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Chapter 14: The Human Genome Section 14-1 Human Chromosomes Slide 1 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Chromosomes Human Chromosomes Cell biologists analyze chromosomes by looking at karyotypes. Cells are photographed during mitosis. Scientists then cut out the chromosomes from the photographs and group them together in pairs. A picture of chromosomes arranged in this way is known as a karyotype. Slide 2 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Chromosomes A Human Karyotype Slide 3 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Chromosomes Two of the 46 human chromosomes are known as sex chromosomes, because they determine an individual's sex. • Females have two copies of an X chromosome. • Males have one X chromosome and one Y chromosome. The remaining 44 chromosomes are known as autosomal chromosomes, or autosomes. Slide 4 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Chromosomes How is sex determined? Slide 5 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Chromosomes Males and females are born in a roughly 50 : 50 ratio because of the way in which sex chromosomes segregate during meiosis. Slide 6 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Traits Human Traits In order to apply Mendelian genetics to humans, biologists must identify an inherited trait controlled by a single gene. They must establish that the trait is inherited and not the result of environmental influences. They have to study how the trait is passed from one generation to the next. Slide 7 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Traits Pedigree Charts A pedigree chart shows the relationships within a family. Genetic counselors analyze pedigree charts to infer the genotypes of family members. Slide 8 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity A horizontal line connecting a male and a female represents a marriage. A circle represents a female. Human Traits A square represents a male. A vertical line and a bracket connect the parents to their children. A circle or square that is not shaded indicates that a person does not express the trait. A shaded circle or square indicates that a person expresses the trait. Slide 9 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Traits Genes and the Environment Some obvious human traits are almost impossible to associate with single genes. Traits, such as the shape of your eyes or ears, eye color, height (e), skin color (e), weight (e), and intelligence (e) are polygenic, meaning they are controlled by many genes. Many of your personal traits are only partly governed by genetics and they do not follow Mendel’s laws of inheritance. (e) = also subject to environmental influences Slide 10 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Genes Human Genes The human genome includes tens of thousands of genes. In 2003, the DNA sequence of the human genome was published. (Took ~ 10 years to complete) Humans have about 25,000 genes each with 3,000 base pairs. Scientists estimate that there are about 3 billion base pairs in the (haploid) human genome. In a few cases, biologists were able to identify genes that directly control a single human trait such as blood type. Copyright Pearson Prentice Hall Slide 11 of 43 End Show 14–1 Human Heredity Human Genes Blood Group Genes Human blood comes in a variety of genetically determined blood groups. A number of genes are responsible for human blood groups. The best known are the ABO blood groups and the Rh blood groups. Slide 12 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Genes The Rh (Rhesus factor) blood group is determined by a single gene with two alleles—positive and negative. The positive (Rh+) allele is dominant, so individuals who are Rh+/Rh+ or Rh+/Rh are said to be Rh positive. About 85% of all people are positive and contain the protein (or antigen). Individuals with two Rh- alleles are said to be Rh negative. Slide 13 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Genes ABO blood group • There are three alleles for this gene, IA, IB, and i. • Alleles IA and IB are codominant. Slide 14 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Genes Individuals with alleles IA and IB produce both A and B antigens, making them blood type AB. Slide 15 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Genes The i allele is recessive. Individuals with alleles IAIA or IAi produce only the A antigen, making them blood type A. Slide 16 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Genes Individuals with IBIB or IBi alleles are type B. Slide 17 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Genes Individuals who are homozygous for the i allele (ii) produce no antigen and are said to have blood type O. Slide 18 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Genes Recessive Alleles The presence of a normal, functioning gene is revealed only when an abnormal or nonfunctioning allele affects the phenotype. Some disorders are caused by autosomal recessive alleles. Each parent must contribute a recessive allele for the disorder to present itself in the offspring. Slide 19 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Genes Slide 20 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Genes Dominant Alleles The effects of a dominant allele are expressed even when the recessive allele is present. Two examples of genetic disorders caused by autosomal dominant alleles are Achondroplasia and Huntington disease. Slide 21 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Genes Slide 22 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Genes Codominant Alleles Sickle cell disease is a serious disorder caused by a co-dominant allele. A person who is co-dominant has the normal allele and the sickle-cell allele (heterozygous) for the disease and does not present the sickle-cell symptoms. A person who is homozygous for the sickle-cell trait presents the sickle-cell trait. Sickle cell is found in about 1 out of 500 African Americans. Slide 23 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity Human Genes Slide 24 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity From Gene to Molecule From Gene to Molecule How do small changes in DNA cause genetic disorders? Slide 25 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity From Gene to Molecule In both cystic fibrosis and sickle cell disease, a small change in the DNA of a single gene affects the structure of a protein, causing a serious genetic disorder. Slide 26 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity From Gene to Molecule Cystic Fibrosis Cystic fibrosis is caused by a recessive allele. Sufferers of cystic fibrosis produce a thick, heavy mucus that clogs their lungs and breathing passageways. Slide 27 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity From Gene to Molecule The most common allele that causes cystic fibrosis is missing 3 DNA bases. As a result, the amino acid phenylalanine is missing from the CFTR protein. (Cystic fibrosis transmembrane conductance regulator) Slide 28 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity From Gene to Molecule Normal CFTR is a chloride ion channel in cell membranes. Abnormal CFTR cannot be transported to the cell membrane. Slide 29 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity From Gene to Molecule The cells in the person’s airways are unable to transport chloride ions. As a result, the airways become clogged with a thick mucus. Slide 30 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity From Gene to Molecule Sickle Cell Disease Sickle cell disease is a common genetic disorder found in African Americans. It is characterized by the bent and twisted shape of the red blood cells. Slide 31 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity From Gene to Molecule Hemoglobin is the protein in red blood cells that carries oxygen. In the sickle cell allele, just one DNA base is changed. As a result, the abnormal hemoglobin is less soluble than normal hemoglobin. Low oxygen levels cause some red blood cells to become sickle shaped. Slide 32 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity From Gene to Molecule People who are heterozygous for the sickle cell allele are generally healthy and they are resistant to malaria. Slide 33 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity From Gene to Molecule There are three phenotypes associated with the sickle cell gene. An individual with both normal and sickle cell alleles has a different phenotype—resistance to malaria— from someone with only normal alleles. Sickle cell alleles are thought to be codominant. Slide 34 of 43 Copyright Pearson Prentice Hall End Show 14–1 Human Heredity From Gene to Molecule Malaria and the Sickle Cell Allele Regions where malaria is common Regions where the sickle cell allele is common Slide 35 of 43 Copyright Pearson Prentice Hall End Show 14–1 Click to Launch: Continue to: - or - Slide 36 of 43 End Show Copyright Pearson Prentice Hall 14–1 A chromosome that is not a sex chromosome is know as a(an) a. autosome. b. karyotype. c. pedigree. d. chromatid. Slide 37 of 43 End Show Copyright Pearson Prentice Hall 14–1 Whether a human will be a male or a female is determined by which a. sex chromosome is in the egg cell. b. autosomes are in the egg cell. c. sex chromosome is in the sperm cell. d. autosomes are in the sperm cell. Slide 38 of 43 End Show Copyright Pearson Prentice Hall 14–1 Mendelian inheritance in humans is typically studied by a. making inferences from family pedigrees. b. carrying out carefully controlled crosses. c. observing the phenotypes of individual humans. d. observing inheritance patterns in other animals. Slide 39 of 43 End Show Copyright Pearson Prentice Hall 14–1 An individual with a blood type phenotype of O can receive blood from an individual with the phenotype a. O. b. A. c. AB. d. B. Slide 40 of 43 End Show Copyright Pearson Prentice Hall 14–1 The ABO blood group is made up of a. two alleles. b. three alleles. c. identical alleles. d. dominant alleles. Slide 41 of 43 End Show Copyright Pearson Prentice Hall END OF SECTION Chapter 14: The Human Genome Section 14-2 Human Genetic Disorders Slide 43 of 25 Copyright Pearson Prentice Hall End Show 14–2 Human Chromosomes Sex-Linked Genes Sex-Linked Genes The X chromosome and the Y chromosomes determine sex. Genes located on these chromosomes are called sex-linked genes. More than 100 sex-linked genetic disorders have now been mapped to the X chromosome. Slide 44 of 25 End Show 14–2 Human Chromosomes Sex-Linked Genes X Chromosome The Y chromosome is much smaller than the X chromosome and appears to contain only a few genes. Duchenne muscular dystrophy Melanoma X-inactivation center X-linked severe combined immunodeficiency (SCID) Colorblindness Hemophilia Y Chromosome Testis-determining factor Slide 45 of 25 End Show 14–2 Human Chromosomes Sex-Linked Genes Why are sex-linked disorders more common in males than in females? Slide 46 of 25 End Show 14–2 Human Chromosomes Sex-Linked Genes For a recessive allele to be expressed in females, there must be two copies of the allele, one on each of the two X chromosomes. Males have just one X chromosome. Thus, all X-linked alleles are expressed in males, even if they are recessive. Slide 47 of 25 End Show 14–2 Human Chromosomes Slide 48 of 25 End Show 14–2 Human Chromosomes Sex-Linked Genes Colorblindness Three human genes associated with color vision are located on the X chromosome. In males, a defective version of any one of these genes produces colorblindness. Slide 49 of 25 End Show 14–2 Human Chromosomes Sex-Linked Genes Possible Inheritance of Colorblindness Allele Slide 50 of 25 End Show 14–2 Human Chromosomes Sex-Linked Genes Hemophilia The X chromosome also carries genes that help control blood clotting. A recessive allele in either of these two genes may produce hemophilia. In hemophilia, a protein necessary for normal blood clotting is missing. Hemophiliacs can bleed to death from cuts and may suffer internal bleeding if bruised. Slide 51 of 25 End Show 14–2 Human Chromosomes Slide 52 of 25 End Show 14–2 Human Chromosomes Sex-Linked Genes Duchenne Muscular Dystrophy Duchenne muscular dystrophy is a sex-linked disorder that results in the weakening and loss of skeletal muscle. It is caused by a defective version of the gene that codes for a muscle protein. Slide 53 of 25 End Show 14–2 Human Chromosomes X-Chromosome Inactivation X-Chromosome Inactivation British geneticist Mary Lyon discovered that in female cells, one X chromosome is randomly switched off. This chromosome forms a dense region in the nucleus known as a Barr body. Barr bodies are generally not found in males because their single X chromosome is still active. Slide 54 of 25 End Show 14–2 Human Chromosomes Chromosomal Disorders Chromosomal Disorders What problems does nondisjunction cause? Slide 55 of 25 End Show 14–2 Human Chromosomes Chromosomal Disorders The most common error in meiosis occurs when homologous chromosomes fail to separate. This is known as nondisjunction, which means, “not coming apart.” Slide 56 of 25 End Show 14–2 Human Chromosomes Chromosomal Disorders If nondisjunction occurs, abnormal numbers of chromosomes may find their way into gametes, and a disorder of chromosome numbers may result. Slide 57 of 25 End Show 14–2 Human Chromosomes Nondisjunction Chromosomal Disorders Homologous chromosomes fail to separate. Meiosis I: Nondisjunction Meiosis II Slide 58 of 25 End Show 14–2 Human Chromosomes Chromosomal Disorders Down Syndrome If two copies of an autosomal chromosome fail to separate during meiosis, an individual may be born with three copies of a chromosome. Down syndrome involves three copies of chromosome 21. Slide 59 of 25 End Show 14–2 Human Chromosomes Down syndrome produces mild to severe mental retardation. Chromosomal Disorders Down Syndrome Karyotype It is characterized by: • increased susceptibility to many diseases • higher frequency of some birth defects Slide 60 of 25 End Show 14–2 Human Chromosomes Chromosomal Disorders Sex Chromosome Disorders In females, nondisjunction can lead to Turner’s syndrome. A female with Turner’s syndrome usually inherits only one X chromosome (karyotype 45,X). Women with Turner’s syndrome are sterile. Slide 61 of 25 End Show 14–2 Human Chromosomes Chromosomal Disorders In males, nondisjunction causes Klinefelter’s syndrome (karyotype 47,XXY). The extra X chromosome interferes with meiosis and usually prevents these individuals from reproducing. Slide 62 of 25 End Show 14–2 Click to Launch: Continue to: - or - Slide 63 of 25 End Show 14–2 The average human gene consists of how many base pairs of DNA? a. 3000 b. 300 c. 20 d. 30,000 Slide 64 of 25 End Show 14–2 Which of the following genotypes indicates an individual who is a carrier for colorblindness? a. XCX b. XCXc c. XcY d. XCY Slide 65 of 25 End Show 14–2 Colorblindness is much more common in males than in females because a. the recessive gene on the male’s single X chromosome is expressed. b. genes on the Y chromosome make genes on the X chromosome more active. c. females cannot be colorblind. d. colorblindness is dominant in males and recessive in females. Slide 66 of 25 End Show 14–2 The presence of a dense region in the nucleus of a cell can be used to determine the a. sex of an individual. b. blood type of an individual. c. chromosome number of an individual. d. genotype of an individual. Slide 67 of 25 End Show 14–2 Nondisjunction occurs during a. meiosis I. b. mitosis. c. meiosis II. d. between meiosis I and II. Slide 68 of 25 End Show END OF SECTION Chapter 14: The Human Genome Section 14-3 Studying the Human Genome Slide 70 of 24 Copyright Pearson Prentice Hall End Show 14–3 Human Molecular Genetics Human DNA Analysis Human DNA Analysis There are roughly 3 billion (haploid) base pairs in your DNA. Biologists search the human genome using sequences of DNA bases. Slide 71 of 24 End Show 14–3 Human Molecular Genetics Human DNA Analysis There are over 1,000 genetic tests available for hundreds of disorders. DNA testing can pinpoint the exact genetic basis of a disorder. Slide 72 of 24 End Show 14–3 Human Molecular Genetics Some Currently Available DNA-Based Gene Tests •Alpha-1-antitrypsin deficiency (AAT; emphysema and liver disease) •Amyotrophic lateral sclerosis (ALS; Lou Gehrig's Disease; progressive motor function loss leading to paralysis and death) •Alzheimer's disease* (APOE; late-onset variety of senile dementia) •Ataxia telangiectasia (AT; progressive brain disorder resulting in loss of muscle control and cancers) •Gaucher disease (GD; enlarged liver and spleen, bone degeneration) •Inherited breast and ovarian cancer* (BRCA 1 and 2; early-onset tumors of breasts and ovaries) •Hereditary nonpolyposis colon cancer* (CA; early-onset tumors of colon and sometimes other organs) •Central Core Disease (CCD; mild to severe muscle weakness) •Charcot-Marie-Tooth (CMT; loss of feeling in ends of limbs) •Congenital adrenal hyperplasia (CAH; hormone deficiency; ambiguous genitalia and male pseudohermaphroditism) •Cystic fibrosis (CF; disease of lung and pancreas resulting in thick mucous accumulations and chronic infections) •Duchenne muscular dystrophy/Becker muscular dystrophy (DMD; severe to mild muscle wasting, deterioration, weakness) •Dystonia (DYT; muscle rigidity, repetitive twisting movements) •Emanuel Syndrome (severe mental retardation, abnormal development of the head, heart and kidney problems) •Fanconi anemia, group C (FA; anemia, leukemia, skeletal deformities) •Factor V-Leiden (FVL; blood-clotting disorder) •Fragile X syndrome (FRAX; leading cause of inherited mental retardation) •Galactosemia (GALT; metabolic disorder affects ability to metabolize galactose) •Hemophilia A and B (HEMA and HEMB; bleeding disorders) •Hereditary Hemochromatosis (HFE; excess iron storage disorder) •Huntington's disease (HD; usually midlife onset; progressive, lethal, degenerative neurological disease) •Marfan Syndrome (FBN1; connective tissue disorder; tissues of ligaments, blood vessel walls, cartilage, heart valves and other structures abnormally weak) •Mucopolysaccharidosis (MPS; deficiency of enzymes needed to break down long chain sugars called glycosaminoglycans; corneal clouding, joint stiffness, heart disease, mental retardation) •Myotonic dystrophy (MD; progressive muscle weakness; most common form of adult muscular dystrophy) •Neurofibromatosis type 1 (NF1; multiple benign nervous system tumors that can be disfiguring; cancers) •Phenylketonuria (PKU; progressive mental retardation due to missing enzyme; correctable by diet) •Polycystic Kidney Disease (PKD1, PKD2; cysts in the kidneys and other organs) •Adult Polycystic Kidney Disease (APKD; kidney failure and liver disease) •Prader Willi/Angelman syndromes (PW/A; decreased motor skills, cognitive impairment, early death) •Sickle cell disease (SS; blood cell disorder; chronic pain and infections) •Spinocerebellar ataxia, type 1 (SCA1; involuntary muscle movements, reflex disorders, explosive speech) •Spinal muscular atrophy (SMA; severe, usually lethal progressive muscle-wasting disorder in children) Slide •Tay-Sachs Disease (TS; fatal neurological disease of early childhood; seizures, paralysis) 73 of 24 •Thalassemias (THAL; anemias - reduced red blood cell levels) •Timothy Syndrome (CACNA1C; characterized by severe cardiac arrhythmia, webbing of the fingers and toes called syndactyly, autism) End Show 14–3 Human Molecular Genetics Human DNA Analysis DNA Fingerprinting DNA fingerprinting analyzes sections of DNA that have little or no known function but vary widely from one individual to another. Only identical twins are genetically identical. DNA samples can be obtained from blood, sperm, and hair strands with tissue at the base. Slide 74 of 24 End Show 14–3 Human Molecular Genetics Human DNA Analysis Chromosomes contain large amounts of DNA called repeats that do not code for proteins. This DNA pattern varies from person to person. Slide 75 of 24 End Show 14–3 Human Molecular Genetics Human DNA Analysis Restriction enzymes are used to cut the DNA into fragments containing genes and repeats. Slide 76 of 24 End Show 14–3 Human Molecular Genetics Human DNA Analysis DNA fragments are separated using gel electrophoresis. Fragments containing repeats are labeled. This produces a series of bands—the DNA fingerprint. Slide 77 of 24 End Show 14–3 Human Molecular Genetics Human DNA Analysis DNA Fingerprint Slide 78 of 24 End Show 14–3 Human Molecular Genetics The Human Genome Project The Human Genome Project What is the goal of the Human Genome Project? Slide 79 of 24 End Show 14–3 Human Molecular Genetics The Human Genome Project In 1990, scientists in the United States and other countries began the Human Genome Project. The Human Genome Project is an ongoing effort to analyze the human DNA sequence. In June 2000, a working copy of the human genome was essentially complete. Slide 80 of 24 End Show 14–3 Human Molecular Genetics The Human Genome Project Research groups are analyzing the DNA sequence, looking for genes that may provide clues to the basic properties of life. Biotechnology companies are looking for information that may help develop new drugs and treatments for diseases. Slide 81 of 24 End Show 14–3 Human Molecular Genetics The Human Genome Project A Breakthrough for Everyone Data from publicly supported research on the human genome have been posted on the Internet on a daily basis. You can read and analyze the latest genome data. Slide 82 of 24 End Show 14–3 Human Molecular Genetics Gene Therapy Gene Therapy What is gene therapy? Slide 83 of 24 End Show 14–3 Human Molecular Genetics Gene Therapy In gene therapy, an absent or faulty gene is replaced by a normal, working gene. The body can then make the correct protein or enzyme, eliminating the cause of the disorder. Slide 84 of 24 End Show 14–3 Human Molecular Genetics Viruses are often used because of their ability to enter a cell’s DNA. Gene Therapy Normal hemoglobin gene Virus particles are modified so that they cannot cause disease. Genetically engineered virus Slide 85 of 24 End Show 14–3 Human Molecular Genetics Gene Therapy A DNA fragment containing a replacement gene is spliced to viral DNA. Bone marrow cell Nucleus Chromosomes Genetically engineered virus Slide 86 of 24 End Show 14–3 Human Molecular Genetics Gene Therapy The patient is then infected with the modified virus particles, which should carry the gene into cells to correct genetic defects. Slide 87 of 24 End Show 14–3 Click to Launch: Continue to: - or - Slide 88 of 24 End Show 14–3 DNA fingerprinting analyzes sections of DNA that have a. Little or no known function but are identical from one individual to another. b. little or no known function but vary widely from one individual to another. c. a function and are identical from one individual to another. d. a function and are highly variable from one individual to another. Slide 89 of 24 End Show 14–3 DNA fingerprinting uses the technique of a. gene therapy. b. allele analysis. c. gel electrophoresis. d. gene recombination. Slide 90 of 24 End Show 14–3 Repeats are areas of DNA that a. do not code for proteins. b. code for proteins. c. are identical from person to person. d. cause genetic disorders. Slide 91 of 24 End Show 14–3 Data from the human genome project is available a. only to those who have sequenced the DNA. b. to scientists who are able to understand the data. c. by permission to anyone who wishes to do research. d. to anyone with Internet access. Slide 92 of 24 End Show 14–3 Which statement most accurately describes gene therapy? a. It repairs the defective gene in all cells of the body. b. It destroys the defective gene in cells where it exists. c. It replaces absent or defective genes with a normal gene. d. It promotes DNA repair through the use of enzymes. Slide 93 of 24 End Show END OF SECTION