Could you please insert ‘Genes and Diseases’ intro slide here?

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On April 25, 1953

Drs. James Watson and Francis Crick determined the structure of DNA

In April 2003,

Human Genome Project determined the entire DNA sequence of a human (3 billion letters)

What is DNA Day?

Protein

RNA copy

Information is stored in DNA

Genes contain instructions to make proteins

Proteins do most of the

work in a cell and provide much of its structure.

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A change in gene result in a change in protein

SAM AND TOM ATE THE HAMPossible Change:

SAM AND TOM ATE THE HIM

Thr Pro GluGlu Lys Leu

ACT|CCT|GAG|GAG|AAG|CTG

ACT|CCT|GAG|GAG|AAG|CGG

Thr Pro GluGlu Lys MetResult: Changed meaning or function

Change in DNA is called a mutation

Variations in the DNA of different individuals can cause phenotypic changes in individuals

• Just by looking around the room, we can see many examples of genetic variation.

• Some genetic traits, such as skin color and eye color, are controlled by multiple genes

• Others are controlled by only one gene

• We are going to look at 7 traits that are each determined by one gene with two possible alleles.

Variations in the DNA of different individuals can cause visible changes

in individuals

Single-gene Traits

Laugh dimples• ll no dimples (homozygous

recessive)• L dimples (heterozygous or

homozygous dominant)Tongue roll• tt can’t roll tongue into “U”

shape (homozygous recessive)

• T can roll tongue into “U” shape (heterozygous or homozygous dominant )

Single-gene TraitsCrossing Thumbs• cc right thumb on top of

clasped hands (homozygous recessive)

• C left thumb on top of clasped hands (heterozygous or homozygous dominant )

Pinkies• pp pinkies are straight when

pressed side by side (homozygous recessive)

• P pinkies bend away from each other, toward the ring fingers, when pressed side by side (heterozygous or homozygous dominant)

Single-gene Traits

Ear lobes• ee attached ear lobe

(homozygous recessive)• E free ear lobe

(heterozygous or homozygous dominant)

Widow’s peak• ww no widow’s peak

(homozygous recessive)• W has a widow’s peak

(heterozygous or homozygous dominant)

Single-gene Traits

Bending thumbs (Hitch-hiker’s thumb)

• bb thumb bends at 90 degree angle (homozygous recessive)

• B thumb is straight (heterozygous or homozygous dominant)

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Genetic Wheel Results

• There are 128 possible combinations from the 7 traits illustrated on the genetic wheel.

• Are you the same as anyone else?

• If this much genetic variation exists in traits that are visible, imagine how different we all are in ways that we can’t see!

Variations in the DNA of different individuals can cause varying traits

in individuals

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These traits can be inherited!

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Traits are inherited through genes

• Genes are on chromosomes

• One chromosome inherited from each parent

• We have two copies of each gene

http://www.biotechnologyonline.gov.au

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Different versions of genes are alleles

• For each gene, you might have…

2 different alleles 2 of same allele

ORCombinations of alleles determine what traits you have

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Can you roll your tongue?

Yes! You carry a copy of the dominant allele.

No! You have two copies of the recessive allele.

Dominant does NOT mean more common!

orIf you inherit both

alleles, the dominant one is expressed.

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Each parent contributes 1 allele to offspring

Father’s alleles

Mother’s alleles

r

r

r

R

r

Rr

r

r

r

r

R

r = No-roll allele

(Recessive)

R = Roll allele

(Dominant)

Inheriting Traits- Tongue Rolling

Disease alleles can be inherited just like a “tongue rolling” allele...

Some diseases are caused by genetic factors and can be inherited

A good example of genetically inherited disease is Cystic Fibrosis

Symptoms of Cystic Fibrosis

• Thick mucus in airways and lungs

• Chronic Lung infections– can cause permanent

lung-cell damage.

• Digestive problems– Lack of nutrient

absorption

What is the cause of Cystic Fibrosis?

The lungs are lined with specialized cells.

Dust

Dust

Mucus gland

Cilia

DustMucus gland

Mucus

Dirt

Out to mouth

Cilia Mucous

These special cells clear mucus

Healthy Airway CF Airway

Cystic Fibrosis patients’ airways are dehydrated and cannot clear mucus.

Thick, dry mucusNormal mucus

As a result, CF airways accumulate bacteria and inflammatory cells.

Pseudomonas aeruginosa

Too many inflammatory cells can cause permanent lung-cell damage.

CFTR protein hydrates and allows mucus clearance

=

Cilia

The CFTR in Lung Cells

CFTR protein

Cell nuclei

Cystic Fibrosis Transmembrane Regulator(CFTR)

Chromosome 7

CFTR protein

RNA

DNA

Protein

transcription

translation

DNA

RNA

Mutations in the CFTR gene blocks CFTR protein function

CFTR

Mutant CFTR

Healthy cell

Cystic fibrosis cell

Changes in the DNA sequence lead to a protein that cannot reach the plasma membrane.

Cystic Fibrosis Activity

You be the investigator…Find a cystic fibrosis patient

Investigate the BALF

A

1. Do not open the tubes!!2. Analyze the contents of each tube for:• Mucus consistency• Presence of inflammatory cells• Evidence of infection with Pseudomonas

aeruginosa (bacterial cells)3. Record your findings on the worksheet

provided.

= inflammatory cell (macrophage)

= bacterium (Pseudomonas)

Who do think has Cystic Fibrosis?

What would you do next to confirm the diagnosis?

Sequence the DNA and look for mutations in the cftr gene.

• There are ~900 different mutations that have been found in the cftr gene.• To save time, we have printed the DNA sequences from the sequencing reactions for you.

Remember the Central Dogma?

DNA RNA Protein

How do mutations in the DNA sequence lead to defective proteins?

AGG TCG GGT CAA CAA TGCDNA

RNA UCC AGC CCA GUU GUU ACG*Convert the DNA sequence into the RNA intermediate.

DNAATCG

RNAUAGC

DNA RNA Protein

Now convert the mRNA message to a protein.

mRNA UCC AGC CCA GUU GUU ACG

Ser Ser Pro Val Val ThrProtein

DNA RNA Protein

Which patient has the defective CFTR protein?

Now you know that mutations in the genes (or DNA) can lead to changes in the protein.

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environmentenvironment

environment

gene

gene

genegene

“family history”

Genes & environment can work together to cause disease

Disease

Diseasegene yes

Will you have the disease?

maybe

What diseases have both a genetic and an environmental component?

Cancer

lack of exercise

smoking bad diet

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mutation

Cancer

• Your own cells dividing out of control– tumor cells behave abnormally, invade tissues

• Why? mutations in DNA

many mutations

tumor

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What causes these mutations?• Environment (carcinogens)

• Can inherit mutations in certain genes

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How does knowing the genetics of diseases help us?

Better understanding of disease can lead to better or safer treatments:

– Better, more specific drugs – Gene replacement therapy– Personalized medicine

Does this mean we can cure everything?

No

END OF PRESENTAION

FEEL FREE TO DISCUSS YOUR RESEARCH AND CAREERS