Introduction
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As our understanding of molecular biology continues to expand, so does our ability to treat diseases at the
molecular level.
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The cancer drug Gleevec, which specifically inhibits an abnormal protein kinase associated with leukemia, is
an example of such a treatment.
Abnormal or Missing Proteins: The Mutant Phenotype
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Genetic mutations are often expressed phenotypically as proteins that differ from the normal wild type.
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Enzymes, receptors, transport proteins, structural proteins, and nearly all other functional classes of proteins
have been implicated in genetic diseases.
Dysfunctional enzymes can cause diseases
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A defect in the gene that codes for the enzyme phenylalanine hydroxylase causes phenylketonuria (PKU), a
cause of mental retardation. (See Figure 17.1.)
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This enzyme catalyzes the conversion of dietary phenylalanine to tyrosine in the liver.
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At position 408 of a 451-amino-acid peptide, most affected individuals have the amino acid tryptophan
instead of arginine.
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Those with PKU have low levels of the amino acid tyrosine because the defective enzymes fail to convert
phenylalanine to tyrosine.
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The lack of conversion causes high levels of phenylalanine in the blood and phenylpyruvic acid in the urine.
The exact cause of the mental retardation is not known.
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Hundreds of human genetic diseases that result from enzyme abnormalities have been discovered.
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Many proteins show variation in amino acid sequence, but not all changes cause problems with function.
Polymorphism does not necessarily mean disease.
Abnormal hemoglobin is the cause of sickle-cell disease
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Sickle-cell disease is caused by a mutation that affects the -globin subunit of hemoglobin.
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It most often afflicts people whose ancestors came from the Tropics or the Mediterranean.
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The abnormal protein results in sickled red blood cells.
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Of the 146 amino acids in -globin subunits, the sixth is changed from a glutamic acid to a valine. (See
Figure 17.2.)
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Because glutamic acid is negatively charged, the replacement changes the charge of the protein, resulting in
long needle-like aggregates in the red blood cells.
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Another disease, called hemoglobin C disease, has a changed amino acid at the same location, but instead of
glutamic acid, there is lysine.
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Whereas sickle-cell disease is severe in homozygotes, hemoglobin C disease is much less so.
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About 5 percent of all humans are carriers for a non-wild-type variant of hemoglobin.
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Fortunately, most of these alterations of hemoglobin have no effect on the protein’s function.
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(See Video 17.1.)
Altered membrane proteins cause many diseases
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Some of the most common human genetic disorders show up as altered proteins in cell membranes.
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Familial hypercholesterolemia (FH) is a disease in which blood cholesterol levels are several times higher
than normal. (See Figure 17.3a.)
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Cholesterol travels in the blood in protein-containing particles called lipoproteins.
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The biochemical basis of FH is an altered cell surface receptor for the lipid carrier protein LDL (low-density
lipoprotein).
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Normally, the receptor is functional and is involved in the uptake of lipoprotein, via endocytosis, by liver
cells.
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In people with FH, the receptor protein is nonfunctional, so cholesterol accumulates in the blood.
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Of the 840 amino acids that make up the receptor, often only one is abnormal in FH, but that is enough to
prevent binding to the lipoprotein.
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Cystic fibrosis is a genetic disease affecting 1 in 2,500 Caucasian babies.
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Its symptoms include unusually thick and dry mucus in the tubes of the respiratory system.
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This interferes with the normal functioning of the cilia that clean the tubes.
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Serious infections may result, as well as liver, pancreas, and digestive failure.
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The defect has been traced to a chloride transporter in a membrane protein. (See Figure 17.3b.)
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Normally, an imbalance of Cl– ions (more of them outside than inside) causes cellular water to leave the cell
and form moist extracellular mucus.
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In people with cystic fibrosis, the lack of functional transporters changes the normal imbalance, and the
mucus becomes dry and thick.
Altered structural proteins can cause disease
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About one in 3,000 people are born with Duchenne muscular dystrophy.
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Patients usually die in their twenties, when the muscles that serve their respiratory system fail.
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Dystrophin, which attaches actin to the plasma membrane in muscle cells, is missing or nonfunctional in
people with this disease.
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Hemophilia is a genetic disease caused by a lack of one of the coagulation proteins. Affected people risk
bleeding to death from even minor cuts.
Prion diseases are disorders of protein conformation
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Transmissible spongiform encephalopathies (TSEs) are degenerative brain diseases that occur in mammals,
including humans.
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Scrapie is a TSE found in sheep and has been known for 250 years.
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In the 1980s, TSE was transferred from sheep to cattle in infected cattle feed.
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In the 1990s, people who had eaten beef from cows with TSE contracted a human version of TSE.
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Kuru is a TSE disease found in the Fore tribe of New Guinea before they ceased their practice of ritual
cannibalism. It was transmitted via the brains of infected people.
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Tikva Alper provided evidence that the infectious agent causing TSE was a protein.
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Stanley Prusiner purified the protein and proved it was free of DNA and RNA. He called it a proteinaceous
infective particle, or prion.
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The mechanism of disease in TSEs:
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Normal brain cells have a membrane protein called PrP c.
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Abnormal TSE-affected brain cells have the same protein but with an altered shape, PrP sc. In PrPsc the amino
acid sequence is the same, but the shape of the protein has been altered. (See Figure 17.4.)
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Insoluble PrPsc accumulates as fibers and causes cell death.
Most diseases are caused by both genes and environment
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Taken together, all human diseases that can be traced to a single altered protein have a 1 percent frequency in
the total population.
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Most diseases are multifactorial, caused by many genes and proteins interacting with one another and with
the environment.
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Estimates suggest that up to 60 percent of all people are affected by diseases that are genetically influenced.
Human genetic diseases have several patterns of inheritance
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Autosomal recessive pattern:
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PKU, sickle-cell disease, and cystic fibrosis are autosomal recessive genetic diseases.
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People who are homozygous for the mutant allele are affected.
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Those who are heterozygous may have less of the normal gene product, but they have enough to have a
normal phenotype.
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Autosomal dominant pattern:
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With this pattern of inheritance, the presence of justone mutant allele is enough to produce the clinical
phenotype.
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An example in humans is familial hypercholesterolemia. Having half the receptors for LDL is inadequate to
prevent accumulation of cholesterol.
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X-linked recessive pattern:
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Hemophilia is inherited as X-linked recessive diseases.
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Sons inherit this condition from their mothers, because the mutant allele is located on the X chromosome.
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If a daughter with an unaffected father inherits a mutant allele from her mother, she will be a heterozygous
carrier (the father’s normal allele will be dominant).
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Until recently, few affected males lived to reproduce, so the most common pattern of inheritance has been
from carrier mother to son.
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Chromosomal abnormalities:
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Chromosomal abnormalities include loss or gain of one or more chromosomes, loss or gain of a piece of a
chromosome, or transfer of a piece from one chromosome to another.
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One newborn in 200 is born with a chromosomal abnormality.
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Some abnormalities are inherited. Some are the result of nondisjunction during meiosis (or early mitosis).
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Of the 20 percent of pregnancies that spontaneously abort during the first 3 months, about half are
chromosomally aberrant.
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About 90 percent of human zygotes that have just one X chromosome and no Y (Turner Syndrome) fail to
survive beyond 4 months of gestation.
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A common cause of mental retardation is fragile-X syndrome.
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About one male in 1,500 and one female in 2,000 are affected.
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Near the tip of the abnormal X chromosome is a constriction. (Its tendency to break during preparation for
microscopy gives the disease its name.)(See Figure 17.5.)
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The basic inheritance pattern is as an X-linked recessive trait, but there are variations.
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Not all people with fragile-X abnormality have mental retardation.
Mutations and Human Diseases
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The isolation and description of human mutant genes relies on mRNA, chromosome deletions, and DNA
markers.
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Some gene mutations associated with human diseases are easy to clone. Hemoglobin abnormalities are an
example.
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Finding the troublesome gene is much more difficult when the molecular causes are unknown.
One way to identify a gene is to start with its protein
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Sickle-cell disease is caused by a single amino acid defect in the -globin subunits of hemoglobin.
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It was possible to find the exact cause of sickle-cell disease because the protein involved was known.
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Once -globin mRNA was isolated, cDNA copies were made and used to probe a human DNA library to find
the -globin gene. (See Figure 17.6a.)
Chromosome deletions can lead to gene and then protein isolation
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In the case of Duchenne muscular dystrophy, deletions helped to identify the gene affected and the protein
defect associated with disease.
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Several boys with the disease were found to have a small deletion in their X chromosome.
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Comparison of the affected chromosomes with normal X chromosomes made possible the isolation of the
gene that was missing in the boys. (See Figure 17.6b.)
Genetic markers can point the way to important genes
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An approach called positional cloning can be used when no candidate protein or deletion is known for a
gene.
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Reference points for positional cloning are genetic markers on the DNA.
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Restriction enzymes are used to cut DNA molecules at specific recognition sequences.
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If a sequence is not recognized by the enzyme, it remains large and intact.
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These become genetic markers called RFLPs (restriction fragment length polymorphisms).
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Thousands of RFLPs have been described for the human genome. (See Figure 17.7.)
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The RFLP band patterns are inherited in a Mendelian fashion and can be followed through a pedigree.
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Marker types and pedigree analysis information are compared. If a marker is found to correspond to a
phenotype, the gene that causes the phenotype must be near the marker.
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The neighborhood around the RFLP can be screened for further RFLPs. If one is linked directly, a DNA
fragment from the region can be used to identify a cDNA sequence.
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The gene from affected and unaffected people is compared to determine the genetic difference responsible for
the disease.
Human gene mutations come in many sizes
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Many human gene mutations, such as those that cause sickle-cell disease, are changes in only one base pair.
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Such a point mutation that alters a protein’s function usually affects its three-dimensional structure. For
example, it might alter the shape at the active site of an enzyme.
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In some people with cystic fibrosis, a codon that would normally code for an amino acid near the beginning
of a long protein has a nonsense mutation that changes it to a stop codon.
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Protein translation stops at the stop codon, and a very short, nonfunctional peptide results.
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Some base pairs are more prone to mutation than others.
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When cytosine is methylated (5-methylcytosine) it sometimes loses its amino group and becomes thymine.
(See Figure 17.8.)
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Regions of DNA with methylated cytosine are prone to mutation and are called “hot spots.”
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Larger mutations may involve many base pairs of DNA.
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Duchenne muscular dystrophy varies in severity depending on how much of the dystrophin gene is deleted.
Expanding triplet repeats demonstrate the fragility of some human genes
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About one-fifth of all males possessing a fragile-X chromosome are phenotypically normal, but many of their
daughters’ sons have mental retardation.
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Fragile-X syndrome is related to the condition of the DNA sequence FMR1.
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This gene contains a repeated triplet sequence, CGG.
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In normal people, this triplet is repeated 6 to 54 times. In those affected with fragile-X, CGG is repeated 200
to 1,300 times.
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Those males with no symptoms have 52 to 200 repeats. The repeats become more numerous in the daughters,
and their sons then get more than 200 copies. (See Figure 17.9.)
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Other diseases that involve expanding triplet repeats are myotonic dystrophy and Huntington’s disease.
Genomic imprinting shows that mammals need both a mother and father
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Just after mammal egg fertilization, there are two haploid pronuclei—one from the sperm, and one from the
egg.
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It is possible to make a mouse zygote with two male or two female pronuclei, but these fail to develop
beyond the diploid cells.
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This shows that the DNA from fathers and mothers is expressed differently, a phenomenon known as
genomic imprinting.
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A genetic disease caused by a small deletion in chromosome 15 produces completely different results
depending on whether the deletion is in the chromosome from the mother or the father.
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If the mutated gene comes from the father, the child is short and obese, with small hands and feet (PraderWilli syndrome).
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If the mutated gene comes from the mother, the child is thin with a wide mouth and prominent jaw
(Angelman syndrome).
Detecting Human Genetic Variations: Screening for Human Diseases
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The determination of the molecular phenotypes and genotypes of human genetic disease has made diagnosis,
and often medical intervention, possible even before symptoms appear.
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Prenatal genetic screening, screening of newborns, and screening of asymptomatic people whose relatives
have a genetic disease are often beneficial to individuals and their offspring, although these techniques also raise
ethical questions.
Screening for abnormal phenotypes can make use of protein expression
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Screening for PKU is legally required in many countries, including the United States. (See Figure 17.10.)
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When babies homozygous for this disease consume protein, phenylalanine enters the blood and within days
the accumulation causes brain damage.
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If PKU is detected early, a diet low in phenylalanine will prevent the damage.
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In a simple screening test devised by Robert Guthrie in 1963, auxotrophic bacteria are used to detect the
presence of phenylalanine. If the test is positive, additional biochemical tests are run.
Several screening methods can find abnormal genes
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DNA testing is the most accurate way to test for an abnormal gene.
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This works best if just a few different allelic forms of the disease gene exist.
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Preimplantation screening:
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The polymerase chain reaction (PCR) allows testing of DNA from a single cell. Occasionally an embryo is
screened in this way before implantation.
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If both parents are heterozygous for a recessive gene, such as the gene for cystic fibrosis, a single cell from an
8-cell zygote can be tested in the laboratory for presence of the disease.
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If it is normal, the remaining embryo cells can then be implanted to develop naturally.
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Preimplantation screening is unusual; there are more genetic tests for diseases that are carried out postimplantation.
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Chorionic villus sampling (tenth week of pregnancy) and amniocentesis (thirteenth to seventeenth week) are
more common forms of prenatal genetic testing.
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Screening for allele-specific cleavage differences:
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This method is similar to the use of RFLPs.
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It works if a restriction enzyme exists that can recognize either the sequence at the mutation or the original
sequence that is altered by that mutation.
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In sickle alleles, for example, changes responsible for the gene defect also change a restriction site, making
the DNA sequence unrecognizable by the restriction enzyme.
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When the enzyme fails to make the cut in the mutant gene, gel electrophoresis detects a larger-than-normal
DNA fragment. (See Figure 17.11 and Animated Tutorial 17.1.)
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Screening for allele-specific oligonucleotide hybridization:
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This method is easier and faster than allele-specific cleavage.
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Oligonucleotides that will hybridize to the denatured DNA sequences for either normal or sickle -globin can
be made in the laboratory.
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Usually, a probe of at least a dozen bases is needed to form a stable double helix with the target DNA.
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If the probe is radioactively or fluorescently labeled, hybridization is readily detected. (See Figure 17.12.)
Cancer: A Disease of Genetic Changes
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•
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One in three Americans will have some form of cancer in their lifetime. One in four will die of it.
Cancer is more frequent than in the past, in part due to longer life spans.
Cancer is caused primarily by genetic changes and is more common in later life.
Cancer cells differ from their normal counterparts
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Cancer cells have lost control over appropriate cell division.
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Cancer cells divide more or less continuously, not responding to growth factor or hormonal control.
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They form tumors (large masses of cells), which often contain millions of cells by the time they are detected.
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A benign tumor resembles the tissue it comes from and remains localized.
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Malignant tumors do not look like parent tissues and often have irregular structures, such as variable sizes
and shapes of nuclei. (See Figure 17.13.)
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Spreading of cancer to surrounding tissue and other body parts is called metastasis.
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The malignant tumor secretes chemical signals that cause blood vessels to grow into it. This is called
angiogenesis.
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Next, the cells of the tumor secrete enzymes that digest and disintegrate other surrounding tissues.
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Then, they erode blood vessels. Some cells gain the ability to divide free from the tumor.
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These enter the bloodstream or lymphatic system. A few of these survive and form additional tumors.
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About 85 percent of all human tumors are carcinomas, which form from epithelial cells.
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Some skin cancers are of this type, as are lung, breast, colon, and liver cancers.
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Sarcomas are cancers of tissues such as bone, blood vessels, and muscle.
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Leukemias and lymphomas affect the cells that give rise to blood cells.
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(See Video 17.2.)
Some cancers are caused by viruses
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Viruses cause at least five types of human cancer. (See Table 17.1.)
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Hepatitis B virus is associated with liver cancers, especially in Asians and Africans, although it does not
cause cancer by itself and its role is unclear.
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Papillomaviruses, spread via sexual transmission, cause genital and anal warts that can often develop into
tumors. These viruses can cause cancer on their own, without mutations in the host tissue.
Most cancers are caused by genetic mutations
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Only about 15 percent of all cancers are caused by viruses. Most cancer is caused by mutations, usually in the
cells of older people.
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These mutations occur usually in the somatic (non-gamete-producing) cells.
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Spontaneous mutations arise because of changes in the nucleotides, damaging DNA.
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Carcinogens can cause mutations that lead to cancer.
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Tobacco smoke, meat preservatives, ultraviolet light from the sun, and ionizing radiation are common
carcinogens.
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An estimated 80 percent or more of human exposure to carcinogens is to naturally occurring agents,
including chemicals naturally present in food.
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Most carcinogens damage DNA by shifting one base to another.
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Cells that divide often, such as epithelial and bone marrow cells, are especially susceptible to genetic damage
because they spend less time on DNA repair. (See Figure 17.14.)
Two kinds of genes are changed in many cancers
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Oncogenes and tumor suppressor genes are the two kinds of genes involved in cancer.
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They can be likened to automobile controls: the first to a gas pedal and the second to a brake.
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Oncogenes:
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Oncogenes act to stimulate cell division; they have been identified as the genes carried by cancer-causing
viruses. (See Figure 17.15.)
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Some oncogenes control apoptosis (programmed cell death).
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Some oncogenes can be activated by point mutations, others by chromosome changes, and others by gene
amplification.
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Tumor suppressor genes:
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About 10 percent of cancers are caused by defective tumor suppressor genes. These are inherited cancers,
which usually appear in the form of multiple tumors and earlier in life than noninherited (or sporadic) cancer.
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When functioning normally, tumor suppressor genes prevent cell division. (See Figure 17.17.)
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People with inherited cancer are born with one mutant allele for the gene; just one mutational event causes
the disease.
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Women with one mutant BRCA1 gene have a 60 percent chance of having breast cancer by age 50 and an 82
percent chance by age 70; women with two normal genes have a 2–7 percent chance.
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A mutant Rb gene contributes to retinoblastoma.
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In its active form, Rb encodes a protein that inactivates transcription during the G1 phase of the cell cycle.
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When the Rb protein is inactivated by mutation, the cell cycle moves forward independently of growth
factors.
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Mutations in the p53 gene are associated with many cancers, including lung and colon cancer.
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The protein product of this gene stops cells during G1 of the cell cycle.
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It achieves this by acting as a transcription factor, and stimulating the production of a protein that blocks the
interaction of a cyclin and a protein kinase.
The pathway from normal cell to cancerous cell is complex
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A sequence of events must occur before a normal cell becomes malignant.
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Figure 17.18 outlines the progress of the formation of colon cancers.
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Colon cancers progress to full malignancy slowly.
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At least three tumor suppressor genes and one oncogene must be mutated in sequence for an epithelial cell in
the colon to become metastatic.
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Although the likelihood of this happening to any given cell is small, the colon has millions of cells that
divide constantly in the presence of carcinogens.
Treating Genetic Diseases
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To treat genetic disease, physicians must have the disease correctly diagnosed, know the molecular
mechanisms of the disease, and be able to intervene early, before the disease causes damage.
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Physicians are now applying the knowledge of pathogenesis at the molecular level to treat genetic diseases.
One approach to treatment is to modify the phenotype
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There are three ways to alter the outcome of genetic disease to benefit patients: restricting the substrate, using
metabolic inhibitors, or supplying the missing protein.
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Restricting the substrate:
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The mutation that causes PKU results in an enzyme that is unable to break down phenylalanine.
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Treatment for PKU involves restricting intake of the substrate for this enzyme.
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Metabolic inhibitors:
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Cholesterol synthesis by the liver can be lowered by metabolic inhibitors such as mevinolin.
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This blocks the patient’s own cholesterol synthesis and helps those with familial hypercholesterolemia.
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Metabolic inhibitors also form the basis of cancer therapy with drugs that kill rapidly dividing cells. (See
Figure 17.19.)
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Supplying the missing protein:
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Hemophilia A can be treated by supplying the protein that people with hemophilia fail to produce, a clotting
factor protein.
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This protein is now produced in a pure form using biotechnology.
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Often a single-gene mutation causes numerous problems that are difficult to treat with a single product.
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Many problems are intracellular, and therefore simple interventions do not always work.
Gene therapy offers the hope of specific treatments
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Gene therapy involves inserting a new gene into a patient’s cells.
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Different methods are being tried to get cells to take up and incorporate the new DNA.
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Cells have been removed from patients, genetically modified ex vivo, and then reintroduced into the same
patient.
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A girl without the enzyme adenosine deaminase had white blood cells modified and then reintroduced. (See
Figure 17.20.)
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The modified white blood cells provided some therapeutic benefit for a time, but eventually died, as is the
normal fate of such cells.
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Insertion of the functional gene into stem cells (precursors of white blood cells) might have been more
effective.
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In people with hemophilia, skin cells have been modified and reintroduced.
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Skin cells from their arms were removed and transfected with a plasmid containing a normal allele for the
clotting protein.
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The cells were then reintroduced into the patients, where they produced adequate protein for normal clotting.
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Attempts also have been made to insert genes directly into cells, the in vivo approach.
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Tumor suppressor genes have been put in vectors and targeted at tumors.
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Vectors carrying functional alleles of the tumor suppressor genes that are mutated in lung cancer, as well as
vectors expressing antisense RNAs against oncogene mRNAs, have been introduced in this way with some clinical
success.
Sequencing the Human Genome
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In 1986 Renato Dulbecco, who won a Nobel prize for his work on cancer-causing viruses, suggested that
determining the normal sequence of human DNA could be a boon to cancer research.
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The Human Genome Project is an internationally funded program to determine the sequences of the human
genome.
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Private industry launched its own sequencing effort in the 1990s.
There are two approaches to genome sequencing
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Chromosomes can be sorted by a machine based on their different sizes.
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The DNA of a chromosome is too long to be sequenced directly.
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The DNA must be fragmented using restriction enzymes into sections of about 700 base pairs, and these
fragments can be mapped.
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Then all the millions of fragments must be put back together like the pieces of a jigsaw puzzle—a formidable
challenge.
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Hierarchical sequencing:
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This “top-down” method is the one used by the publicly funded effort. (See Figure 17.21a and Animated
Tutorial 17.2.)
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This method can be compared to making a road map, with towns representing marker sequences and the
mileages between them representing the base pairs.
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Restriction enzymes recognizing longer 8–12 base pair sequences are used to generate a small number of
relatively large DNA fragments.
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These large fragments can be added to a vector called a bacterial artificial chromosome (BAC) and inserted
into bacteria to create a gene library.
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The fragments of this library can be arranged in the proper sequences by using the marker sequences. (See
Figure 17.21a.)
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This method is slow.
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Shotgun sequencing:
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This “bottom-up” approach is the one followed by private industry. (See Figure 17.21b and Animated
Tutorial 17.2.)
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Human DNA is randomly broken into fragments that are 500–800 base pairs long.
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Each fragment is sequenced.
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A computer then finds and uses overlapping sequences shared by fragments to align them.
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The entire 180-million-base-pair fruit fly genome was sequenced by the shotgun method.
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This method is much faster than the hierarchical approach because there is no need for physical or genetic
maps.
The sequence of the human genome has been determined
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Two teams of scientists announced a draft human genome sequence in June 2000 and published their data
simultaneously in February 2001.
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The sequencing of the human genome revealed several interesting characteristics.
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Of the 3.2 billion base pairs, less than 2 percent are coding regions, containing a total of 30,000–35,000
genes.
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The average gene has 27,000 base pairs. (See Figure 17.22.)
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Over 50 percent of the genome is made up of highly repetitive sequences.
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Almost all (99.9 percent) of the genome is the same in all people. Over 2 million single-nucleotide polymorphisms (SNPs), which are bases that differ in at least 1 percent of people, have been mapped.
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Genes are not evenly distributed over the genome.
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The functions of many genes are not known.
The human genome sequence has many applications
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Many simple organisms have gene sequences in common with humans. Determining the functions of the
sequences in simple creatures is useful to understanding their functions in humans.
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Mapping technologies make isolation of genes easier and allow disease-causing genes to be identified.
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Better drug treatments based on determining genetic variations in drug metabolism (pharmacogenomics) may
be developed.
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Differential gene expression can be studied using DNA chips, potentially improving diagnosis and treatment
of disease.
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The Cancer Genome Anatomy Project is seeking to make a “fingerprint” of a tumor at each stage of its
development.
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“Genome prospecting” initiatives are looking for subpopulation differences to reveal genes predisposing
subgroups to certain diseases.
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Knowledge of the human genome may lead to new approaches to medical care based on the individual’s
genetic predisposition and potential. (See Figure 17.23.)
How should genetic information be used?
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Many people are uninterested in their genetic makeup unless they or a close relative are known to have a
genetic disease.
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There is fear that insurance companies may try to use the information for health insurance exclusions.
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Many concerns have been raised about commercialization of people’s DNA sequences.
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The question of who will profit from the project has not yet been resolved.
The proteome is more complex than the genome
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Genome sequencing revealed about one-third as many genes in humans as had been predicted based on the
number of proteins found in human cells.
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There are explanations for this observation. (See Figure 17.24a.)
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Alternative splicing leads to different combinations of exons in mature mRNAs transcribed from a single
gene.
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Posttranslational modifications can add to the forms of a protein that can be made from one gene.
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The sum total of the proteins produced by an organism is call its proteome.
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The one-gene, one-polypeptide relationship that was once a central theme of biology has been laid to rest by
genomics.
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The proteome can be analyzed using two-dimensional gel electrophoresis or mass spectrometry. (See Figure
17.24b.)
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The field of proteomics seeks to describe the phenotypes of expressed proteins.
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Proteomics has been used in conjunction with DNA chip technology to compare brain proteins in
chimpanzees and humans.
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12,000 DNA sequences from the cortex of human and chimpanzee brains were tested for expression as
mRNA.
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Only 1.4 percent showed differences between the two species.
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Proteomics, however, showed that the kinds of proteins produced by the two species differed by 7.4 percent,
probably due to alternative splicing.
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The amounts of proteins produced were also quite different.
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These results suggest that what makes a human brain different from the brain of a chimpanzee is more
quantitative than qualitative.
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Control of gene expression may be the key to human evolution.