CHAPTER 18 Molecular Biology and Medicine

Chapter 18: Molecular Biology and Medicine

CHAPTER 18Molecular Biology and

Medicine


Chapter 18: Molecular Biology and MedicineProtein as PhenotypeProtein as Phenotype

Mutations and Human DiseasesMutations and Human Diseases

Detecting Human Genetic VariationsDetecting Human Genetic Variations

Cancer: A Disease of Genetic ChangesCancer: A Disease of Genetic Changes

Treating Genetic DiseasesTreating Genetic Diseases

Sequencing the Human GenomeSequencing the Human Genome


Protein as Phenotype• In many human genetic diseases, a In many human genetic diseases, a

single protein is missing or single protein is missing or nonfunctional.nonfunctional.

• Therefore, the one-gene, one-Therefore, the one-gene, one-polypeptide relationship applies to polypeptide relationship applies to human genetic diseases.human genetic diseases.

Review Figure 18.1Review Figure 18.133


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Figure 18.1Figure 18.1

figure 18-01.jpgfigure 18-01.jpg


Protein as Phenotype• A mutation in a single gene causes A mutation in a single gene causes

alterations in its protein product that alterations in its protein product that may lead to clinical abnormalities or may lead to clinical abnormalities or have no effect. have no effect.



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Protein as Phenotype• Some diseases are caused by Some diseases are caused by

mutations that affect structural mutations that affect structural proteins.proteins.

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Protein as Phenotype• Genes that code for receptors and Genes that code for receptors and

membrane transport proteins can also membrane transport proteins can also be mutated and cause other diseases. be mutated and cause other diseases.



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Figure 18.3 – Part 1Figure 18.3 – Part 1

figure 18-03a.jpgfigure 18-03a.jpg


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figure 18-03b.jpgfigure 18-03b.jpg


Protein as Phenotype• Prion diseases are caused by a protein Prion diseases are caused by a protein

with an altered shape transmitted from with an altered shape transmitted from one person to another and altering the one person to another and altering the same protein in the second person.same protein in the second person.

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Protein as Phenotype• Few human diseases are caused by a Few human diseases are caused by a

single-gene mutation. single-gene mutation.

• Most are caused by interactions of Most are caused by interactions of many genes and proteins with the many genes and proteins with the environment.environment.

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Protein as Phenotype• Human genetic diseases show Human genetic diseases show

different inheritance patterns. different inheritance patterns.

• Mutant alleles may be inherited as Mutant alleles may be inherited as autosomal recessives, autosomal autosomal recessives, autosomal dominants, X-linked conditions, or dominants, X-linked conditions, or chromosomal abnormalities.chromosomal abnormalities.

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Mutations and Human Diseases• Molecular biology techniques have Molecular biology techniques have

made possible the isolation of many made possible the isolation of many genes responsible for human diseases.genes responsible for human diseases.

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Mutations and Human Diseases• One method of identifying the gene One method of identifying the gene

responsible for a disease is to isolate responsible for a disease is to isolate the mRNA for the protein in question the mRNA for the protein in question and use the mRNA to isolate the gene and use the mRNA to isolate the gene from a gene library. from a gene library.

• DNA from a patient lacking a piece of a DNA from a patient lacking a piece of a chromosome can be compared to that chromosome can be compared to that of a person not showing this deletion of a person not showing this deletion to isolate a missing gene. to isolate a missing gene.

• Review Figure 18.6Review Figure 18.61515


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Mutations and Human Diseases• In positional cloning, DNA markers are In positional cloning, DNA markers are

used to point the way to a gene. used to point the way to a gene.

• Markers may be restriction fragment Markers may be restriction fragment length polymorphisms linked to a mutant length polymorphisms linked to a mutant gene. gene.



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Mutations and Human Diseases• Human mutations range from single Human mutations range from single

point mutations to large deletions.point mutations to large deletions.

• Some common mutations occur where Some common mutations occur where the modified base 5-methylcytosine is the modified base 5-methylcytosine is converted to thymine. converted to thymine.

Review Figure 18.8, Table 1Review Figure 18.8, Table 11919


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Mutations and Human Diseases• Effects of the fragile-X chromosome Effects of the fragile-X chromosome

worsen with each generation. worsen with each generation.

• This pattern is caused by a triplet repeat This pattern is caused by a triplet repeat that tends to expand with each that tends to expand with each generation. generation.



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figure 18-09figure 18-09


Mutations and Human Diseases• Genomic imprinting results in a gene Genomic imprinting results in a gene

being differentially expressed being differentially expressed depending on which parent it comes depending on which parent it comes from.from.

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Detecting Human Genetic Variations• Genetic screening detects human gene Genetic screening detects human gene

mutations.mutations.• Some protein abnormalities can be Some protein abnormalities can be

detected by tests for the presence of detected by tests for the presence of excess substrate or lack of product. excess substrate or lack of product.



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Detecting Human Genetic Variations• The advantage of testing DNA for The advantage of testing DNA for

mutations directly is that any cell can mutations directly is that any cell can be tested at any time in the life cycle.be tested at any time in the life cycle.

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Detecting Human Genetic Variations• There are two methods of DNA testing: There are two methods of DNA testing:

allele-specific cleavage and allele-allele-specific cleavage and allele-specific oligonucleotide hybridization. specific oligonucleotide hybridization.

Review Figures 18.11, 18.12Review Figures 18.11, 18.122727


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Cancer: A Disease of Genetic Changes• Tumors may be benign, growing to a Tumors may be benign, growing to a

certain extent and stopping, or certain extent and stopping, or malignant, spreading through organs malignant, spreading through organs and to other parts of the body.and to other parts of the body.

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Cancer: A Disease of Genetic Changes• At least five types of human cancers At least five types of human cancers

are caused by viruses, accounting for are caused by viruses, accounting for about 15 percent of all cancers. about 15 percent of all cancers.

Review Table 18.2Review Table 18.23131


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Table 18.2Table 18.2

table 18-02.jpgtable 18-02.jpg


Cancer: A Disease of Genetic Changes• Eighty-five percent of human cancers Eighty-five percent of human cancers

are caused by genetic mutations of are caused by genetic mutations of somatic cells. somatic cells.

• These occur most commonly in These occur most commonly in dividing cells. dividing cells.



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Cancer: A Disease of Genetic Changes• Normal cells contain proto-oncogenes, Normal cells contain proto-oncogenes,

which, when mutated, can become which, when mutated, can become activated and cause cancer by activated and cause cancer by stimulating cell division or preventing stimulating cell division or preventing cell death.cell death.



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Cancer: A Disease of Genetic Changes• About 10 percent of all cancer is About 10 percent of all cancer is

inherited as a result of mutation of inherited as a result of mutation of tumor suppressor genes, which tumor suppressor genes, which normally slow down the cell cycle.normally slow down the cell cycle.

• For cancer to develop, both alleles of a For cancer to develop, both alleles of a tumor suppressor gene must be tumor suppressor gene must be mutated.mutated.

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Cancer: A Disease of Genetic Changes• In inherited cancer, an individual In inherited cancer, an individual

inherits one mutant allele and somatic inherits one mutant allele and somatic mutation occurs in the second one. mutation occurs in the second one.

• In sporadic cancer, two normal alleles In sporadic cancer, two normal alleles are inherited, so two mutational events are inherited, so two mutational events must occur in the same somatic cell. must occur in the same somatic cell.

Review Figures 18.16, 18.17Review Figures 18.16, 18.173838


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Cancer: A Disease of Genetic Changes• Mutations must activate several Mutations must activate several

oncogenes and inactivate several oncogenes and inactivate several tumor suppressor genes for a cell to tumor suppressor genes for a cell to produce a malignant tumor.produce a malignant tumor.



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Treating Genetic Diseases• Most genetic diseases are treated Most genetic diseases are treated

symptomatically.symptomatically.• As more knowledge is accumulated, As more knowledge is accumulated,

specific treatments are being devised.specific treatments are being devised.4343


Treating Genetic Diseases• One treatment approach is to modify One treatment approach is to modify

the phenotype, for example, by the phenotype, for example, by manipulating diet, providing specific manipulating diet, providing specific metabolic inhibitors to prevent metabolic inhibitors to prevent accumulation of a harmful substrate, accumulation of a harmful substrate, or supplying a missing protein. or supplying a missing protein.



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Treating Genetic Diseases• In gene therapy, a mutant gene is In gene therapy, a mutant gene is

replaced with a normal one. replaced with a normal one.

• Either the affected cells can be Either the affected cells can be removed, the new gene added, and removed, the new gene added, and the cells returned to the body, or the the cells returned to the body, or the new gene can be inserted directly. new gene can be inserted directly.



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Sequencing the Human Genome• Human genome sequencing is Human genome sequencing is

determining the entire human DNA determining the entire human DNA sequence, which requires sequencing sequence, which requires sequencing many 500-base-pair fragments and many 500-base-pair fragments and fitting the sequences back together.fitting the sequences back together.

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Sequencing the Human Genome• In hierarchical gene sequencing, marker In hierarchical gene sequencing, marker

sequences are identified and mapped, then sequences are identified and mapped, then sought in sequenced fragments and used to sought in sequenced fragments and used to align the fragments. align the fragments.

• In the shotgun approach, the fragments are In the shotgun approach, the fragments are sequenced, and common markers identified sequenced, and common markers identified by computer. by computer.



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figure 18-21a.jpgfigure 18-21a.jpg


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figure 18-21b.jpgfigure 18-21b.jpg


Sequencing the Human Genome• The identification of more than 30,000 The identification of more than 30,000

human genes may lead to a new human genes may lead to a new molecular medicine. molecular medicine.



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Sequencing the Human Genome• As more genes relevant to human As more genes relevant to human

health are described, concerns about health are described, concerns about how such information is used are how such information is used are growing.growing.

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CHAPTER 18 Molecular Biology and Medicine