Download DNA

Genomics and
Inheritance
What is DNA?
What is DNA Day?
What is DNA Day?
April 1953
Drs. James Watson and
Francis Crick determined
the structure of DNA
(double helix)
What is DNA Day?
April 1953
April 2003
Drs. James Watson and
Francis Crick determined
the structure of DNA
(double helix)
Human Genome Project
determined the entire DNA
sequence of a human
(3 billion letters)
A Genome is an entire set of an
organism’s DNA
• 23 pairs of
chromosomes
J Craig Venter Institute
The Human Genome
A Genome is an entire set of an
organism’s DNA
• 23 pairs of
chromosomes
Mother
(Maternal)
Father
(Paternal)
• One from your
mother, one from
your father
J Craig Venter Institute
The Human Genome
Cell
J Craig Venter Institute
The Human Genome
DNA holds instructions for the cell
DeoxyriboNucleic Acid (DNA) contains all the information
necessary to make a complete organism
DNA is composed of a combination of 4 nucleotides
DNA holds instructions for the cell
DeoxyriboNucleic Acid (DNA) contains all the information
necessary to make a complete organism
DNA is composed of a combination of 4 nucleotides
A
T
C
G
Adenine
Thymine
Cytosine
Guanine
DNA holds instructions for the cell
DeoxyriboNucleic Acid (DNA) contains all the information
necessary to make a complete organism
Two DNA
molecules
DNA holds instructions for the cell
DeoxyriboNucleic Acid (DNA) contains all the information
necessary to make a complete organism
Base Pair
A pairs with T
Adenine Thymine
C pairs with G
Cytosine Guanine
Which is how DNA forms a double helix.
Two DNA
molecules
“DNA sequence” is the order of
nucleotides on a DNA molecule
DNA double
helix
“DNA sequence” is the order of
nucleotides on a DNA molecule
DNA double
helix
If we unwind
it and look at
one strand…
“DNA sequence” is the order of
nucleotides on a DNA molecule
DNA double
helix
If we unwind
it and look at
one strand…
A C C A T C G T G C A T G T C T C we can see
its sequence
The entire human genome comprises over 3
billion base pairs. Here’s just the beginning.
CGCAAATTTGCCGGATTTCCTTTGCTGTTCCTGCATGTAGTTTAAACGAGATTGCCA
GCACCGGGTATCATTCACCATTTTTCTTTTCGTTAACTTGCCGTCAGCCTTTTCTTTGA
CCTCTTCTTTCTGTTCATGTGTATTTGCTGTCTCTTAGCCCAGACTTCCCGTGTCCTTT
CCACCGGGCCTTTGAGAGGTCACAGGGTCTTGATGCTGTGGTCTTCATCTGCAGGT
GTCTGACTTCCAGCAACTGCTGGCCTGTGCCAGGGTGCAAGCTGAGCACTGGAGTG
GAGTTTTCCTGTGGAGAGGAGCCATGCCTAGAGTGGGATGGGCCATTGTTCATCTT
CTGGCCCCTGTTGTCTGCATGTAACTTAATACCACAACCAGGCATAGGGGAAAGAT
TGGAGGAAAGATGAGTGAGAGCATCAACTTCTCTCACAACCTAGGCCAGTAAGTA
GTGCTTGTGCTCATCTCCTTGGCTGTGATACGTGGCCGGCCCTCGCTCCAGCAGCTG
GACCCCTACCTGCCGTCTGCTGCCATCGGAGCCCAAAGCCGGGCTGTGACTGCTCA
AGCCAGCCGGCTGGAGGGAGGGGCTCAGCAGGTCTGGCTTTGGCCCTGGGAGAG
CAGGTGGAAGATCAGGCAGGCCATCGCTGCCACAGAACCCAGTGGATTGGCCTAG
GTGGGATCTCTGAGCTCAACAAGCCCTCTCTGGGTGGTAGGTGCAGAGACGGGAG
GGGCAGAGCCGCAGGCACAGCCAAGAGGGCTGAAGAAATGGTAGAACGGAGCAG
CTGGTGATGTGTGGGCCCACCGGCCCCAGGCTCCTGTCTCCCCCCAGGTGTGTGGT
GGCTCTGGATGCCAGGCATGCCCTTCCCCAGCATCAGGTCTCCAGAGCTGCAGAAG
ACGACGGCCGACTTGGATCACACTCTTGTGAGTGTCCCCAGTGTTGCAGAGGTGAG
Gene – DNA instructions to make a protein
Protein – a large molecule that
does work for the cell
rcsb.org
Some sections of the genome are genes
The genome is like a cookbook for the cell
A
T
C
G
Nucleotides
Letters
The genome is like a cookbook for the cell
A
T
C
G
Nucleotides
Letters
Gene
Recipe
A sequence of nucleotides composes a gene.
The genome is like a cookbook for the cell
A
T
C
G
Nucleotides
Letters
Gene
Recipe
A sequence of nucleotides composes a gene.
Gene
Genome
Cookbook
Cell
Billions of nucleotides are packaged into chromosomes.
Wikimedia commons
Refresher: What are each of these?
nia.nih.gov
Refresher: What are each of these?
Cell
Genes
Chromosome
Genome
Nucleotides
DNA
nia.nih.gov
Please PAUSE
to complete
the DNA
extraction activity
DNA Isolation Method
• Step 1: Add your saliva to the tube
• Step 2: Add 1-2 drops of soap to tube and mix well
• Step 3: Add a pinch of salt and mix well
• Step 4: Add several droppers full of ethanol and mix
well
• Step 5: Spool your DNA with stick
No two genomes are the same
Individuals differ at about .1% of their nucleotides.
Variant
Variant - A position in the genome
where individuals have different
nucleotides
Broad Institute
No two genomes are the same
Individuals differ at about .1% of their nucleotides.
.1%
Variant - A position in the genome
where individuals have different
nucleotides
3 million variants
3 billion nucleotides
No two genomes are the same
Individuals differ at about .1% of their nucleotides.
Variant - A position in the genome
where individuals have different
nucleotides
.1%
3 million variants
3 billion nucleotides
A
G
C
T
A
G
C
T
1
2
……………………………..
A
G
C
T
3 million
4 choices at 3 million places  43million unique genomes
Actually, some genomes are the same
Identical twins have the same genome.
Martin Schoeller for National Geographic
Normal zygotes vs. identical twins
Normal Zygote: A fertilized egg develops into one individual.
A zygote multiplies and
develops.
A single individual is produced.
Adapted from http://www.mun.ca/biology/desmid/brian/BIOL3530/
Normal zygotes vs. identical twins
Identical Twins: A fertilized egg splits into two identical zygotes
early on.
A zygote splits into two
independent zygotes.
The zygotes develop into two
individuals with identical
genomes.
Adapted from http://www.mun.ca/biology/desmid/brian/BIOL3530/
Clones also have the same genome
How Dolly was cloned
To clone an animal you need a body cell and an egg cell.
Body cell
Egg cell
bbc.co.uk
How Dolly was cloned
Replace the genome of the egg cell with that of the cell to be
cloned.
Body cell
Extract
genome
Replace egg
cell’s genome
Egg cell
bbc.co.uk
Remove genome
How Dolly was cloned
Place the dividing egg cell into the uterus of a foster mother.
Body cell
Place egg into
foster mother
Extract
genome
Replace egg
cell’s genome
Clone of
sheep A
Egg cell
bbc.co.uk
Remove genome
Your list of variant nucleotides is your genotype
Example chromosome
Variants
.
G
T
T
.…..
…
A
C
A
Maternal
Your list of variant nucleotides is your genotype
Example chromosome
Variants
.
G
T
T
.…..
…
A
C
Genotype
G
T
T
A
C
A
A
Maternal
M
T
T
C
A
A
G
Your list of variant nucleotides is your genotype
Example chromosome
Variants
T
T
C
.
.
G
T
T
A
G
…
.…..
A
A
…
.…..
A
C
Maternal
Variants
Paternal
Genotype
G
T
T
A
C
A
M
T
T
C
A
A
G
P
Your list of variant nucleotides is your genotype
Example chromosome
Variants
T
T
C
.
.
G
T
T
A
G
…
.…..
A
A
…
.…..
A
C
Maternal
Variants
Paternal
Genotype
G
T
T
A
C
A
M
T
T
C
A
A
G
P
Genotype – The variant nucleotides on both maternal and paternal
chromosomes. Your full genotype is unique.
Genomic variants result in unique
individuals
Big genomic variations allow for many
different forms of life
Morten Koldby
Leila Jeffreys
Jennifer Cottom
A.R. Valentien
Insects.org
Joel Sartore
Reo Kometani & Shinji Matsui
Variations in the DNA of different individuals
can cause changes in physical appearance
or can even cause disease.
Variants can result in big changes
University of Michigan
The A variant at position 5,248,232 on chromosome 11 causes
Sickle Cell Anemia.
Normal red blood cell
Sickle-shaped
diseased red blood cell
Variants can result in big changes
University of Michigan
The A variant at position 5,248,232 on chromosome 11 causes
Sickle Cell Anemia.
…CTC…
Normal red blood cell
Sickle-shaped
diseased red blood cell
Variants can result in big changes
University of Michigan
The A variant at position 5,248,232 on chromosome 11 causes
Sickle Cell Anemia.
…CTC…
…CAC…
Variant
Normal
Normal red blood cell
Disease
Sickle-shaped
diseased red blood cell
Different genotypes result in different outcomes
Genotypes observed
T T
A T
A A
Different genotypes result in different outcomes
Genotypes observed
T T
A T
A A
Normal
Mostly Normal
Sickle Cell Anemia
micro-scopic.tumblr.com
microscopyu.com
http://legacy.owensboro.kctcs.edu/
The variant is correlated to the disease
Sickle Cell
count
T T
micro-scopic.tumblr.com
A T
A A
microscopyu.com
Genotype
http://legacy.owensboro.kctcs.edu/
The variant is correlated to the disease
Sickle Cell
count
T T
A T
A A
Genotype
The variant is correlated to the disease
Sickle Cell
count
steep slope = correlation
T T
A T
A A
Genotype
Other variants show no disease correlation
The Sickle Cell A/T variant is the only variant correlated to the
disease.
Any other variant will not be correlated. For example:
C/A variant
Chr11:119,553,795
Other variants show no disease correlation
The Sickle Cell A/T variant is the only variant correlated to the
disease.
Any other variant will not be correlated. For example:
C/A variant
Chr11:119,553,795
Sickle Cell
count
C C
C A
A A
Genotype
Other variants show no disease correlation
The Sickle Cell A/T variant is the only variant correlated to the
disease.
Any other variant will not be correlated. For example:
C/A variant
Chr11:119,553,795
Sickle Cell
count
no slope = no correlation
C C
C A
A A
Genotype
Plot genotype vs. disease state to find how
correlated a variant is to the disease
Disease
Correlated
TT
AT
AA Genotype
Disease
Not Correlated
CC
CA
AA Genotype
Genome Wide Association Studies find
variants correlated to a disease or trait
1. Pick a disease or trait to test
2. Find individuals with and without the disease/trait
Disease
No Disease
Genome Wide Association Studies find
variants correlated to a disease or trait
3. Get genotypes of the individuals
TT
AT
AT
AA
CA
CC
CA
AA
4. Test variants for their correlation to disease/trait
Disease
Disease
or
AA
AT
TT
Genotype
CC CA
AA
Genotype
Sturm, R.A. Hum Mol Gen
Most traits are controlled by more than one variant
Skin color is determined by 12 different variants.
531,441 different combinations of these variants!
Please PAUSE
to complete
the activity
Every cell in your body has the same
genome, except…
If some cells in your body carry a different genome, you
are a mosaic or a chimera.
Nature Review Genetics
Every cell in your body has the same
genome, except…
If some cells in your body carry a different genome, you
are a mosaic or a chimera.
One zygote
Mutation
Mosaic
Two zygotes
Fusion or
exchange
of cells
Chimera
© Garland Science
Every cell in your body has the same
genome, except…
If some cells in your body carry a different genome, you
are a mosaic or a chimera.
One zygote
Mutation
Mosaic
Two zygotes
Fusion or
exchange
of cells
Chimera
© Garland Science
Ben Moore, wikipedia.org
The first human genome was sequenced in 2001
The 1000 Genomes Project
medschool.wustl.edu
Genomics tells us about our ancestry
Thousands of years
before present
Klyosov and Rozhanskii, 2012
Genomics created the field of “personalized
medicine”
Medical treatments may
one day be customized to
your genome.