Genomics
Genomics
Genome.
The
first sequencing of a small bacterial virus in 1977 was a milestone because it
showed that the exact location of every gene can be
found.
Sequencing DNA Fig
15.1 and image
Amplification
by PCR
Need
fragments of DNA, nucleotides, primers and DNA polymerase plus four different chain-terminating chemical tags
that mimic nucleotides.
Gel
electrophoresis
X-ray and computer analysis.
Automated
sequencing machines
The Human Genome: Example:
the mapping of chromosome 3.
Geography
of the Genome Fig 15.2
There
are about 25,000
genes in the human genome and 3.2 billion base pairs.
exons
introns.
If
stretched out, the DNA of a human cell would be 6 ft long and only 1-1.5% of it
is coding.
Noncoding
DNA Table 15.1
The
human genome possesses a startling amount of noncoding
DNA, up to 99% of the total.
Comparing Genomes (Fig 15.3)
Comparing
genomes of different species reveals relationships between species and provides
a powerful new tool to explore relationships between organisms.
1.
More complex organisms tend to have
more genes.
2.
All mammals have the same size genomes.
3.
A large number of genes are new to
science.
4.
Large differences in genome sizes
sometimes arise through duplication of chromosomes or entire genomes.
5.
Key genes tend to be conserved.
6.
Rates of evolution tend to vary.
7.
Darwin was right: genomes of relatives
are more alike.
8.
Noncodng
DNA is not junk.
Primate
evolution Fig. 27.1
Chimpanzees
and humans diverged about 6 million years ago.
Just
1.4 % of the DNA is different at the level of single letters of the genetic
code.
Can use sequenced genomes to explore
evolutionary changes that have occurred between species. (Fig 15.5)
Can design a phylogenetic tree.
Can also use them to discover
differences between individuals. Y-chromosome
DNA Image
Variation Within the Genome
Single
Nucleotide Polymorphisms (SNPs)
SNPs have
a low rate of mutation and thus are good markers of human history. Most useful for
comparing entire genomes.
Gene Microarrays Figs. Fig 15.6
Screen
for gene activity.
Microarrays
are small glass squares covered with millions of strands of DNA that can be
scanned using a beam of light. Each spot has many
copies of the same gene, each different. There will be thousands of
different genes present. These are
known as probes.
From
cells to be studied, the mRNA is removed and used to make complementary DNA (cDNA) (no junk in it).
This
is washed across the chip and different cDNA molecules
join with some of the different genes on the
chip.
How
Microarray Gene Chips Can Be Used to Screen for Cancer Fig 15.7
Identify
types of cancer
Genetic
diseases.
the revolution in cell technology
Cloning -To make an exact genetic copy; can be a gene, a cell, or an
entire organism.
Cloning by embryo splitting
Wilmut's Lamb (Dolly) (Fig 16.2a
and Fig 16.2b)
Reproductive
cloning.
Cloned animals Fig 16.3
Cloning humans
Problems With Reproductive
Cloning
The
Importance of Genomic
Imprinting Fig 16.4
gametic
imprinting
zygotic
imprinting
Embryonic Stem Cells
Totipotent
Each
major tissue is formed from its own kind of tissue-specific adult stem cell.
Embryonic
Stem Cells
May
offer the possibility of restoring damaged tissue.
Therapeutic Cloning
(Fig 16.8)
cloned
embryo.
The
cloned embryo is cloned from the personÕs skin cells.
The
cloned embryo is then destroyed to obtain embryonic stem cells.
The
embryonic stem cells are used to replace the patientÕs damaged or disabled
tissue.
Passes
immune systemÕs self-identity check.
Some
fear that a cloned embryo might be brought to term if inserted into a human
uterus.
This
is impossible because of the genetic imprinting problem.
Initial Attempts at Gene Therapy Movie
Early Success ADA
deficient gene
In 1990, two
girls were cured of a rare blood disorder by injections of gene-modified
proliferated bone marrow.
Problems With the Vector (Fig 16.9)
adenovirus
vector
More Promising Vectors Fig 16.10 Retrovirus
adeno-associated
virus [AAV]
In 1999, AAV successfully
cured anemia in rhesus monkeys.
AAV cured dogs of
a hereditary disorder leading to retinal degeneration and blindness.
In 2000, the
first gene therapy for muscular dystrophy occurred.
Trials
are also under way for cystic fibrosis, rheumatoid arthritis, hemophilia, and
types of cancer.
Ethical Issues Raised by Gene Therapy
Ethicists prefer
the term gene
intervention because gene therapy implies a cure.
Gene intervention
of somatic tissues is what is meant by gene therapy.
Gene intervention
of germ-line tissue has not yet been attempted in humans because the changes
induced are inherited.