Genetic Engineering: Where Are We?!
Genetic Engineering!
•! Identifying genes and gene expression!
–! DNA microchips!
Brave New World !
or!
Ecological Nightmare!
or!
Overblown Hopes!
?!
DNA Microchip Arrays!
•! Genetically Modified Organisms!
–! Plants!
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Round Up-ReadyTM soybeans!
BT-corn!
Golden rice!
tobacco, cotton ….!
•! Cloning!
–! animals!
–! humans?!
–! therapeutic!
•! SCID; Angina?!
•! cancer treatments!
Microchip Arrays and Uses!
Microchip Arrays!
Genetic Engineering: in
Agriculture!
Uses:!
tumor subtypes!
drug use by athletes!
developmental pathways!
mechanisms of toxicity!
etc, etc, etc!
•! Make plants resistant to herbicides!
–! RoundUp-Ready soybeans!
•! Include the insecticide in the plant!
–! BT corn!
•! Make animal hormones available cheaply!
–! Transgenic bovine growth hormone!
–! Increases milk production 10%-40%!
•! High-carotene rice!
–! “Golden rice”!
–! Provides adequate Vitamin A precursor!
–! Could prevent blindness in millions!
•! Controversies include!
–! Human health effects!
–! Ecological consequences!
–! Socioeconomic consequences!
GMOs: Genetically Modified Organisms!
Objections to GMOs!
•!
•! Inserting genes into plants is
relatively easy.!
•! Major uses so far:!
–! resistance to herbicides allows
use of the relatively benign
herbicide glyphosate (Round
Up) on otherwise sensitive
crops.!
–! inserting the gene for Bt toxin
gives plant a built-in
insecticide; saves spraying!
•! insecticide is produced in
pollen as well as leaves!
•! in corn kernels?!
•!
Health risks!
–! allergies!
–! toxicity!
Ecological risks!
–! non-target species!
–! super-pests!
•! insect resistance!
–! selection of pests!
•! weed resistance!
–! selection of previously nonpest species!
•! genes jumping to related weeds,
animals!
–! farmed salmon!
•!
Social consequences!
–! favors large farms!
–! seeds are patented - no saving!
–! fertilizer requirements may be high!
Cloning mammals:
Dolly!
Cloning Mammals - 2. Pigs!
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Mammary cell from Finn-Dorsett sheep!
Fused to enucleated egg!
Implanted into black-faced sheep!
Result: !
–! Dolly!
–! Genetically identical to Finn-Dorsett!
•! Died young!
–! developed problems of older sheep!
–! died roughly at age of Finn-Dorsett
nucleus!
Cloning Mammals - "
State of the Art, 2010!
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Success rate is low: 10% or less.!
Many offspring do not survive!
Calves are often very large!
Seem to age rapidly!
–! Variable, but not uncommon!
•! Mice !
–! poor health!
–! die young!
–! compromised genomes!
•! 4% of genes are abnormally
expressed (liver, placenta)!
•! imprinting problems?!
Medical Genetics "
1. Personalized
therapies!
•! Identify gene expression in
tumor!
•! Decide on therapy based on!
–! specific genes !
•! e.g.: HER2+ means
herceptin helps!
–! larger pattern!
•! e.g.: Oncotype dx!
•! predicts recurrence risk
for ER+ breast cancer!
Mouse cloned from brain cells of male mouse,
frozen for 16 years.!
Medical Genetics: "
2. Somatic Gene
•!
Therapy!
Gene Therapy"
(continued)!
Vector!
–! DNA Virus!
•!
–! Mutation in adenine deaminase
(ADA)!
–! Infect blood cells with retrovirus
containing normal ADA!
–! Successful in ~ 20 cases!
–! 4 or 5 cases of leukemia resulted!
•! lytic or lysogenic!
•! incorporated into host genome!
–! Retrovirus (RNA genome)!
•! incorporated into host genome!
–! Adenoviruses!
•! not incorporated into host
genome!
•! does not replicate when cell
does!
•! effects eventually lost!
–! Naked DNA!
•! not very effective so far!
•! methods for enhancing
effectiveness needed!
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Genetic Engineering of
Insects?!
Goal:!
–! Use transposons to generate mosquitos
that cannot transmit disease!
Can be done in lab.!
–! Will transgenic mosquitos survive in the
wild?!
Will developing countries allow use of this
technology?!
SCID!
•!
Cystic fibrosis!
–! Inhalation of transgenic
adenovirus carrying normal
CFTR gene!
–! Under investigation!
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Angina pectoris!
–! Inject retrovirus with genes for
angiogenesis!
–! Some success (anecdotal)!