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

Totipotent cells (any) Pluripotent cells (many

Human morphogenesis disorder Cleft palate- upper wall of the mouth cavity

fails to close completely

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

• Reproductive Organism

• Therapeutic Tissues & Organs

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/

Induced Pluripotent Stem Cells (iPSC)

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

Single Nucleotide Polymorphism (SNP)

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