CYTOGENETICS – MEDT 07

Lesson 1: Introduction

Genetics - Comes from the Greek word “gen” meaning to become or grow into
something
- Branch of Biology that deals with the principles of heredity and variation of
living things
- Affects all aspects of biology, as well as natural and behavioral sciences
William Bateson Coined the term GENETICS (1906)
Genetics Seeks to 1. The molecular and physical bases of biological diversity
Understand: 2. Mechanism resulting from these diversities
3. Principles that govern their heredity from one generation to another
Inheritance Theories (BTTCG)
throughout the years
1. Blending
2. Theory of Pangenesis
3. Theory of Inheritance of Acquired Characteristics
4. Chromosome Theory of Inheritance
5. Germplasm Theory
Blending - 19th century (by different biologists including Charles Darwin)
- the offspring have a blend or mix of the characteristics of their parents
Theory of Pangenesis - 1868, Charles Darwin
- Development theory of Heredity
- Suggested that all cells in an organism are capable of shedding minute
particles called gemmules, that can circulate throughout the body and
finally congregate in gonads (then transferred to offspring). Gemmules are
carried in the blood stream and are believed to be capable of self-replication
- Gemmules develop in their associated body parts as offspring matures
- Implied that changes to the body during an organism’s life would be
inherited (as proposed in Lamarckism)
- Darwin also hypothesized that gemmules can survive and multiply outside
the body
- Led to the proposed theory of Lamarckism
- Was also proposed by Aristotle (if you removed a part of a plant, those
same part/s removed will be absent in the offspring’s phenotype)
Theory of Inheritance of - Jean Baptiste De Lamarck
Acquired Characteristics - Also known as Lamarckism
- With evolutionary thought
- Example: giraffes were once short necked, but slowly developed long
necks upon reaching the tall trees for food (after consuming the food on the
lower parts of the land)
- The long-necked giraffes then passed the characteristics to its offspring
Chromosome Theory of - Boveri and Sutton (1902)
Inheritance - States that genes are found on specific locations on chromosomes, and
that behavior of chromosomes during meiosis explains the Mendel’s law of
inheritance
- Homologous chromosome pairs are independent of other chromosome
 pair
- Chromosome from each homologous pairs are sorted randomly in pre-
gametes, and the parents synthesize gametes that contain only half of their
chromosomes
- Gametic chromosomes combine during fertilization to produce offspring
with the same chromosome number as their parents
Thomas Hunt Morgan Led to the theory of Gregor Mendel that is accepted today (experiment
Experiment about fruit flies – eye color in fruit flies; first x linked trait discovered)
Germplasm Theory - By August Weismann
- Heritable information is transmitted only by germ cells (sperm, eggs) in
gonads (ovaries, testes), and not by somatic cells

History of Genetics

Year Person/s Contributions

Greeks Lineages of gods and kings
Aristotle Theory of Pangenesis
1842 Karl Wilhelm von Nageli Discovered chromosomes in plant cells
1865 Gregor Mendel Published his experiments on pea plants (Pisum
sativum) “Father of Modern Genetics”
1873 A. Schneider First account of mitosis
1879 W. Flemming Longitudinal splitting of chromosomes during cell
division
1883 Beneden Showed that somatic cells contain diploid number
of chromosomes while gametes contain haploid
number
1902 Sutton and Boveri Proposed the “chromosome theory of
inheritance”
1902 Archibald Garrod Discovered the inheritance pattern and metabolic
nature of alkaptonuria; Coined the term “inborn
error of metabolism”
1905 Wilson and Stevens Proposed that certain chromosomes determine
sex
Year Person/s Contributions
1906 Bateson Coined the term “genetics”
1909 Wilhelm Johannsen Coined the terms gene, genotype, and phenotype
1910 Thomas Hunt Morgan Proved that genes are carried on chromosomes.
He also showed that some characteristics are
carried on the sex chromosomes
1928 Frederick Griffith Discovered “transformation” in bacteria
1944 Avery, MacLeod, and McCarty Identified DNA as the genetic material
1952 Alfred Hershey and Martha Chase Further confirmed that DNA is the genetic material
1953 James Watson and Francis Crick DNA Structure
1958 Meselson and Stahi Semi-conservative DNA replication
1985 Robert Sinsheimer Pioneered discussions to sequence human genome
1986 Fred Sanger Polymerase chain reaction (PCR)
 1990s- Human Genome Project
2000s

Importance of Genetics

Plant, Animal, and GMO (Genetically Modified Organism) for the development of food (e.g., US
Microbial Improvement grows tomatoes that don’t naturally grow in their country due to weather
conditions, disadvantage: will not have the same benefits)
Medicine Supplements, cure treatment

Genetic Counselling Biological relations (e.g., knowing biological parents, ancestors, etc.)

Legal Applications Medico legal, forensics (DNA from site then tested for matching), rape cases,
etc.

Branches of Genetics

Branch Description
Cytogenetics Study of chromosomes, provides cytological explanation of different genetic
principles
Molecular Genetics Study of chemical structures of genes at a molecular level; also includes the
function of the gene and the regulation of its activity
Biochemical Genetics Study of metabolic processes in association with the generic control of
enzyme production; deals with the “inborn errors of metabolism”
Cancer Genetics Study of genetic mutations that lead to cancer
Immunogenetics Study of the genetics of antibody production
Developmental Genetics Study of the genetic control throughout the embryonic development
Behavioral Genetics Study of the influence of genes on the behavior of an individual
Population Genetics Study of the laws of genetics acting on human population, deals with the
frequencies of genes in human population and the rate at which they mutate

Karyotype An individual’s complete set of chromosomes. The term also refers to a

laboratory-produced image of a person’s chromosomes isolated from an
individual cell and arranged in numerical order.
Karyogram A diagram or photograph of the chromosomes of a cell, arranged in
homologous pairs and in a numbered sequence. Also called ideogram.
Diploid Refers to the presence of two complete sets of chromosomes in an
organism’s cells, with each parent contributing a chromosome to each pair.
Humans are diploid, and most of the body’s cells contain 23 chromosome
pairs. Human gametes (egg and sperm cells), however, contain a single set of
chromosomes and are said to be haploid.
Haploid Refers to the presence of a single set of chromosomes in an organism’s
cells. Sexually reproducing organisms are diploid (having two sets of
chromosomes, one from each parent). In humans, only the egg and sperm
cells are haploid.
 Homozygous Refers to having inherited the same versions (alleles) of a genomic marker
Chromosomes from each biological parent. Thus, an individual who is homozygous for a
genomic marker has two identical versions of that marker. By contrast, an
individual who is heterozygous for a marker has two different versions of
that marker.
Heterozygous Refers to having inherited different versions (alleles) of a genomic marker
Chromosomes from each biological parent. Thus, an individual who is heterozygous for a
genomic marker has two different versions of that marker. By contrast, an
individual who is homozygous for a marker has identical versions of that
marker.
Hemizygous A chromosome in a diploid organism is hemizygous when only one copy is
Chromosomes present. The cell or organism is called a hemizygote. Hemizygosity is also
observed when one copy of a gene is deleted, or, in the heterogametic sex,
when a gene is located on a sex chromosome.
Genotype A scoring of the type of variant present at a given location (i.e., a locus) in
the genome. It can be represented by symbols. For example, BB, Bb, and bb
could be used to represent a given variant in a gene. Genotypes can also be
represented by the actual DNA sequence at a specific location, such as CC,
CT, TT. DNA sequencing and other methods can be used to determine the
genotypes at millions of locations in a genome in a single experiment. Some
genotypes contribute to an individual’s observable traits, called the
phenotype.
Phenotype Refers to an individual’s observable traits, such as height, eye color, and
blood type. A person’s phenotype is determined by both their genomic
makeup (genotype) and environmental factors.
Dominant Allele Refers to the relationship between an observed trait and the two inherited
versions of a gene related to that trait. Individuals inherit two versions of
each gene, known as alleles, from each parent. In the case of a dominant
trait, only one copy of the dominant allele is required to express the trait.
The effect of the other allele (the recessive allele) is masked by the
dominant allele. Typically, an individual who carries two copies of a
dominant allele exhibits the same trait as those who carry only one copy.
This contrasts to a recessive trait, which requires that both alleles be present
to express the trait.
Recessive Allele Refers to the relationship between an observed trait and the two inherited
versions of a gene related to that trait. Individuals inherit two versions of
each gene, known as alleles, from each parent. In the case of a recessive
trait, the alleles of the trait-causing gene are the same, and both (recessive)
alleles must be present to express the trait. A recessive allele does not
produce a trait at all when only one copy is present. This contrasts to a
dominant trait, which requires that only one of the two alleles be present to
express the trait.
Codominant Alleles Refers to a type of inheritance in which two versions (alleles) of the same
gene are expressed separately to yield different traits in an individual
Gene Considered as the basic unit of inheritance. Genes are passed from parents
to offspring and contain the information needed to specify physical and
biological traits. Most genes code for specific proteins, or segments of
 proteins, which have differing functions within the body. Humans have
approximately 20,000 protein-coding genes.
Chromosomes Chromosomes are threadlike structures made of protein and a single
molecule of DNA that serve to carry the genomic information from cell to
cell. cell. In plants and animals (including humans), chromosomes reside in
the nucleus of cells. Humans have 22 pairs of numbered chromosomes
(autosomes) and one pair of sex chromosomes (XX or XY), for a total of 46.
Each pair contains two chromosomes, one coming from each parent, which
means that children inherit half of their chromosomes from their mother
and half from their father. Chromosomes can be seen through a microscope
when the nucleus dissolves during cell division.
Autosome One of the numbered chromosomes, as opposed to the sex chromosomes.
Humans have 22 pairs of autosomes and one pair of sex chromosomes (XX
or XY). Autosomes are numbered roughly in relation to their sizes. The
largest autosome – chromosome 1 – has approximately 2,800 genes; the
smallest autosome – chromosome 22 – has approximately 750 genes
Sex Chromosomes A type of chromosome involved in sex determination. Humans and most
other mammals have two sex chromosomes, X and Y, that in combination
determine the sex of an individual. Females have two X chromosomes in
their cells, while males have one X and one Y
Homologous Two chromosomes in a pair – normally one inherited from the mother and
Chromosomes one from the father. For example, the two copies of Chromosome 1 in a cell
would be referred to as homologous chromosomes
Locus As related to genomics, it is a physical site or location within a genome (such
as a gene or another DNA segment of interest), somewhat like a street
address. The plural of locus is loci.
Allele One or two or more versions of DNA sequence (a single base or a segment
of bases) at a given genomic location. An individual inherits two alleles, one
from each parent, for any given genomic location where such variation
exists. If the two alleles are the same, the individual is homozygous for that
allele. If the alleles are different, the individual is heterozygous.
Mutation A change in the DNA sequence of an organism. Mutations can result from
errors in DNA replication during cell division, exposure to mutagens or a
viral infection. Germline mutations (that occur in eggs and sperm) can be
passed on to offspring, while somatic mutations (that occur in body cells) are
not passed on.

MITOSIS AND MEIOSIS

PHASE SUB-PHASE PROCESSES

Resting/Quiescent Gap 0 Resting Stage
(G0)
 Interphase Gap 1 Growth phase; synthesis of
(G1) amino acids and other
*non-mitotic phase necessary biochemicals for S
*period between 2 successive phase
mitoses *Cells increase in volume (by
*preparation for cell division water and nutrients)
*distinguishable biochemically, *Build new cytoplasm and
but not morphogically cytoplasmic organelles
*Chromosomes not visible
*It takes 9 hours
Synthesis DNA Replication
(S)

*most important cellular

activity
*formation of sister chromatids
held by centromere
Gap 2 Synthesis of chemicals
(G2) necessary for microtubule
production
*RNA and protein synthesis for
chromosome and mitotic
spindle synthesis, condense
*3 hours
M Phase/Dividing Stage Karyokinesis Nucleus divides
Cytokinesis Cell divides into daughter cells

Mitosis - Genetic and chromosome composition of a cell is faithfully

reproduced in each daughter cell.
- Reproduction for unicellular organisms; growth and replacement for
multicellular organisms
- Occurs in somatic cells of eukaryotes
Consequences of 1. Product of mitosis: two daughter cells with the same chromosomal
Mitosis compositions as the parent cell.
2. A different allele may arise only by mutation. Chromosomes may,
also be visibly altered.
3. Altered genes and chromosomes may be replicated to their new
form.
Meiosis - Special kind of cell division in sexually reproducing organisms
- Reduction of chromosome number to half of usual number in
preparation of the fusion of male and female gametes during
fertilization
- Like mitosis, preceded by interphase
- Unlike mitosis, consists of two nuclear divisions in rapid sequence:
a. Meiosis I
b. Interkinesis
c. Meiosis II
 Meiosis I Reduction division – Prophase I (with 5 stages), Metaphase I, Anaphase I,
Telophase I
Interkinesis Transitional phase

Meiosis II Equation division – Prophase II, Metaphase II, Anaphase II, Telophase II;
proceeds like mitosis but with only half the chromosome number

MEIOSIS

STAGE DESCRIPTION

Leptotene Almost the same as the prophase stage in mitosis; chromosomes condense
to form visible strands
Zygotene Pairing of homologous chromosomes (each chromosome “searches” for its
homologous pair which will later show tetrads/bivalents)
Synaptonemal complex – zipper-like pairing
Pachytene Thickening of chromosomes, exhibiting tetrads/bivalents (four chromatids).
Break, repair, crossing-over, formation of chiasma
Diplotene Longitudinal separation initiates diplonema. Homologues separate from
the centromere toward both ends except at the chiasmata: later chiasmata
move toward the end.
Diakineses Chromosomes are more contracted: nucleolus disintegrate spindle
formation.

Consequences of 1. Product of Meiosis I: two daughter cells with half the chromosomal
Meiosis compositions of the parent cell. They may have different genetic
composition due to initial differences between the parent cells and
due to chiasmata formation.
2. Because of the reduction division, the conservation of the number
of chromosomes from generation to generation is possible in
sexually producing organisms.
3. Product of Meiosis II: each of the four daughter cells contains one
representative for each pair of chromosomes (different genetic
composition)

INTRODUCTION TO CYTOLOGY

CELL STRUCTURE AND FUNCTION

Constituents of Cell a. Phospolipid bilayer (continuous barrier)

Membrane b. Cholesterol – fluid, reduced permeability, increased packing of
phospholipids
c. Proteins:
Integral membrane (transmembrane) protein
- permanently attached, bilayer
- transporters, linkers, channels, receptors, enzymes
 - involved in accumulation and transduction of energy
- responsible for cell adhesion
Peripheral membrane proteins (inner/outer)
- semi-fixed, one layer
- attached to integral membrane protein/penetrate peripheral regions
of the lipid bilayer
- membrane binding proteins
- promote rearrangement, dissociation, conformational changes
within many protein structural domain (resulting in activation of
biological activity
- facilitates the assembly of multiprotein complexes
d. Glycocalyx (cell coat): glycoprotein and glycolipids
- Barrier containing glycoprotein and glycolipids
e. Unit membrane
- Limiting membrane of cells and various organelles
Cytoplasm a. Cytoplasmic Matrix (Cytosol)
- Where organelles float
- Contains proteins, amino acids, mRNA, ribosomes, sugar, ions,
messenger molecules, etc.
b. Cytoskeleton
- Enhance structural integrity, cell shape, and cell and organelle
motility.
- Microfilaments
- Intermediate filaments
- Microtubules
Organelles in Cytoplasm 1. Mitochondria – generate mist chemical energy to power the cell,
powerhouse, produces ATP.
2. Ribosomes – synthesis of protein, link amino acids together in the
order specified by the codons of mRNA to form polypeptide chains.
3. Endoplasmic Reticulum (Rough and Smooth) – synthesis, folding
and transport of proteins.
4. Golgi Complex – membrane bound sacks, process, and package
macromolecules.
5. Lysosomes – intracellular digestion, removal of dead cells, role in
metamorphosis, help in protein synthesis, help in fertilization, role
in osteogenesis, malfunction (autolysis in cartilage and bone
tissue)/
6. Peroxisomes (microbodies) – breakdown of long, fatty acids
through beta oxidation, then shuttles to mitochondria where it is
eventually broken down to carbon dioxide and water.
7. Centrosome (2 centrioles, diplosomes) – involved in cell division,
proteins called microtubules assemble into a spindle between 2
centrosomes and help separate the replicated chromosomes into
the daughter cells.
Mitotic Apparatus 1. Spindle – segregates chromosomes into the daughter cells during
mitosis.
2. Microtubules – conveyer belts (moves vesicles, organelles, via
 special attachment proteins).
3. Centrosome – main microtubule organizing centers.
4. PCM (Pericentriolar Material) – platform for protein complex that
regulates the organelles trafficking, protein degradation and
spindle assembly.
5. Centrioles – help in the formation of spindle fiber that separate the
chromosome during cell division/mitosis
6. Kinetochore – where microtubules of the spindle attach
Nucleus - Contains genetic material (DNA)
- Facilitate transcription and replication.
- Largest organelle.

1. Nuclear Membrane: outer, perinuclear space, inner

- Aka nuclear envelope
- Protect the genetic material from the chemical reactions that take
place outside the nucleus.

2. Nuclear Matrix
- Chromatin (Chromosomes at interphase) – composed of DNA and
Histones (packages into thin, stringy fibers), undergoes further
condensation to form chromosomes.
- Chromatid – either of the 2 strands of replicated chromosomes. Are
connected by a centromere and are called sister chromatids.
Human Genome - The full genetic complement of a mitochondrion
(Mitochondrial) - Small portion of the DNA of the total DNA and eukaryotic cells
- In most species is solely inherited from the mother
- In humans, mitochondrial DNA contains approx. 16,600 base pairs
encoding 37 genes.
Human Genome - Histones – a family of basic proteins that associate with DNA in the
Chromosomes: DNA and nucleus
Histones - Nuclear DNA – does not appear in linear strands (highly condensed
and wrapped around histones to fit inside the nucleus)
- Homologous/sister chromosomes – similar but not identical, either
one of the 2 chromatids of the same chromosome joined together
by a common centromere
- Centromere – links the pair of sister chromatids
- Non-homologous/non-sister chromatids – either one of the 2
chromatids of the paired homologous chromosome
- Nucleolus – has ribosomal RNA, rRNA synthesis and ribosome
biogenesis
Chromosome (process) 1. Chromatins are connected by centromere.
2. Duplicated DNA (sister chromatids) – also connected with
centromere in the middle.
3. Chromatids wrap into histone will form chromosome

Mendelian Genetics
 Gregor Mendel - Published Chromosome Theory of Inheritance using Garden Peas
(Pisum sativum)
- His work lasted for 8 years
- Reported in 1865 in a lecture of 40 members of Brunn Natural
Science Society
- Published in 1866
- Work was left unappreciated
Possible reasons why 1. No one really understood it. Knowledge of statistics was necessary
Mendel’s Work for proper understanding of the results. People were not ready to
Remained neglected for believe that the inheritance is statistical in nature.
35 years: 2. Biologists were preoccupied. Darwin’s theory of evolution appeared
in 1859, a few years prior to Mendel’s report on his experiment.
3. Relevant details about cell division and chromosomes were not
known
Mendel’s 1. Use of garden peas, Pisum sativum L.: self-pollinated, relatively
methodologies homozygous, produced high number of seeds.
2. Focused on the single trait at a time: chose plan traits with clear-cut
differences
3. Use of true breed (pure breed): grew them for 2 years, chose
parental materials
4. Quantitative approach: classifies hybrids and determined
frequencies
5. Formulated theories to explain experimental results
6. Formulated appropriate experimental tests to validate his theories
(self-pollination vs cross-pollination, monohybrid vs dihybrid)
Monohybrid Cross - Mendel selected pure/homozygous variety for a single pair of
contrasting characters known as the parental plants (P generation)
Example: pure tall and pure dwarf plants
- Cross Pollination of the P generation: 1st filial generation
Result: all are tall plants
- F1 self pollinated: 2nd filial generation
Result: 75% tall, 25% short
- F2 allowed to self pollinate: 3rd filial generation
Result: 3:1 ratio
Dihybrid Cross - Conducted by mendel to know how different pairs of character
would behave in relation to each other in their inheritance from a
generation to another.
- Two pairs of contrasting characters.
Example: yellow round and green wrinkled seeds.
Result: 9:3:3:1
Mendel’s conclusion 1. Each inheritable character is determined by factors – elementen:
now known as genes.
2. These factors are transmitted from one generation to the next
through gametes.
3. The factor for each character come in pairs (homologous
chromosomes).
4. At the time of formation of gametes, members of the pair of genes
 separate from each other (meiosis).
5. In monohybrid cross, only one character is expressed in the F1,
while both characters are expressed in F2.
6. When characters are transmitted from one generation to the next,
they follow statistical laws.
7. In dihybrid cross, it was observed that the assortment of genes of
one pair was independent of the other pair.
Punnett Squares - Named after and developed by Reginald Crundall Punnett
- A visual representation of Mendelian inheritance: chart or graphic
way to show and predict all possible gene combinations in a cross of
parents, whose genes are known.
- May be used for monohybrid, dihybrid, and even trihybrid crosses
(for trihybrid crosses, the fork-line method may be used due to
confusing combinations)
Test Cross - Developed by Mendel to know whether an organism that expressed
a dominant trait is heterozygote or homozygote.
- The dominant-expressing organism is crossed with a homozygote
recessive organism for the same characteristic.
- If the entire F1 generation exhibits the dominant trait, then the
organism in question is homozygote.
- If 50% of the F1 generation exhibits the recessive trait, then the
organism in question is heterozygote for the dominant allele.
Punnett Square - Usually, the one on the top is the dominant parent.
- Dominant is represented by capital letter
Genotype - Genetic constitution of an individual for any particular character or
trait.
- Represented by letters/symbols (e.g., TT, Tt, tt)
Genotypic Ratio - The ratio of different genotypes
- Order: dominant first, then recessive
Phenotype - Physical appearance of an individual for any particular trait
- Observable characteristic (e.g., tall, short)

Phenotypic Ratio - The ratio of different phenotypes

- Order: dominant first, then recessive
Dominance and - Take root from the fundamental concept of one allele of a gene
Recessiveness masking the effect of another allele at the same locus.
- Resulting phenotype is affected by what the dominant allele codes
for (usually a protein which directs how attributes or processes are
to be carried on).
- Recessive alleles usually do not code for any protein when in
combination with its dominant counterpart.
- Denotation: Capital letters for dominant allele, lowercase of the
same letter for recessive.
Mendelian Laws of 1. Law of Uniformity
Inheritance 2. Law of Segregation
3. Law of Independent Assortment
Law of Uniformity Cross of plants with two contrasting traits do not cause the blending of
 traits. If any trait is not expressed in the first generation, it may reappear
without change in the subsequent generation.
Law of Segregation - Each individual possesses two factors for a particular trait. During
gamete formation, each member of the pair of genes separates
from one another so that each gamete carries only one factor.
- When the factors of a pair separate during gamete formation, they
are completely unaltered, neither factor has “taken over anything
from the other”
Law of Independent - Members of different gene pairs assort independently of one
Assortment another during gamete formation; therefore, new combination of
traits is produced in offspring

Terminologies (Cells)

Cells - Our bodies include more than 290 specialized, or differentiated, cell
types that aggregate and interact from the four basic tissue types.
No. of Cells in the Healthy human body includes about 39 Trillion cells that are bacterial,
Human Body fungal, or protozoan, as well as many viruses.
Four basic tissue types - Epithelial
- Connective
- Muscle
- Nervous
Somatic Cells - Aka: body cells
- Most cells are somatic.
- Have 2 copies of the genome.
- Diploid
Germ Cells - Sperm and egg cells
- Have 1 copy of the genome
- Haploid
Stem Cells - Diploid cells that divide to give rise to differentiated cells and to
other stem cells in a process called self-renewal.
Three General Sources 1. Embryonic Stem Cells
of Stem Cells 2. Induced Pluripotent Stem Cells
3. Adult Stem Cells
Progenitor Cell - Cannot self-renew, and its daughters specialize as any of a restricted
number of cell types.

Number of possible 1. Totipotent

fates of daughter cells 2. Pluripotent
(stem cells and 3. Multipotent
progenitor cells)
Totipotent Means that it can give rise to every cell type, including cells of the
membranes that support the embryo.
Pluripotent Daughter cells have fewer possible fates.
Multipotent Daughter cells have only a few developmental “choices”
Cell Components

Basic Life Functions All cells have features to perform basic life functions of (RGRE)
- Reproduction
- Growth
- Response to stimuli
- Energy use
Single Celled Organisms - Amoeba, paramecium (have complex cells)
- Bacteria (most abundant)
3 Major Domains of Life 1. Archaea – single celled, prokaryotic
2. Bacteria – single celled, prokaryotic
3. Eukarya – multicellular (but includes single-celled that have nuclei),
eukaryotic
 All contain globular assemblies of RNA and protein called
Ribosomes.
Prokaryotic Cells Do not have nucleus
Eukaryotic Cells Distinguished from Prokaryotic by structures called organelles, may have
risen from an ancient fusion of a bacterium with an Archaean.
Organelles Perform specific functions within a cell.
Cell essentials - Cells are composed of molecules.
- Cells require vitamins and minerals in much smaller amounts.
Macromolecules Large biochemicals of life
Major Macromolecules 1. Carbohydrates (sugar and starch)
2. Lipids (fats and oil)
3. Protein
4. Nucleic Acids (DNA and RNA)
Carbohydrates - Provide energy
- Contribute to cell structure
Lipids - Form the basis of some hormones
- Form membranes
- Provide insulation
- Store energy
Protein - Enable blood clot
- Form contractile fibers of muscle cells
- Form the bulk of connective tissues
Enzymes Important protein that facilitate/catalyze biochemical reactions (to occur
fast and sustain life).
Nucleic Acid - DNA and RNA – important to the study of genetics
- Translate information from past generations into specific collections
of protein that give a cell its characteristics
3 cellular functions 1. Secretion
2. Digestion inside cells
3. Energy production
Secretion The release of a substance from a cell (begins when the body sends a
biochemical message to a cell to begin producing substance)
Human Microbiome Cells within and on us that are not actually of us
Probiotics Live microorganisms, such as bacteria and yeasts, that, when ingested,
 confer a health benefit.
(e.g., certain Lactobacillus strains added to yogurt help protect against
salmonella foodborne infection)
Fecal Transplantation A treatment based on altering the microbiome that replaces hundreds of
bacterial species at once.

Non-Mendelian Genetics

Law of Linkage Parental Types – offspring with phenotypes that matches with one of the
parental phenotypes.

Recombination Types – offspring with phenotypes that do not match either

parent (new combination) = caused by genetic recombination

*50% frequency of recombination is observed

William Bateson, Edith Cross-bred pea plants, similar to Mendel’s, that resulted to the discovery of
Rebecca Saunders, exceptions to Mendel’s, that resulted to the discovery of exceptions to
Reginald Punnett (1905) Mendel’s law of independent assortment
Exception to Dihybrid Rate of recombination is not 50% (greatly less than recessive), found out
Cross that there was partial linkage
Does this disprove NO, in fact, this is an improvement in Mendel’s observations, now we know
Mendel’s Law of that genes are in the Chromosomes.
Independent
Assortment? - Further evaluated by THOMAS HUNT MORGAN
Experimented Using Thomas Hunt Morgan
Flies
Thomas Hunt Morgan Experimented using flies. Supported the Chromosome Theory of
Inheritance
Thomas Hunt Morgan’s 1. Wild phenotypes vs Mutant phenotype
Experiment 2. Linkage of eye color and wing size
Chromosome Theory of 1. Mendelian genes have specific loci (positions) on chromosomes.
Inheritance 2. It is the chromosomes that undergo segregation and independent
assortment.
*50% of frequency of recombination is observed for genes on different
chromosomes
Linkage (unlinked) - Genes found on different chromosomes are unlinked (if they
crossover, 50% of recombination is observed)
- Genes found on the same chromosome, but the distance is large are
unlinked (can travel independently onto the next generation, chance
for crossing over is very high, resulting to more percentage of
recombinant, and less percentage of parental offspring)
Linkage (linked) - Genes found on the same chromosomes are linked.
- Genes found on the same chromosome, but distance is small are
linked (can travel as a whole to the next generation, resulting to less
percentage of recombinant, and more percentage of parental
offspring)
Types of Linkage 1. Complete Linkage
 2. Incomplete Linkage
Complete Linkage - Genes are so closely associated that they are always inherited
together. Result is always parental type (100%).
Incomplete Linkage - Linkage is not complete and gene pairs assort at least partially
independent of each other (less than 50% recombination).
- Morgan pointed out that genes were arranged in a linear order
along the length of the chromosome and linkage was an indication
of their relative proximity to each other.
- Genes close to each other = higher chance of being inherited
together
- Recombinants are formed by “an exchange of parts between
homologous chromosomes.”
- Crossing-over between sister chromatids will NOT produce
recombinant types (because they have the same set of genes)
Crossing over between - If there will be crossing-over between genes, the result will still
sister chromatids have the same order since Sister Chromatids have the same set of
genes.
- No recombinant type.
Crossing over between Will give these combinations:
non-sister chromatids 1. Single crossover
2. Two-strand double crossover
3. Three-strand double crossover
4. Four-strand double crossover
2 Types of Forms in 1. Cis form
Crossover - There is coupling phase.
- The link genes enter the zygote together
2. Trans form
- There is repulsion phase
- The link genes enter the zygote separately and become located on
different chromosomes.

The Human Chromosomes

Chromosomes - Present in the nuclei of cells but only detectable during the mitotic
stage (most condensed form in mitotic stage)
- During the cell cycle, the absolute length of chromosomes differ
Chromatin - Strands/thin threads dispersed throughout the nucleus, showing
both coiled and extended portions
- Formed from binding of nucleosomes
- Nucleosomes formed from binding of histone proteins and DNA
- Coiling from chromatin leads to the formation of chromosomes (in
the mitotic stage)
- Most condensed form is reached in the metaphase (can most easily
be observed)
Heterochromatin Dark-staining coiled portions
 Euchromatin Light-staining extended portions
Metaphase Basis for most cytogenetic studies
chromosomes
Deoxyrbonucleic Acid Primary chemical constituent of chromatin, where genes are encoded
(DNA)
Mitosis or Meiosis Chromatin strands condense into compact structures by helical tight coiling
and can be seen through the light microscope as discrete entities: thick rod-
like structures.
Karyotype Analysis Complete evaluation of a set of chromosomes
Karyogram An ordered image of the chromosomes from a cell
Chromosome Number In humans:
- Each somatic cell has 46 chromosomes, referred to as the diploid
set (2n) – one inherited from each parent.
- Gametes have 23 chromosomes, referred to as the haploid set (n)
- When fertilization takes place, the haploid sets of the sperm and
ovum fuse, restoring the original 46 chromosomes in each cell in the
embryo.
Autosomes Consists of 22 pairs of chromosomes that are exactly alike (homologous);
one chromosome of each pair come from the father, the other from the
mother.
Sex Chromosomes Composed of two different kinds: X and Y (determines sex)
Human Female 44 autosomes and two X chromosomes (44 + XX), the two X chromosomes
being homologous.
Human Male 44 autosomes, one X chromosome and one Y chromosome (44 + XY). Are
morphologically dissimilar and are thus non-homologous.
Chromosome average 5 micrometers
size during metaphase
Centromere or Primary Held together by a light staining composed of unreplicated region of DNA
Constriction which is responsible for the movement of chromosomes during cell division
Telomeres - Form the ends of human chromosomes
- Shorten with each round of cell division, which limits proliferation of
human cells to a finite number of cell divisions by inducing
replicative senescence, differentiation, or apoptosis.
- Shortening can act as a tumor suppressor.
Classification of 1. Metacentric
Chromosomes Base on 2. Submetacentric
The Position of the 3. Acrocentric
Centromere 4. Telocentric
Metacentric Centromere located near the center; arms have almost equal lengths
Submetacentric Centromere slightly away from the center, forming a short arm and a long
arm.
Acrocentric Centromere is very close to one end, producing a very short arm and a long
arm
Telocentric Centromere is at one end, causing the chromosome to only have one arm
Classification of - Chromosomes are classified into seven groups, in accordance with
Chromosomes Based on their descending length
Standard (Denver) - Groups are designated A to G
 Classification
Group A - Chromosomes 1-3
- Largest
- Metacentric and Submetacentric
Group B - Chromosomes 4 and 5
- Large
- Submetacentric
Group C - Chromosomes 6-12
- Medium
- Submetacentric
- Where chromosome X is assigned
Group D - Chromosomes 13-15
- Medium
- Acrocentric
Group E - Chromosomes 16-18
- Short
- Metacentric/submetacentric
Group F - Chromosomes 19 and 20
- Short
- Metacentric
Group G - Chromosomes 21 and 22
- Very Short
- Acrocentric
- Where Chromosome Y is assigned
Meeting in Paris - About 50 scientists actively engaged in research about human
chromosomes (September 1971), meeting about naming and
describing the regions of chromosomes.
- Not only individual chromosomes are identified, but also locations in
the chromosomes (help in detecting minor structural abnormalities)
Paris Nomenclature - After the invention of banding techniques, more accurate methods
for identification of chromosomes existed.
- In this method, the long and short arms of a chromosome are
divided into regions starting from the centromere, which in turn, are
further subdivided into bands.
- Not only individual chromosomes are identified, but locations on the
chromosomes can be identified, aiding in the detection of minor
structural abnormalities.
Steps in Naming (Paris 1. Determine the chromosome where the abnormality is
Nomenclature) 2. Determine the arm
3. Determine the region no.
4. Determine the band no.
5. If there is a sub band, put dot (.) then write the sub band number
Chromosome Analysis Is indicated in many clinical conditions for proper diagnosis of genetic
diseases that causes:
- Congenital malformations
- Mental retardation
- Repeated abortion
 - Sex determination
- Prenatal diagnosis
Chromosome To obtain metaphase cells for chromosome analysis, patient somatic cells
Preparation are cultured in vitro.
Heparinized Peripheral Preferred specimen for routine cytogenetic studies
Blood
Bone Marrow Samples Best results for hematologic disorders (origin of disease)
Fibroblast from skin Adequate source of metaphase cells
biopsies or skin punches
Tissues such as liver, - Not routinely used.
kidney, lung, and - These tissues frequently provide an excellent resource if obtained
muscle soon after death during autopsy or from fetal loss
Amniotic fluid cells - Most common specimen for prenatal analysis
- 16-18 weeks
- Lowest percentage of risk factor for fetal loss (0.5% risk of fetal loss)
- Obtained via amniocentesis
Chorionic villi - Also for prenatal analysis
(developing placenta) - Developing placenta, 10-14 weeks
- 1% risk of fetal loss
- via Chorionic Villus Sampling
Percutaneous Blood - Also for prenatal analysis
- For rapid Karyotyping or molecular studies
- 2-5% risk of fetal loss
- Via Cordocentesis/Percutaneous Umbilical Cord Blood Sampling
Cell Culture Techniques 1. Suspension floating – blood and bone marrow
2. Monolater (fixed to a surface) – amniotic fluid cells, chorionic villi,
and solid tissue
Culture Time per - Bone Marrow: 24-48 hours
Sample - Blood (lymphocytes): 3-4 days
- Amniocytes and chorionic villi: 5-7 days
- Solid tissue culture: Up to 2 weeks
Chromosome - G-Banding: most common method, stained with Giemsa solution
Banding/Staining - Q-Banding: uses quinacrine mustard stain, was originally used in
routine chromosome analysis
- R-Banding: uses Giemsa stain, however, chromosomes are pre-
heated prior to staining
- C- Banding: regions of the centromere and secondary constrictions
are stained, used to evaluate constitutive heterochromatin or to
determine whether a chromosome has two centromeres (dicentric)

The Genetic Material and Central Dogma

Frederick Griffith - Tried to develop vaccine against pneumonia

- Studied 2 strains of Streptococcus pneumoniae (S and R strains)
- S (smooth): pathogenic
- R (rough): non-pathogenic
- Reported results in 1928
 Transformation Discovered by the Griffith Experiment (first widely accepted demonstration
of bacterial transformation). Bacteria changes form and functions.
Griffith’s 1st experiment - He injected R-cells in the 1st mouse, and S- cells on the 2nd mouse
- Mouse with R-cells: alive, with R-cells in the biopsy
- Mouse with S-cells: dead, S-cells found in autopsy
Griffith’s 2nd experiment - S-cells are heated= resulted to heat killed S-cells
- Injected the heat-killed S-cells to a mouse – alive, no cells from the
healthy mouse in the biopsy
Griffith’s 3rd experiment - R cells + heat-killed S cells are injected into the mouse
- Mouse died
- Griffith discovered transformation
- Remains of the heat-killed S-cells are added to the R-cells making it
pathogenic
- Conclusion: a chemical substance from one cell is capable of
genetically transforming another cell
Oswald Avery, Colin - Tried to counter the virulence of Streptococcus pneumoniae
MacLeod, Macyln - Replicated the third part of Griffith’s Experiments
McCarty - Removed specific compounds (e.g., proteins, fats, nucleic acids,
carbohydrates) that are present in the dead S strain
- Conclusion: Transformation requires DNA; therefore, it is the genetic
material of the cell.
Alfred Hershey and - 1952: experiments to determine the composition of the genetic
Martha Chase material of a bacteriophage (nucleic acid and protein coat)
- Used Escherichia coli and T2 virus (a bacteriophage)
Transduction Transfer of portion of DNA from one bacteria to another by Bacteriophages.
1. Phage injects DNA
2. Phage enzyme breaks down host DNA
3-4. Cell creates new phages, including phage and host DNA
5-6. Transducing phage inserts donor DNA
6. Donor DNA included in recipients chromosome due to
recombination
Edwin Chargaff Discovered 2 rules which led to the discovery of the molecular structure of
DNA.
1. Nitrogenous base pair content of DNA
2. Amounts of nitrogenous base pairs vary from one specie to another
DNA Molecular King’s College: Maurice Wilkins and Rosalind Franklin – contributed images
Structure (X-ray Crystallography) that provided evidence to the molecular structure of
DNA.

Cambridge University: Francis Crick and James Watson – came up with the
chemically stable model of the DNA
Johann Friedrich Isolated DNA (nuclein) from WBC nuclei
Miescher
Deoxyribonucleic Acid The molecule that carries the genetic instructions important for the growth,
development, function, and reproduction of all known living organisms.

Composed of sugar group, phosphate group, and nitrogenous bases. 1 turn

 of the helix is approximately 3.4 nm. Diameter is approximately 2 nm.

Eukaryotes – linear DNA

Prokaryotes – circular DNA
Functions of DNA 1. Replication
2. Information
3. Instruction
4. Variation
Ribonucleic Acid 1. Messenger RNA (mRNA)
2. Ribosomal RNA (rRNA)
3. Transfer RNA (tRNA)
Messenger RNA - 10% total cell RNA
- Hundreds to thousands of nucleotides
- Synthesized in the nucleus
- Formed as a complementary chain to the DNA strand via
transcription
- after its formation, it comes out through the nuclear pores into the
cytoplasm and get attached to ribosomes
Ribosomal RNA - 80% total cell RNA
- Synthesized in the nucleus
- Part of DNA that codes for rRNA is the nucleolar organizer region
- They are synthesized and organized into small and large ribosomal
subunits which migrate to the cytoplasm through the nuclear pores
Transfer RNA - 10% of total cell RNA
- 75 to 80 nucleotides
- Synthesized in the nucleus
- Clover leaf model: polynucleotide chain is bent in the middle,
forming two arms on sides
- Attaches to specific amino acid in the cytoplasm, then transported to
the ribosome where it plays the main role for protein synthesis

Four special sites of the 1. Amino acid recognition site

tRNA 2. Amino acid attachment site
3. Codon recognition site
4. Ribosomal recognition site
Central dogma of A theory stating that genetic information flows only in one direction, from
molecular biology DNA, to RNA, to protein, or RNA directly to protein
Three basic models of 1. Conservative Model
DNA Replication 2. Semiconservative Replications
3. Dispersive Replication
DNA Replication 1. Opening of the double helix and separation of DNA strands
2. The priming of the template strand
3. The assembly of the new DNA segment
DNA Repair The cellular responses that are associated with the restoration of the
normal-base pair sequence and structure of damaged DNA.
Molecular Structure of a - Genes: chemically composed of DNA and are situated in the
Gene chromosomes and are responsible for the determination of
 inheritable characters
- Estimated that there are 30,000 to 35,000 genes located on 23
human chromosomes.
- Arranged in a single linear order in the chromosomes like the
arrangement of beads on a string
Two kinds of Genes in 1. Structural Genes – synthesis of specific proteins; a segment of DNA
the Chromosomes which contains the information/code for synthesis of one complete
polypeptide chain (or an enzyme).
2. Control/Regulatory Genes – regulation of the activity of a
structural gene by either promoting or inhibiting the sequences of
events by which a structural gene is translated to a product.
Parts of a Structural 1. Exons – coding sequences nucleotides that codes for amino acids
Gene 2. Introns – non-coding sequences interposed between exons
3. Flanking Regions – important for gene regulation
Transcription The process by which the information in a strand of DNA Is copied into a new
molecule of messenger RNA (mRNA).
Alternative Splicing - A process that causes one gene to give rise to more than one
protein.
- Exons are spliced in different patterns. The absence of one or two
exons in the mRNA changes the sequences of amino acids present
in the resulting polypeptide chain.
- Similarly, the function of the protein produced from the mRNA can
also be modified by:
a. Phosphorylation
b. Combination with other proteins
Translation 1. Initiation – tRNA attaches to AUG codon in mRNA via hydrogen
bonds.
2. Elongation – polypeptide chain extends by one amino acid residue
during one elongation cycle.
3. Termination – stop codon UAA or UAG sequence is encountered on
the mRNA strand, causing the binding of a release factor (RF) to the
ribosome.

Mutations and Genetic Disorders

Mutation Changes in the genetic material of an individual, seen in all living organisms
and the ultimate source of all genetic variations.

Most mutations are harmful

Point/Gene Mutation - A permanent alteration in the DNA sequence that makes up a gene.
- Mutation ranges in size – affect anywhere from a single DNA
building block (base pairs) to a large segment of chromosome that
includes multiple genes
Chromosomal Mutation - Involves a long segment of DNA
- Can involve deletion, insertions, and inversions of sections of DNA
- Some deleted sections may attach to other chromosomes disrupting
the chromosome that loses the DNA and the one that gains it.
 - Also called chromosomal rearrangement
- Responsible for greater than 50% of spontaneous abortion and 1%
of congenital/childhood disabilities and malignancies.
Somatic Mutation - Genetic alteration acquired by a cell that can be passed on the
progeny (offspring) of the mutated cell in the course of cell division
- Frequently caused by environmental factors (e.g., exposure to UV
radiation and chemicals)
- Not inherited (produce only a certain phenotypical change that can
be transferred
- Mosaic
Germinal Mutation - Inherited genetic alteration that occurs in germ cells (sperm and
egg)
- With generalized effect
- Not mosaics
Loss of Function - A type of mutation in which the altered gene product is missing a
molecular function of the wild type gene
- There’s an inactivation/reduced activity
- Mostly the product is recessive
- Aka knockout or null
Gain of Function - A type of mutation in which the altered gene product possess new
molecular function or a new pattern of gene expression
- There’s an overexpression/active (on genes that are not normally
active)
- Mostly the product is dominant or semi dominant
Mutagenic Agents 1. Ionizing Radiation
2. Chemical Mutagens
- Toxic inorganic compounds
- Toxic organic compounds
3. Extreme conditions
4. Chemicals in the environment
5. Infections
6. Stress
Ionizing Radiation Cosmic rays of sun
UV lamps
Radioactive elements
X-rays
ABG rays
Chemical Mutagens 1. Toxic Inorganic Compounds – acids and bases
2. Toxic Organic Compounds – formaldehyde, benzene, thalidomide
Extreme Conditions Extreme temperature
Centrifugation
Chemicals in the Smoking
Environment Alcohol
Drugs (including oral contraceptives and fertility drugs)
Pesticides
Infections Viral
Bacterial
 Fungal
Parasitic
Toxins
Stress Can cause cancer:
- If a person is stressed it reduces p53 gene, which controls cancer
cells
Gene/Point Mutation 1. Base Pair Substitution Mutation
a. Transition
b. Transversion
2. Frameshift Mutations
a. Deletion
b. Insertion/Addition
3. Transposons/Jumping Genes (Bacteria)
Base Pair Substitution Purine – adenine, guanine
Mutation Pyrimidine – cytosine, thymine

- Transition – point mutation that changes in purine nucleotide to

another purine, or a pyrimidine to another pyrimidine.
- Transversion – point mutation in which a single purine is changed
into pyrimidine and vice-versa
Frameshift Mutations Often little mutation but can cause changes that often lead to death.
- Deletion
- Insertion/Addition
Transposons/Jumping - Class of genetic elements that can jump into different locations
Genes (Bacteria) within a genome.
- Always maintained in an integrated site in a genome
- Most transposons eventually become inactive and no longer move
- Although called jumping genes, they are fixed in a specific
location/site in the genome (only changes sequence within that
specific genome)
Numerical Changes of 1. Euploidy
Chromosomes 2. Aneuploidy
3. Mosaicism and Chimaerism
Euploidy - Complete set of changes in the chromosomes
- Mostly results in spontaneous abortions (most survives but only
until birth (stillbirth)).
- Monoploid/Haploid, Diploid, Triploid, Tetraploid, Polypoid
Aneuploidy - Specific chromosome
- Monosomy – Turner Syndrome (XO), missing sex chromosome X,
mostly affects women
- Trisomy – Down’s (21), Patau’s (13), Edward’s (18), Klinefelter’s
(XXY), Jacob’s (XYY) (XXX)
Turner Syndrome - Short stature
- Small mandible
- Low-set ears
- Low hair line
- Webbed neck
 - Minimal breast development
- Lack of pubic hair
- Ovarian dysgenesis (Amenorrhea -> Infertility)
- Short 4th and 5th metacarpal bones
- Widely spaced nipples
- Lymphedema of hands/feet
- Bicuspid aortic valve
- Coarctation of aorta
Down Syndrome - Presence of 3 chromosome 21
- Curve little finger (clinodactyly)
- Single palmar crease
- Brush field spots on iris
- Epicanthic folds
- Small ears
- Upward slanting eyes
- Flat, round face
- Fissured tongue
- Cardiac defects
- Gap between 1st and 2nd toes
- Duodenal atresia
Patau’s Syndrome - Presence of 3 chromosome 13
- With cleft lip or palate
- Most of the time, eyebrows are absent
- Dysplastic/malformed ears
- Clenched hands, and polydactyly or extra fingers
- Undescended or abnormal testes
Edward’s Syndrome - Congenital heart defects
- Growth retardation
- Dysmorphic features
- Facial clefts
- Spina bifida
- Severe developmental delay
- Dysplastic/malformed ears
- With prominent part in the skull
- Prominent heels, flexed big toe
Klinefelter Syndrome - Tall, slim, narrow shoulder, eunuchoid stature, sparse body hair
- Has extragonadal germ cell tumors
- Broad hip
- Testicular atrophy
- Taurodontic teeth
- Gynecomastia
- Osteoporosis
- Diabetes
- Varicose veins
- Leg ulcer and hyperpigmentation of skin
- Long arms and legs
Jacob’s Syndrome - Taller than most men
 - Acne
- Aggression
- Tall stature
- Superior muscle strength
- Reduced muscle coordination
Mosaicism and 1. Mosaic – has 1 zygote and the most common cause is
Chimaerism nondisjunction in the developing zygote.
2. Chimera/Chimaerism – fusion of 2 or more zygotes (aka true
hermaphrodites)
Alteration of 1. Deficiencies/Deletion
Chromosome Structure 2. Duplication/Repeats
3. Inversions
4. Translocation
Deficiencies/Deletion 1. Cri-du-chat (5p-) – cat’s cry syndrome
2. Wolf Hirschorn (4p-) – petite arm, affects many parts of the body,
delayed growth and development, intellectual disability, low muscle
tone (hypotonia), seizures
3. DiGeorge (22q11.2-) – deletion of a small segment of chromosome
22 , requires FISH procedure, congenital heart problems, specific
facial features, frequent infections, developmental delays, cleft
palate, learning problems
Duplication/Repeats - Very rare
- Causes spontaneous abortions
Inversions - Not responsible for any clinical problems because there is no
chromosomal material lost.
- If there is important function genes disrupted, it will lead to
spontaneous abortion or congenital abnormality
Translocation - Reciprocal: CML -t(9q,22q), ALL – t(12p, 21q)
- Robertsonian: t (12q, 14q), Down’s Syndrome -t
- (14q, 21q)