WHAT IS CYTOGENETICS?

Cytogenetics

 It is essentially a branch of genetics, but is also part of cell biology/cytology.

Cytogenetics by Sutton

 Study of chromosomes, their behaviors, and abnormalities

 Goals:

- Diagnosis of chromosomal abnormalities and

- Localization od any (often abnormal) chromosomal region/DNA sequence

Chromosomes

 Genetic structures of cells containing DNA

 Carry inherited traits
 Carry the organization of the cell life
 Heredity

Genetics

 Study of inherited traits and their variations

 Heredity -> Similarities
 Variations -> Differences

Genes

 Units of hereditary

- DNA = deoxyribonucleic acid

- Exons = any part of the final mature RNA produces by genes after introns.

- Introns = any nucleotide sequence within a gene that is removed by RNA splicing during maturation of
the finals RNA product.

Central Dogma

 Explanation of the flow of genetic instructions characteristic of an organism

- Genome = the complete set of genetic instructions characteristic of an organism.
Levels of Genetics

 DNA
 Gene
 Chromosome
 Human Genome (23 chromosome pairs)
 Cell
 Tissue
 Organ
 Organ System
 Organism

HISTORICAL CONTEXT OF CYTOGENETICS

Prehistoric Times

 Successful domestication of animals and cultivation of plants

- Between 8000 and 1000 B.C. = domestication and selective breeding

- 5000 B.C. = Cultivation of plants began

The Greek Influence

 Hippocrates

- On the Seed = Hippocratic treatise that active “humors” resided in various parts of the body

 Aristotle

- proposed that the generative power of male semen resided in a “vital heat” that is contained

1600 – 1900s

 Roman times

- plant grafting and animal breeding were common

 1600s – William Harvey

- Epigenesis = organism is derived from substances present in the egg that differentiate into adult
structures during embryonic development.

 17th Century

- Theory of Preformation

 John Dalton (1808)

- Atomic Theory

 Matthias Schleiden & Theodor Schwann (1830)

- Cell Theory

 Carl Linnaeus
- Fixity of Species
  Joseph Gottlieb Kolreuter

- illustrated the influence of the belief of fixity of species

 Karl Wilhelm von Nageli (1842)

- the 1st to describe and discover chromosomes (plant cells – transitory cytoblasts)

 Gregor Johann Mendel (1856 – 1863)

- Father of Genetics

- Inheritance and theory involving hereditary factors in the germ cells

 Charles Darwin

- The Origin of Species

- Natural Selection

 Alfred Russel Wallace

- Natural Selection is based on the observation that populations tend to consist of more offspring than
the environment can support leading to a struggle for survival among them.

= Primary gap

> Lack of understanding of the genetic basis of variation and inheritance

= Variations in Animals and Plants under Domestication

 Walther Flemming (1882)

- described their behavior in animal (salamander) cells

- discover of Mitosis

 Heinrich Wilhelm Gottfried von Waldeyer - Hartz

- coined the term “Chromosome”

 Albert Levan and Joe Hin Tjio (1955 – 1956)

- correct determination of the human diploid chromosome number as 46

1900 – Present

 1912
- Hans von Winiwarter
= estimated that men have 47 chromosomes and 48 in women
 1921
- Theophilus Shickel Painter
= discovered the Y chromosome in testicular cells from 3 male; 48 chromosomes
  Albert Levan and Joe Hin Tjio (1955 – 1956)

- correct determination of the human diploid chromosome number as 46

 Francis Crick and James Watson

- constructed the DNA double helical model in 1953
 Jerome Lejeune (1959)

- discovered patients with Down syndrome had an extra copy of chromosome 21

 Torbjorn Caspersson

- developed banding techniques which differently stain chromosomes

 1980s
-FISH

= Flouresence in Situ Hybridization

- Chromosome microdissection

FUTURE OF CYTOGENETICS

 Molecular Cytogenetics

- Comparative genetic hybridization (CGH) assays

- SNP = array-based karyotyping

- Automated systems for counting the results of standard FISH preparations

APPLICATIONS AND IMPORTANCE OF CYTOGENETICS

 DNA profiling

- Comparing of DNA sequences (DNA Fingerprinting)

- Purpose

= to establish/rule out identity, relationship or ancestry

- Forensic Science

= collecting of physical evidence of a crime

 Cytogenetic research
 Selective breeding
 Genetic Modification
 Precision Medicine
 Exome Sequencing

 Most diseases arise from interactions between chromosomes (genes) and environmental factors and some
diseases were cured with the help
 Plants
- enhanced potential
  Selective breeding
- Purpose
= to develop superior breeds of livestock
- Produces chickens that grow faster, yield high quality meat, lays greater number of larger eggs
- Larger animals
= pigs
= cows
= artificial insemination

CYTOLOGY

Cytology

 The biological science which deals with the study of structure, function, molecular organization, growth,
reproduction and genetics of the cells

- Cells = basic unit of Iife

- Somatic cells = diploid

- Germ cells = haploid

Function of the Cells

 Cell metabolism and energy use

- Cell activities, such as the synthesis of new molecule, muscles contraction, and heat production

 Synthesis of molecules
- Proteins
- Nucleic acids
- Lipids
 Communication

- Produce and receive chemical signals that allow them to communicate with one another

 Reproduction and Inheritance

- Cell division

- Re vidual

Cell Components and Cell Constituents

 Prokaryotic cell
- no nucleus
 Eukaryotic cell
- nucleus and other organelles are present
 Macromolecules:

- Carbohydrates

-Lipids
 - Proteins

- Nucleic acids

 Micromolecules

-Vitamins

-Minerals

Anatomy of the Cell

 Cells are organized into 3 main regions:

- Plasma Membrane
- Cytoplasm
- Nucleus
 Plasma Membrane
- Outermost component of a cell
- Selective Barrier
- Cellular communication
- Major Components

= Phospholipids

= Proteins

- Other molecules

= Cholesterol

= Carbohydrates

 Fluid – mosaic model

- Lipid bilayer

- Polar, phosphate – containing ends of the phospholipids (hydrophilic)

- Nonpolar, fatty acid ends of the phospholipids (hydrophobic)

 Cholesterol

- Strength and flexibility

 Proteins

- “float” among the phospholipid molecules

- Functions: membrane channels, carrier molecules, receptor molecules, enzymes, or structural supports
in the membrane

- Carbohydrates may bind

 Cytoplasm

- All the cellular contents between the plasma membrane and nucleus

- Cytosol and organelles

 Ribosomes

- Site of protein synthesis

- May be attached to other organelles (endoplasmic reticulum)

 Endoplasmic Reticulum

- Series of membranes forming sacs and tubules that extends from the outer nuclear membrane into
the cytoplasm

- Rough ER

= Site of protein synthesis

- Smooth ER

= Site of lipid synthesis

 Golgi Apparatus
- Closely packed stacks of curved, membrane-bound sacs
- Collect, sort, package, and distribute proteins and lipids
 Secretory Vesicles

- Small membrane-bound sac that transports or stores materials within cells

 Lysosomes

- Membrane – bound vesicles formed from the Golgi Apparatus

- Contain enzymes that digest foreign material

- Vesicles formed by endocytosis by fuse

- Autophagy

- Autolysis

 Peroxisomes

- Small, membrane – bound vesicles containing enzymes that break down fatty acids, amino acids, and
hydrogen peroxide

- Usually present in cells that are active in detoxification

 Mitochondria

- Small organelles with inner (cristae, folds) and outer membrane (smooth) separated space

- Major sites of ATP production

 Cytoskeleton

- Consist of protein that support the cell, hold organelles in place, and enable the cell to change shape

- Microtubes
 = Support cytoplasm

= Assist cell division

= Form essential components of certain organelles (cilia and flagella)

- Microfilaments

= Support cytoplasm

= Some are involved with cell movement

- Intermediate filaments

= Mechanical support to the cell

 Centrioles

- Small, cylindrical organelle composed of 9 triplets

- Play an in

 Cilia, Flagella, Microvilli

- Motile projections of cell surface

- Cilia

= Microtubules

= Numerous and project from the surface of cells (respiratory tract)

- Flagella

= Microtubules

= Occur only 1 per cell (sperm cell)

= Move an entire cell

- Microvilli

= Microfilaments

= Numerous on cells that have them (intestine, kidney)

= increase the surface area of those cells

 Nucleus

- Large organelle usually located near the center of the cell

- Houses most of a cell’s DNA

- Nuclear Envelope

= Located at the edge of the nucleus

= Separates the nucleus from the cytoplasm

- Nuclear pores
 = Located at the surface of the nucleus

= Materials pass in and out of nucleus

- Nucleolus

= Located inside the nucleus

= Produces ribosomes

Cell Cycle

 Cell Division

- Process by which cells reproduce themselves

- Uses mitosis and meiosis

- Each cell (except sperm and egg) contains 23 pairs = 46 chromosomes (diploid)

- Sperm and egg contain 23 chromosomes (haploid)

 Cell Cycle
-An orderly sequence of events in which a somatic cell duplicates its contents and divides in 2

- 2 major periods:

= Interphase

= Mitosis

 Interphase

- Time between cell divisions

= Gap phases (G1 and G2)

= Synthesis phase (S)

 Mitosis

- Cell division that occurs in all cells except sex cells

- A parent cell divides to form 2 daughter cells with the same amount and type of DNA as the parent cell

-Nuclear division and cytoplasmic division (cytokinesis)

= Prophase

= Metaphase

 Prophase

- DNA coils tightly

- Chromosomes appear condensed/compact

- Centrioles move to opposite ends

- Formation of spindle
 - Nuclear envelope begins to break down and gradually disappears

- Nucleolus is no longer visible

 Metaphase

- Chromosome alignment in the center of the cell (metaphase plate)

- Attachment of spindle fibers to the chromosomes

 Anaphase

- Separation of sister chromatids of each chromosome

- Migration of the sister chromatids to opposite ends of the cell

 Telophase

- Chromosomes are the poles

- Spindle falls apart

- Reformation of nuclear envelope

- May undergo cytoplasmic division

 Cytokinesis

- Cytoplasmic division

Meiosis

 Reproductive cell division that occurs in the gonads, produces gametes in which the 1 number of chromosomes
is reduced by half.
 Gametes contain 23 different chromosomes
 Produces gametes and mixes up trait combination
 Meiosis I: reduction division
 Meiosis Il: equational division

 Meiosis I – Reduction Division

- Prophase I

= Leptonema

> Replicated chromosomes condense and become visible

= Zygonema
 > chromosomes continue to shorten and thicken, formation of synaptonemal complex

= Pachynema

> Coiling and shortening of chromosomes continue and further development of

synaptonemal complex

> Spindle forms, homologs, line up next to one another, gene by gene (synapsis)

= Diplonema

> Synapsed chromosomes separate but remain attached

> Crossing – over occurs

> Chiasmata

= Diakinesis

> Final stage of prophase I, separation of the homologous chromosome pair proceeds as
the chromosomes become maximally condensed

- Metaphase I

= Nuclear membrane disappears

= Alignment of the homologs down the center of the cell

- Anaphase I

= Separation of homologs

- Telophase I and Cytokinesis

= Each set of haploid chromosomes has now separated completely to opposite ends of the cell,
which cleaves into 2 new daughter gametes.

 Meiosis II – Equational Division

- Essentially similar to an ordinary mitotic division

- Each chromosome, which exists as a pair of chromatids, becomes aligned along the center of the cell
and then splits leading to the formation of 2 new daughter gametes (total of 4)

-Prophase Il, Metaphase I, Anaphase Il, Telophase

Development and Aging

 Reproductive System
- Functions:
= Production of gametes
= Fertilization
= Development and nourishment of individual
= Production of reproductive hormones
 Male Reproductive System

- Duct deferens

- Urinary bladder

- Pubic bone

- Penis

- Urethra

- Scrotum

- Testis

 Female Reproductive System

- Ovary

- Uterine tube

- Cervix

- Rectum

- Vagina

- Anus

- Vaginal Orifice

 Spermatogenesis

- Sperm only develop in 74days

- Spermatogonium > Primary Spermatocyte > Secondary Spermatocyte > Spermatid > Sperm

 Oogenesis

First polar body may divide > Polar bodies die

- Oogonium > Primary oocyte >

Ovum > Mature egg

Secondary oocyte >

Second polar body

 Prenatal Development

- Fertilization

- Cleavage

= from ovulation to implantation

- Gastrula (primordial embryo)

 Multiples

- Fraternal (dizygotic) twins

= 2 sperm fertilized

= 2 oocytes

= Can happen if ovulation occurs in two ovaries in the same month, or if two oocytes leave the
same ovary and are both fertilized

- Identical (monozygotic) twins

= descend from a single fertilized ovum

 Embryo Development

- Organogenesis

= Transformation of the simple three layers of the embryo onto distinct organs.

 Fetus

- Week 6

= anatomical differences between sexes appear, after SRY gene is expressed in males

- Week 12

= fetus sucks its thumb, kicks, makes fists and faces, and has the beginnings of teeth

- 4th month

= fetus has hair, eyebrows, lashes nipples, and nails

- End of 5th month

= fetus curls into a head – to – knees position

- 6th month

= skin appears wrinkled

- Final trimester

= development of organ systems

 Birth Defects

- Critical Period

= The time when genetic abnormalities, toxic substances, or viruses can alter a specific structure

- Teratogens

= Thalidomide

> mild tranquilizer, to alleviate nausea early in pregnancy

= Alcohol

> risks a fetal alcohol spectrum disorder in the unborn child

> fetal alcohol syndrome (severe)

- Nutrients

= Excesses of Vitamin A-based drugs and 3 vitamin A itself

> congenital malformations (central nervous & cardiovascular systems) and

spontaneous abortion

= Excess vitamin C

= Malnutrition

>stillbirth, low birthweight, wasting & developmental delays

- Viral infection

= Chickenpox virus

> baby may have an increased risk for congenital varicella syndrome or neonatal
varicella

= Zika virus

> microcephaly & other brain problems

= HIV

> low birthweight, prematurity, & stillbirth

= German measles

> 1st trimester cataracts, deafness, & heart defects

> 2nd/3rd trimester learning disabilities, speech & hearing problems, & type 1 diabetes
melitus
 Maturation and Aging

- Aging

= Moving through the life cycle

- Resveratrol

= type of enzyme called a sirtuin that regulates energy use in cells by altering the expression of
certain sets of genes

- Adult – Onset Inherited Diseases

= genetic disorder may manifest themselves after childhood and adolescence

- Progeria

- Longevity

= Scientists study people in their 90s and 100s, including ages 105 and above to determine what
contributes to their long lives

= Reflect their lifestyle

= Review: Genes and Longevity of Life Span

>Bin-Jumah et al., 2022

> more than 50 genes contributed to the longevity of life