Genomics

MUPGRET Weekend Workshop

Timeline Answers http://www.jgi.doe.gov/education/ti

meline_2.html

Another timeline at http://www.dnai.org/index.htm .

Reviewing the basics Cells are the basic working unit of

an organism. DNA (deoxyribonucleic acid)

contains all of the instruction needed to direct the activities in the cell.

DNA is arranged into chromosomes.

More reviewing Chromosomes are visible with high

powered microscopes.

Human Chromosomes Metaphase Chromosome

Chromosomes are Dynamic Structures

Fruit Fly

CONDENSED EXTENDED

More review Chromosomes contain hundreds of

genes encoded within their DNA. Genes compromise a very small

percentage of the DNA that makes up the chromosome, <5% generally.

DNA containing genes is called euchromatin.

Heterochromatin Non-genic DNA is called

heterochromatin. Heterochromatin and euchromatin

stain differently. This difference causes the bands

we see in a karyotype.

Human karyotype

Genome composition Euchromatin (genes) usually

contains a higher proportion of GC. Euchromatin has more unique DNA

sequences. Heterochromatin (non-coding)

usually contains a higher proportion of AT.

Heterochromatin contains more repetitive sequence.s

DNA Content The amount of heterochromatin varies

dramatically between organisms. Much of the difference in DNA content

among closely related organisms is often due to changes in heterochromatin amount. Maize 2500 Mb Wheat 16,000 Mb Rice 430 Mb Mb=Mega base pairs

A NOVA look into DNA.

http://www.pbs.org/wgbh/nova/photo51/jour-nf.html

PCR Polymerase Chain Reaction A way to “xerox” a DNA fragment.

Electrophoresis A way to separate DNA molecules. http://gslc.genetics.utah.edu/units/

biotech/gel/

What is genomics? The study of the entire DNA

complement of an individual. The term genome refers to all of

the DNA contained in one copy of the chromosomes of an organism.

It contains both coding (genes) and non-coding DNA sequences.

The Genome Nearly every cell in an organims

contains a full copy of the genome. Most mammal cells contain two

complete copies of the genome. Skin Lung Heart

The Genome II Gametic cells like sperm, ovules,

or pollen contain one copy of the genome.

Some special cell types contain more than two copies of the genome. Human bone marrow Regenerating liver cells

Plant Genome Corn plants contain two copies of

the genome in their cells except for pollen, ovules, and endosperm (the fleshy part of the corn kernel).

Pollen and ovules have one copy of the genome.

Endosperm has three copies.

Plant Genome Other plants like corn include:

Arabidopsis Barley Beans Tomato Pepper Rice

Multicopy Plant Genomes Some plants normally have more

than two copies of the genome in their cells. Wheat – six copies Potato – four copies Sugarcane – >twelve copies Strawberry – >eight copies Banana – three copies Watermelon – three copies

Chromosome number The term haploid refers to the base

number of chromosomes in an organism.

Diploid cells have two copies of all the chromosomes.

Bacteria usually have one circularchromosome and no nucleus

Organisms with nuclei have variable numbers of chromosomes depending on the species:

• Mosquito 6• Chimpanzees 48• Goldfish 94

How Many Chromosomes Are There?

 

Some plants have few chromosomes like Arabidopsis.

Others, like sugarcane, have many.

How Many Chromosomes Are There?

 

Wheat

Rice

Arabidopsis

Sugarcane

Maize

Potato

Tomato

Cabbage

Carrot

10

20

+100

48

24

24

42

20

18

Ploidy vs. chromosome number Organism Ploidy Chromosome

number

Corn Diploid (2X) 20

Tomato Diploid (2X) 24

Arabidopsis Diploid (2X) 10

Potato Tetraploid (4X) 48

Wheat Hexaploid (6X) 42

How many genes? The number of genes varies

between organisms. Humans – 30,000 to 40,000 Maize – 55,000 Most genes between closely

related species are conserved. Many genes between less closely

related species are conserved.

The human genome project Complete DNA sequence Understand the sequence variation

between individuals. Understand the function of genes. Compare the sequences to other

related organisms. Study the ethical, legal and social

implications.

The human genome project http://www.genome.gov/Pages/Edu

cationKit/download.html

Exploring our molecular selves video.

Ethical legal and social implications video.

Insight from the human genome draft sequence

Protein coding region <2%. Repetitive DNA minimum of 50%. Genes are randomly distributed. 3X as many proteins as Drosophila

or C. elegans because of post-transcriptional modifications.

Insight from the human genome draft sequence II

Humans, C. elegans, Drosophila, and plants have most of the same proteins.

There are 2X as many germline mutations in males vs. females.

DNA sequence between two individuals is almost identical.

Only 0.1% of sequence is different.

Where do we go from here? Gene Expression Proteomics Structural genomics Mutagenesis Comparative genomics

Medicine and the New Genomics Gene Testing Gene Therapy Pharmacogenomics

Human Genome Program, U.S. Department of Energy, Genomics and Its Impact on Medicine and Society: A 2001 Primer, 2001

•improved diagnosis of disease •earlier detection of genetic predispositions to disease •rational drug design •gene therapy and control systems for drugs •personalized, custom drugs

Anticipated Benefits

Ethical Considerations Privacy/confidentiality Reproductive issues Accuracy of genetic testing Access to technology Genetically modified foods and

microbes Commercialization/Patents

Benefits of Genomics Improved diagnostic tools. Rational drug design. Rapid identification of pathogens. Better understanding of

mutagenesis. DNA forensics Improved agricultural products

Plant Genome Projects Initiative began in 1998. Arabidopsis was the first model

plant. Small genome size. Little repetitive DNA. Short life cycle.

Arabidopsis 2010 Project Complete sequence of Arabidopsis

in 2000. 2010 Project started in 2001. Goal was to determine the function

of the 25,000 genes in Arabidopsis by the year 2010 (ie. functional genomics of Arabidopsis).

Tools for genomics Sequencing video from human

genome project. Downloadable from

http://www.genome.gov/Pages/Hyperion/educationkit/download.html