Guide for Lecture Test 1. The goals of the exams are to evaluate your basic comprehension of vocabulary as well as your ability to fully understand the concepts, as if you had to explain them to a patient or family member. This guide is in outline form: Refer to textbook/class lectures for details of cell cycle etc. Know correct answers from previous quizzes and homework. Review all course documents posted on Blackboard, including ? in class work? and ?Math help?. 1.1 Levels of Genetics 1. Genetics is a branch of biology concerned with heredity and variation. 2. Genes are the unit of inheritance and are composed of the DNA molecule. 3. An organism?s genome is its complete set of genetic information. 5. The effects of genes are noticeable at the molecular, cellular, individual, and population levels. 6. Genes are DNA sequences that instruct cells to produce particular proteins, which in turn determine traits. 9. Genes can exist in more than one form and the variants, termed alleles, arise by mutation. 10. A polymorphism is a particular sequence of DNA that varies in one percent or more of the population. 12. Chromosomes consist of genes and associated proteins. 13. The human genome consists of 22 pairs of autosomes and one pair of sex chromosomes. 14. A karyotype is a size-order chart of the human chromosomes. 15. Specialized cells and tissues arise by differentiation from the stem cells of the early embryo. 16. The allelic makeup of an individual is termed the genotype, while phenotype refers to observable expression of the alleles. 17. Dominant alleles are expressed when one copy is present. Recessive alleles generally require two copies for expression. 18. Pedigree diagrams enable recessive and dominant traits to be followed through multiple generations of a family. 19. A gene pool is the collection of alleles in a population. 1.2 Most Genes Do Not Function Alone 1. Traits are determined by single genes have traditionally been called Mendelian traits. 2. Mendelian disorders are generally rare. 3. Most traits are multifactorial traits and are determined by multiple genes and environmental effects. 4. Many common illnesses have a multifactorial basis. 1.3 Applications of Genetics Establishing Identity and Ancestry 1. Genetic tools are used in diverse areas such as establishing identity, forensics, establishing paternity, agriculture, and health care. 2. DNA profiling can exclude an individual from being biologically related to someone else, or from having committed a crime. 3. DNA profiling can be used to characterize living and dead populations of humans or other organisms. Health Care 1. Genomics is changing patient care as genetic information is being incorporated into diagnosis and treatment. 2. Genetic diseases differ from infectious diseases in that the recurrence risks are predictable, pre-symptomatic diagnosis using genetic testing is possible, and characteristic frequencies are observed in different populations. 3. After identifying underlying genetic abnormalities (mutations), gene therapy can be used to treat and possibly prevent certain genetic disorders. Agriculture 1. Agriculture, both traditional and biotechnological, applies genetic principles. 2. Traditional agriculture involves controlled breeding to select new combinations of inherited traits. 3. Using organisms for the production of products or services is termed Biotechnology. 4. Genetically modified (GM) foods have genes introduced from the genomes of other organisms. 2.1 The Components of Cells 1. All cells must maintain basic functions for growth and reproduction, responding to the environment, and utilizing energy. 2. Specialized cells in humans and other multicellular organisms perform additional functions related to their role within tissues or organs. 3. There are three broad varieties of cells ? Eubacteria (the more common forms of bacteria), Archaea (the extreme bacteria), and Eukaryotes (higher cells) ? based on cellular complexity. 4. The Archaea and Eubacteria are similar in that they are single-celled organisms, but they differ in certain features of their RNA and membranes. These cells lack nuclei and other organelles (except for ribosomes) and therefore are categorized as prokaryotes. 5. Eukaryotic cells are complex, with abundant and diverse organelles that compartmentalize biochemical reactions. Human cells are therefore eukaryotic. Organelles 1. Organelles represent the compartments (and unique microenvironments) in the cell and are involved in a variety of functions (division of labor). 2. The nucleus (the storehouse of the majority of DNA in the cell) has a double membrane and nuclear pores, which allow macromolecular traffic in and out of the nucleus. 3. Functions of the rough endoplasmic reticulum (ER), smooth ER, and Golgi body 4. Lysosomes contain enzymes that degrade cellular debris. 5. Peroxisomes house enzymes that detoxify certain substances, break down lipids, and synthesize bile acids. 6. A mitochondrion has a double membrane whose inner folds carry enzymes that catalyze reactions that extract energy from nutrients. The Plasma Membrane 1. The plasma membrane surrounds the cell and regulates which molecules enter and leave. 2. Biological membranes are composed of a bilayer of phospholipids. 3. Proteins, glycoproteins and glycolipids residing in the cell membrane function as enzymes, signal transduction receptors, transport proteins, and cell adhesion proteins. Signal transduction receptors transmit outside signals to inside the cell to evoke the correct response. 2.2 Cell Division and Death Stages of The Cell Cycle and Mitosis 1. The cell cycle consists of interphase, when a cell is not dividing, and mitosis. 2. During interphase, proteins, lipids, and carbohydrates are produced in the G1 phase; DNA and proteins are made during S phase; and more proteins are produced in G2. Replicated chromosomes have two sister chromatids attached at their centromeres. Non-dividing cells may become arrested during interphase and enter a quiescent phase (G0). 3. In mitotic prophase, replicated chromosomes condense, a spindle forms, and the nuclear membrane breaks down. In metaphase, chromosomes align down the center of the cell (equator or metaphase plate). In anaphase, centromeres part, one chromatid from each pair is pulled to opposite ends of the cell. In telophase, the cell pinches in the middle (cytokinesis), and the two new cells separate. 4. The cell cycle is tightly controlled and regulated at several "checkpoints." DNA damage checkpoint is mediated by p53. 5. A cellular clock that limits the number of divisions is based on shrinking telomeres. 6. Crowding, hormones, and growth factors are extracellular influences on mitosis. 7. Within cells, kinases and cyclins activate the genes whose products carry out mitosis. Apoptosis 1. Mitosis (cell division) and apoptosis (cell death) are continuous processes that are both initiated by signals in the extracellular environment. 2. The balance between cell division and death maintains tissues in growth, development, and repair. 3. In prenatal development, coordination of these processes sculpts body form. After birth, mitosis and apoptosis protect and maintain the body. 4. Disruption of the balance between cell division and cell death can lead to cancer or other disorders. 2.4 Stem Cells and Cell Specialization 1. Stem cells are unique non-specialized cells that retain the potential to differentiate and enable a tissue to grow or repair itself. 2. A fertilized egg is totipotent, capable of producing any cell type. 3. Cells of the early embryo are pluripotent, meaning they can differentiate into some but not all types of cells. 4. Later in development, pluripotent stem cells give rise to progenitor cells that are committed to a particular pathway. 5. Stem cells persist in many adult tissues and have the potential, through regenerative medicine, to replace injured or diseased tissue. 6. Types and origins of stem cells used in regenerative medicine, steps in SCNT 3.2 Meiosis 1. Meiosis forms haploid (n) gametes (sperm and oocytes) from diploid (2n) germline cells. 2. Meiosis conserves chromosome number and generates genetic variability. 3. Stages of meiosis: Meiosis I and Meiosis II. 4. compare meiosis and mitosis 5. Reduction division (meiosis I) halves the chromosome number from diploid into haploid. 6. Equational division (meiosis II) mitotically divides each of the two cells from meiosis I, yielding four haploid cells. 7. Chromosome number is halved because there are two cell divisions, but only one DNA replication. 8. Crossing over (occurring during prophase I) and independent assortment (due to the random alignment of homologous chromosomes on the equator during metaphase I) generate genetic diversity. 9. For 23 pairs of chromosomes, over 8 million combinations are possible. 10. Over 70 trillion combinations are possible when a sperm fertilizes an egg. Multiples 1. Monozygotic twins (Identical) result from splitting of one fertilized ovum. 2. Dizygotic twins (fraternal) result from two fertilized ova. 3. role of genetics in having twins (lecture) 3.5 Birth Defects The Critical Period 1. The critical period is when a prenatal structure is sensitive to damage by a faulty gene or environmental insult. 2. Most birth defects originate in the embryo stage, and are generally more severe than problems that arise later in pregnancy. 3. Teratogens are chemicals or agents that cause birth defects (i.e. alcohol, cigarettes, cocaine, certain nutrients, malnutrition, occupational hazards, and infectious agents such as HIV, rubella (German measles), herpes simplex and hepatitis) to offspring from affected ova and sperm 13.1 Portrait of a Chromosome 1. Cytogenetics is the study of chromosome abnormalities and associated effects on health or other traits. 2. Excess or deficient genetic material can cause medical syndromes or damage prenatal development. 3. Chromosomes consist of DNA and proteins. Staining reveals dark regions termed heterochromatin and lighter areas called euchromatin. Euchromatin consists of genes encoding proteins while heterochromatin is mainly satellite sequences. Required Parts: Telomeres and Centromeres 1. Telomeres consist of repeat sequences and protect chromosome tips. 2. A centromere is a constricted site where spindle fibers attach during cell division. 3. Centromeres are regions of repeated DNA bound to centromere-associated proteins. 4. Origins of replication are needed for DNA replication (synthesis) Karyotypes Chart Chromosomes 1. Karyotypes are charts that display chromosomes in size order. 2. Chromosomes are numbered from largest to smallest, 1 through 22, plus X and Y. 3. Chromosomes are distinguished by size, centromere location, differential staining, and DNA probes. 4. The short arm of a chromosome is called the "p" arm and the long arm is designated "q." 6. Translocations result in exchanges of material between two chromosomes. 7. Some cancers arise from translocations. 13.2 Visualizing Chromosomes Obtaining Cells for Chromosome Study 1. Any cell with a nucleus can be used to obtain chromosomes to prepare a karyotype. 2. Fetal karyotypes are constructed from cells obtained by amniocentesis, chorionic villus sampling, and by fetal cell sorting from maternal blood. 3. Fetal karyotypes are prepared for patients with advanced maternal age, repeated miscarriages, and increased risk of a chromosomal anomaly as indicated by a maternal serum marker test or family history. Preparing Cells for Chromosome Observation 1. To obtain chromosomes for karyotyping, cells are halted in metaphase, broken open on a glass slide, and the chromosomes spread over the surface. 2. Traditionally, chromosomes were stained, identified, and arranged in order of size and centromere location. 3. Newer, fluorescent in situ hybridization (FISH) techniques use chromosome specific probes and fluorescent dyes to "paint" chromosomes and create karyotypes. 4. Chromosomal shorthand describes the total number of chromosomes, types of sex chromosomes, and any aberrations present. 13.3 Abnormal Chromosome Number Polyploidy 1. Polyploid cells have extra chromosome sets and are designated by the number of complete sets they contain ? triploid, tetraploid, etc. 2. They may result from fertilization of an oocyte by two sperm or one sperm fertilizing a diploid oocyte. 3. Polyploidy is tolerated in plants, but is a common cause of spontaneous abortion in humans. Aneuploidy 1. Aneuploidy refers to the loss or gain of individual chromosomes. A euploid cell has a normal chromosome number (46). 2. Individuals with trisomies are more likely to survive than those with monosomies. 3. Sex chromosome aneuploidy is less severe than autosomal aneuploidy. 4. This condition most often results from meiotic nondisjunction. 5. The most common autosomal aneuploids seen in newborns is trisomies 21 (Down syndrome). 6. Sex chromosome aneuploids include XO (Turner syndrome), triplo-X females, XXY males (Klinefelter syndrome), and XYY males. 13.4 Abnormal Chromosome Structure Deletions and Duplications 1. Deletions and duplications can result when translocations or inversions disrupt pairing of chromosomes in meiosis. 2. Many microduplications and microdeletions are too small to be detected by traditional karyotyping techniques but have important implications for health. Translocations 1. In a Robertsonian translocation, the two long arms of nonhomologous chromosomes fuse, creating one large translocation chromosome. The short arms are lost. 2. In a reciprocal translocation, two nonhomologous chromosomes exchange parts. In an insertional translocation, genetic material is deleted from one chromosome and inserted into another. 3. A translocation that deletes, duplicates, or disrupts a gene can harm health. 4. Translocation carriers may have a normal phenotype but may have affected children due to unbalanced gametes. Inversions 1. Inversions result when part of a chromosome flips, and may affect health. Isochromosomes and Ring Chromosomes 1. An isochromosome has two identical arms and therefore introduces duplications and deletions. 2. Isochromosomes arise in meiosis when the centromere splits in the wrong plane. 3. Ring chromosomes arise when telomeres are lost, leaving sticky ends that close and form rings. 4. Ring chromosomes can produce symptoms when they result in additional genetic material 18.1 Cancer is Genetic, But Usually Not Inherited 1. The term tumor is used for abnormal cell growth that does not invade surrounding tissue. 2. Cancer, or a malignant tumor, spreads locally and usually also metastasizes to distant sites. 3. Carcinogens, most of which are mutagens, are cancer producing agents. 4. The search for cancer genes in families has given way to a genomic approach to identifying oncogenes and anti-oncogenes. 5. More than 100 oncogenes and 30 tumor suppressor genes have been identified. 6. DNA microarrays can be used to identify and distinguish different types of tumors. Loss of Cell Cycle Control 1. Cancer is caused by a loss of cell division control. 2. Genes involved in the onset and progression of cancer include those encoding growth factors, transcription factors, DNA repair genes, and telomerase. Inherited Versus Sporadic Cancer 1. Several mutations may contribute to the development of cancer. 2. Most cancers are sporadic and therefore, the causative mutation occurs in cells of the affected tissue. 3. Cancer may develop when an environmental trigger causes mutations in a somatic cell or when a somatic mutation compounds an inherited susceptibility. 18.2 Characteristics of Cancer Cells 1. Cancer cells do not respond to normal cell cycle control signals and as a result they grow vigorously and continuously. 2. The cancer phenotype is heritable and transmitted to daughter cells. 3. A cancer cell differs from normal cells in that it is transplantable (can grow in a susceptible animal), dedifferentiated (less specialized), lacks contact inhibition (pile up in culture), and can invade healthy tissue or metastasize to distant sites, can cause adjacent angiogenesis (new blood vessel formation). 18.3 Origins of Cancer Cells 1. Cancer cells have a phenotype that is more specialized than stem cells but less differentiated than normal tissue. 2. This may result from dedifferentiation of a normal cell or the proliferation of cancer stem cells. 18.4 Cancer Genes: caretakers, gatekeepers Oncogenes 1. Many genes that normally control the cell cycle are proto-oncogenes. 2. Proto-oncogenes are transformed into oncogenes by genetic changes that increase their expression or alter the biological activity of their protein product : gain of function. Know mechanisms how this may occur including fusion proteins (leukemias) Tumor Suppressors 1. Tumor suppressor genes down regulate cell growth. 2. Deletions of tumor-suppressor genes or other mutations that result in loss of function may lead to cancer. 3. Loss of tumor-suppressor function allows cells to ignore normal constraints on cell division. 4. The RB, p53, and BRCA1 genes are examples of tumor suppressors. 18.5 A Series of Genetic Changes Causes Some Cancers A Rapidly Growing Brain Tumor 1. Astrocytoma and FAP are two cancers that require several mutations to develop. Colon Cancer 1. FAP begins in early childhood with precancerous growths called polyps. 2. An autosomal dominant pattern of inheritance is associated with FAP and it occurs with a frequency of one in 5000 people in the United States. 3. A dominant mutation in the APC gene on chromosome 5 is the first step in the multi-step model for FAP colon cancer. 4. Subsequent mutations cause the transformation of the polyp into a tumor. 18.6 Environmental Causes of Cancer 1. Epidemiological studies are used to identify risk factors in a population; know 3 types of studies. 2. Many environmental carcinogens have been identified along with factors that lower the risk of cancer. Smoking and excess exposure to the sun are linked with increased risk of cancer. 3. Avoiding fats along with eating more fruits, vegetables, and whole grain cereals is associated with a lower cancer risk. 18.7 Evolving Cancer Diagnosis and Treatment 1. Treatments for cancer target the characteristics of cancer cells. 2. Surgery removes tumors. Chemotherapy and radiation nonselectively destroy rapidly dividing cells. 3. Newer treatments target cancer cell characteristics: receptors on cancer cells, block telomerase, trigger redifferentiation, or attack a tumor's blood supply. 4. DNA microarrays and human genome data are being used to diagnose and manage cancer. 4.1 Following the Inheritance of One Gene-Segregation Mendel the Man 1. Born in what is now the Czeck Republic. 2. Grew up in an agricultural environment. 3. Became a priest-teacher at a local monastery. 5. Carried out "hybridization" experiments with the common garden pea. 6. Mendel's hypotheses became the laws of inheritance in modern genetics. Mendel's Experiments 1. Chose to work with the common garden pea. 2. Monohybrid cross: Hybrid cross involving a single trait with two expressions (i.e. plant height: short vs. tall) 3. Results of a monohybrid cross demonstrates dominant vs. recessive behavior and the law of segregation (i.e. tall pea plants could produce short offspring). 4. Mendel's "elementen" are what we call genes (or alleles). Terms and Tools to Follow Segregating Genes 1. A homozygous individual possesses two identical alleles (i.e. TT or tt). A heterozygous individual possesses two different alleles (i.e. Tt). 2. Phenotype is the outward expression of a trait (i.e. tall vs. short; blue eyes vs. brown eyes). 3. Genotype is the actual genetic makeup of the individual (i.e. TT, Tt, tt). 4. Wild type refers to the most common form. A mutant is a variant that has undergone a mutation (change in the DNA). 5. The physical nature of meiosis (chromosome behavior) explains the law of segregation. The law of segregation states that inherited "characters" (alleles) separate during meiosis, so that each offspring receives one copy of each allele from each parent. 6. Punnett squares are a convenient method for diagramming a genetic cross. Inspection of the square gives you the genotypic and phenotypic results and ratios. 7. The genotypic ratio for a monohybrid cross is 1:2:1, and the phenotypic ratio is 3:1. 8. A test cross reveals the presence of recessive genes in an individual with an unknown genotype by crossing them with an individual homozygous recessive for the genes in question. 4.2 Single-gene Inheritance in Humans Modes of Inheritance 1. Modes of inheritance are the rules explaining the common patterns of inheritance. 2. A Mendelian trait is caused by a single gene. 3. Traits can be dominant or recessive and recur in a predictable pattern in subsequent generations. 4. Autosomal Dominant Inheritance: Autosomal dominant traits do not generally skip generations and can affect both sexes. 5. Autosomal Recessive Inheritance: Autosomal recessive traits can skip generations and can affect both sexes. 6. Blood relatives that have children together have a much higher risk of having a child with a rare recessive disorder. 7. Punnett squares apply Mendel's first law to predict recurrence risks for inherited disorders or traits. 8. A Mendelian trait applies anew to each child. On the Meaning of Dominance and Recessiveness 1. At the biochemical level, recessive disorders often result from alleles that cause a loss of function or loss of a normal protein. 2. Dominant disorders can result from production of an abnormal protein that interferes with the function of a normal protein or imparts a gain of function. 4.3 Following the Inheritance of Two Genes-Independent Assortment 1. Mendel's law of independent assortment considers genes transmitted on different chromosomes. 2. The phenotypic ratio of 9:3:3:1 of a dihybrid cross indicates that a gene on one chromosome does not influence transmission of a gene on a different chromosome. 3. In meiosis, random assortment of maternally and paternally derived chromosomes results in gametes that have different combinations of genes. 4. Punnett squares and probability are used to predict recurrence of more than one trait. 4.4 Pedigree Analysis 1. Pedigree charts depict family relationships and transmission of inherited traits. 2. Squares represent males and circles represent females. 3. Horizontal lines indicate parents, vertical lines show generations, and elevated horizontal lines depict siblings. 4. Symbols for heterozygotes (carriers) are half-shaded, and for individuals with a particular phenotype, completely shaded. Pedigrees Then and Now 1. Pedigrees have been in use since antiquity. 2. They have been used throughout history to show family relationships, particularly royal bloodlines. Pedigrees Display Mendel's Laws 1. Pedigrees can reveal mode of inheritance, and can suggest molecular information, carrier status, and input from other genes and the environment. 2. Interpretation of pedigrees can be inconclusive when more than one mode of inheritance can explain the pattern seen.
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