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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.