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2. Many human disorders follow Mendelian
patterns of inheritance
• Thousands of genetic disorders, including disabling
or deadly hereditary diseases, are inherited as simple
recessive traits.
• These range from the relatively mild (albinism) to lifethreatening (cystic fibrosis).
• The recessive behavior of the alleles occurs because
the allele codes for either a malfunctioning protein or
no protein at all.
• Heterozygotes have a normal phenotype because one
“normal” allele produces enough of the required protein.
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• A recessively inherited disorder shows up only in
homozygous individuals who inherit one recessive
allele from each parent.
• Individuals who lack the disorder are either
homozgyous dominant or heterozygotes.
• While heterozygotes may have no clear phenotypic
effects, they are carriers who may transmit a
recessive allele to their offspring.
• Most people with recessive disorders are born to
carriers with normal phenotypes.
• Two carriers have a 1/4 chance of having a child with the
disorder, 1/2 chance of a carrier, and 1/4 free.
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• Genetic disorders are not evenly distributed among
all groups of humans.
• This results from the different genetic histories of
the world’s people during times when populations
were more geographically (and genetically)
isolated.
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• One such disease is cystic fibrosis which strikes
one of every 2,500 whites of European descent.
• One in 25 whites is a carrier.
• The normal allele codes for a membrane protein that
transports Cl- between cells and the environment.
• If these channels are defective or absent, there are
abnormally high extracellular levels of chloride that
causes the mucus coats of certain cells to become
thicker and stickier than normal.
• This mucus build-up in the pancreas, lungs, digestive
tract, and elsewhere favors bacterial infections.
• Without treatment, affected children die before five, but
with treatment can live past their late 20’s.
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• Tay-Sachs disease is another lethal recessive
disorder.
• It is caused by a dysfunctional enzyme that fails to
break down specific brain lipids.
• The symptoms begin with seizures, blindness, and
degeneration of motor and mental performance a few
months after birth.
• Inevitably, the child dies after a few years.
• Among Ashkenazic Jews (those from central Europe)
this disease occurs in one of 3,600 births, about 100
times greater than the incidence among non-Jews or
Mediterranean (Sephardic) Jews.
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• The most common inherited disease among blacks
is sickle-cell disease.
• It affects one of 400 African Americans.
• It is caused by the substitution of a single amino acid in
hemoglobin.
• When oxygen levels in the blood of an affected
individual are low, sickle-cell hemoglobin crystallizes
into long rods.
• This deforms red blood cells into a sickle shape.
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• This sickling creates a cascade of symptoms,
demonstrating the pleiotropic effects of this allele.
• Doctors can use
regular blood
transfusions to
prevent brain
damage and new
drugs to prevent
or treat other
problems.
Fig. 14.15
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• Although most harmful alleles are recessive, many
human disorders are due to dominant alleles.
• For example, achondroplasia, a form of dwarfism,
has an incidence of one case in 10,000 people.
• Heterozygous individuals have the dwarf phenotype.
• Those who are not achodroplastic dwarfs, 99.99% of the
population are homozygous recessive for this trait.
• Lethal dominant alleles are much less common than
lethal recessives because if a lethal dominant kills an
offspring before it can mature and reproduce, the
allele will not be passed on to future generations.
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• A lethal dominant allele can escape elimination if
it causes death at a relatively advanced age, after
the individual has already passed on the lethal
allele to his or her children.
• One example is Huntington’s disease, a
degenerative disease of the nervous system.
• The dominant lethal allele has no obvious phenotypic
effect until an individuals is about 35 to 45 years old.
• The deterioration of the nervous system is irreversible
and inevitably fatal.
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• Any child born to a parent who has the allele for
Huntington’s disease has a 50% chance of
inheriting the disease and the disorder.
• Recently, molecular geneticists have used pedigree
analysis of affected families to track down the
Huntington’s allele to a locus near the tip of
chromosomes 4.
Fig. 14.15
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• While some diseases are inherited in a simple
Mendelian fashion due to alleles at a single locus,
many other disorders have a multifactorial basis.
• These have a genetic component plus a significant
environmental influence.
• Multifactorial disorders include heart disease, diabetes,
cancer, alcoholism, and certain mental illnesses, such a
schizophrenia and manic-depressive disorder.
• The genetic component is typically polygenic.
• At present, little is understood about the genetic
contribution to most multifactorial diseases
• The best public health strategy is education about the
environmental factors and healthy behavior.
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CHAPTER 15
THE CHROMOSOMAL BASIS OF
INHERITANCE
Section B: Sex Chromosomes
1. The chromosomal basis of sex varies with the organism
2. Sex-linked genes have unique patterns of inheritance
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• This X-Y system of
mammals is not the only
chromosomal mechanism
of determining sex.
• Other options include the
X-0 system, the Z-W
system, and the haplodiploid system.
Fig. 15.8
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• In the X-Y system, Y and X chromosomes behave
as homologous chromosomes during meiosis.
• In reality, they are only partially homologous and rarely
undergo crossing over.
• In both testes (XY) and ovaries (XX), the two sex
chromosomes segregate during meiosis and each
gamete receives one.
• Each egg receives an X chromosome.
• Half the sperm receive an X chromosome and half
receive a Y chromosome.
• Because of this, each conception has about a fiftyfifty chance of producing a particular sex.
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2. Sex-linked genes have unique patterns of
inheritance
• In addition to their role in determining sex, the sex
chromosomes, especially the X chromosome, have
genes for many characters unrelated to sex.
• These sex-linked genes follow the same pattern of
inheritance as the white-eye locus in Drosophila.
Fig. 15.9
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• If a sex-linked trait is due to a recessive allele, a
female have this phenotype only if homozygous.
• Heterozygous females will be carriers.
• Because males have only one X chromosome
(hemizygous), any male receiving the recessive
allele from his mother will express the trait.
• The chance of a female inheriting a double dose of
the mutant allele is much less than the chance of a
male inheriting a single dose.
• Therefore, males are far more likely to inherit sexlinked recessive disorders than are females.
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• Several serious human disorders are sex-linked.
• Duchenne muscular dystrophy affects one in
3,500 males born in the United States.
• Affected individuals rarely live past their early 20s.
• This disorder is due to the absence of an X-linked gene
for a key muscle protein, called dystrophin.
• The disease is characterized by a progressive weakening
of the muscles and loss of coordination.
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• Hemophilia is a sex-linked recessive trait defined
by the absence of one or more clotting factors.
• These proteins normally slow and then stop bleeding.
• Individuals with hemophilia have prolonged
bleeding because a firm clot forms slowly.
• Bleeding in muscles and joints can be painful and lead
to serious damage.
• Individuals can be treated with intravenous
injections of the missing protein.
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• Breakage of a chromosome can lead to four types
of changes in chromosome structure.
• A deletion occurs when a chromosome fragment
lacking a centromere is lost during cell division.
• This chromosome will be missing certain genes.
• A duplication occurs when a fragment becomes
attached as an extra segment to a sister chromatid.
Fig. 15.13a & b
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• An inversion occurs when a chromosomal
fragment reattaches to the original chromosome
but in the reverse orientation.
• In translocation, a chromosomal fragment joins a
nonhomologous chromosome.
• Some translocations are reciprocal, others are not.
Fig. 15.13c & d
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• Deletions and duplications are common in meiosis.
• Homologous chromatids may break and rejoin at
incorrect places, such that one chromatid will loose more
genes than it receives.
• A diploid embryo that is homozygous for a large
deletion or male with a large deletion to its single X
chromosome is usually missing many essential
genes and this leads to a lethal outcome.
• Duplications and translocations are typically harmful.
• Reciprocal translocation or inversion can alter
phenotype because a gene’s expression is influenced
by its location.
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• One aneuploid condition, Down syndrome, is due
to three copies of chromosome 21.
• It affects one in 700 children born in the United States.
• Although chromosome 21 is the smallest human
chromosome, it severely alters an individual’s
phenotype in specific ways.
Fig. 15.14
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• Most cases of Down syndrome result from
nondisjunction during gamete production in one
parent.
• The frequency of Down syndrome correlates with
the age of the mother.
• This may be linked to some age-dependent abnormality
in the spindle checkpoint during meiosis I, leading to
nondisjunction.
• Trisomies of other chromosomes also increase in
incidence with maternal age, but it is rare for
infants with these autosomal trisomies to survive
for long.
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• Klinefelter’s syndrome, an XXY male, occurs once
in every 2000 live births.
• These individuals have male sex organs, but are sterile.
• There may be feminine characteristics, but their
intelligence is normal.
• Males with an extra Y chromosome (XYY) tend to
somewhat taller than average.
• Trisomy X (XXX), which occurs once in every
2000 live births, produces healthy females.
• Monosomy X or Turner’s syndrome (X0), which
occurs once in every 5000 births, produces
phenotypic, but immature females.
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• Structural alterations of chromosomes can also
cause human disorders.
• Deletions, even in a heterozygous state, cause
severe physical and mental problems.
• One syndrome, cri du chat, results from a specific
deletion in chromosome 5.
• These individuals are mentally retarded, have a small
head with unusual facial features, and a cry like the
mewing of a distressed cat.
• This syndrome is fatal in infancy or early childhood.
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