Transcript Chapter 18 Molecular Biology and Medicine

Chapter 18: Molecular Biology and Medicine
CHAPTER 18
Molecular Biology and
Medicine
Chapter 18: Molecular Biology and Medicine
Chapter 18: Molecular
Biology and Medicine
Protein as Phenotype
Mutations and Human Diseases
Detecting Human Genetic Variations
Cancer: A Disease of Genetic Changes
Treating Genetic Diseases
Sequencing the Human Genome
Chapter 18: Molecular Biology and Medicine
Protein as Phenotype
• In many human genetic diseases, a single
protein is missing or nonfunctional.
• Therefore, the one-gene, one-polypeptide
relationship applies to human genetic
diseases.
Review Figure 18.1
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figure 18-01.jpg
Chapter 18: Molecular Biology and Medicine
18.1
Figure 18.1
Chapter 18: Molecular Biology and Medicine
Protein as Phenotype
• A mutation in a single gene causes
alterations in its protein product that may
lead to clinical abnormalities or have no
effect.
Review Figure 18.2
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figure 18-02.jpg
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18.2
Figure 18.2
Chapter 18: Molecular Biology and Medicine
Protein as Phenotype
• Some diseases are caused by mutations that
affect structural proteins.
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Chapter 18: Molecular Biology and Medicine
Protein as Phenotype
• Genes that code for receptors and
membrane transport proteins can also be
mutated and cause other diseases.
Review Figure 18.3
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figure 18-03a.jpg
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18.3
Figure 18.3 – Part 1
figure 18-03b.jpg
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18.3
Figure 18.3 – Part 2
Chapter 18: Molecular Biology and Medicine
Protein as Phenotype
• Prion diseases are caused by a protein with
an altered shape transmitted from one
person to another and altering the same
protein in the second person.
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Chapter 18: Molecular Biology and Medicine
Protein as Phenotype
• Few human diseases are caused by a singlegene mutation.
• Most are caused by interactions of many
genes and proteins with the environment.
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Chapter 18: Molecular Biology and Medicine
Protein as Phenotype
• Human genetic diseases show different
inheritance patterns.
• Mutant alleles may be inherited as
autosomal recessives, autosomal dominants,
X-linked conditions, or chromosomal
abnormalities.
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Chapter 18: Molecular Biology and Medicine
Mutations and Human
Diseases
• Molecular biology techniques have made
possible the isolation of many genes
responsible for human diseases.
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Chapter 18: Molecular Biology and Medicine
Mutations and Human
Diseases
• One method of identifying the gene
responsible for a disease is to isolate the
mRNA for the protein in question and use
the mRNA to isolate the gene from a gene
library.
• DNA from a patient lacking a piece of a
chromosome can be compared to that of a
person not showing this deletion to isolate a
missing gene.
• Review Figure 18.6
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figure 18-06.jpg
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18.6
Figure 18.6
Chapter 18: Molecular Biology and Medicine
Mutations and Human
Diseases
• In positional cloning, DNA markers are used
to point the way to a gene.
• Markers may be restriction fragment length
polymorphisms linked to a mutant gene.
Review Figure 18.7
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figure 18-07.jpg
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18.7
Figure 18.7
Chapter 18: Molecular Biology and Medicine
Mutations and Human
Diseases
• Human mutations range from single point
mutations to large deletions.
• Some common mutations occur where the
modified base 5-methylcytosine is converted
to thymine.
Review Figure 18.8, Table 1
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figure 18-08.jpg
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18.8
Figure 18.8
Chapter 18: Molecular Biology and Medicine
Mutations and Human
Diseases
• Effects of the fragile-X chromosome worsen
with each generation.
• This pattern is caused by a triplet repeat
that tends to expand with each generation.
Review Figure 18.9
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figure 18-09
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18.9
Figure 18.9
Chapter 18: Molecular Biology and Medicine
Mutations and Human
Diseases
• Genomic imprinting results in a gene being
differentially expressed depending on which
parent it comes from.
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Chapter 18: Molecular Biology and Medicine
Detecting Human Genetic
Variations
• Genetic screening detects human gene
mutations.
• Some protein abnormalities can be detected
by tests for the presence of excess
substrate or lack of product.
Review Figure 18.10
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Figure 18.10
figure 18-10.jpg
Chapter 18: Molecular Biology and Medicine
Detecting Human Genetic
Variations
• The advantage of testing DNA for mutations
directly is that any cell can be tested at any
time in the life cycle.
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Chapter 18: Molecular Biology and Medicine
Detecting Human Genetic
Variations
• There are two methods of DNA testing:
allele-specific cleavage and allele-specific
oligonucleotide hybridization.
Review Figures 18.11, 18.12
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18.11
Figure 18.11
figure 18-11.jpg
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Figure 18.12
figure 18-12.jpg
Chapter 18: Molecular Biology and Medicine
Cancer: A Disease of Genetic
Changes
• Tumors may be benign, growing to a certain
extent and stopping, or malignant,
spreading through organs and to other parts
of the body.
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Chapter 18: Molecular Biology and Medicine
Cancer: A Disease of Genetic
Changes
• At least five types of human cancers are
caused by viruses, accounting for about 15
percent of all cancers.
Review Table 18.2
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table 18-02.jpg
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Table 18.2
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Cancer: A Disease of Genetic
Changes
• Eighty-five percent of human cancers are
caused by genetic mutations of somatic
cells.
• These occur most commonly in dividing
cells.
Review Figure 18.14
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18.14
Figure 18.14
figure 18-14.jpg
Chapter 18: Molecular Biology and Medicine
Cancer: A Disease of Genetic
Changes
• Normal cells contain proto-oncogenes,
which, when mutated, can become
activated and cause cancer by stimulating
cell division or preventing cell death.
Review Figure 18.15
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Figure 18.15
figure 18-15.jpg
Chapter 18: Molecular Biology and Medicine
Cancer: A Disease of Genetic
Changes
• About 10 percent of all cancer is inherited
as a result of mutation of tumor suppressor
genes, which normally slow down the cell
cycle.
• For cancer to develop, both alleles of a
tumor suppressor gene must be mutated.
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Chapter 18: Molecular Biology and Medicine
Cancer: A Disease of Genetic
Changes
• In inherited cancer, an individual inherits
one mutant allele and somatic mutation
occurs in the second one.
• In sporadic cancer, two normal alleles are
inherited, so two mutational events must
occur in the same somatic cell.
Review Figures 18.16, 18.17
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Figure 18.16
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Figure 18.17
figure 18-17.jpg
Chapter 18: Molecular Biology and Medicine
Cancer: A Disease of Genetic
Changes
• Mutations must activate several oncogenes
and inactivate several tumor suppressor
genes for a cell to produce a malignant
tumor.
Review Figure 18.18
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Figure 18.18
figure 18-18.jpg
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Treating Genetic Diseases
• Most genetic diseases are treated
symptomatically.
• As more knowledge is accumulated, specific
treatments are being devised.
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Chapter 18: Molecular Biology and Medicine
Treating Genetic Diseases
• One treatment approach is to modify the
phenotype, for example, by manipulating
diet, providing specific metabolic inhibitors
to prevent accumulation of a harmful
substrate, or supplying a missing protein.
Review Figure 18.19
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Figure 18.19
figure 18-19.jpg
Chapter 18: Molecular Biology and Medicine
Treating Genetic Diseases
• In gene therapy, a mutant gene is replaced
with a normal one.
• Either the affected cells can be removed,
the new gene added, and the cells returned
to the body, or the new gene can be
inserted directly.
Review Figure 18.20
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Figure 18.20
figure 18-20.jpg
Chapter 18: Molecular Biology and Medicine
Sequencing the Human
Genome
• Human genome sequencing is determining
the entire human DNA sequence, which
requires sequencing many 500-base-pair
fragments and fitting the sequences back
together.
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Chapter 18: Molecular Biology and Medicine
Sequencing the Human
Genome
• In hierarchical gene sequencing, marker sequences
are identified and mapped, then sought in
sequenced fragments and used to align the
fragments.
• In the shotgun approach, the fragments are
sequenced, and common markers identified by
computer.
Review Figure 18.21
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Figure 18.21 – Part 1
figure 18-21a.jpg
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18.21
Figure 18.21 – Part 2
figure 18-21b.jpg
Chapter 18: Molecular Biology and Medicine
Sequencing the Human
Genome
• The identification of more than 30,000
human genes may lead to a new molecular
medicine.
Review Figure 18.22
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18.22
Figure 18.22
figure 18-22.jpg
Chapter 18: Molecular Biology and Medicine
Sequencing the Human
Genome
• As more genes relevant to human health are
described, concerns about how such
information is used are growing.
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