel examined the
characteristics in the F1 generation of plants, he allowed them to
self-fertilize naturally. He then collected and grew the seeds from
the F1 plants to produce the F2, or second filial, generation.
Mendel’s experiments extended beyond the F2 generation to the
F3 generation, F4 generation, and so on, but it was the ratio of
characteristics in the P, F1, and F2 generations that were the most
intriguing and became the basis of Mendel’s postulates.

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 In his 1865 publication, Mendel reported the results of his
crosses involving seven different characteristics, each with two
contrasting traits. A trait is defined as a variation in the physical
appearance of a heritable characteristic. The characteristics
included plant height, seed texture, seed color, flower color, pea-
pod size, pea-pod color, and flower position. For the characteristic
of flower color, for example, the two contrasting traits were white
versus violet. To fully examine each characteristic, Mendel
generated large numbers of F1 and F2 plants and reported results
from thousands of F2 plants.

Importantly, Mendel did not stop his experimentation there. He

allowed the F1 plants to self-fertilize and found that 705 plants in
the F2 generation had violet flowers and 224 had white flowers.
This was a ratio of 3.15 violet flowers to one white flower, or
approximately 3:1. When Mendel transferred pollen from a plant
with violet flowers to the stigma of a plant with white flowers and
vice versa, he obtained approximately the same ratio irrespective
of which parent—male or female—contributed which trait. This is
called a reciprocal cross—a paired cross in which the respective

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traits of the male and female in one cross become the respective
traits of the female and male in the other cross. For the other six
characteristics that Mendel examined, the F1 and F2 generations
behaved in the same way that they behaved for flower color. One
of the two traits would disappear completely from the
F1 generation, only to reappear in the F2 generation at a ratio of
roughly 3:1

Upon compiling his results for many thousands of plants, Mendel

concluded that the characteristics could be divided into expressed
and latent traits. He called these dominant and recessive traits,
respectively. Dominant traits are those that are inherited
unchanged in a hybridization. Recessive traits become latent, or
disappear in the offspring of a hybridization. The recessive trait
does, however, reappear in the progeny of the hybrid offspring.
An example of a dominant trait is the violet-colored flower trait.
For this same characteristic (flower color), white-colored flowers
are a recessive trait. The fact that the recessive trait reappeared
in the F2 generation meant that the traits remained separate (and
were not blended) in the plants of the F1 generation. Mendel

30
proposed that this was because the plants possessed two copies
of the trait for the flower-color characteristic, and that each parent
transmitted one of their two copies to their offspring, where they
came together. Moreover, the physical observation of a dominant
trait could mean that the genetic composition of the organism
included two dominant versions of the characteristic, or that it
included one dominant and one recessive version. Conversely,
the observation of a recessive trait meant that the organism
lacked any dominant versions of this characteristic.

Phenotypes and Genotypes

Two alleles for a given gene in a diploid organism are expressed

and interact to produce physical characteristics. The observable
traits expressed by an organism are referred to as its phenotype.
An organism’s underlying genetic makeup, consisting of both the
physically visible and the non-expressed alleles, is called
its genotype.

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 The P plants that Mendel used in his experiments were each
homozygous for the trait he was studying. Diploid organisms that
are homozygous for a gene have two identical alleles, one on
each of their homologous chromosomes. The genotype is often
written as YY or yy, for which each letter represents one of the
two alleles in the genotype. The dominant allele is capitalized and
the recessive allele is lower case. The letter used for the gene
(seed color in this case) is usually related to the dominant trait
(yellow allele, in this case, or “Y”). Mendel’s parental pea plants
always bred true because both produced gametes carried the
same allele. When P plants with contrasting traits were cross-
fertilized, all of the offspring were heterozygous for the
contrasting trait, meaning their genotype had different alleles for
the gene being examined. For example, the F1 yellow plants that
received a Y allele from their yellow parent and a y allele from
their green parent had the genotype Yy.

Law of Dominance

Our discussion of homozygous and heterozygous organisms

brings us to why the F1 heterozygous offspring were identical to
one of the parents, rather than expressing both alleles. In all
seven pea-plant characteristics, one of the two contrasting alleles
was dominant, and the other was recessive. Mendel called the
dominant allele the expressed unit factor; the recessive allele was
referred to as the latent unit factor. We now know that these so-
called unit factors are actually genes on homologous
chromosomes. For a gene that is expressed in a dominant and
recessive pattern, homozygous dominant and heterozygous
organisms will look identical (that is, they will have different
genotypes but the same phenotype), and the recessive allele will
only be observed in homozygous recessive individuals.
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 Correspondence between Genotype and Phenotype for a
Dominant-Recessive Characteristic.

Homozyg
Homozygous Heterozygous
ous

Genotype YY Yy Yy

Phenotype yellow Yellow green

Mendel’s law of dominance states that in a heterozygote, one

trait will conceal the presence of another trait for the same
characteristic. For example, when crossing true-breeding violet-
flowered plants with true-breeding white-flowered plants, all of the
offspring were violet-flowered, even though they all had one allele
for violet and one allele for white. Rather than both alleles
contributing to a phenotype, the dominant allele will be expressed
exclusively. The recessive allele will remain latent, but will be
transmitted to offspring in the same manner as that by which the
dominant allele is transmitted. The recessive trait will only be
expressed by offspring that have two copies of this allele.

To demonstrate this with a monohybrid cross, consider the case

of true-breeding pea plants with yellow versus green seeds. The
dominant seed color is yellow; therefore, the parental genotypes

33
were YY for the plants with yellow seeds and yy for the plants with
green seeds. A Punnett square, devised by the British geneticist
Reginald Punnett, is useful for determining probabilities because
it is drawn to predict all possible outcomes of all possible random
fertilization events and their expected frequencies. Shows a
Punnett square for a cross between a plant with yellow peas and
one with green peas.
Law of Segregation

Observing that true-breeding pea plants with contrasting traits

gave rise to F1 generations that all expressed the dominant trait
and F2 generations that expressed the dominant and recessive
traits in a 3:1 ratio, Mendel proposed the law of segregation.
This law states that paired unit factors (genes) must segregate
equally into gametes such that offspring have an equal likelihood
of inheriting either factor. For the F2 generation of a monohybrid
cross, the following three possible combinations of genotypes
result: homozygous dominant, heterozygous, or homozygous
recessive. Because heterozygotes could arise from two different
pathways (receiving one dominant and one recessive allele from
either parent), and because heterozygotes and homozygous
dominant individuals are phenotypically identical, the law supports
Mendel’s observed

3:1 phenotypic ratio.

The equal segregation of alleles is the reason we can apply the

Punnett square to accurately predict the offspring of parents with
known genotypes. The physical basis of Mendel’s law of
segregation is the first division of meiosis in which the
homologous chromosomes with their different versions of each
gene are segregated into daughter nuclei. This process was not
understood by the scientific community during Mendel’s lifetime

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Law of Independent Assortment

Mendel’s law of independent assortment states that genes do

not influence each other with regard to the sorting of alleles into
gametes, and every possible combination of alleles for every
gene is equally likely to occur. Independent assortment of genes
can be illustrated by the dihybrid cross, a cross between two
true-breeding parents that express different traits for two
characteristics. Consider the characteristics of seed color and
seed texture for two pea plants, one that has wrinkled, green
seeds (rryy) and another that has round, yellow seeds (RRYY).
Because each parent is homozygous, the law of segregation
indicates that the gametes for the wrinkled–green plant all are ry,
and the gametes for the round–yellow plant are all RY. Therefore,
the F1 generation of offspring all are RrYy

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Pedigrees and Punnett Squares

PEDIGREES

Inheritance of a trait through generations can be shown visually

using a pedigree, such as is pictured in Figure 1. Square shapes
represent males; circles represent females. Filled-in shapes are
individuals that have whatever trait is being shown in the
pedigree. Two individuals connected together with a horizontal
line between them are the parents of the individuals that are
connected by vertical lines below them. Siblings are typically
shown in birth order with the oldest sibling to the left.

Figure 1 A simple pedigree. In this

pedigree, the parents (at the top) have produced three children: a male and two
females. The first female has the condition being shown in the pedigree.

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PUNNETT SQUARES

As discussed above, diploid individuals have two copies of each

chromosome: one from their male parent, one from their female
parent. This means they have two copies of each gene. They can
have two of the same alleles (homozygous) or two different alleles
(heterozygous). Regardless of their genotype, they will randomly
pass only one copy of each chromosome to their offspring. This is
because meiosis produces haploid gametes that contain one copy
of each chromosome, and those chromosomes are assorted into
gametes randomly. Since genes are present on chromosomes,
this means they will pass one copy of each gene to their offspring.
That means that an offspring inherits one allele of each gene from
each of its two parents. This is illustrated in Figure 2. This concept
is called Mendel’s Law of Segregation.

Figure 2 Two parents who are heterozygous each pass one chromosome / gene
/ allele to each offspring. Each resulting offspring has two of each chromosome /
gene. The individual can have two of the same or two different alleles.

37
 An easy, organized way of illustrating the offspring that can result
from two specific parents is to use a Punnett square. The
gametes that can be generated by each parent are represented
above the rows and next to the columns of the square. Each
gamete is haploid for the “A gene”, meaning it only contains one
copy of that gene. In the Punnett square seen in Figure 3, haploid
eggs are above each column and haploid sperm are next to each
row. When a haploid sperm and a haploid egg (each with 1 copy
of the “A gene”) combine during the process of fertilization, a
diploid offspring (with 2 copies of the A gene) is the result.

Figure 3: A Punnett square showing a

cross between two individuals who are both heterozygous for A.

A Punnett square shows the probability of an offspring with a

given genotype resulting from a cross. It does not show actual
offspring. For example, the Punnett square in Figure 3 shows that
there is a 25% chance that a homozygous recessive offspring will
result from the cross Aa x Aa. It does not mean that these parents
must have 4 offspring and that they will have the ratio 1 AA : 2 Aa
: 1 aa. It’s just like flipping a coin: you expect 50% heads, but you
wouldn’t be too surprised to see 7 heads out of 10 coin
flips. Additionally, the probability does not change for successive
offspring. The probability that the first offspring will have the
genotype “aa” is 25% and the probability of the second offspring
having the genotype “aa” is still 25%. Again, it’s just like flipping a

38
coin: if you flip heads the first time, that doesn’t change the
probability of getting heads on the next flip.
Organisms don’t just inherit one trait at a time, though. They
inherit all their traits at once. Sometimes, we want to determine
the probability of an individual inheriting two different traits. The
easiest way to do this is to determine the probability of the
individual inheriting each trait separately, then multiply those
probabilities together. An example of this can be seen in Figure
4. In order for this to work, we must assume that genes do not
influence each other with regard to the sorting of alleles into
gametes, and every possible combination of alleles for every
gene is equally likely to occur. This is called Mendel’s Law of
Independent Assortment.

Figure 4: These two Punnett square show the cross between two
individuals who are both heterozygous for two different genes: BbAa x
BbAa. We can determine the probability of an offspring having the

39
recessive trait for “B” and the dominant trait for “A”. The probability of the
offspring having the recessive phenotype for “B” is 1/4. The probability of
the offspring having the dominant phenotype for “A” is 3/4. 1/4 x 3/4 = 3/16.

Figure 5: This dihybrid cross shows the expected offspring from the F2 generation after
crossing YYRR x yyrr. Compare the results from this Punnett square to the results seen
in the previous figure.

Another way of determining the probability of getting two different

traits is to use a dihybrid Punnett square. Figure 5 shows three
generations of the inheritance of pea seed color and shape. Peas
can be either yellow or green, and they can be either round or
wrinkled. These are two of the traits that Mendel studied in his
work with peas. In the first generation (the “P” generation), two
true-breeding (homozygous) individuals are crossed. Their
offspring will get one allele of the Y gene and one allele of the R
gene from each parent. This means that all their offspring (the
“F1” generation) will be heterozygous for both genes. The results
(the “F2” generation) from crossing two heterozygous
individuals can be seen in the 4×4 Punnett square in Figure 5.
The gametes produced by the F1 individuals must have one
allele from each of the two genes. For example, a gamete could
get an R allele for the seed shape gene and either a Y or

40
a y allele for the seed color gene. It cannot get both an R and
an r allele; each gamete can have only one allele per gene. The
law of independent assortment states that a gamete into which
an r allele is sorted would be equally likely to contain either a Y or
a y allele. Thus, there are four equally likely gametes that can be
formed when the RrYy heterozygote is self-crossed, as
follows: RY, rY, Ry, and ry. Arranging these gametes along the
top and left of a 4 × 4 Punnett square (Figure 5) gives us 16
equally likely genotypic combinations. From these genotypes, we
find a phenotypic ratio of 9 round–yellow:3 round–green:3
wrinkled–yellow:1 wrinkled–green (Figure 5). These are the
offspring ratios we would expect, assuming we performed the
crosses with a large enough sample size.
We can look for individuals who have the recessive
phenotype for Y and the dominant phenotype for R. These
individuals must have two little y’s and at least one big R. The
possible genotypes are yyRR or yyRr. Examining the Punnett
square in Figure 5, we can find 3 individuals with these
genotypes (they are round and green). If you compare the results
from Figure 4 and Figure 5, you’ll see that we have arrived at the
same value: 3/16!

41
 Chapter 6 — Matters of Sex
6.1 Sexual development
Sexual Development
Most sexual development occurs in late childhood and
adolescence. This period of rapid growth and development is
called puberty. Puberty involves physical growth and sexual
maturation, as well as psychological and social development.
Puberty usually begins between the ages of eight and 12 in
girls and between the ages of 10 and 14 in boys. In some cases,
puberty does not occur within the normal age range. This
condition is called late puberty or delayed puberty.

Adolescents who experience delayed puberty should be

evaluated by a health care specialist to rule out genetic disorders,
such as Klinefelter syndrome (condition caused by an extra X
chromosome in males) and Turner syndrome (condition caused
by an incomplete or missing X chromosome in females), and
other medical conditions (e.g., disorders of the thyroid or pituitary
gland, diabetes, kidney disease).

Puberty occurs as a result of increased hormone levels

triggered by an area of the brain called the hypothalamic-pituitary-
gonadal axis. At the onset of puberty, the hypothalamus begins
secreting gonadotropin-releasing hormone (GnRH) to the pituitary
gland. The pituitary gland then begins secreting leutenizing
hormone (LH), which stimulates special cells in the testes and
ovaries to produce sex hormones called testosterone and

42
estrogen. The increase in these hormones results in maturity
associated with adulthood.

Signs of puberty in girls include the following:

 Appearance of underarm and pubic hair

 Breast development
 Growth spurt (period of rapid growth; girls usually reach their
adult height by about 16 years of age)
 Menstruation (menstrual periods)
 Increase in subcutaneous (under the skin) fat in the pelvis,
breasts, and upper back
Signs of puberty in boys include the following:
 Appearance of underarm, chest, facial, and pubic hair

 Deepening of the voice

 Ejaculation (reflex in which semen is ejected from the penis;
usually follows an erection and may happen during sleep)
 Growth spurt (period of rapid growth; boys usually reach their
adult height by about 18 years of age)
 Gynecomastia (condition in which a hard nodule forms under
each nipple; usually disappears within 2 years)
 Growth of the penis and testes (testicles)
 Increase in muscle mass

6.1 Sex chromosomes

● Human males & females have equal number of chromosomes.
Males- have x and y chromosomes.

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Females- have two x chromosomes.
Heterogametic sex Heterogametic sex- w/ 2 different sex
chromosomes
Homogametic Sex Homogametic sex – w/ 2 same sex
chromosomes
Females are the homogametic sex (XX)
Males are the heterogametic sex (XY)

X chromosome
– Contains 1,500 genes
- Larger than the Y chromosome
- Acts as a homolog to Y in males
Y chromosome
- Contains 231 genes, Many DNA segments are palindromes
and may destabilize DNA

Anatomy of the Y chromosome

● Y chromosome has SRY (sex-determining region of the Y)
SRY- the master regulator of maleness.
- turns on genes for production of male hormones.
Y chromosome
● human Y chromosome is particularly exposed to high mutation
rates due to highly oxidative environment of the testis.

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6.1 The phenotype
● SRY gene encodes a very important type of protein called
transcription factor. - it stimulates male development by sending
signals to the indifferent gonads
Sustentacular cells in the testis secrete anti-Mullerian anti-
Mullerian hormone, which destroys potential female structures.
Interstitial cells in the testis secrete testosterone, Which
stimulates the development of male structures.
Some testosterone is also converted to dihydrotestosterone
(DHT), which directs development of the urethra, prostate gland,
penis, and scrotum.
Genetic abnormalities can intervine in different points.
For example:
In Androgen Insensitivity
Syndrome (OMIM 300068) (OMIM
300068), caused by mutation in X
chromosome, the absence of
receptors for androgen, stops cells in
early reproductive structures from
receiving the signal to develop as
male. The person looks female but is XY.

Hermaphroditism-a term for an

individual with both male and
female sexual structures.
Intersex-refers to individuals
whose individuals whose internal structures are internal structures
are inconsistent with inconsistent with external structures.

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 Pseudohermaphroditism- presence of both types of structures
but at different stages of life.
6.1 Is Homosexuality inherited?
- a person's phenotype and genotype are consistent, and
physical attraction genotype are consistent, and physical
attraction is toward members of the same sex.
6.1 Sex ratio
In Mendel's law of segregation, populations should have
approximately equal numbers of male and female new-born
Sex ratio- proportion of males to females in a human population.
Primary sex ratio – At conception
Secondary sex ratio – At birth
Tertiary sex ratio – At maturity Sex ratios can change markedly
with age.
6.2 Traits Inherited on the Sex Chromosomes
Y-linked – genes carried on Y chromosome.
In females :
2 copies of X-linked = recessive allele
1 copy of X-linked = dominant allele
In males :
single copy of X-linked = dominant (expression of trait or illness
because there's no copy of gene on the 2nd X chromosome.)

SEX DETERMINATION
In humans an oocyte has a single X chromosome. A sperm cell
has either an X or Y chromosome. If a Y-bearing sperm cell with a
functional SRY gene fertilizes an oocyte, the zygote is a male
(XY). If an X-bearing sperm fertilizes an oocyte, the zygote is a
female (XX).

Human male is considered homozygous for X linked trait

because he has only one set of X linked genes.
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 A male inherits his Y chromosome from his father and X
chromosome from his mother. A female inherits one X
chromosome from each parent.

6.2 X-Linked Recessive

Inheritance
An X-linked trait passes from an
unaffected heterozygous mother to
an affected son.
6.2 X-Linked Dominant
Inheritance
A female who inherits a dominant X-linked allele has the
associated traits or illness, but a male who inherits the allele is
usually more severely affected because he has only on copy of X-
linked allele.

Incontinentia Pigmenti (IP)

A newborn girl with IP has yellow,
pus-filled vesicles on her limbs
that come and go over the 1st few
weeks. Then the lesions become
warty to brown splotches that may
remain for life, although they
remain for life. Males with this
condition are so severely affected
that they do not survive to be
born.

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Congenital Generalized Hypertrichosis
- produces many extra hair
follicles, and hence denser
and more abundant in upper
body hair. - Hair growth is
milder and patchier in
females because of
hormonal differences and the
presence of a second X
chromosome.
6.2 solving a problem: X-linked Inheritance
(using Mendel's Law of Segregation)
Consider a Kallmann syndrome (OMIM 308700), which causes
very poor or absent sense of smell and small testes or ovaries. It
is X-linked recessive. Tanisha does not have Kallmann syndrome,
but her brother Jamal and her maternal cousin Malcolm have it.
Tanisha's and Malcolm's parents are unaffected, as is Tanisha's
husband Sam. Tanisha and Sam wish to know the risk that a son
would inherit the condition. Sam has no affected relatives.

Steps to follow:
1) Look at the inheritance pattern
2) Draw a pedigree
3) List genotypes & phenotypes and their probabilities
4) Assign genotypes and phenotypes
5) Use Punnett square to determine ratios
6) Repeat for next generation

6.3 Sex-Limited and Sex-Influenced Traits

6.3 sex-limited traits

A sex-limited trait affects a structure or function of the body that
is present in only males or only females.

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6.3 sex-influenced trait
In a sex-influenced trait, sex-influenced trait, an allele is
dominant in one sex but recessive in the other.
Pattern baldness is a sex-influenced trait. Male pattern baldness
is related to your genes and male sex hormones. It usually follows
a pattern of receding hairline and hair thinning on the crown, and
is caused by hormones and genetic predisposition.

6.4 X Inactivation
X inactivation- is a process by which one of the two copies of
the X chromosome present in female is inactivated. The inactive
X chromosome is silenced by its being packaged in such a way
that it has a transcriptionally inactive structure is called
heterochromatin.

6.4 Equaling out the sexes

Females have two alleles for X chromosome genes but males
have only one but males have only one
In mammals, X inactivation balances this inequality and one X
chromosome is randomly inactivated in each cell
The inactivated X chromosome is called a Barr body
X inactivation occurs early in prenatal development. A gene
called XIST controls the inactivation. It encodes an RNA that
binds to a specific site on the (inactive) X chromosome and
inactivates it.

6.4 effect on the phenotype

A carrier of an X-linked trait that expresses the phenotype is
called a manifesting heterozygote.
A female who is heterozygous for an X-linked recessive gene
can expressed the associated condition if the normal allele is
inactivated in the tissues that the illness affects.

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Hunter Syndrome (mucopolysaccharidosis II)
- cells that make
the enzyme
readily send it to
neighboring cellz
essentially
correcting the
defect in cells that
can't make the
enzyme.
Affected boys
are deaf, mentally
retarded, have
dwarfism and
abnormal facial features, heart damage,
and enlarged liver and spleen.

Fabry Disease (alpha-galactosidase A deficiency)

- cells that make the enzyme
readily send it to neighboring
cells essentially correcting the
defect in cells that can't make
the enzyme.
Affecteentally retarded, have
dwarfism and abnormal facial
features, heart damage, and
enlarged liver and spleen.

6.5 Genomic Imprinting

The phenotype of an individual differs depending on the gene’s
parental origin.
Genomic Imprinting - a molecule covers a gene or several
linked genes and prevents them from being accessed to
synthesize protein.

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6.5 the silencing the contribution from one parent
Importance of Genomic Imprinting
Imprints are erased during meiosis - Then reinstituted according
to the sex of the individual It takes two opposite sex parents to
produce a healthy embryo
- Male genome controls placenta development
- Female genome controls embryo development
Genomic imprinting can explain incomplete penetrance, in which
an individual is known to have inherited a genotype associated
with a particular phenotype, but has no signs of the traits. The
predicted genotype is present, but the associated phenotype is
not expressed.
Imprinting may be an important concern in assisted reproductive
technologies that manipulate gametes to treat infertility.
For example:
Angelman syndrome (OMIM
105830) and Becwith
Wiedemann syndrome (OMIM
130650) are more prevalent
among the offspring of
people who used in vitro
fertilization and
intracytoplasmic sperm
injection to become pregnant.

6.5 Imprinting Disorders in Humans

Increased severity depends on whether it is inherited from the
father or mother or may depend on uniparental disomy. It means
''two bodies from one parent'', and refers to an offspring who
inherits both copies of a gene from one parent and none from the
other.

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