Genomics

GENOMICS

The science of studying

whole genomes.

Genomics

• (1980s) the nucleotide sequences of many important genes from human and other organisms had been determined.

• (1990s) a team of scientists determined the nucleotide sequence of the entire genome of Haemophilus influenzae.

• The first targets of genomics research were pathogenic bacteria.

The Human Genome Project

• (1990) an international consortium of government-funded researchers began the Human Genome Project.

• (April 14, 2003) the Human Genome Project was successfully completed more than 2 years head of schedule.


• The 24 different kinds of chromosomes in the human genome (22 autosomes plus the X and Y chromosomes) contain approximately 3.2 billion nucleotide pairs of DNA and 30,000 to 40,000 genes.

• Most complex eukaryotes have huge amount of noncoding DNA – about 97% of human DNA is made up of gene control type.


• The remaining DNA has been called “junk DNA”, a tongue-in-cheek way of saying that scientists don’t understand its functions.

• Much of the DNA between genes consists of repetitive DNA.


Repetitive DNANucleotide sequences present in many copies in the genome.

Main Types:1. A unit of just a few nucleotide pairs is repeated

many times in a row.2. Each repeated unit is hundreds of nucleotides

long and the copies are scattered around the genome.

Tracking the Anthrax Killer

• (October 2001) Bob Stevens, a 63-year-old editor at a Florida media company, died from inhalation anthrax, a disease caused by breathing spores of the bacterium Bacillus anthracis.

• Examining the genomes of the spores could answer several crucial questions.

• Investigators compared the genomes – which were 3 million nucleotides long – of the mailed anthrax spores with several laboratory strains.


• They were able to match the deadly spores with a laboratory subtype called the Ames strain.

• The Ames strain was first isolated from a dead Texas cow in 1981.

• The samples were sent to U.S. Army Medical Research Institute in Fort Detrick, Maryland.

• From there, it was sent to at least 14 other labs for use in experiments.


• Unfortunately, the date were not detailed enough to tie the mailed samples to any particular laboratory.

• The anthrax investigation is a prominent example of the new field of comparative genomics, the comparison of whole genomes.

Genome-Mapping Techniques

Genetic (Linkage) Mapping• Scientists combined pedigree analysis of large

families with DNA technology to map over 5,000 genetic markers.

• These markers included both coding regions (genes) and noncoding regions (such as strands of repetitive DNA).

• The low-resolution genetic map provided anchor points that enabled researchers to map other markers by testing for genetic linkage to the known markers.


Physical Mapping• Researchers used several different restriction

enzymes to break the DNA of each chromosome into a number of identifiable fragments, which they cloned.

• They then determined the original order of the fragments in the chromosome by overlapping the fragments and matching up their ends.

• They used probes to relate the fragments to the markers mapped in stage 1.

• The end result was a series of DNA segments that spanned the genome in a known order.


DNA Sequencing

• As the sequence of each cloned fragment from the physical map of stage 2 was determined, the fragments were reassembled in their proper order, producing large-scale sequences.


The Whole Genome Shotgun Method• The procedure essentially skips the first two

stages described and proceeds directly to the third.

• An entire genome is chopped by restriction enzymes into fragments that are cloned and sequenced.

• High-performance computers running specialized mapping software can reassemble the millions of partial sequences into a entire genome.

HUMAN GENE THERAPY

A recombinant DNA procedure that seeks to treat disease by altering an

afflicted person’s genes.

Human Gene Therapy

1. A gene from a normal individual is isolated and cloned by recombinant DNA techniques.

2. The gene is inserted into a vector, such as a nonharmful virus.

3. The virus is then injectedto the patient.

Treating Severe Combined Immunodeficiency

Severe Combined Immunodeficiency (SCID)

A fatal inherited disease caused by a single defective gene.

Treating Severe Combined Immunodeficiency

• The first trial of began at the National Institutes of Health in 1990 on a 4-year-old girl with SCID.

• Immune system cells were periodically removed from her blood, infected with a virus engineered to carry the normal allele of the defective gene, then reinjected into her bloodstream.

• Her gene therapy lasted a limited time and was only one of the several treatments she received.

SAFETYAND

ETHICAL ISSUES

The Controversy OverGenetically Modified Foods

• Advocates of a cautious approach fear that crops from other species might be hazardous to human health or harm the environment.

Ethical Questions Raised byDNA Technology

• DNA technology raises many questions – moral, legal, and ethical – few of which have clear answers.

• Advances in genetic fingerprinting raise private issues.

• There is a danger that information about disease-associated genes could be abused.

Ethical Questions Raised byDNA Technology

• Should we try to eliminate genetic defects in our children and their descendants?

• Should we interfere with evolution this way?• Are we willing to risk making genetic changes

that could be detrimental to our species in the future?

• How do we really feel about wielding one of nature’s singular powers – the ability to make new microorganisms, plants, and even animals?