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Essentials of Biology
Sylvia S. Mader
Chapter 13
Lecture Outline
Prepared by: Dr. Stephen Ebbs
Southern Illinois University Carbondale
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
13.1 Counseling Chromosome
Disorders
• As awareness of genetic disorders increases, so
has the interest in genetic counseling.
• Couples seek genetic counseling to determine
the risk of inherited disorders in a family.
• Even after conception tests such as karyotyping
can be used to insure that the proper number of
chromosomes is present in the fetus.
13.1 Counseling Chromosome
Disorders (cont.)
Karyotyping
• A karyotype is a visual display of the
chromosomes arranged by size, shape,
and banding pattern.
• The chromosomes can be obtained from
blood cells or from amniotic fluid obtained
from an amniocentesis.
Karyotyping (cont.)
Karyotyping (cont.)
• Another approach used to obtain chromosomes
for karyotyping is by chorionic villi sampling.
• Cells are obtained from the region between the
uterus and the chorionic villi.
• The chromosomes are isolated from the cells,
stained, photographed, and digitally arranged
into homologous pairs.
Karyotyping (cont.)
Karyotyping (cont.)
Chromosomal Mutations
• A chromosomal mutation is a change in
chromosome number or structure.
• Specific medical syndromes can occur when
chromosomes break and fail to reunite properly.
• Several types of mutations can occur.
– Deletion and duplication
– Translocation
– Inversion
Deletions and Duplications
• A deletion occurs when a single break causes
the chromosome to lose a piece of an internal
segment.
• In a duplication mutation, a section of the
chromosome is repeated so that there are more
than two alleles for a trait.
• A translocation is the exchange of chromosome
segments between two non-homologous
chromosomes.
Deletions and Duplications
(cont.)
Deletions and Duplications
(cont.)
Translocation
Inversion
• An inversion mutation occurs when a
chromosome segment is turned 180º.
• Although the same genes are present, the
triplet code has been reversed and will not
produce the same protein.
Inversion (cont.)
13.2 Counseling for Genetic
Disorders: The Present
• Biochemical tests are available to check
for over 400 different genetic disorders.
• A genetic counselor may recommend one
or more tests based upon the family
medical history.
• This history is usually depicted as a
pedigree.
Family Pedigrees
• From a pedigree, the pattern of inheritance
for a genetic trait can be determined.
• This information can allow the genetic
counselor to estimate the probability that a
child might inherit a genetic disorder.
Pedigrees for Autosomal Disorders
• If the genetic disease is an autosomal recessive
disorder, the child may be affected but not the
parents.
• In that case, the parents were carriers of the
genetic disease.
• For a disorder inherited through an autosomal
dominant pattern, a child may be unaffected
even if the parents are.
Pedigrees for Autosomal Disorders
(cont.)
Pedigrees for Autosomal Disorders
(cont.)
Pedigrees for Sex-Linked Disorders
• In an X-linked recessive disorder, sons
inherit the disease from mothers who are
carriers.
• Females are less likely to experience the
disorder because another X chromosome
is present.
• The daughters of a male with an X-linked
disorder are all carriers.
Pedigrees for Sex-Linked Disorders
(cont.)
Pedigrees for Sex-Linked Disorders
(cont.)
• There are a few X-linked dominant
disorders.
• Daughters of affected males have a 100%
chance of having the disorder.
• Females can transmit the disorder to all
children.
Pedigrees for Sex-Linked Disorders
(cont.)
• There are few genetic disorders carried on
the Y chromosome, such as those
associated with the SRY-determining
region.
• For Y-linked disorders, fathers and sons
experience the disorder, but not
daughters.
Genetic Disorders of Interest
• The field of medical genetics focuses on
genetic disorders caused by single gene
mutations.
• Several of these diseases are well-known
and have been thoroughly studied.
Autosomal Disorders
• Autosomal disorders are caused by
mutated alleles on the autosomal
chromosomes, not the sex chromosomes.
• Some autosomal disorders are recessive
while others are dominant.
Autosomal Disorders (cont.)
• Tay-Sachs is a recessive disorder that typically
occurs among Jewish people of European
descent.
• Cystic fibrosis is a recessive disorder that
generally affects Caucasians in the U.S.
• Phenylketonuria (PKU) is a recessive disorder
that affects nervous system development.
Autosomal Disorders (cont.)
• Sickle cell disease is a recessive disease in
which the red blood cells have a disk-like shape.
• Marfan syndrome is a dominant disorder caused
by a defect in a connective tissue protein.
• Huntington disease is a neurological disease
that causes a progressive degeneration of the
neurons.
• Familial hypercholesterolemia (FH) is a disorder
that displays incomplete dominance.
X-Linked Recessive Disorders
• Mutated alleles on the X-chromosome are the
cause of X-linked recessive disorders.
• Sons inherit color blindness from mothers who
are carriers.
• Duchenne muscular dystrophy is a disorder that
causes the wasting of muscles.
• For people with hemophilia, the blood does not
clot properly.
Testing for Genetic Disorders
• Genetic testing can be done on parents
before they have a child or on a child after
it is conceived.
• Genetic tests check for the presence or
absence of a certain protein or the
presence of a certain mutated allele.
Testing for a Protein
• Genetic disorders frequently affect enzymes in
essential biochemical pathways.
• Some tests measure the level of relevant
enzyme, as for Tay-Sachs disease.
• Some tests measure the level of a particular
substrate that should be removed by the
enzyme, such as the phenylalanine that builds
up during PKU.
Testing the DNA
• There are several strategies that can be
used to test DNA for a genetic disorder.
– Check for a unique abnormal sequence in the
DNA called a genetic marker.
– Cut the DNA with restriction enzymes to see if
a different set of fragments is obtained from
DNA with the abnormal sequence.
– Use a specific DNA probe.
Testing the DNA (cont.)
Testing the DNA (cont.)
Testing the Fetus
• If a child has already been conceived, it is
also possible to test the fetus for genetic
disorders.
• An ultrasound can be used to check for
abnormalities of fetal anatomy.
• Fetal cells can also be tested for genetic
disorders.
Testing the Fetus (cont.)
Testing the Fetus (cont.)
Testing the Embryo and the Egg
• In vitro fertilization (IVF) can be used to
conceive a child and also to help test for
genetic disorders.
• Once the fertilized egg has reached the 68 cell stage, one of these cells can be
safely removed and tested for genetic
disorders.
Testing the Embryo and the Egg
(cont.)
13.3 Counseling for Genetic
Disorders: The Future
• The future of genetic research lies in the
study of genomics.
• This approach studies all of an organism’s
genes to understand how they direct
growth and development.
Sequencing the Bases of the
Human Genome
• The Human Genome Project took 13
years to determine a draft sequence of
DNA in humans.
• Much of this work was done by automated
sequencers that can determine up to
350,000 base pairs per day.
Genome Comparisons
• The genomes of several other organisms has
also been determined.
• A comparison of the human genome to the
genomes of these organisms has revealed that
all organisms share a large number of genes.
• There are also numerous differences that make
each organism unique.
Genetic Profiling
• DNA chips, also called DNA microarrays will
ultimately be able to determine a person’s
genotype for all genes.
• This complete genotype would comprise a
person’s genetic profile.
• With this profile, genetic counselors could advise
people about risks of genetic disorders and
suggest lifestyle changes to reduce risk.
Proteomics and Informatics
• A new tool useful in the development of
treatments for genetic disorders is proteomics.
• Proteomics studies the structure, function, and
interaction of proteins in an organism.
• By studying the collection of proteins present in
an organism (the proteome), new drugs to treat
genetic disorders can be developed.
Proteomics and Informatics
(cont.)
• Another tool is bioinformatics, which uses
computers to study the genome.
• This analysis may help to uncover causeeffect relationships between genetic
profiles and genetic disorders.
13.4 Gene Therapy
• Gene therapy involved the insertion of genetic
information to treat a genetic disorder.
• The genetic information replaces mutated or
defective genes with healthy ones.
• Gene therapy includes two approaches.
– Ex vivo (outside the body)
– In vivo (inside the body)
Ex Vivo Gene Therapy
• The treatment of severe combined
immunodeficiency syndrome (SCID) is an
example of ex vivo gene therapy.
• Children with SCID lack a key enzyme involved
in the maturation of cells from the immune
system.
• If bone marrow is removed from these children,
an RNA retrovirus can be used to insert the
normal gene into the marrow cells.
Ex Vivo Gene Therapy (cont.)
Ex Vivo Gene Therapy (cont.)
• Ex vivo gene therapy is also being used to
treat other genetic disorders.
– Hypercholesterolemia
– Certain forms of cancer
In Vivo Gene Therapy (cont.)
• For in vivo gene therapy, adenoviruses or
liposomes deliver to the body the gene needed
to treat cystic fibrosis.
• The gene for vascular endothelial growth factor
(VEGF) can be injected or carried by a virus to
treat problems with poor coronary circulation.
• In vivo gene therapy is also being used to treat
cancer.