Genetics

● 21st century
● built on rich tradition of discovery & experimentation.
● 19th cen. to present

Transmission Genetics
● general proces
● traits are controlled by genes are transmitted through "gametes" from generation to
generation.

Mutant Strains
● used in genetic crosses to:
- map the LOCATION AND DISTANCE between genes on chromosomes.

Watson-Crick model of DNA

● explains how genetic information is STORED and EXPRESSED
● foundation of molecular genetics

Recombinant DNA technology

● revolutionized genetics
● foundation for the Human Genome Project
● new fields that combine:
genetics + information technology

Biotechnology
● provides genetically modified organisms and their products
● used across a wide range of fields (agriculture, medicine, industry)

Model Organisms
● used in genetics research
● utilized in combination with:
- RECOMBINANT DNA technology + genomics (to study human diseases).

Genetic Technology
● developing faster than policies, laws, conventions

Newer model organisms

1. Caenorhabditis elegans (roundworm)
2. Danio rerio (zebrafish)
3. Arabidopsis thaliana (mustard plant)

CRISPR-Cas (Clustered Regularly Interspersed Short Palindromic Repeats-Associated)

● major diverse impact on human lives
● molecular mechanism found in bacteria
 ● with potential to revolutionize ability to REWRITE THE DNA SEQUENCE OF GENES
FROM ANY ORGANISM
● ultimate tool in genetic technology (genome of humans can precisely be edited/
sequencing of genome/ gene modification)

● method of choice for gene modification

● more: ACCURATE, EFFICIENT, VERSATILE, EASIER TO USE
● initially discovered as "seek and destroy" mechanism bacteria use to fight off viral
infection

CRISPR - Clustered Regularly Interspersed Short Palindromic Repeats

● part of bacterial genome which produces RNA MOLECULES
● CRISPR-RNA: binds to a matching sequence in the viral DNA (seek) & recruits the Cas
nuclease to cut it (destroy)
● lab experiments: CRISPR-Cas has been used to:
- REPAIR MUTATIONS IN CELLS DERIVED FROM INDIVIDUALS WITH
GENETIC DISORDERS
- E.G (cystic fibrosis, Huntington disease, sickle-cell disease, muscular dystrophy)
● In US: clinical trial using CRISPR-Cas for genome editing in cancer therapy is recruiting
participants; proposals for treating a genetic form of blindness & genetic blood disorders
are in preparation
● In China: 86 patients received CRISPR-Cas clinical trials for cancer
● CRISPR-cas: has many targets & application:
- (edited gene in mosquitoes; prevents them from carrying the parasite that causes
malaria in humans
- (edited gene of algae; to double output for biofuel production
- (created disease-resistant strains of wheat & rice)
● Ethical Concerns:
- (genetic modification of human embryos would change the genetic info carried by
future generations)
- International panel of experts (2017) discussed: SCIENCE, ETHICS,
GOVERNANCE OF HUMAN GENOME EDITING
- Genome editing: caution but not ban; for compelling reasons & strict oversight

CAS (CRISPR- associated)

● refers to a NUCLEASE/ DNA CUTTING ENZYME

Gene editing
● 1st made possible w/ other methods

________________________________________
1.1 Genetics Has an Interesting Early History

1. Aristotle (350 B.C)

 ● "active humors" served as bearers of hereditary traits
● "active humors": make-up & workings of the human body
● 4 HUMORS: ( blood, yellow bile, black bile, phlegm)

1600
● initial strides/progress were made to understand biological basis of life.

2. William Harvey (16th century)

● physician & anatomist
● theory of epigenesis: organism develops from the FERTILIZED EGG by a succession
of developmental events that eventually transform the egg into adult;
● embryo develops progressively from an undifferentiated egg cell (cell that has yet to
develop into a particular cell variant); a way gene changes in the face of environmental
influences; w/ positive or negative impact
● conflicted with theory of preformationism

3. Swammerdam & Bonnet (17th century)

● theory of preformationism:FERTILIZED EGG CONTAINS A MINIATURE ADULT/
"homunculus"; miniature human was already present in gametes (egg & sperm)

4. (Matthias Schleiden; plants) & (Theodor Schwann; animals) ; (1830)

● proposed "cell theory"
● i. organisms are composed of "cells"
● ii. basic structural unit
● iii. derived from pre-existing cells

Theory of spontaneous generation (1860)

● life can arise from a non-living material
● creation of living organisms from non-living components
● 4.1 Louis Pasteur disproved this theory (boiled a meat in a flask w/long neck curved
downward w/c prevents falling particles from reaching the broth while still allowing air to
flow.

5. Charles Darwin & Gregor Mendel (mid 1800)

● set the stage for rapid development of genetics in 20th & 21st centuries

● 5.1 Origin of Species by Darwin (1859): ideas about evolution.

- geological, geographical, biological observations: existing species arose by descent with
modification from anscestral species.
- HMS Beagle (1831-36) voyage
- theory of Natural Selection (mechanism of evolutionary change)
- lacked understanding of the genetic basis of variation & inheritance; w/gap
 ● 5.2 Alfred Russel Wallace
- formulated & proposed independently (natural selection)
- natural selection observation: (populations tend to produce more offspring THAN the
environment can support; struggle to survival among indivs)
- individuals WITH heritable traits: can adapt; ABLE TO SURVIVE AND REPRODUCE
- if a population carrying inherited variations becomes reproductively isolated, new
species may result.

● 5.3 Gregor Johann Mendel paper (1866)

- showing how traits were passed from generation to generation in PEA PLANTS
- general model of how traits are inherited
- his research serves as: FOUNDATION OF GENETICS

● 5.4 Carl Correns, Hugo de Vries, Erich Tschermak (1900)

- partially duplicates & brought to light Mendel's paper

Early 20th century

● HEREDITY & DEVELOPMENT - were dependent on GENETIC INFORMATION residing
in GENES, CONTAINED in CHROMOSOMES, which were then contributed to each
individual by GAMETES — chromosome theory of inheritance (gap in Darwin's theory
was closed !!)

________________________________________
1.2 Genetics Progressed from Mendel to DNA in < a century

Transmission of traits
● by Gregor Johann Mendel
● Augustinian monk
● experimental using pea plants
● applied quantitative data analysis to his results; traits are passed from parents to
offspring in predictable ways
● EACH TRAIT in pea plants is CONTROLLED by a PAIR OF FACTORS called "genes"
& members of a gene pair SEPARATE from each other during "gamete formation"
(egg cell & sperm)
● transmission of traits in pea plants and all other higher organisms
● foundation for genetics (study of heredity & variation)

Chromosome Theory of Inheritance: Mendel & Meiosis

● in most eukaryotes, members of each species have a characteristic number of
chromosomes called "diploid number (2n)" in most of their cells
● humans: diploid number of 46
● chromosomes in diploid cells EXIST PAIRS called "homologous chromosomes"

19th Century
 ● chromosome behavior during 2 forms of cell division: MITOSIS & MEIOSIS

● MITOSIS: chromosomes are COPIED & DISTRIBUTED so that each daughter fell
receives a DIPLOID SET OF CHROMOSOMES IDENTICAL TO THOSE IN PARENTAL
CELL

● MEIOSIS/reduction in chromosome number: gamete formation; cells produced

receive only 1 chromosome from each chromosome pair; resulting number of
chromosomes is called "haploid number (n)"
● essential to maintain constant number of chromosome char. of their parents & other
members of their species

6. Walter Sutton & Theodor Boveri (early 20th cen)

● noted the behavior of chromosomes during MEIOSIS / identical to behavior of genes
during gamete formation described by Mendel (ex. genes & chromosomes exist in pairs,
members of a gene pair & members of a chromosome pair SEPARATE FROM EACH
OTHER DURING GAMETE FORMATION
● proposed that genes are carried ON chromosomes
● formulated CHROMOSOMAL THEORY OF INHERITANCE: inherited traits are
controlled by genes residing on chromosomes faithfully transmitted through gametes;
MAINTAINING GENETIC CONTINUITY from generation to generation

GENETIC VARIATION
● inheritance of traits in the:
- fruitfly Drosophila melanogaster
- white eyed mutation/ variant is an allele (wild-type); red -eyed (normal)
- variation was produced by mutation in 1 of the genes controlling eye color
- Alleles: alternative forms of a gene
- different alleles = different phenotypes/observable features
- genotype: set of alleles for a given trait carried by an organism
- mutant genes as markers: to MAP THE LOCATION OF GENES IN CHROMOSOMES

SEARCH FOR CHEMICAL NATURE OF GENES: DNA OR PROTEIN?

● white-eyes Drosophila: mutant trait could be traced to a single chromosome (genes are
carried on chromosome) ((which chemic component of chromosomes carries genetic
information tho?))
● 1920: PROTEINS AND DNA; Major chemical components of chromosomes
● large number of proteins present in both NUCLEUS & CYTOPLASM; they thought
proteins carried genetic information

7. Oswald Avery, Colin McLeod, & Maclyn McCarty (1944)

● researchers at Rockefeller Institute in New York
● experiments showing DNA was the carrier of genetic information in bacteria; failed to
convince
 8. Alfred Hershey & Martha Chase
● DNA as a carrier of genetic information
● work with viruses

________________________________________
1.3 DOUBLE HELIX; ERA OF MOLECULAR GENETICS

● DNA carries genetic information, what's the structure?

STRUCTURE OF DNA & RNA

9. James Watson & Francis Crick (1953; 20th cen)

● described the structure of DNA
● DNA: long, ladder-like macromolecule that twists to form a double helix
● each LINEAR STRAND of the helix is made up of SUBUNITS called "nucleotides"
● 4 nucleotides: Adenine, Guanine, Thymine, Cytosine; encode genetic information
● 2 strands of DNA = exact complements of one another, A=T, C=G base pairs
● 9.1 Maurice Wilkins, Watson, & Crick: awarded NOBEL PRIZE (1962) ON THE
STRUCTURE OF DNA
● RNA: another nucleic acid; chemically similar to DNA; SINGLE-STRANDED

GENE EXPRESSION: FROM DNA TO PHENOTYPE

● genetic info encoded is expressed in a series of steps = formation of a functional gene
product = PROTEIN (in majority of cases)
● in eukaryotic cells: process leading to PROTEIN PRODUCTION:
- (begins in NUCLEUS with TRANSCRIPTION. The nucleotide sequence in 1
strand of DNA = used to construct complementary RNA sequence
- once RNA molecule is produced, it moves to the CYTOPLASM.
- RNA called messenger RNA/ mRNA; binds to a ribosome
- TRANSLATION: synthesis of proteins under the direction of mRNA
- genetic code: information encoded in mRNA consists of LINEAR SERIES OF
NUCLEOTIDE TRIPLETS (each triplet is called "codon"); specifies the
INSERTION OF A SPECIFIC AMINO ACID INTO A PROTEIN
- proteins are polymers made up of amino acid monomers
- there are 20 amino acids found in proteins
- PROTEIN ASSEMBLY - accomplished with the aid of ADAPTER molecules
called "transfer RNA (tRNA)
- within the RIBOSOME, tRNA recognize the info encoded in the mRNA codons
and carry the proper amino acids for construction of protein during translation.

PROTEINS & BIOLOGICAL FUNCTION

● proteins - end product of gene expression; diversity of proteins = diversity of life;
mainstay of biological systems; structural diversity
 ● proteins are made from combinations of 20 diff. amino acids
● protein chain: 100 amino acids; 20 position = 20^100
● enzymes: largest category of proteins; biological catalysts; lowering the energy of
activation in reactions & allowing cellular metabolism to proceed at body temperature
● proteins: critical components of cells & organisms (hemoglobin, oxygen binding
molecule in red blood cell, collagen, connective tissue molecule, actin & myosin,
contractile muscle proteins
● protein's SHAPE & CHEMICAL BEHAVIOR: determined by LINEAR SEQUENCE OF
AMINO ACIDS; dictated by stored info in the DNA OF A GENE TRANSFERRED TO
RNA, DIRECTS PROTEIN SYNTHESIS

GENOTYPE TO PHENOTYPE: SICKLE-CELL ANEMIA

● once a protein is made, BIOCHEMICAL & STRUCTURAL PROPERTIES play a role in
producing a PHENOTYPE
● mutation/altering of gene: modify/eliminate encoded protein's usual function = altered
phenotype
● ex. sickle-cell anemia (human genetic disorder)
● normal red blood cells (round); sickled-red blood cells (block capillaries & small blood
vessels) causing severe pain, damage to the heart, brain, muscles, kidneys = all
symptoms is caused by a change of a single nucleotide; close relationship of phenotype
& genotype
● sickle-cell anemia: caused by a mutant form of hemoglobin (protein that transports
oxygen from the lungs to cells in the body)
● hemoglobin: composite molecule made up of 2 diff. proteins (à-globin & B-globin)
● mutation in B-globin: causes an amino acid substitution in 1 of the 146 amino acids in
protein; change in 1 DNA nucleotide; other 145 aren't changed
● central dogma: DNA is a template for making RNA, directs the synthesis of
proteins(how genes control phenotypes)
● individuals with 2 mutant copies of B-globin: have sickle-cell anemia
● mutant B-globin proteins: cause hemoglobin molecules in red blood cells to
POLYMERIZE WHEN BLOOD'S OXYGEN IS LOW = long chains of hemoglobin that
distort shape of red blood cells (anemia; insufficiency of red blood cells)
● deformed cells: fragile; break easily; reducing the number of circulating red blood cells

________________________________________
1.4 RECOMBINANT DNA TECHNOLOGY; ERA OF DNA CLONING (1970)

● restriction enzymes: used by bacteria to CUT & INACTIVATE THE DNA OF

INVADING VIRUSES; to CUT any organism's DNA at SPECIFIC NUCLEOTIDE
SEQUENCES = producing a reproducible set of fragments
● ways to insert DNA fragments produced by the action of restriction enzymes into carrier
DNA molecules called "vectors" to form "recombinant molecules"
● clones: transferred into bacterial cells; thousands of copies (bacterial reproduction:
vector + DNA fragments)
 ● DNA fragments: can be used to isolate genes; to STUDY ORGANIZATION,
EXPRESSION, NUCLEOTIDE SEQUENCE, EVOLUTION
● collection of clones: represent an organism's genome (complete HAPLOID DNA
content of a specific organism called "genomic libraries" ; available for hundreds of sp.
● recombinant DNA technology: given rise to biotechnology industry; contributor to US
economy
________________________________________
1.5 IMPACT OF BIOTECHNOLOGY IS EXPANDING

● biotechnology: use of RECOMBINANT DNA technology and other MOLECULAR

TECHNIQUES TO MAKE PRODUCTS
● In US: it quietly revolutionized many aspects of everyday life (products in supermarket,
healthcare in agriculture, court system)

PLANTS, ANIMALS, & FOOD SUPPLY

● recombinant DNA:
- genetically modify crop plants (agriculture)
- resistance to herbicides insects, & genes for nutritional enhancement have been
introduced to crop plants.
● transgenic organisms - transfer of heritable traits across species using recombinant
DNA technology
- herbicide-resistant corn & soybeans planted (mid 1990)
- transgenic strains: 88% of US corn crop; 93% soybean crop
- transgenic crops: more than 70% of processed foods in US

Dolly (finn dorset sheep) CLONED from the genetic material of an adult mammary cell &
Bonnie (first-born lamb)
● cloning livestock: sheep & cattle
● 1996: Dolly the sheep cloned by a NUCLEAR TRANSFERER (nucleus of an adult is
transferred into an egg that has had its nucleus removed); possible to produce
hundreds of genetically identical offspring with desirable traits
● gene transfer to transgenic animals = synthesize therapeutic proteins
● Anticlotting protein (2009):from milk of transgenic goats; approved by US Food & Drug
Administration
● human proteins from transgenic animals are used in clinical trials to treat diseases
● biotechnology will continue to expand as gene editing by CRISPR-Cas

BIOTECHNOLOGY IN GENETICS & MEDICINE

● More than 10 million children/adults in US suffer from genetic disorder
● child bearing couple: 3% risk of having a child with genetic anomaly
● molecular basis for hundreds of genetic disorders are: known & most of these have been
MAPPED, ISOLATED, CLONED
 ● biotechnology-derived genetic testing: available to perform PRENATAL DIAGNOSIS
OF HERITABLE DISORDERS & to TEST PARENTS FOR THEIR STATUS AS
HETEROZYGOUS CARRIERS OF MORE THAN 100 INHERITED DISORDERS
● newer methods: scanning an entire genome: to establish individual's risk of developing
GENETIC DISORDER / HAVING AN INFECTED CHILD
● genetic testing: raises ETHICAL CONCERNS !; impact on diagnosis of genetic
diseases
● biotechnology: revolutionized AGRICULTURE & PHARMACEUTICAL

________________________________________
1.6 GENOMICS, PROTEOMICS, BIOINFORMATICS

● genomic libraries: sequencing all clones in a library to derive the nucleotide sequence
of an organism's genome; identify each gene in the genome & establish functional
● Human Genome Project (HGP) in 1990 : intl effort to sequence human genome
● 2003: publicly funded & a private industry funded genome project completed sequencing
of the gene containing portion of the genome

BIOLOGICAL DISCIPLINES/FIELDS
1. genomics
- study of genomes
- STRUCTURE, FUNCTION, EVOLUTION OF GENES & GENOMES

2. proteonemics
- IDENTIFIES SET OF PROTEINS PRESENT IN CELL UNDER SET OF
CONDITIONS
- FUNCTIONS & INTERACTIONS

3. bioinformatics
- Store, retrieve, analyse massive amount of data gathered
- specialised subfield of info
- software/hardware for processing nucleotide & protein data
- nucleic acid sequences, protein sequences, gene interaction networks

MODERN APPROACHES TO UNDERSTANDING GENE FUNCTIONS

● Classical/ forward genetics - imp in understanding gene function; naturally occurring

mutations/intentionally induced mutations (chemicals, xrays uv light = to cause altered
phenotypes)
● reverse genetics - molecular techniques ; DNA sequence is known, BUT the ROLE &
FUNCTION is NOT
● gene knockout - molecular techniques; render targeted genes NON FUNCTIONAL
(phenotype changes, cellular, molecular level)
________________________________________
1.7 GENETICS STUDIES RELY ON THE USE OF MODEL ORGANISMS

● rediscovery of Mendel's work (1900)

● principles of inheritance: universal importance among plants and animals
● ex. fruitfly Drosophila melanogaster & mouse Mus musculus
● 2 main reasons of trend:
- i. genetic mechanisms were the SAME in most organisms
- ii. organisms have char. that made them suitable for genetic research (easy to
grow, short life cycles, many offspring, genetic analysis fairly straightforward)

● fruitfly Drosophila melanogaster

- mutant strains: carefully STUDIED, CHARACTERIZED, MAPPED
- model organisms: organisms used to study basic biological processes; because
of their well-characterized genetics
- shedding light to bio (aging, cancer, behavior)

MODERN SET OF GENETIC MODEL ORGANISMS

● another sp to their model organisms: "viruses" ( T phage & lambda phage)
● microorganisms; "bacterium" (Escherichia coli & Saccharomyces cerevisiae)
● nematode: ( Caenorhabditis elegans ); model system to study the development &
function of the nervous system because its nervous system CONTAINS ONLY A FEW
HUNDRED CELLS
● small plant with short life cycle; model organisms: (Arabidopsis thaliana)
● zebrafish; vertebrate development; small; reproduces rapidly: (Danio rerio ) EGG,
EMBRYO, LARVAE = ALL TRANSPARENT

MODEL ORGANISMS & HUMAN DISEASES

● development or recombinant DNA technology + results in genome sequencing = all life
has a common origin
● genes with similar functions in diff. organisms tend to be SIMILAR/IDENTICAL IN
STRUCTURE & NUCLEOTIDE SEQUENCE
● transgenic organisms: transferring genes bet. species = scientists developed human
diseases in organisms (bacteria to fungi, plants & animals)
● colon cancer: E. coli (basic steps of DNA repair is defective in some forms of colon
cancer)
● gene involved in DNA repair:
- mutL (E. coli)
- MLH1 (humans)

● E. coli: easier to grown; divides every 20 mins.

- can easily create and study mutations in mutL gene

● fruitfly Drosophila melanogaster

 - study human diseases
- mutant genes: produce phenotypes with structural abnormalities of the
NERVOUS SYSTEM
- ALL THESE GENES HAVE HUMAN COUNTERPARTS
- retinitis pigmentosa: complex human disease of the RETINA; identical to
Drosophila genes (involved in retinal degeneration)
- transfer human disease genes to Drosophila using recombinant DNA
technology
- transgenic files: used for studying mutant human genes
- transfer approach: human neurodegenerative disorders: Huntington disease,
Machado-Joseph disease, myotonic dystrophy, Alzheimers disease

________________________________________
1.8 GENETICS: PROFOUND IMPACT ON SOCIETY

● Mendel: inheritance in pea plants (1865) @ Natural History Society of Brünn in

Moravia)
● Nobel Prize (1962): awarded to James Watson, Francis Crick, Maurice Wilkins: work
on the structure of DNA;genes are on chromosomes;DNA encodes genetic info.
;molecular basis for DNA replication
● Mendel's monastery garden to Human Genome Project & beyond!!

NOBEL PRIZE GENETICS

● Nobel Prizes in Medicine or Physiology & Chemistry: CONSISTENTLY AWARDED
FOR WORK IN GENETICS & RELATED FIELDS
● 10. THOMAS H. MORGAN (1933) : CHROMOSOME THEORY OF INHERITANCE;
● flowed by others: discovery of genetic combination, relationship bet. genes & proteins,
structure of DNA & genetic code

GENETICS, ETHICS, SOCIETY

● APPLICATIONS: policies, laws,
● prenatal testing, genetic discrimination, ownership of genes, access to and safety of
gene therapy & genetic privacy