AMYA

POLYTECHNIC COLLEGE MEDICAL LABORATORY

Bonum Est Sui Diffusivum SCIENCE PROGRAM

COURSE MODULE
Cytogenetics
Course No.: MT 209
Course Title: Cytogenetics
Unit: 2 Units Lecture
Pre-/Co-Requisite: BIO 101
Year Level: 2nd Year, 2nd Semester

Course Description:
The course deals with the study of concepts related to the study of heredity and inheritance: genetic
phenomena; sex determinations; and human chromosome structure, function, and abnormalities. Nucleic acids
(DNA and RNA) and their application to medical science are given emphasis.

Course Objectives:
At the end of the course, the learners are expected to:

COGNITIVE
1. Describe heredity and genetic structures and physiologic processes, concepts, and principles.
2. Discuss how the environment affects various living system.
3. Recognize the common cytogenetic abnormalities encountered in the population.
PSYCHOMOTOR
1. Identify the chemical and physical nature of the genetic materials present in parents that are transmitted
to the offspring
2. Apply the principle that the gene is the basic unit of heredity that shares the properties of function,
recombination, and mutation.
AFFECTIVE
1. Apply the principles and concepts of cytogenetics in medical technology practice.
2. Integrate the scientific ethics and humanistic values when dealing with application of genetics in
everyday life.
3. Manifest the values of honesty, critical thinking, empathy, and value for life.

Learning Module No. 1

Topic: Introduction to Cytogenetics

Materials: Laptop and Internet Connection
Assessment: MCQ Post-Test via Infinit
Learning Outcomes:
At the end of the session, the students should be able to:
1. Define cytogenetics
2. introduce and explain genes and genomes
3. describe the levels of genetics from molecular level to populations

 INTRODUCTION
 Genetics – the study of genes; inheritance is how traits, or characteristics, are passed from
generation to generation.
 Chromosomes – are made up of genes, which are made up of DNA.
 Genetic Material – composed of genes, chromosomes, and DNA.
HISTORY OF GENETICS
 People have known about inheritance for a long time.
o Children resemble their parents.
o Domestication of animals and plants, selective breeding for good characteristics.
o Sumerian horse breeding
o Egyptian data palm breeding
o Bible and haemophilia

Mid 1800’s Discoveries

 Three major events in the mid-1800s led directly to the development of modern genetics.
 1859, Charles Darwin publishes “The Origin of Species”, which describes the theory of
evolution by natural selection. This theory required heredity to work.
 1866, Gregor Mendel (Father of Genetics), publishes experiments in plant hybridization,
which lays out the basic theory of genetics. It is widely ignored until 1900.
Major Events in the 20th Century
 1900 – Medel’s work by Robert Comens, Hugo de Vried, and Erich Von Tschermak.
 1902 – Archibald Garrod Alkaptonuna, a human disease, has a genetic basis.
 1904 – Gregory Bateson linkage between genes. Coined the word “genetics”.
 1910 – Thomas Hunt Morgan, genes located on the chromosomes (Drosophilia).
 1918 – R.A. Fisher, study of quantitative genetics by partitioning phenotypic variance into a
genetic and an environmental component.
 1926 – Herman J Muller shows that X-rays induce mutation.
 1944 – Oswald Avery, Colin Macleod, and Maclyn McCarty shows that DNA can transform
bacteria, demonstrating that DNA is the heredity material.
 1953 – James Watson & Francis Crick, structure of the DNA molecule. Which leads directly
to knowledge of how replication
 1966 – Marshall Wirenberg solve the genetic code, showing that three DNA bases code for
one amino acid.
 1972 – Stanley Cohen & Herbert Boyer combine DNA from two different species in vitro,
then transform it into bacterial cells; first DNA cloning
 2001 – Sequence of the entire human genome is announced.
SCOPE OF GENETICS
 Cytogenetic
 Molecular Genetic
 Genomics
 Classical Genetic
 Population genetic
 Genetic of Behaviour
 Biotechnology
Level of Genetic
DNA
Genes
Cells
Tissue
Organs
System
Individual
Family
Population
Evolution
Application of Genetics
 Establishing Identity
 Health Care
 Agricultural
 Ecology
 Global Perspective
Human & Medical Application
 Production of Insulin
 Genetic Screening History
 Gene Therapy
 Vaccine

CELL DIVISION: Cell Cycle

Cell Cycle
 A sequence of cell growth and division
 The period from the beginning of one division to the beginning of the next
 The time it takes to complete one all cycle is the generation time.
 Cell divide when they reach certain size
 Nerve, skeletal muscle, and red blood cells NOT undergo cell division.
Cell Division
 It involves mitosis and cytokinesis.
 Mitosis – division of chromosomes
 Cytokinesis – division of cells.

Eukaryotic Cell Cycle Stages – main stages (G2, S Phase, G2, and Mitosis)
 Interphase:
o First Gap Phase/G1 Phase – cell growth and normal functions, synthesizes proteins,
carbohydrates, lipids (varies in many cells) – liver – G0, early embryo
o Synthesis Phase/S Phase – copies DNA, chromosomes replicate, and divide to form
identical sister chromatid
o Second Gap Phase/G2 Phase – additional growth, cell continue to grow and produce the
protein necessary for cell division
 M Phase/Mitosis: division of the cell nucleus and division of the cytoplasm.
o Mitosis: Prophase, Metaphase, Anaphase, and Telophase
o Cytokinesis

Overview of Cell Cycle Control

 Two irreversible points in cell cycle:
o Replication of genetic material
o Separation of sister chromatids
 Checkpoints – process is assessed and possibly halted.
 Three (3) Checkpoints:
1. Between G1 and S Phase – controls the passage of eukaryotic cells from the first gap
phase into the DNA synthesis phase.
 Checks: size and environment
 Most critical: primary decision point “restriction point”; if cell receives “Go” signal it
divides internal (cell growth nutrition) and external (growth factor); if not receives
the signal it switch to G0 Phase and not divide.
 G0 Phase – non-dividing, differentiated state.
 Most Human Cells:
o Liver Cells – callback
o Nerve and Muscle Cells – highly specialized; G0 arrested and not divided
 Factors might assess: nutrients, size, molecular signals and DNA integrity
 2. Between G2 and Mitosis – checks DNA damage, prevent the cell from entering mitosis if
the genome is damage; if DNA is damage, pauses the integrity of cell cycle and
replication
3. Between Mitosis Processes – attachment of the spindle fibers to centromeres is
assessed; only if this is correct can mitosis proceed; failure to attach spindle fiber
correctly would lead to failure to separate chromosomes.
 Spindle Checkpoint – formation of spindle fiber and the attachment to kinetochore
of chromatid.
Mitosis Promoting Factor may:
 Phosphorylate histone protein H1 to condense chromatin.
 Phosphorylate nuclear lamins to break nuclear envelope.
 Phosphorylate Microtubule Associated Proteins resulting the formation of spindle fiber.

APOPTOSIS – Cell Death

 Programmed cell death
 Orderly cellular self destruction
 Evolutionarily conserved
 Occurs in all multicellular animals studies (plants too)
 a pathway of cell death induced by tightly
regulated intracellular program in which
the cell that is destined to die activates
certain enzymes that degrade cell's own
nuclear DNA and cytoplasmic protein
Killer Enzymes
 destroy enzymes that replicate and repair
DNA
 activate enzymes that cut DNA into
similarly sized pieces;
 tear apart the cytoskeleton, collapsing the nucleus and condensing the DNA;
 cause mitochondria to release molecules that increase caspase activity and end the energy
supply;
 abolish the cells ability to adhere to other cells;
 Attract phagocytes that dismantle the cell remnants.

Importance of Apoptosis
 Maturing organisms (development)
 Viral infections
 Immune System
 DNA damage

Characteristics of Apoptosis
 Shrinks
 Blebbing – first stage of apoptosis
 Nucleus breaks down, breaks into small
membrane wrapped fragments

Apoptosis: Important in Adults

 Tissue remodelling (eliminates cells no
longer needed):

Apoptosis: Role in Disease

 Too Much: Tissue Atrophy
o Neurodegeneration
 Neurons are post-mitotic (cannot
replace themselves; neuronal stem
cell replacement is inefficient)
 Neuronal death caused by loss of proper connections, loss of proper growth factors
(e.g. NGF), and/or damage (especially oxidative damage)
 Neuronal dysfunction or damage results in loss of synapses
 or loss of cell bodies (synaptosis, can be reversible; apoptosis, irreversible)
 Example: Parkinson's Disease; Alzheimer's Disease: Huntington's Disease
o Thin Skin
 Too Little: Hyperplasia
o Cancer
 Apoptosis eliminates damaged cells (damage - mutations - cancer
 Tumor suppressor p53 controls senescence and apoptosis responses to damage
 Most cancer cells are defective in apoptotic response (damaged, mutant cells
survive)
 High levels of anti-apoptotic proteins or Low levels of pro-apoptotic proteins lead to
CANCER
o Atherosclerosis
 Aging - both too much and too little apoptosis (evidence for both)
o Too much (accumulated oxidative damage?) – tissue degeneration
o Too little (defective sensors, signals?) – dysfunctional cells accumulate hyperplasia
(precancerous lesions)

STEM CELL - A cell that has the ability to continuously divide and differentiate (develop) into
various other kind(s) of cells/tissues
 ‘Blank cells’ (unspecialized)
 Capable of dividing and renewing themselves for long periods of time (proliferation and
renewal)
 Have the potential to give rise to specialized cell types (differentiation)

Kinds of Stem Cells

 Embryonic stem cells – come from a five to six-day-old embryo. They have the ability to
form virtually any type of cell found in the human body. It is derived from the part of a
human embryo or fetus that will ultimately produce eggs or sperm (gametes).
 Adult stem cells – undifferentiated cells found among specialized or differentiated cells in a
tissue or organ after birth. Based on current research they appear to have a more restricted
ability to produce different cell types and to self-renew.

Stem Cell Type Description Example

Each cell can Cells from early
Totipotent develop into a (1 to 3 days)
new individual embryos
Cells can form Some cells of
Pluripotent any (over 200) blastocyst (5 to
cell types 14 days)
Cells Fetal tissue,
differentiated, cord blood, and
Multipotent but can form a adult stem cells
number of
other tissues
 Stem cells can be classified into three broad categories, based on their ability to
differentiate. Totipotent stem cells are found only in early embryos. Each cell can form a
complete organism (e.g., identical twins). Pluripotent stem cells exist in the undifferentiated
inner cell mass of the blastocyst and can form any of the over 200 different cell types found
in the body. Multipotent stem cells are derived from fetal tissue, cord blood and adult stem
cells. Although their ability to differentiate is more limited than pluripotent stem cells, they
already have a track record of success in cell-based therapies. Here is a current list of the
sources of stem cells:

1. Embryonic stem cells - are harvested from the inner cell mass of the blastocyst seven to
ten days after fertilization.

2. Fetal stem cells - are taken from the germline tissues that will make up the gonads of
aborted fetuses.

3. Umbilical cord stem cells - Umbilical cord blood contains stem cells similar to those
found in bone marrow.
 4. Placenta derived stem cells - up to ten times as many stem cells can be harvested from
a placenta as from cord blood.

5. Adult stem cells - Many adult tissues contain stem cells that can be isolated.

Stages of Embryogenesis
 The early stages of embryogenesis are the point at which embryonic stem cell lines are
derived.
o The fertilized egg (day 1) undergoes cell division to form a 2-cell embryo.
o Followed by 4-cell, etc. until a ball of cells is formed by the fourth day.
o The ball becomes hollow, forming the blastocyst. This is the stage at which pluripotent
embryonic stem cell lines are generated.
o Following the blastocyst stage, the tissues of the embryo start to form and the cells
become multipotent.

Derivation and Use of Embryonic Stem Cell Lines

 The inner cell mass (the part that would form the fetus) of the embryo is isolated and
disrupted to form embryonic cell lines. This process destroys the embryo. Under special
culture conditions, the cells of the embryonic lines can be coaxed to form certain kinds of
differentiated cell types. In theory, these differentiated cells could be used to repair or
replace defective cells or tissues.

Application
 Disease
o Diabetes, Spinal cord injury, Parkinson’s disease, heart disease
 Genetic based Disease
o Cystic fibrosis, Huntington’s Disease

How They Could Treat Certain Types of Diseases?

 Tissue Repair – regenerate spinal cord, heart tissue or any other major tissue in the body
 Heart Disease – Adult bone marrow stem cells injected into the heart arteries are believed
to improve cardiac function in victims of heart failure
 Leukemia and Cancer – Studies show leukemia patients treated with stem cells emerge free
of disease. Injections of stem cells have also reduced pancreatic cancers in some patients
 Rheumatoid Arthritis – Adult stem cells may be helpful in jumpstarting repair of eroded
cartilage
 Parkinson’s Disease
 Diabetes – Pancreatic cells do not produce insulin. Basic research focused on understanding
how embryonic stem cells might be trained to become pancreatic islets cells needed to
secrete insulin.
Learning Module No. 2

Topic: History and Importance of Cytogenetics

Materials: Laptop and Internet Connection
Assessment: MCQ Post-Test via Infinit
Learning Outcomes:
At the end of the session, the students should be able to:
1. explain and synthesize the origin and importance of cytogenetics

HISTORY AND IMPORTANCE OF CYTOGENETICS

GENETICS- study of HEREDITY and GENES
- Central pillar of Biology

CYTOGENETICS- study of CHROMOSOMES and their ABNORMALITIES

 Microbial Genetics- genes of MICROBES (bacteria, fungi, viruses)
 Molecular Genetics- molecular structure of DNA and its influence to overall make up of
an individual (DNA is the BLUEPRINT of life)
 Classical Genetics- study of TRAITS
o Dominant- always expressed
o Recessive- not always expressed
o Intermediate- partially expressed
o Polygenic- Multiple genes
> ALL ARE SEX LINKED/ AUTOSOMAL
 Behavior Genetics- BEHAVIOR of human and animals
 Population Genetics- study of genes of population of ANIMALS, PLANTS, MICROBES
(environmental factors)
 Genomics- study of GENOMES (complete set of genes to create a genetic sequence)
 Human Genetics- gives emphasis on the understanding and treating genetic diseases
GENE- UNIT of hereditary; BIOCHEMICAL INSTRUCTION that tells the cell to manufacture or
produce a certain type of PROTEIN
Ribosomes- responsible for PROTEIN SYNTHESIS
DNA- sugar, phosphate groups, nitrogenous bases
Humans have 20,000- 25,000 genes and some changes in combination of genes may lead to
genetic disorders
Antigenic traits are the reason to why you have to be vaccinated every year
TYPES OF GENETICS DISEASES
 CHROMOSOME DISORDERS
o Entire chromosomes (or large segments of them) are missing, duplicated, or
altered
o Examples: Down and Turners Syndrome
 SINGLE-GENE DISORDERS
o Disorders in which single genes are altered, these are often termed medelian
conditions
o Examples: Sickle cell disease, Hemophilia, and Cystic fibrosis (can be from
infection from other organisms like Pseudomonas aeruginosa)
 MULTIFACTORIAL DISORDERS
o Result from a combination of multiple genetic and environmental causes
o Examples: Birth defects (cleft lip, cleft palate) and Adult disorders (heart disease
and diabetes)
 MITOCHONDRIAL DISORDERS
 o Caused by alterations in the small cytoplasmic mitochondrial chromosome
o Examples: Lactic acidosis

HISTORY OF GENETICS
 1866- GREGOR MENDEL (Austrian), FATHER OF GENETICS, published the results of
his experiments with PEA PLANTS. His work later provided the mathematical foundation
of the SCIENCE of GENETICS.
 1869- JOHANN FRIEDRICH MIESCHER (Swiss), first to isolate nuclein- now known as
DNA
 1900- Modern Science of Genetics:
o HUGO DE VRIES- Dutch botanist and geneticist
o CARL ERICH CORRENS- German
 1944- OSWALD AVERY
 1950- ERWIN CHARGAFF (Austrian- born American biochemist), components of DNA
are paired in a 1:1 ratio
 1951-
 1953-
 1960-
 1970- DNA SEQUENCING was introduced
 1983- Kary B. Mullis invented POLYMERASE CHAIN REACTION (amplifies the target
DNA/ RNA sequence)
Viruses have their own genetic sequences that are unique from each other
We use PCR to detect BACTERIA, FUNGI, and VIRUSES; aids in DIAGNOSIS especially in
MICROBIOLOGY
 1990- Human Genome Project
 2002- International HapMap Project
 2008- 1000 Genomes Project

GENETICS IMPORTANCE AND APPLICATIONS

 MEDICINE
o Genetic Techniques- cancer and enzyme deficiencies (newborn screening)
o Gene Therapy- recombinant DNA technology
o Bioinformatics- Genome and gene products for production of pharmaceutical
drugs
 AGRICULTURE AND ANIMAL HUSBANDRY
o Breeding Analysis- artificial insemination (injection of semen to vagina), hormone
treatment (triggers more egg cells), and cloning
o Cross Breeding- budding (bud to stem) and grafting
o Transgenic Modification- colchicine- doubles the number of plant chromosomes
resulting to new variety of fruits, vegetables, and flowers
 INDUSTRY
o Brewing Industry- yeast to produce alcohol
 Beer is made of fungi called Saccharomyces cereviceae
 o Pharmaceutical Industry- antibiotic such as penicillin (made of fungi called
Penicillum notatum, to treat SYPHILLIS) and cyclosporine (made of fungi called
Tolypocladium inflatum for immunosuppressing drug for ORGAN TRANSPLANT)
o Biotechnology- recombinant DNA technology for bacteria, plants, and animals

Learning Module No. 3

Topic: The Cell and the Cell Cycle
Materials: Laptop and Internet Connection
Assessment: MCQ Post-Test via Infinit

Learning Outcomes:
At the end of the session, the students should be able to:
1. review, illustrate, and describe the functions of the different parts of the cell
2. explain, illustrate, and differentiate the process of mitosis and meiosis
3. explain the importance of mitosis and meiosis

Cell Parts and Their Functions

What is the structure of cells?
Each cell is surrounded by a membrane and contains parts called cellular organelles.
Each cellular organelle has a specific function. Some parts of a cell are involved in converting
energy from nutrients in the food you eat into a form of energy that the cell can use. Other parts
of the cell are involved in storing the genetic information that serves as the blueprint that makes
you different from a gorilla or a hummingbird. Still other parts of a cell are responsible for
building the proteins that enable the cell to do its many tasks.

The Cell Membrane

Every cell has a thin outer covering called the cell membrane, or plasma membrane. The
cell membrane surrounds the contents of the cell and separates it from other cells and the
environment. The cell membrane also controls what materials go into and out of the cell. For
example, the cell membrane allows nutrients and oxygen to move into the cell, and carbon
dioxide and waste materials to move out of the cell.
The cell membrane is made of molecules called proteins and lipids arranged in an orderly
manner. You could think of the cell membrane as two sheets or layers of lipid molecules with
different kinds of proteins positioned in the sheets. The lipids making up the bilayer membrane
are arranged in a special way. Each lipid molecule has a head and a tail.

The head ends of the lipid molecules are attracted by water, and the tail ends are
repelled by water. In a watery environment, the lipid tail ends tend to associate with (face) each
other. Since the head ends are attracted by water, they face the watery environment, some
toward the inside of the membrane and some to the other side of the membrane. In a cell
membrane, each lipid layer has its molecules lined up in the same way. The two layers are
arranged so the tails of the lipid molecules face each other.

A Drawing or Model of a Cell Membrane Draw your own picture or build a model to show
the arrangement of lipids in a cell membrane.
Think of a troop of scouts all sleeping in their sleeping bags in a rectangular tent. They want to
arrange themselves so no one's feet are in someone else's face. One arrangement would be
two rows of sleeping scouts with feet pointing toward each other as shown in Figure 2.3. That
arrangement is similar to the composition of the lipid bilayer of the cell membrane.

Did You Know?

A person coming out of the bath carries away a film of water about 1/50 of an inch thick.
This water weighs about a pound. A mouse getting out of the same tub carries away water
about equal to its own weight. A fly or honey bee coming out of a pool of water carries a film of
water that weighs many times more than its own weight.
The organized lipid bilayer allows water and molecules that dissolve in water to come right up to
the membrane, but not pass freely through the membrane. Because of the lipid bilayer, water
molecules can only pass through protein channels in the membrane. Other molecules that
dissolve in water must go through protein channels to move into or out of cells. The lipid bilayer
helps control the environment inside a cell, and the proteins of the cell membrane determine
which substances can move into and out of a cell through the cell membrane.

Soap Bubbles Have you ever noticed a swirl of subtle colors on a large soap bubble?
This free movement is similar to the movements of molecules within the membrane of a cell. Try
the following activities to help you imagine the direction of free movement or the fluidity of
proteins and lipids in a cell membrane.
Blow soap bubbles in the light and watch the movement of the colors on the surface of the
bubbles. Cells allow movement somewhat like this.
Straighten a paper clip. Dip the straightened paper clip into a bubble solution. Move the paper
clip into a bubble and then across a bubble. What happens? Repeat using many different
objects (or your finger).
Also try bubbles of different sizes and see which size bubbles last longest. Try to make
elongated bubbles and see if those ever divide into two spherical bubbles. Why do you think
that occurs?

The proteins have different functions. Some might be receptors for hormone signals.
Others might be channels.

Passage through a Cell Membrane

Assume that all factors influencing the movement of molecules are the same except for
the molecular size of the substance. If we know the size of the pore opening of the membrane,
we can estimate the size of the substances based on their ability to move through the
membrane pores.

Cytoplasm and Organelles

The cytoplasm and specialized working parts called organelles are inside the cell
membrane. The cytoplasm is a sea-like fluid that contains water and other chemicals. Some of
these chemicals are found throughout the cytoplasm. Some of the chemicals are found just near
the cell membrane, around the edges of the cytoplasm. Because the cytoplasm is fluid, the cell
can change shape, much like a bag of water changes shape.
The parts of the cell that are organized for specific functions are called organelles. The
organelles include such structures as the nucleus and the mitochondria. The nucleus contains
the genetic material and the mitochondria convert energy. shows some of the major organelles
of a typical animal cell.
Each of these organelles has a special role to play in the way the cell works. The role of control
center goes to the nucleus.

The Nucleus
 The nucleus is the most important part of a cell. It is the “information” headquarters and
is in charge of the cellular activities. It contains the information that will tell the cell what to do,
what to make, and when to divide. A nucleus is a small and very powerful part of a cell.

All cells contain genetic material in units called genes. Genes control what a cell looks
like, what it can do, and how it functions. In the cells of higher organisms, including humans, the
genetic material is found inside the nucleus. A nucleus is a region within the cell that is
surrounded by a membrane, called the nuclear membrane. The nuclear membrane controls
which molecules enter and leave the nucleus.

Chromosomes
If you looked at one of your cells under a microscope, you would see that under certain
conditions, structures called chromosomes appear in the nucleus of the cell.
There are 23 pairs of chromosomes in the nucleus of human cells. Of these 23 pairs there are
two main kinds-22 pairs of matched chromosomes (autosomes) and a pair of sex
chromosomes. Each chromosome is a particular length and has a short arm and a long arm.
Besides size and shape, the banding pattern of a chromosome is also distinctive. The
chromosomes are not found in any particular order within a nucleus. However, in the laboratory,
scientists can sort them into pairs and identify each chromosome, as shown in the diagram.
Each chromosome is made up of two parts-DNA (deoxyribonucleic acid)and proteins. The DNA
is the genetic material that codes for the characteristics of a person. A chromosome contains
one long molecule of DNA. Every cell in a healthy human female has these chromosomes in the
nucleus.

Mitochondria
Cells require a continuous supply of energy. Mitochondria have the job of converting energy in
the food you eat to a form that is usable by cells. Mitochondria are fairly large organelles that
look like this:
1. Mitochondria are present in the cytoplasm of all cells. In a typical cell the mitochondria
might be located randomly throughout the cytoplasm.
2. Mitochondria make a compound called adenosine triphosphate (ATP)from other
molecules. When the chemical bonds of food molecules, such as sugar, are broken,
energy in the form of ATP is produced. The ATP is then stored in the mitochondria until it
is needed elsewhere in the cell
3. ATP contains the energy that is used by the cell to make all of its products and to carry
out its functions. ATP is like cash. It can be used to make goods and services. There are
other forms of energy around the cell, but the cell must convert this energy into ATP to
make products that help the cell to live and to function normally.

Ribosomes
Proteins are important molecules produced by cells. Ribosomes are the organelles
where proteins are produced or synthesized. Ribosomes are themselves made up of proteins.
The ribosomes are scattered throughout the cytoplasm or are attached to part of another
organelle called the endoplasmic reticulum.

Endoplasmic Reticulum
The endoplasmic reticulum is a series of folded membranes that is used to move
materials around the cell. All cells have endoplasmic reticulum (or ER). The ER also is involved
in helping to make different kinds of cell membranes, including the outer (plasma) cell
membrane, mitochondrial membrane, and nuclear membrane.
 There are two main kinds of ER-rough and smooth. Rough ER has ribosomes attached
to it and makes proteins, including many important proteins for the plasma membrane. Smooth
ER does not have ribosomes but is involved in modifying proteins synthesized by the rough ER.

Golgi Apparatus
The Golgi apparatus is a series of flattened sacs. When you observe the Golgi
apparatus through a powerful microscope, the sacs appear to lie on top of one another in a
stack. The bottom of the stack lies near the nucleus, or part of the rough ER. The top of the
stack lies closer to the outer cell membrane. The Golgi apparatus helps sort the proteins
synthesized on the rough ER. The proteins are transported to the Golgi apparatus where they
may be stored or chemically modified and then packaged for delivery to the cell membrane for
export outside the cell or to other places inside the cell.

The Two Faces of Cell Division

There are two kinds of cell division: mitosis and meiosis. Mitosis is essentially a duplication process: It
produces two genetically identical "daughter" cells from a single "parent" cell. You grew from a single
embryonic cell to the person you are now through mitosis. Even after you are grown, mitosis replaces
cells lost through everyday wear and tear. The constant replenishment of your skin cells, for example,
occurs through mitosis. Mitosis takes place in cells in all parts of your body, keeping your tissues and
organs in good working order.

Meiosis, on the other hand, is quite different. It shuffles the genetic deck, generating daughter cells that
are distinct from one another and from the original parent cell. Although virtually all of your cells can
undergo mitosis, only a few special cells are capable of meiosis: those that will become eggs in females
and sperm in males. So, basically, mitosis is for growth and maintenance, while meiosis is for sexual
reproduction.

The Cycling Cell

A typical animal cell cycle lasts roughly 24 hours, but depending on the type of cell, it can vary in length
from less than 8 hours to more than a year. Most of the variability occurs in G 1.

Before focusing on mitosis, let's take a step back and look at the big picture. The illustration shows the
cell cycle of a eukaryotic plant or animal cell. This cycle begins when the cell is produced by mitosis and
runs until the cell undergoes its own mitosis and splits in two. The cycle is divided into distinct phases:
G1 (gap 1) S (synthesis), G2 (gap 2), and M (mitosis). As you can see, mitosis only occupies a fraction of
the cycle. The rest of the time-phases G1 through G2—is known as interphase.
During interphase that chromosomes—the genetic material—are copied, and cells typically double in size.

Checkpoints: Cellular Inspectors

At first glance, the orderly progression of the cell through the phases of the cell cycle may seem perfectly
straightforward. When building a house, the walls aren't erected until after the foundation has been laid.
Likewise, in the cell, mitosis doesn't begin until after the genetic material has been copied. Otherwise, the
daughter cells would end up with less than a complete set of chromosomes and would probably die. So in
the cell cycle, just as in housebuilding, certain steps need to precede others in an orderly fashion for the
process to work.

How does the cell "know" when a step has been completed and it's time to move on to the next? The
answer is that the cell has several molecular "inspectors" stationed at intervals—called checkpoints—
throughout the cell cycle. These cellular inspectors function much like building inspectors do: If a step has
been completed to their satisfaction, they give the OK to move forward. If not, they halt progress until the
cellular construction workers finish the task. There are three major checkpoints in the cell cycle: one
between G1 and S phase, one between G2 and mitosis, and one during mitosis itself.

Phases of Mitosis

Mitosis: Let's Split!

Mitosis is the most dramatic event in a cell's life. Cellular structures that have always been there suddenly
disintegrate, new structures are constructed, and it all culminates in the cell splitting in half. Imagine
quietly going about your business one day, when you suddenly feel the bones of your skeleton
rearranging themselves. Then, you find yourself being pinched apart from your midline, and before you
know it, someone who looks just like you is sitting beside you. That's akin to what happens to a cell during
mitosis.

Mitosis is divided into six

phases: prophase, prometaphase, metaphase, anaphase, telophase, and cytokinesis. The first five
phases do the job of splitting the nucleus and its duplicated genetic information in two, while in the final
step, the entire cell is split into two identical daughter cells.

Cancer: Careening Out of Control

A number of environmental factors cause DNA mutations that can lead to cancer:
toxins in cigarette smoke, sunlight and other radiation, and some viruses.
Your body carefully controls which cells divide and when they do so by using molecular stop and go
signals. For example, injured cells at the site of a wound send go signals to the surrounding skin cells,
which respond by growing and dividing and eventually sealing over the wound. Conversely, stop signals
are generated when a cell finds itself in a nutrient-poor environment. Sometimes, however, go signals are
produced when they shouldn't be, or stop signals aren't sent or heeded. Both scenarios can result in
uncontrolled cell division and cancer. Mitosis then becomes a weapon turned against the body, spurring
the growth of invasive tumors.

Fortunately, it takes more than one mistaken stop or go signal for a cell to become cancerous. Because
our bodies are typically quite good at protecting their essential systems, it usually requires a one-two
punch for healthy cells to turn malignant. The punches come in the form of errors, or mutations, in DNA
that damage a gene and result in the production of a faulty protein. Sunlight, X rays and other radiation,
toxins such as those found in cigarette smoke and air pollution, and some viruses can cause such
mutations. People also can inherit mutations from their parents, which explains why some families have
higher rates of certain cancers: The first punch is delivered at conception. Subsequent mutations can then
push a cell down the path toward becoming cancerous.

Ironically, mitosis itself can cause mutations too, because each time a cell's DNA is copied, errors are
made. (Fortunately, almost all of these errors are corrected by our extremely efficient DNA repair
systems.) So there's an inherent tradeoff in mitosis: It allows us to grow to maturity and keeps us healthy,
but it's also the source of potentially damaging DNA mutations. We'll come back to the link between cell
division and DNA damage when we talk about aging in the next chapter.

Phases of Meiosis

Meiosis is used to make sperm and egg cells. During meiosis, a cell’s chromosomes are copied once, but
the cell divides twice. For simplicity, we have illustrated cells with only three pairs of chromosomes.

 Prophase I : The matching chromosomes from your mother and father pair up.

 PrometaphaseI : While paired up, maternal and paternal chromosomes can swap matching
sections. This process, called crossing over, increases genetic diversity.

 Second Meiotic Division - Cytokinesis : The four daughter cells have half as many
chromosomes as the parent cell and are called haploid.

 
Comparison Between Mitosis and Meiosis

Questions

1. What is the difference between Mitosis and Meiosis?

2. During which phase in the cell cycle is genetic material copied?

3. During the cell cycle what prevents a cell form completing the cell cycle if a mistake has
been made?

4. What is the last step of Mitosis called?

5. Name two potential causes of cancer?

6. During meiosis, how many times are the cells chromosomes copied?

7. Why are you different from your relatives?

8. What are some advantages of Meiosis?

Learning Module No. 4

Topic: Mendelian Genetics

Materials: Laptop and Internet Connection
Assessment: MCQ Post-Test via Infinit

Learning Outcomes:
At the end of the session, the students should be able to:
1. explain how a gene alone usually does not solely determine a trait
2. explain how the law of segregation reflects the events of meiosis
3. describe and explain the Punnett square
4. distinguish between autosomal recessive and autosomal dominant inheritance
5. explain how the law of independent assortment reflects the events of meiosis
6. explain how pedigrees show single-gene transmission

MENDELIAN GENETICS

Genes
- Segment of DNA that code for a polypeptide chain or a tRNA or an rRNA
- There is no mRNA because POLYPEPTDE CHAIN is mentioned (the end product is the
polypeptide chain, not the mRNA)
Genetics
- study of heredity and diversity

Gregor Mendel
- Father of Genetics

*Central Dogma of molecular biology

- DNA is the genetic material of all cells
-DNA is the one that produces poly peptide chains, rRNA, proteins and tRNA

*Every time an RNA is made, the blueprint/transcription is the DNA

*the DNA has the function of replication. EVERY CELL UNDERGOES REPLICATION ONCE EVERY CELL
DIVISION. Replication is needed to let the next generation of daughter cells carry the same genes.

RNA
-tRNA
- transfer
-rRNA
-forms the ribosome
-mRNA
-messenger
-goes to the ribosome and the ribosome reads the codes that the mRNA carries which is called the process
of translation.
-Not a last product that’s why it is not included

Slide 2

Homozygous: 2 identical alleles for a given gene

Heterozygous: 2 different alleles for a given gene

Dominant allele: full expressed in the phenotype of the heterozygote

Recessive allele: phenotypic effect not expressed in a heterozygote

Slide 4

Gregor Mendel used peas

Cross pollinated purple and white flowers

Generation1 showed purple flowers
Generation 2 showed purple and white flowers

1st law of MENDEL

Law of segregation
-homologous pair of chromosomes separates during Anaphase I

2nd law of MENDEL

Law of Independent Assortment
-separation of alleles

Dihybrid Cross
-shows the law of independent assortment
-talks about one set of genes
-hypothesis of independent and depend assortment

Mendel’s studies involved characteristics determined by:

 one gene producing one phenotype
 with only two alleles
 completely dominant or completely recessive

Degree of Dominance
 complete: phenotypes of dominant homozygote and heterozygote are not distinguishable  purple flowers (can’t
be determined if PP or Pp)

 Incomplete: neither allele is dominant, phenotype of heterozygote is intermediate of the homozygotes with the
dominant or recessive genes  Purple flowers (it is neither white or purple, it’s light purple)

 Codominance : phenotypes of both alleles are dominantly expressed  Blood type (Blood type AB)

Incomplete Dominance
 neither allele is dominant, phenotype of heterozygote is intermediate of the homozygotes with the dominant or
recessive genes  Purple flowers (it is neither white or purple, it’s light purple)
Multiple Allelism
 A particular trait may have more than 2 alleles

ABO BLOOD GROUPS

Blood types are determined by BLOOD GROUP ANTIGENS on the Red Blood Cell Membrane
Blood type O is Recessive
Blood Type A and B is Codominant
Mendelian Genetics for 2 or more Genes
O O
Epistasis: gene at one locus alters phenotypic expression of
another gene at a second locus
A AO AO

O AO OO

B black coat, dominant

b brown coat, recessive
C for colour disposition
C no colour disposition

BOMBAY PHENOTYPE

You need the H antigen (Big H) to have

An O Blood type, if you have the small h
antigen, you have a Bombay blood type.
H – dominant
h- recessive
H Antigen - precursor (backbone) of A
Antigen , precursor for formation of B
 Antigen
H antigen – no disposition of the A or
B antigen
Pleiotropy
 one gene has multiple phenotypic effects
 one gene, many phenotypes

e.g. gene associated with hereditary diseases that gives rise to multiple symptoms

Polygenic Inheritance
 one phenotype, many genes
 additive effect of two or more genes on a single phenotypic character
quantitative characteristics
 example : skin pigmentation
Learning Module No. 5

Topic: Modification of Mendelian Ratios

Materials: Laptop and Internet Connection
Assessment: MCQ Post-Test via Infinit

Learning Outcomes:
At the end of the session, the students should be able to:
1. discuss phenomena that can appear to alter expected Mendelian ratios
2. discuss the mode of inheritance of a mitochondrial of a mitochondrial trait
3. differentiate mitochondrial DNA from nuclear DNA

Modifications of Mendelian Ratios

Extensions and modifications

 Sometimes, inheritance patterns are more complicated than simple dominance

Incomplete dominance
 This is seen when heterozygotes have phenotypes that are intermediate between the two
homozygotes
 In incomplete dominance, the phenotypic and genotypic ratios are equal
 Each genotypic class has a separate phenotype

Codominance
 Heterozygotes simultaneously express the phenotypes of both homozygotes

Multiple alleles
 When there are more than two alleles controlling a trait, we have multiple alleles
 ABO blood group
o This is a classic example of both codominance and multiple alleles
o There are three alleles controlling this trait - IA, IB, i
o The presence or absence of the different blood type antigens on the red blood cells
determines blood type
o Your blood type also determines the type or types of blood that you can receive in a
transfusion

Lethal alleles
 1905 - Lucien Cuenot mated two yellow mice
 ~2/3 of the offspring were yellow; ~1/3 were not
 All of the yellow mice were heterozygous; none of the yellow mice bred true
 So there were two strange findings here
 The phenotypic ratio was 2:1, not a Mendelian ratio
 There were no homozygous yellow mice
 The 2:1 ratio is almost always indicative of the presence of a recessive lethal allele

 Achondroplasia
o Affects about 1 in 25,000 people
o Head and torso develop normally but arms and legs are short
 o It is inherited in a dominant manner

In the dihybrid crosses previously considered, each gene exhibited simple dominance/recessiveness
If either or both genes exhibits a different mode of inheritance, we see a modification of the 9:3:3:1
ratio.

Gene interaction - epistasis

 Sometimes one gene can mask the effect of another gene at a different locus in determining a
single characteristic
 The gene that does the masking is the epistatic gene; the gene that is masked is the hypostatic
gene
Recessive epistasis
 The Bombay phenotype and blood typing
 In very rare instances, a person can have an ABO blood type genotype that doesn’t match their
blood type (O) phenotype
 Individuals who are homozygous recessive (hh) do not produce the enzyme required to produce
the precursor to the A, B, and O antigens
 Without any antigen, they have the O phenotype

We can also consider inheritance of the more common mouse coat colors
 Two genes, two enzymes in a multi-step pathway

Dominant epistasis
 Sometimes the presence of only one allele can produce the masking effect

Bateson and Punnett looked at flower color in sweet pea, not the garden pea that Mendel investigated
 They crossed two true-breeding strains of white-flowered plants and got all purple F1 plants!
 Allowing the F1 plants to self-fertilize gave plants with both purple and white flowers in a 9
purple: 7 white ratio
 In this case, at least one dominant allele of each gene is required to complete the conversion of
white flowers to purple

In the case of summer squash shape, you can cross plants with disc-shaped fruit (AABB) with plants
with long fruit (aabb)
 All of the F1 plants have disc-shaped fruit
 However, if you allow the F1 plants to self-fertilize, a new shape (sphere) is seen in the F2 as well
as the parental shapes

So, it really just new groupings of the 9:3:3:1 ratios

Complementation analysis
 Consider two mutants that display a similar phenotype
 This may be due to mutations in the same gene or in different genes
 Complementation analysis can distinguish between these two possibilities

Pleiotropy
 Sometimes, one gene can have multiple effects
 Human examples include Marfan syndrome and porphyria variegata
Sex-linked characteristics
 Most are X-linked; few are Y-linked characteristics

 Morgan noticed a lone white-eyed male among his thousands of red-eyed laboratory flies
o Naturally, he carried on a number of crosses with this white-eyed fly and his offspring
 Morgan’s results
o Pure-breeding, red-eyed female x white-eyed male gave all red-eyed F (only 3/1237
1
had white eyes)
o Conclusion: Simple dominance/recessive trait
o However, a cross between two F flies produced all red-eyed F females
1 2
o Half of the F males had red eyes; half had white eyes!
2
o Conclusion: Male fruit flies are hemizygous for X-linked loci
o Morgan was able to make predictions based on his hypothesis
o Subsequent crosses confirmed the hypothesis

 X-linked inheritance
o Red-green color blindness
o Cone cells that line the retina contain one of three pigments capable of absorbing blue,
green, or red light
o The gene for the blue pigment is found on chromosome 7; the genes for the red and
green pigments are on the X
o Affected women pass the X-linked recessive trait to their sons
o Affected men pass the trait to their grandsons through their daughters
o This pattern is known as crisscross inheritance

Sex and heredity

 Some characteristics, even though they are controlled by genes on autosomes, are affected by
the sex of an individual
Sex-limited characteristics
 Gene is only expressed in one sex
Sex-influenced characteristics
 Determined by autosomal genes
 Appears to have different inheritance patterns in females and males
 Pattern baldness in humans
o Appears to be dominant in males; recessive in females
o Related to the production of male sex hormones

Penetrance and expressivity

Incomplete penetrance
 Not all persons having the genotype for a particular trait will express the phenotype
 Penetrance is the percentage of individuals having that genotype and actually expressing the
phenotype
Variable expressivity
 Different affected individuals will display the phenotype to different degrees
 Expression of mutations in the eyeless gene in Drosophila can produce a range from wild type to
reduced to eyeless
  Polydactyly is a classic example of both incomplete penetrance and variable expressivity

Genes and the environment

 In many cases, the genotype determines a range of phenotypes
 The environmental conditions determine the norm of reaction
 Himalayan rabbits
o Black is seen at the extremities if the rabbit is reared at 20°C or less
o No black is seen if the rabbit is reared at 30°C or above

Genomic imprinting
 Differential expression of genetic material depending on which parent contributed the allele
 Birth weight in mice and humans is affected by a number of genes including Igf2
o Oddly, only the paternal copy is expressed in the fetus and placenta; the maternal copy
of the gene is completely silent
 Genetic-conflict hypothesis
o This seems to occur because the paternal copy promotes placental and fetal growth by
directing more of the maternal nutrients to the fetus
o Non-expression of the maternal copy would select for smaller fetal size
 One deletion, two disorders
o Prader-Willi and Angelman syndromes
o There is a deletion in chromosome 15
o If inherited from the father, Prader-Willi
o If inherited from the mother, Angelman

Cytoplasmic inheritance
o Inheritance of mitochondria (and chloroplasts) occurs only through the egg
o The sperm contributes no cytoplasm

Mitochondria
o Contain DNA
o ~15,000 bp; 37 genes, most involved in energy metabolism
o Most cells contain 2-10 mitochondria, therefore 2-10 copies of mtDNA
o Because mitochondria segregate randomly when the cell divides, mitochondrial disorders are
highly variable
It also holds for the inheritance of cpDNA
o One variety of four-o’clock plants has variegated leaves and shoots
o Some branches of the variegated strain had all-green leaves while others had all-white leaves
Genetic maternal effect
o The offspring’s phenotype is determined by the mother’s genotype
o Shell coiling in the snail Limnaea peregra is determined very early and depends on a substance
present in the egg
o In this case, all of the F are dextral
2
o But, the F phenotypes would depend on the genotype of the mothers
3