Module 1.

The space of genomics

Lecture 1.4 – Major advances in

genomics (2/2)
Outline
• Major advances in DNA sequencing
• Methods of gene detection
• Genetic markers
• Human genome project
• Genetic testing
Genetic markers
• A genetic marker is a gene (or a gene product) or
DNA sequence with a known location on a
chromosome that can be used to
• Identify individuals or species.
• Locate gene with known function
• Study genetic variation
• Using genetic markers is a major step in
genetics/genomics
Genetic markers - isozymes
Heterozygote
• Isozymes (or allozymes) are proteins have
the same function but differ in size,
shape, and the amount of charge
• Can be separated in a starch gel under an
electrical current (electrophoresis)
• Allozyme polymorphism
• Detect genetic variation in 1980-1990s
• Limited number of markers available
Homozygote
Genetic markers - DNA Sequence Variation in length

• RFLP - Restriction fragment length

polymorphism (1990-)
• Cut genomic DNA into pieces by restriction
enzymes
• Separate the DNA segments
• Detect genetic variation
• Limited number of markers available
• RAPD - Random Amplification of
Polymorphic DNA
• Not reliable
• SSRs – Simple sequence repeats, also
called microsatellite
• Still in use http://en.wikipedia.org/
SNP - Single-nucleotide polymorphism
• A SNP represents a difference in a single nucleotide of a
DNA sequence.

Emaze.com
www.pinterest.com
How to use SNPs

https://youtu.be/4b3ywzMqCQ4
Summary of genetic markers
• Three categories
• Polymorphism in proteins
• Allozymes
• Polymorphism in the length of DNA fragments
• RFLP
• RAPD
• SSR
• Single nucleotide polymorphism
• DNA sequence-based
Outline
• Major advances in DNA sequencing
• Methods of gene detection
• Genetic markers
• Human genome projects
• Genetic testing
The Human Genome Project
• Started in 1990, completed in 2003, $3 billion.
• Coordinated by US, contributed by UK, France, Germany, Japan,
China, …
A clip showing the HGP
Major findings about the human genome:

• ~3 billion base pairs

• 20, 500 genes (~ 80, 000 expected)
• Similar as in mice
• More “control genes”
• Our DNA consists of repetitive DNA-segments of
mostly unknown function
By Originally Ben Moore, rewritten in gnuplot by grendel|khan
Precision medicine aims to improve treatments for individuals, but to do so it
needs information from crowds.
1 November 2018, a number of research organisations and funders announced
the official launch of the Earth BioGenome Project in the next 10 years.
Some new facts about human genome
• Any two people – except for identical siblings – have genomic
sequences that differ at approximately 0.1% of the positions.
• Most of the variation takes the form of isolated base substitutions, or
SNPs.
• How much is the 0.1% here?
• Entire genome: 3 billion bp x 0.1% = 3 million bp
• 4 ~ 5 million SNPs have been found, actually.
• 98% is non-coding DNA
NEWS 19 JUNE 2018
 Facts about conifer trees

Conifer genomes are huge due to:

• highly repetitive elements
• long introns
• ~1.5 to 2 times as many genes as other plants
Human vs. conifer trees
Conifer genome size
20 billion DNA “letters”;
~30,000 genes

Can study genetic

Human genome size
3 billion DNA “letters”;
variation within genes or
21,000 genes in non-coding regions

Genes
<1% of DNA
Genes
<2% of DNA
What can we do with genomic information?
• Knowing the sequence of the
genome of an organism is similar
to have a book written in a
language that we basically do not
understand
• To understand the 4-D life with the
one-dimension letter sequence is
not an easy task
What can we do with genomic information?
• Determine the function of genes and the elements that regulate genes
throughout the genome.
• Find variations in the DNA among individuals using SNPs and determine
their significance
• Genotype – phenotype relationships through genome-wide association studies
(GWAS)
• Explore how DNA and proteins interact with one another, and with the
environment to create complex living systems.
• Develop and apply genome-based strategies for the early detection,
diagnosis, and treatment of diseases.
• E.g., The Precision Medicine Initiative
• Continue to explore the ethical, legal, and social issues raised by genomic
research.
In plants
Questions and a break for 5 min
Genetic testing
Genetic testing - medical
• Genetic testing is a type of medical test that identifies
changes in chromosomes, genes, or proteins.
• More than 1,000 genetic tests are currently in use at
the following levels :
• Gene tests – test single genes or short lengths of DNA to
identify variations or mutations that lead to a genetic
disorder.
• Chromosomal tests - analyze whole chromosomes or long
lengths of DNA to see if there are large genetic changes, such
as an extra copy of a chromosome.
• Biochemical genetic tests - study the amount or activity level
of proteins.
What genetic testing can do?
• Confirm or rule out a suspected genetic condition
• Determine a person’s chance of developing or passing on a genetic
disorder.
• Identify alleles that may increase the risk to develop a disease
• Guide doctors in deciding on the best medicine or treatment to use
for certain individuals
• Determine a person's ancestry or biological relationship between
people
• Forensic testing
Genetic testing – commercial
Genetic testing or DNA testing – basically SNP-based
100 health conditions and traits
• Genetic Risk Factors (11)
• Genetic variants that are risk factors for various health conditions.
• Inherited Conditions (43)
• Genetic variants that have been linked to recessive conditions (homozygotes)
• Drug Response (12)
• Traits (41)
• genetic variants that may influence different non-health related traits, e.g.,
eye color
Genotyping vs. sequencing
• Genotyping is the process of determining which genetic variants
an individual possesses. It is also called:
• DNA profiling,
• DNA fingerprinting
• DNA testing, or
• DNA typing
• Genotyping methods
• DNA length polymorphism markers: RFLP, STR,..
• Genotyping chips: SNP array
• Require prior knowledge of the variants
• Sequencing is to sequence parts or entire genome
• To identify the variants
• Genetic testing services, e.g., 23andMe
• Genotyping (not sequencing)
Benefits of genetic testing
• Test results serve as a relief
• May help doctors make recommendations for treatments
• Monitoring vulnerable individuals for early development of some
diseases
Drawbacks of genetic testing
• Emotional: if you or someone in your family has or is at risk for a
disease
• Financial: Genetic testing can cost anywhere from less than $100 to
more than $2,000.
• Worried about discrimination by employers and insurance companies
• Limitations: vulnerable <> have or will have a disease
Questions
Group discussion assignments
• Required Readings
• 1. 23andMe Is Terrifying, but Not for the Reasons the FDA Thinks (Links to an external site.)
• 2. DNA Profiling_ How Is It Used in Criminal Justice?
• 3. Scientists discover 17 genetic variations that raise risk of depression
• 4. mRNA COVID-19 Vaccines_ An Incredible Feat of Genomic Technology
• Optional Readings
•
• Activities
• Group 1 and 2 work on paper #1. Group 1 will be presenting.
• Group 3 and 4 work on paper #2. Group 3 will be presenting.
• Group 5 and 6 work on paper #3. Group 5 will be presenting.
• Group 7 and 8 work on paper #4. Group 7 will be presenting.
• For procedures, please refer to "Flipped Classes"
Procedures of the discussion
• Read the assigned articles
• Write down the following major points (if they apply):
• What is the issue?
• How the issue was addressed (no tech details)?
• Major results (or main points)
• Conclusions
• Your opinion and taking home messages
• Download the template sheet
Questions