CHAPTER 18 Molecular Biology and Medicine

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CHAPTER 18Molecular Biology and Medicine
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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

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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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18.1
figure 18-01.jpg

• Figure 18.1

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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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18.2
figure 18-02.jpg

• Figure 18.2

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Protein as Phenotype

• Some diseases are caused by mutations that affect
  structural proteins.
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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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18.3
figure 18-03a.jpg

• Figure 18.3 Part 1

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18.3
figure 18-03b.jpg

• Figure 18.3 Part 2

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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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Protein as Phenotype

• Few human diseases are caused by a single-gene
  mutation.
• Most are caused by interactions of many genes and
  proteins with the environment.
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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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Mutations and Human Diseases

• Molecular biology techniques have made possible
  the isolation of many genes responsible for human
  diseases.
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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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18.6
figure 18-06.jpg

• Figure 18.6

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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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18.7
figure 18-07.jpg

• Figure 18.7

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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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18.8
figure 18-08.jpg

• Figure 18.8

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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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18.9
figure 18-09

• Figure 18.9

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Mutations and Human Diseases

• Genomic imprinting results in a gene being
  differentially expressed depending on which
  parent it comes from.
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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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18.10
figure 18-10.jpg

• Figure 18.10

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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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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.jpg

• Figure 18.11

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18.12
figure 18-12.jpg

• Figure 18.12

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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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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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18.2
table 18-02.jpg

• 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.jpg

• Figure 18.14

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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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18.15
figure 18-15.jpg

• Figure 18.15

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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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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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18.16
figure 18-16.jpg

• Figure 18.16

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18.17
figure 18-17.jpg

• Figure 18.17

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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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18.18
figure 18-18.jpg

• Figure 18.18

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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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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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18.19
figure 18-19.jpg

• Figure 18.19

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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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18.20
figure 18-20.jpg

• Figure 18.20

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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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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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18.21
figure 18-21a.jpg

• Figure 18.21 Part 1

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18.21
figure 18-21b.jpg

• Figure 18.21 Part 2

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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.jpg

• Figure 18.22

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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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