Transcript Zebrafish - yourgenome

Zebrafish in
genome research
Can you spot the difference?
What is a zebrafish?
• Danio rerio
• Small freshwater fish
from South Asia.
• 4 cm long when fully
grown.
• Common aquarium
fish.
• Very easy to look after.
Image: Wikimedia commons/Marribio2
What is a model organism?
• Non-human species widely studied to
understand human disease.
• Model organisms are used when
experimentation using humans is unfeasible or
unethical.
• Can you think of a model organism?
Types of model organism
Genetic model organisms
Experimental model
organisms
Genomic model organisms
Good candidates for
genetic analysis.
Good candidates for
research into
developmental biology.
Good candidates for
genome research.
Breed in large numbers.
Produce robust embryos
that can be easily
manipulated and studied.
Easy to manage genomes
e.g. small genome size or
limited number of repeats.
Have short generation
times so large scale crosses
can be followed over
several generations.
Genome is similar to a
human.
Images: Wellcome Trust Sanger Institute
Why use zebrafish?
• Small size.
• All major organs present
within 5 days post fertilisation.
• Short generation time
(3-4 months).
• Produces 300-400 eggs every
2 weeks.
• Translucent embryos.
• Lots of genome resources available.
Image: TBC
The zebrafish embryo
brain
ear
eye
heart
swim
bladder
muscle
block
segments
~3.5 mm
notochord
Zebrafish and human disease
• Zebrafish mutants have been produced to model
human diseases such as:
– Alzheimer's disease
– congenital heart disease
– polycystic kidney disease
– Duchenne muscular dystrophy
– malignant melanoma
– leukaemia
Forward screening for mutants
ENU-treated male
P
+/+ female
x
+/M
F1
+/+
x
F2
+/+ (50%)
+/M (50%)
x
F3
+/+ (25%)
+/M (50%)
M/M (25%)
Reverse screening for mutants
Potential human
disease gene
Exciting gene
expression pattern
Gene of interest
Potential new player in
developmental
pathway
Gene knockout
Phenotype analysis
The activity
• Identify differences between the wildtype
zebrafish and mutant zebrafish.
• A glossary is provided to help you with scientific
terms.
Image: Rodrigo Young, University College London
Flash cards & worksheets
Answers
Image 1
What’s the difference?
Embryo B has no eye.
Image: Rodrigo Young, University College London
Image 2
What’s the difference?
Fish B is a lighter, golden colour compared to fish A.
Image: Keith C. Cheng, Penn State College of Medicine and Wellcome images
Image 3
What’s the difference?
The body of fry B is curved. If you look closely you’ll also see that its
mouth is open. This is because it is unable to fully close its mouth as
its muscles are too weak.
Image: Elisabeth Busch, Wellcome Trust Sanger Institute and Lehtokari et al 2008, European Journal of Human Genetics
Image 4
What’s the difference?
The zebrafish embryos in picture B look paler and are not stained
red.
Image: Ana Cvejic, Wellcome Trust Sanger Institute
Image 5
What’s the difference?
There are bright green blobs in picture B.
Image: Elisabeth Busch, Wellcome Trust Sanger Institute
Image 6
What’s the difference?
Embryo A has more blue dots than embryo B.
The blue dots are stained neutrophils moving towards a wound on
the zebrafish fin.
Image: Ana Cvejic, Wellcome Trust Sanger Institute