The Age Of Genomics

Rachel and Olga

THE AGE OF GENOMICSOutline

How Genetics Became Genomics

The Human Genome Project Begins

Technology drives the sequencing effort

Comparative Genomics

How Genome Information Will Affect You

How Genetics Became Genomics

•Human Genome sequencing was built on linkage and cytogenic information from decades

•Different types of genetic maps took genetic analysis to a new level.

Levels of genetic maps

Positional Cloning• Identifying parts of the genome

corresponding to a genetic disorder

• Positional cloning located specific disease-causing genes in families using RFLP ( Restriction Fragment Length Polymorphimisms) mapping of linked single nucleotide polymorphimisms (SNP’s) that affect fragment size

– This was done by beginning with phenotype and gradually identifying a causative gene, localizing it to a particular part of a chromosome.

1.Define the candidate region 2.Obtain clones

of all the DNA of the region

3.Identify all of the genes

of the region

4.Prioritizing them for mutation

screening

5.Test candidate genes for

mutations in affected people

Steps

Of

Positional Cloning

* Attention has shifted to understanding hierarchies of multi-gene function instead of identifying single genes in comparing genomes of different species.

HumansMammals

BirdsReptiles

InsectsFish

PlantsMicroorganisms

Human Genome Project• Obtain nucleotide base

sequence of pieces of DNA

• DNA sequencing and computer software to align the DNA pieces were needed for the genome projects to start

• Francis Crick sequenced genes of E.coli

Francis Crick

Sanger MethodSanger Method

Complementary copies of unknown DNA sequence

Are terminated early by incorporating

Dideoxynucleotides.Computer then deduces

sequence by placing fragments in size order.

Radioactive or fluorescent labels are used to visualize

quantities of each fragment

Technologies drives the Sequencing Effort

• In general, genome sequencing cuts several copies of a genome , sequencing the pieces, then uses algorithms to overlap the pieces and derive sequence.

Sequencing Assembly

AnnotationGene expression

profiles and proteomics

Sequencing Genomes

Expressed Sequence Tag Expressed Sequence Tag TechnologyTechnology

• EST’sEST’s are landmarks in genome are landmarks in genome sequencing that represent protein-sequencing that represent protein-encoding genes.encoding genes.

• Identifying EST’s enables researchers Identifying EST’s enables researchers to quickly pick out genes most likely to quickly pick out genes most likely to be implicated in diseases, because to be implicated in diseases, because they encode protein and are they encode protein and are expressed in all cell types affected in expressed in all cell types affected in particular illness.particular illness.

Clone-by-CloneClone-by-Clone and and Whole Genome Whole Genome Shot-gunShot-gun Sequencing Sequencing

• Clone-by-clone sequencing assembles chromosomes individually, using a great deal of existing cytogenic and linking data to assign pieces to chromosomes.

• Whole genome shot- gunning shatters the entire genome and rebuilds it by using a computer algorithm to identify overlaps and align them to obtain a continual sequence.

Comparative Genomics

• Seeks conserved sequences among species to correlate them with evolutionary transitions

Chimp and human genomesChimp and human genomes

• Focuses on differences that help to distinguish between species

Into the Future

• Comparing the genomes of healthy cohort to groups of people with certain diseases may reveal how gene combinations maintain health.

• Clues to health also lie in the genome sequences of people at high risk for certain disorders who do not become ill.

Genome information will help you

• DNA microarray test for medical condition

• Serve on jury and look at DNA profiling evidence

• Panel genetic tests before having a child

• a body part from a pig with cell surfaces that are the same as yours

• Help someone through chemotherapy

• Eat genetically modified food

• Genetic diagnose to see if child has a particular gene

Things to Remember• The expressed sequence tag helped the

discovery of protein-encoding genes by working with cDNA’s reverse transcribed from mRNA’s

• Positional cloning helped identify many genes that cause diseases.

• Automated DNA sequencing helped determine the base sequence of the genome

• Assembler computer programs helped put the pieces of the genome together

• Comparative genomics investigates the relationship between single genes and specific diseases

• The human genome project officially began in 1990 under the direction of James Watson

• The first draft of the human genome was unveiled in 2003 to correspond with the fiftieth anniversary of the discovery of the DNA structure

• The first organism to have it’s genome sequenced was E. coli

Bibliography

Genetics and Public Issues. “Identifying Human Disease Genes by Positional Cloning” Odyssey. 1997. http://www.csu.edu.au/learning/ncgr/gpi/odyssey/cloning/poclo.html. Mar. 1, 2006

Human Genome Program. “About the Human Genome Project.” Human Genome Project Information. 2004.

http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml. Mar. 3, 2006.

Lewis Ricki. “The Age of Genomics.” Human Genetics. McGraw Hill: Boston. 2007.