The Human Genome Chapter 14

Human Heredity 14-1

NOVA: Cracking the Code of Life Chapter 1: Instructions for Making a Human Being

Human Chromosomes A karyotype is a picture of chromosomes from a cell arranged in homologous pairs.

Human Chromosomes Humans have 46 chromosomes. 44 autosomes 2 sex chromosomes Normal female: 46 XX Normal male: 46 XY Sperm: 23 X or 23 Y Egg: 23 X

Human Chromosomes

Human Chromosomes What determines the sex of a child? The sperm……

Human Traits To study the inheritance of human traits genetic counselors use a pedigree chart. From this, geneticists can infer genotypes of family members.

Human Traits Draw a pedigree chart.

Human Traits Associating an observed human trait with a gene is difficult. Many human traits are polygenic. The environment influences the expression of a trait.

Human Genes Humans have 4 blood types caused by 3 alleles. A & B – codominant O – recessive Types: A, B, AB, O Blood types must be matched for a safe transfusion. Draw blood type chart…………………..

Human Genes Rh factors represent another group of antigens found on some red blood cells. Rh+ = present. Rh- = absent.

Human Genes Most genetic disorders are caused by recessive alleles. To have the disorder an individual must inherit two recessive alleles. Ex: PKU, Tay-Sachs, Cystic Fibrosis, Albinism

Cystic Fibrosis Figure 14-8 The Cause of Cystic Fibrosis Chromosome # 7 CFTR gene 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. Normal CFTR is a chloride ion channel in cell membranes. Abnormal CFTR cannot be transported to the cell membrane. The cells in the person’s airways are unable to transport chloride ions. As a result, the airways become clogged with a thick mucus.

Human Genes A few are caused by dominant alleles. Only one allele needs to be inherited to be expressed. Ex: Huntington’s disease, Dwarfism

Human Genes Sickle cell anemia is caused by a codominant allele. One normal allele and one abnormal allele are inherited for making the protein hemoglobin. The sickle cell allele is inherited among many African Americans. Carrying this allele produces resistance to the Malaria parasite.

Sickle Cell Anemia

NOVA: Cracking the Code of Life Chapter 2: Getting the Letters Out

Human Chromosomes 14-2

Human Genes and Chromosomes Only 2% of your DNA functions as genes.

Human Genes and Chromosomes Genes located on the same chromosome are linked. They tend to be inherited together. They can be separated by crossing-over during meiosis.

Crossing-Over

Sex-Linked Genes Sex-linked genes are located on the sex chromosomes. More genes are on the X than the Y.

Sex-Linked Genes Genes on the X chromosome are always expressed in males even if recessive. Males get sex-linked disorders more often than females. Colorblindness, hemophilia, muscular dystrophy

X-Chromosome Inactivation In females, one X chromosome is randomly switched off. Calico cats are always female.

X-Chromosome Inactivation The switched off X chromosome becomes a dense region in the nucleus known as a Barr body. Barr bodies aren’t found in males.

Olympics and Barr Bodies Sex testing was introduced in competitive sports in the mid-1960s, amid rumor that some competitors in women's events were not truly female - especially two Soviet sisters who won gold medals at the 1960 and 1964 Olympics, and who abruptly retired when gender verification testing began.

Olympics and Barr Bodies The first tests, at the European Championships in 1966 and the Pan- American Games in 1967, required female competitors to undress before a panel of doctors. Other methods used during this period included manual examination or close-up scrutiny of the athlete's genital region.

Olympics and Barr Bodies When athletes complained that these tests were degrading, the IOC at the Mexico City Olympics in 1968 introduced genetic testing in the form of a sex chromatin (Barr body) analysis of cells from a buccal smear. The procedure was further modified at the Barcelona games, using the polymerase chain reaction to amplify the DNA extracted from a specimen to allow detection of a Y chromosome gene, SRY, that codes for male determination. Journal of the American Medical Association, July 17, 1996, vol. 276, no. 3, pp. 177-178

Chromosomal Disorders Caused by nondisjunction during meiosis. Homologous chromosomes fail to separate resulting in sex cells with one too many or one too few chromosomes.

Non disjunction Nondisjunction Section 14-2 Homologous chromosomes fail to separate Meiosis I: Nondisjunction Meiosis II

Chromosomal Disorders Down’s syndrome = 47,XX or 47,XY Turner’s syndrome = 45,X Klinefelter’s syndrome = 47,XXY

Down’s Syndrome

Turner’s Syndrome

Kleinefelter’s Syndrome

Human Molecular Genetics 14-3

Human DNA Analysis Even though the human genome is over 6 billion bases long, genetic tests exist for detecting the presence of defective recessive genes. Prospective parents can now be tested to determine if they carry recessive alleles for hundreds of disorders. Is this a good idea?

DNA Fingerprinting All humans share the same genes. The 98% of DNA that is not encoded in genes is what makes us different from each other. DNA fingerprinting makes use of this difference to identify individuals.

DNA Fingerprinting4-18 DNA Fingerprinting Restriction enzyme Chromosomes contain large amounts of DNA called repeats that do not code for proteins. This DNA varies from person to person. Here, one sample has 12 repeats between genes A and B, while the second sample has 9 repeats. Restriction enzymes are used to cut the DNA into fragments containing genes and repeats. Note that the repeat fragments from these two samples are of different lengths. The DNA fragments are separated according to size using gel electrophoresis. The fragments containing repeats are then labeled using radioactive probes. This produces a series of bands—the DNA fingerprint.

The Human Genome Project In 2000, the entire human genome was sequenced. Dr. Francis Collins, Dr. Eric Lander and Dr. Craig Venter (NOVA – Cracking the Code of Life) Advances in technology allowed this to happen in several years rather than the predicted 20.

Rapid Sequencing Gene Sequence Promoter Start signal Gene Stop signal

Gene Therapy The process of changing a gene that causes a disorder. An absent or defective gene is replaced by a normal functioning gene. Viruses are often used to deliver functional genes to affected cells.

Gene Therapy Bone marrow cell Normal hemoglobin gene Nucleus Chromosomes Bone marrow Genetically engineered virus

Ethical Issues… Genetic cures Designer babies Medical costs Research costs