Genetic Basis of Development & Biotechnologies 1. Steps of embryonic development: cell division,
morphogenesis, differentiation • Totipotency and pluripotency
2. Plant cloning 3. Animal cloning
• Reproductive versus therapeutic cloning • Nuclear transplantation • Stem cells: adult and embryonic • Somatic Cell Reprogramming (2007)/ Induced Pluripotent Stem Cells
(iPSC)
4. Molecular mechanisms of embryonic morphogenesis and differentiation
5. Animal body plan: homeotic genes 6. Cell death: necrosis and apoptosis
Genetic Basis of Development
From a diploid zygote to a multi-cellular organism
Sperm cell
Nuclei containing DNA
Egg cell
Fertilized egg with DNA from both parents
Embyro’s cells with copies of inherited DNA
Offspring with traits inherited from both parents
Three processes of embryonic development: • Cell division- increase n cell number • Morphogenesis- “creation of form” • Cell differentiation- specialization in
structure and function
Embryonic Development • a single-celled zygote many different types
of cells • higher-level structures organs arranged in a
particular way in three dimensions • cells-- tissues--- organs--- organ systems–
whole organism
Cell & tissue movement
Growth in size
Animals Necessary for embryonic transformation
Limited to embryonic and juvenile stages
Plants Does not take place
Continues throughout the life of the plant
Morphogenesis
Differentiation produces a variety of cell types, each expressing a different combination of genes
Muscle cell Pancreas cells
Blood cells Nerve cell
Plant cloning Used extensively in agriculture
Plant cell remain totipotent and can dedifferentiate.
Cloning of Organisms
Animal cloning
Nuclear transplantation
-only 2% develop normally from nuclei of differentiated cells
Different types of cell in an organism have the same DNA but they transcribe different genes
Nuclei do change as cells differentiate: DNA sequences do not change Chromatin structure and methylation patterns do
Cloning of a Mammal In 1997 by Ian Wilmut
http://learn.genetics.utah.edu/units/cloning/whatiscloning/
Other mammals have been cloned
The possibility of cloning humans raises unprecedented ethical issues.
Stem Cell Research Stem cells
– unspecialized cells, continually reproduce can differentiate into specialized cell types.
– can differentiate into multiple cell types are multipotent or pluripotent.
Two types of stem cells 1. Adult stem cells & Cord Blood stem cells 2. Embryonic stem cells
Under the right conditions, cultured stem cells derived from either source can differentiate into specialized cells.
Omnipotent
Adult stem cells • Pluripotent: bone marrow stem cells-
different kinds of blood cells
Embryonic stem cells • Totipotent- immortal
Somatic Cell reprogramming (2007) Induced Pluripotent Stem Cells (iPSC) Oct 20 2009, 11:21 AM EST Induced Pluripotent Stem Cell Technology Used to Generate Hepatocytes from Skin Cells GEN News Highlights http://learn.genetics.utah.edu/content/tech/stemcells/ips/
Morphogenesis & Differentiation during embryonic development
• Tissue-specific gene expression
• Controlled at level of transcription by - unequal distribution of RNA and proteins in
the cytoplasm
- Signals received from other nearby embryonic cells
Maternal mRNA and proteins are not uniformly distributed in the cytoplasm of unfertilized eggs
• Daughter cells of first mitotic
division exposed to different cytoplasmic environments contribute to pattern formation, spatial organization of tissues and organs
Homeotic Genes • Highly conserved in evolution, including humans • Encode for master transcription factors
Animal body plan: Homeotic genes ancient direct the identity of body parts
Mutations to homeotic genes produce flies with such strange traits as legs growing from the head in place of antennae.
Cancer Genes (Learning Objectives)
1. Recognize programmed cell death (Apoptosis) as a integral part of the life of multi-cellular organisms
2. Compare and contrast control of cell division and cell death in normal and cancer cells
3. Identify the types of genes that can lead to cancer. Define the terms: tumor suppressor, proto-oncogene and oncogene.
4. Recognize the role of different mutations in genetic alterations that can lead to cancer.
Normal Controlled Cell Death • Cell Growth and cell Death • Necrosis versus apoptosis
http://www.youtube.com/watch?v=IsexrAFghdA
Normal Cells Normal cell division is a tightly controlled
sequence of events resulting from the action of genes that balance cell division and cell death
Cancer Cells Uncontrolled cell division can result from
genes that stimulate cell replication or loss of function of genes that cause cell death
Genes whose products enhance growth and inhibit cell death
• Tumor suppressor genes: proteins that inhibit cell division (P53 & BRCA genes)
• Proto-oncogenes: normal proteins that stimulates cell division of normal cells under certain conditions.
• Cancer cells have oncogenes.
Genetic Basis of Cancer
Cell cycle-stimulating pathway
Growth factor
G protein
Receptor
MUTATION
Protein kinases (phosphorylation cascade)
NUCLEUS
Hyperactive Ras protein (product of oncogene issues signals on its own.
Transcription factor (activator)
DNA
Gene expression
Protein that stimulates the cell cycle
The Signal Transduction Pathway (Quicktime Movie) http://www.learner.org/courses/biology/units/cancer/images.html
Active form of p53
DNA DNA damage in genome
UV light
Protein kinases MUTATION
Defective or missing transcription factor, such as p53, cannot activate transcription
Cell cycle-inhibiting pathway
Protein that inhibits the cell cycle
p53's Role in the Cell (Quicktime Movie) http://www.learner.org/courses/biology/units/cancer/images.html
Molecular Genetic basis of Cancer • Mutations affecting control sequence of genes or coding sequences of genes • Movement of DNA within the genome • Gene amplification
Genetic Testing & Personalized Medicine
(Learning Objectives)
1. Recognize the presence of common mutation within members of the human population (polymorphisms)
2. Recognize that information about such polymorphisms can be used for several purposes, such as:
• Mutational analysis of disease causing genes • Genome –wide scanning for disease predisposition genes • Personalized Medicine
Variations in the DNA sequences of humans affect :
- Disease development - Response to: toxins, drugs, vaccines,
and chemotherapy. http://www.youtube.com/watch?v=dUL5f8nB
-8w
Genome-wide screening • Genetic variation in human population • Correlation of certain base variability with
proximity to a disease causing gene • SNPs- single nucleotide polymorphisms
http://topics.nytimes.com/top/news/national/series/dnaage/i
ndex.html http://www.pathway.com/
Pros & Cons
Genetic Information Nondiscrimination Act GINA Bill