Genetic Basis of Development & Biotechnologies

Transcription

1 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

2 Genetic Basis of Development From a diploid zygote to a multi-cellular organism Nuclei containing DNA Sperm cell Egg cell Fertilized egg with DNA from both parents Embyro s cells with copies of inherited DNA Offspring with traits inherited from both parents

3 Three processes of embryonic development: Cell division- increase n cell number Morphogenesis- creation of form Cell differentiation- specialization in structure and function

4 a single-celled zygote of cells Embryonic Development many different types higher-level structures organs arranged in a particular way in three dimensions cells-- tissues--- organs--- organ systems whole organism

5 Morphogenesis Cell & tissue movement Growth in size Animals Plants Necessary for embryonic transformation Does not take place Limited to embryonic and juvenile stages Continues throughout the life of the plant

6 Totipotent cells (any) Pluripotent cells (many

7 Human morphogenesis disorder Cleft palate- upper wall of the mouth cavity fails to close completely

8 Differentiation produces a variety of cell types, each expressing a different combination of genes Muscle cell Pancreas cells Blood cells Nerve cell

9 Cloning of Organisms Plant cloning Used extensively in agriculture Plant cell remain totipotent and can dedifferentiate.

10 Animal Cloning Reproductive Organism Therapeutic Tissues & Organs

11 Animal cloning Nuclear transplantation -only 2% develop normally from nuclei of differentiated cells

12 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

13 Cloning of a Mammal In 1997 by Ian Wilmut edu/units/cloning/whatiscl oning/

14 Other mammals have been cloned The possibility of cloning humans raises unprecedented ethical issues.

15 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

16 Under the right conditions, cultured stem cells derived from either source can differentiate into specialized cells. Omnipotent

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18 Adult stem cells Pluripotent: bone marrow stem cellsdifferent kinds of blood cells Embryonic stem cells Totipotent- immortal Somatic Cell reprogramming (2007) Induced Pluripotent Stem Cells (ipsc) Oct , 11:21 AM EST Induced Pluripotent Stem Cell Technology Used to Generate Hepatocytes from Skin Cells GEN News Highlights

19 Induced Pluripotent Stem Cells (ipsc)

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21 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

22 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

23 Homeotic Genes Highly conserved in evolution, including humans Encode for master transcription factors

24 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.

25 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.

26 Normal Controlled Cell Death Cell Growth and cell Death Necrosis versus apoptosis

27 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

28 Genetic Basis of Cancer 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.

29 Cell cycle-stimulating pathway Growth factor G protein MUTATION Hyperactive Ras protein (product of oncogene issues signals on its own. Receptor Protein kinases (phosphorylation cascade) NUCLEUS Transcription factor (activator) DNA Gene expression Protein that stimulates the cell cycle The Signal Transduction Pathway (Quicktime Movie)

30 Cell cycle-inhibiting pathway Protein kinases MUTATION UV light DNA damage in genome DNA Active form of p53 Defective or missing transcription factor, such as p53, cannot activate transcription Protein that inhibits the cell cycle p53's Role in the Cell (Quicktime Movie)

31 Molecular Genetic basis of Cancer Mutations affecting control sequence of genes or coding sequences of genes Movement of DNA within the genome Gene amplification

32 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

33 Variations in the DNA sequences of humans affect : - Disease development - Response to: toxins, drugs, vaccines, and chemotherapy. -8w

34 Single Nucleotide Polymorphism (SNP)

35 Genome-wide screening Genetic variation in human population Correlation of certain base variability with proximity to a disease causing gene SNPs- single nucleotide polymorphisms ndex.html Pros & Cons Genetic Information Nondiscrimination Act GINA Bill