1 CYTOGENETICS LECTURE 1: INTRODUCTION TO CYTOGENETICS
Cytogenetics
 Branch of genetics
 The study of chromosomes which are the visible
carriers of the hereditary material
- Chromosome is located in the nucleus of a
eukaryotic cell
 A fusion:
- Science
- Cytology (study of cells)
- Genetic (study of inherited variation)
What is Genetics?
 The study of heredity and variation
 Heredity – study of transmission of traits and biological
information between generations
 Variation – are simply differences in genetic sequence
2 Fundamental Terms in Genetics
 Genotype – the set of genes in its DNA
responsible for a particular trait
o Genetic material, genetic make-up
 Phenotype – the physical expression of those
genes
o Whatever is your genotype, it will be
expressed in a form of phenotype
Genotype has a direct effect on the phenotype
Examples of Genetic Variation (within species)
1. Domesticated species
o Dogs, cats
o Observable difference in color, fur and size
2. Human genetics
o Variation in skin color, height, eye color
3. Natural populations
o However, in the natural population, genetic
composition of a population gene pool may
change over time because of evolution
Genetic Variation  Phenotypic variation
- If DNA changes, so does your physical
characteristic.
- However, the environment can indirectly affect
phenotypic characteristic.
o Ex. Physical characteristic adapting on an
environment to survive
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Genetic Variation can be observed on:
- Cultivated varieties (fruits, pepper, tomatoes, and
flowers)
- Animal breeds (different colors)
- Human Genetic Variation (skin color, eye color)\
- Natural Population (sea shells, snake stripes,
flowers)
What is Genetics?
 Three (3) primary sources of genetic variation:
 Mutations
- Changes in DNA
- Single mutation can have large effect
- However, evolutionary change is based on the
accumulation of many mutation
 Gene flow
- Any movement of genes from one population to
another
- Important source of genetic variation
 Sex
- Can introduce new gene combinations into a
population
- Important source of genetic variation
- Sex-linked characteristics
 The Cell contains a nucleus where the genetic
material is located – chromosome.
- DNA molecule is packaged into a thread-
like structure of chromosome
- Chromosome: a tightly coiled compactly
dense structure inside the nucleus; each
chromosome is made of DNA tightly coiled
many times around proteins called histones
(forming nucleosome, undergoing
condensation, forming chromatin, after
further condensation, forms chromosomes)
 Chromosome is made of a very long strand of DNA
and contains many genes (hundreds to thousands)
 Gene: basic physical unit of inheritance
- Gene on each chromosome are arranged
in a particular sequence, and has a
particular location on the chromosome
(called locus)
 Difference of DNA and Gene
- DNA is the molecule that is the hereditary
material of all living cells (composed of
nucleotides)
o Nucleotides: basic building block of
nucleic acids
 2 CYTOGENETICS LECTURE 1: INTRODUCTION TO CYTOGENETICS
o Nucleic Acids can either be DNA or
RNA
o Nucleotides consists of:
 Sugar molecule – ribose
(RNA) and deoxyribose
(DNA)
 Attached to a phosphate
group
 Nitrogen-containing base
- Genes are made up of DNA (One gene =
one protein)
HISTORY OF GENETICS
 People have known about inheritance for a long time.
o Children resemble their parents
- Children have common characteristic similar to
their parents
o Domestication of animals and plants, selective
breeding for good characteristics
- Good breed is crossbred to another good breed
to have a good offspring
o Sumerian horse breeding records
o Egyptian data palm breeding
o Bible and hemophilia
Old Ideas
Despite knowing about inheritance in general, a
number of incorrect ideas had to be generated and
overcome before modern genetics could arise.
1. All life comes from other life. Living organism are
not spontaneously generated from non-living
material. Big exception: origin of life
- Based on biogenesis; all life comes from
another life
- Abiogenesis: spontaneous generation;
living organism comes from a non-living
matter
2. Species concept: offspring arise only when two
members of the same species mate. Monstrous
hybrids don’t exist.
- No cross-species type of breeding
- Nowadays, there are cross species
breeding but of the same family (zebra and
horse)
Older Ideas
3. Organisms develop by expressing information
carried in their hereditary material. As opposed to
“preformation”, the idea that in each sperm (or egg)
is a tiny, fully-formed human that merely grows in
size.
4. The environment can’t alter the hereditary material
in a directed fashion. There is no “inheritance of
acquired characteristics”. Mutations are random
events.
- Environment indirectly affects the
phenotype
- Acquired characteristics from the
environment should not be transmitted from
one generation to another; it is not inherited
5. Male and female parents contribute equally to the
offspring.
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o Ancient Greek idea: male plants a “seed” in
the female “garden”
o Alleged New Guinea belief: sex is not
related to reproduction
 Wrong idea
Major 1800’s Discoveries
Three (3) major events in the mid-1800’s led
directly to the development of modern genetics.
o The Origin of Species (Charles Darwin)
o Experiments in Plant Hybridization (Gregor
Mendel – father of modern genetics)
o Isolation of Nucleic Acid (Miescher)
 1859: Charles Darwin
- published The Origin of Species, which describes
theory of evolution by natural selection
o This theory requires heredity to work.
o Evolution: the change in the characteristics of a
species over several generations and relies on
the process of natural selection
o Theory of Evolution: based on the idea that all
species are related but gradually change over
time.
o Evolution is related to genetic variation:
Evolution relies on their being genetic variation
in a population which affects physical
characteristics of organism
o Genetic variation has a great effect on the
physical trait (phenotype)
- Natural Selection
o Give individuals an advantage over other
individuals
o Evolution happens by natural selection
o Process where organism better adapt to the
environment, survive and produce more
offspring
o Individuals in a species show variation in
physical characteristics
o Individuals with characteristics best suited to
their environment are more likely to survive,
finding food, avoiding predators and resisting
disease.
o Survival of the fittest (Herbert Spencer): More
fit in the environment, mas better chance of
surviving
 Those most suited to the environment will
survive and gradually evolve
Natural Selection in Action: The Peppered Moth
 3 CYTOGENETICS LECTURE 1: INTRODUCTION TO CYTOGENETICS
 Types of Evolution
 Convergent Evolution
- Takes place when species of different
ancestry begin to share analogous traits
because of a shared environment or other
selection pressure.
 EX. Bats, Birds and Butterflies
have wings (analogous structure)
which is used to fly but they differ
on the developmental and
anatomical feature.
 EX. Sharks (fish), ichthyosaurs
(Reptile), and cetaceans (mammal)
have fins
 Divergent Evolution
- In which two species gradually become
increasingly different
- This often occurs when closely relates
species diversify to new habitats
 Convergent: different ancestry but
shares the same analogous trait
because they stay in the same
environment; Divergent: closely
related species become different
because of the difference in
environment
 EX. Humans and Apes
 EX. Finches on the Galapagos
Islands – different shapes of beaks
to take advantage of the different
kinds of food on different islands.
 Parallel Evolution
- Occurs when 2 independent but similar
species evolve in the same direction and
thus independently acquire similar
characteristics
 Sometimes difficult to differentiate
from convergent (different species
not closely related, but because of
the same environment, they
acquire the same trait); parallel
(closely related species in the
same environment)
 Ex. Flying Frog
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 Coevolution
- Occurs when closely interacting species
exert selective pressures on each other, so
they evolve together in a kind of
conversation of adaptations.
- EX. Predator to prey, bees to flowers –
coevolve together to adapt together
 Apes and Humans: it’s not true that humans came
from monkeys
 Origin of Humans according to evolution: Common
lineage of monkey and humans (common ape
ancestor with chimpanzees)
 Evolved differently from that common ancestor
because of the differences of environment
 1866: Gregor Johann Mendel (Austrian monk)
- Published Experiments in Plant Hybridization,
which lays out the basic theory of genetics
o It is widely ignored until 1900
o Rediscovered by other scientists
- Father of Genetics
 1869: Friedrich Miescher (Swiss physician)
- Isolated “nucleic acid” from pus cells
o Used to be called “Nuclein” (nucleus of the
WBC)
o Neither a protein, carbohydrate, nor lipid,
thus it was a novel type of biological
molecule
o After further study, it was found that
Nuclein was acidic
- Richard Altmann coined the word “nucleic acid”
- Now known as the DNA
 1871: The experiments of Ernst Haeckel proved that
the genetic material is indeed located in the nucleus
- DNA is located in the nucleus of eukaryotic cells
Major Events in the 20th Century
 1900: rediscovery of Mendel’s work by Robert Correns,
Hugo de Vries, and Erich von Tschermak
 1902: Archibald Garrod discovered that alkaptonuria, a
human disease, has a genetic basis.
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- Missing of HGD gene (codes Homogentisate More 20th Century Events

oxidase, important in the phenylalanine tyrosine  1926: Hermann J. Muller shows that x-rays induce
pathway) mutations.
 1904: William Bateson discovered linkage between - Radiation is capable of mutating gene
genes. Also coins the word “genetics”
- On the study of Mendel, there is “Independence
Assortment” (Law of Segregation, Law of
Independent Assortment), which means that if this
gene undergo cell division it will not affect another
gene. This gene has no interaction with another
gene.
- However, Bateson discovered 3 linkage or
interaction between genes (Non-Mendelian
concept)
 1928: Frederick Griffith – transformation and mice
- Genetics: “genno” greek word; to give birth
- Used Streptococcus pneumonia (caused
 1910: A year after, together with Reginald Punnett and
Pneumonia)
Bateson discovered the science of genetic linkage.
- 2 strains: S Strain (Virulent: can cause disease)
- They also coined the term “epistasis” (genetic
and R Strain (Non virulent: cant cause disease)
linkage) to describe the interaction between two
different traits
- Epistasis: interaction between genes that
influences a phenotype

 2 genes that controls 2 expression of hair (Brown

and Red)
- Mix living R strain and dead S strain killed the
 2 involve genes: Brown hair and MCR1 gene
mouse because the R strain developed the virulent
 Brown hair will only be acquired if it is paired with
characteristic of the S strain making it a virulent
MCR1 genes
strain
 If paired with an MCR1 variant, it will acquire red
- This experiment proved that DNA is a genetic
hair.
material
 2 different genes that affects phenotype
 1944: Oswald Avery, Colin MacLeod, and Maclyn
 1910: Thomas Hunt Morgan proved that genes are
McCarty show that DNA can transform bacteria,
located on the chromosomes (using Drosophila)
demonstrating that DNA is the hereditary material.
- Subject: Fruit Fly
- Chromosomal Theory of Inheritance: Genes are
located on the chromosomes like beads of strings
- Some genes are linked (on the same chromosome)
and always inherited together
- Eye color of fruit flies are sex-linked (Female – red
eye; Male – white eye)
 1918: Ronald Aylmer Fisher began the study of
quantitative genetics by partitioning phenotypic
variance into a genetic and an environmental
component
- Used mathematics to combine Mendelian genetics
and Natural Selection
- Contributed to the revival of Darwinism in the early
20th century revision of the Theory of Evolution
- Known as “Modern Synthesis” (Revived Darwin’s
 Remove lipids and carbs (they may affect the
study combined with Mendel’s)
results), leaving protein, RNA and DNA
- Used Quantitative Genetics
 Aliquoted into 3 set-ups
1. Proteinases (No protein)
2. Ribonuclease (No RNA)
3. Deoxyribonuclease (No DNA)
 5 CYTOGENETICS LECTURE 1: INTRODUCTION TO CYTOGENETICS
 3rd step: S Cells appeared on the 1st and 2nd set up
but not on the 3rd
o Because of the absence of DNA
 Conclusion: Transformation cant occur unless DNA
is present. DNA must be the hereditary material.
 1952: Alfred Hershey – Martha Chase, DNA is not a
protein
- In this experiment (Mid 20th cen), scientists were
still unsure if DNA or protein was the genetic
material of the cell
- Some viruses consisted solely of DNA or protein
(Bacteriophage – virus that infect a bacterium)
 2 Bacteriophages
1. Sulfur labeled protein capsule (sulfur is present
in proteins, not in DNA)
2. Phosphorus labeled DNA (present in DNA, not
in proteins)
 Viruses were allowed to infect the bacterium (e.coli)
 Virus and bacteria were separated by centrifugation
 After centri, the larger bacteria formed a solid pellet
while the smaller ones remained in the supernatant
 Bacterial pellet was found to be radioactive when
infected by the phosphorus labeled DNA
 DNA is the genetic material because it was
transferred to the bacterium
 1952: Rosalind Franklin – used a technique called x-ray
crystallography, it revealed
the helical shape of the DNA
molecule
- First to prove the double
helix structure of DNA
(however, she wasn’t the
one who received the
noble prize)
- Photo 51: an x-ray crystallography type of photo
- Fuzzy x-ray depicting a strand of DNA extracted
from human calf tissue
 1953: James Watson, Francis Crick, and Maurice
Wilkins determine the structure of the DNA molecule,
which leads directly to knowledge of how it replicates
- Maurice Wilkins was with Rosalind Franklin
- They determined the structure of DNA structure
which leads to the study of how it replicates
- Recognized as the one who discovered the
secondary structure of DNA – Double helix
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 Mid 1958: Matthew Meselson-Franklin Stahl, DNA
replication details
- DNA replication follows a semiconservative model
of replication
 Product is a combination of a parent strand
and a daughter strand
 1966: Marshall Nirenberg solves the genetic code,
showing that 3 DNA bases code for one amino acid
- 64 possible codons
- 3 do not code for amino acids (Stop codons: UAA,
UAG, UGA)
- Start codon: AUG
 1970: the independent and simultaneous discovery of
reverse transcriptase in retroviruses (then RNA tumor
viruses) by David Baltimore and Howard Temin
revolutionized molecular biology and laid the
foundations for retrovirology and cancer biology.
- Only nucleic acid capable of replication is DNA
- For the RNA to replicate, the process must be
reversed
- Reverse Transcriptase: from RNA to DNA with the
use of this enzyme
- HIV: reproduces itself despite being an RNA with
the use of reverse transcriptase enzyme
 1970: Reverse transcriptase – an enzyme found in
retroviruses, was discovered and was used in cloning
genes.
- Reverse transcriptase makes DNA from an RNA
template – it does the opposite of transcription
 1972: Stanley Cohen and Herbert Boyer combine DNA
from two different species in vitro, then transform it into
bacterial cells: first DNA cloning
- Removed a plasmid from a bacterium (Plasmid:
extra chromosomal DNA in a bacterium)
- Treated with a restriction enzyme (removed a part
from a plasmid and replaced with a Frog DNA
fragment)
- Forming a recombinant DNA (2 different genetic
material)
 6 CYTOGENETICS LECTURE 1: INTRODUCTION TO CYTOGENETICS 01/23/2021

 1977: Scientist Frederick Sanger o Alleles separate during the formation of

- Introduced the process of sequencing the genome
(set of genes of an organism) of a bacteriophage.
- Later, scientists have done it in other organisms as
well.
 1983: Kary Mullis
- Invented the process called Polymerase Chain
Reaction (PCR)
o In this technique, a segment of the DNA is
amplified until millions of copies are
produced in just a short period of time
o In vitro version of DNA Replication
o Inside the body – DNA repli; in the
laboratory – PCR
 1990: The Human Genome Project was started
- GOAL: To sequence and map the genome
(collection of all the genes) of man
 1996: Ian Wilmut and Keith Campbell
- They have successfully cloned Dolly the sheep
- Dolly was the first mammal to be cloned from an
adult cell.
 There were animals who were cloned
before Dolly (cloned from Embryo)
 Dolly is the first one to be cloned
successfully from adult cell (mammary
gland of sheep)
 Scientists of Roslin Institute of Scotland,
Dolly was the only lamb born from 277
attempts and it was a major story around
the world
 Dolly the sheep died early (adult genetic
material)
 2003: Sequence of the entire human genome is
announced
gametes, half of the germ cells carry one
allele and half carry the other
o Result of the behaviour of chromosomes
during meiosis
 2nd Law of Mendel (Law of Independent
Assortment)
o Alleles at separate loci are inherited
independently
 3rd Law of Mendel (Law of Dominance)
 Mitosis
o Cell division in somatic cells (non germ cell)
o Muscle, White blood cells
o Nonreductional mitosis
 Daughter cells has the same number of
chromosome with the parent cell
 Meiosis
o Cell division in developing germ cell in the
ovary and the testis
o Reductional
 As meiosis goes on, number of
chromosome is reduced into half
(diploid to haploid)

Areas of Genetics  Chromosomal Mapping

o Assignment of genes to specific locations
Classical Molecular Evolutionary on a chromosome
Genetics Genetics Genetics
(Transmission)
Mendel’s Genom - total set Quantitative
principles of genes in a genetics
particular
organism
Meiosis + mitosis DNA structure Population
genetics
Sex Chemistry of Evolution
determination DNA (replication,
o Map locations of different genes which calls
mutation and
for different traits in a particular
repair)
chromosome
Sex linkage Transcription Speciation
 Extrachromosomal inheritance (extranuclear
Chromosomal Translation
inheritance)
mapping o A non-mendelian pattern of inheritance
Cytogenetics Control of gene governed by the DNA present in the
expression cytoplasm
DNA Cloning o Outside the
nucleus
 Classical Genetics (based on Mendel’s 1st and 2nd o Mitochondrial
laws) inheritance
 1st Law of Mendel (Law of Segregation)
 7 CYTOGENETICS LECTURE 1: INTRODUCTION TO CYTOGENETICS 01/23/2021

 Sex determination o There are gene expression controls (gene

o The establishment of the sex of an regulation)
organism

o Inheritance at the time of fertiization of

certain genes
o As early as fertilization, by the union of the
egg cell and sperm cell, we can already
identify the sex based on the number of
chromosome (23rd position of the
chromosome)
o XX – female; XY – male
 Sex linkage
o The phenotypic expression of an allele
related top chromosomal sex of an
individual
o Association between genes in sex
chromosomes such that the characteristics
determined by these genes appear
frequently in one sex than the other.
 Sex-linked characteristics
o There is a link or connection between the
expression of the gene and the sex of the
organism
 Cytogenetics
o Focuses on the chromosomes and the
conditions/abnormalities associated with
chromosomes.
 Molecular Genetics (based on the Central Dogma of
Molecular Genetics)
 Gene activity is controlled first at the level of
transcription
o Achieved through the interplay within
proteins that bind to a specific DNA
sequence and DNA binding sites
- Ex. First gene expression control
happens before the initiation phase of
transcription
- Remember: there are transcription
factors that will bind to the promoter
sequence of the DNA, those are
activators and will try to attract RNA
polymerase II
- Bind to the promoter sequence and
start transcription
- If those are inhibitors, transcription will
not be initiated.
 Gene expression are controlled along the way

 DNA Cloning – is a molecular biology technique

that makes many identical copies of DNA such as a
gene
o New gene will be used for research or other
study

 DNA
o Structure
o Chemistry
o Replication
o Mutation
o Repair
 Transcription and
Translation
o Transcription: copying DNA to mRNA
o Translation: mRNA will be transported to
the ribosome for protein synthesis
 Control of Gene Expression (Gene expression
regulation)
o Process of controlling which genes in a
cell’s DNA are expressed (used to make a
functional product such as protein)
o 2 steps: Transcription and Translation
 8 CYTOGENETICS LECTURE 1: INTRODUCTION TO CYTOGENETICS 01/23/2021

 Evolutionary Genetics (based on the theory of
National Selection proposed by Darwin)
 Hardy-Weinberg Equilibrium
o The genetic variation in a population will
remain constant from one generation to the
next in the absence of disturbing factors
o When mating is random in a large
population without disturbing factors, the
law predicts that both genotypes and the
allele frequencies will remain constant
because they are in equilibrium
o Can’t be applied all the time, because it can
be disturbed by a number of forces
 Ex. Mutations (introduction of new
alleles), natural selection (not all
can pass genetic variation from
one generation to another because
not all can survive), non- random
mating, genetic drift, gene flow
o All this disturbing factors commonly occur
in nature, this principle rarely applies in
reality
o Hardy-Weinberg Equilibrium describes an
ideal state that there is no disturbing factor
and genetic variations in nature can be
measured as changes from this equilibrium
state
 Evolution – the change in the characteristics of a
species over several generations and relies on the
process of natural selection
 Natural selection: only those with best
characteristics who can adapt to the
environment can survive and pass his/her
characteristic from one generation to
another
 This theory of evolution is based on the
idea that all species are related and
gradually change over time
 Speciation – evolutionary process by which
populations evolve to become distinct species
 Ex. Finch Bird from Galapagos Island
(same characteristics, but this species of
birds went to different environment, and
they need to adapt to survive) = changes in
beak
o Divergent evolution

 Quantitative Genetics (R.A Fisher)

o Study of the genetic bases underlying
phenotypic variation among individuals
 Physical characteristic differences
among individuals
o With a focus primarily on traits that take a
continuous range of values
 Ex. Height (variation in height) and
Skin Color
 Population Genetics
o The study of genetic variation within
populations
 This type of genetic involves the
examination and modelling of
changes in the frequencies of
genes and alleles in a population
over space and time
 In a natural population, the genetic
populations gene pool may change
over time (because of evolutionary
events, mutations which will really
change the characteristic of the
population)