HUMAN GENETICS - BIO 442
SYLLABUS
Instructor: Carol D. Guze, Professor of Biology and Ph.D. Medical Geneticist, ABMG
Office: NSM E-116 Phone: Email:
Web Site: http://
Office Hours: Mon 1-5 p.m. Class Time: Mon Wed 5:30-6:45 p.m. Classroom: NSM B122
Course Prerequisites: Upper division cell biology and genetics.
Textbooks: Genetics in Medicine 6th Edition,by Nussbaum, McInnes & Willard and Color Atlas of Genetics, 2nd edition by Passarge.
T = Thompson P = Passarge
COURSE TOPICS
The Genome, DNA, Chromosomes and Gene Structure P 20-77, 80-83, 170-183 T Ch 1,2,3,4
Cell Cycle, Mitosis and Meiosis and Non Disjunction P 112-121 T Ch 2, 9
Karyotyping Cells and tissues used and identification techniques: banding methods, high resolution banding and fluorescence in situ hybridization (FISH) and microdeletions P 184-7, 122-3, 190-5 T Ch 4, 9
Chromosome Abnormalities: Autosomes and Sex Chromosomes P 188-202, 314, 334-5, 400-5 T Ch 9, 10
Changes in number
Non disjunction and changes in number (pre and post zygotic); polyploidy, aneuploidy, spontaneous abortions (SABs), advanced maternal age (AMA)
Changes in structure
Inherited and de novo structural changes; translocations, deletions and inversions, isochromosomes; normal variants
Genetic disorders associated with chromosome breakage
Sex determination: P 386-393; T Ch 10
X and Y chromosomes, pseudoautosomal region, X inactivation, SRY/TDF, DSS (DAX), SOX 9, abnormal sexual development
(CAH, AI, 5 alpha reductase deficiency, Müllerian agenesis, persistence of Müllerian ducts)
Prenatal Diagnosis and Genetic Counseling: T Ch 18, 19
Mutations: Somatic and Germinal, Single Gene and Chromosomal P 68-73, 76-7, 316-35 T Ch 9, 16
Gene mutations, cancer, gonadal mosaicism and sporadics, polymorphisms, allelic and locus heterogeneity, VNTRs, STRs
Patterns of Inheritance: See center section of Clinical Case Studies and P 124-43, 378, 394-7, 396, 398 T Ch 5, 9,12,15
Mendelian Genetics P 132-43, 378 T Ch 5
AD, AR, XD, XR, CD: Patterns of Mendelian inheritance
Allelic and locus heterogeneity (complementation tests)
Variable expressivity and incomplete penetrance
Multifactorial inheritance P 152 T Ch 15
Height, skin color, NTD, cleft lip/cleft palate, common
Non Traditional Inheritance P 78, 124-31, 314, 394-8, 404 T Ch 5, 9, 12
Microdeletion Syndromes (contiguous gene syndromes, segmental aneusomy)
Mosaicism: Somatic, gonadal, placental
Imprinting: Moles and teratomas, mules and hinnies, Prader Willi and Angelman Syndromes (PWS/AS), uniparental disomy (UPD), heterodisomy and isodisomy
Trinucleotide Repeat Syndromes: Fragile X, Huntington, Myotonic dystrophy, Friedrich's ataxia, Kennedy Disease, etc.
Mitochondrial Inheritance: Nuclear and mitochondrial DNA,MERFF, LHON, etc.
Clinical Genetic Disorders: P 276, 284, 316-7, 334-49, 352-61, 380-2, 384-5 T Ch 11, 12 Hemoglobinopathies, blood types, enzyme deficiencies, lysosomal storage diseases, peroxisomal diseases, CF, NF1, OI, DMD/BMD, DeLange, TSD, PKU, FH, galactosemia, Marfan, achondroplasia, FGFRs, skeletal disorders, hemochromatosis, etc.
Newborn and Carrier Screening and Gene Therapy: T Ch 13, 14, 20
Teratogens and Development: T Ch 17
Phenocopies, maternal diabetes, Fetal Alcohol Syndrome (FAS/FAE), Seizure medications, viruses, heat,
Linkage and Chromosome Mapping: P 144 T Ch 6, 8
DNA Profiling: T Ch 6, 7
Paternity and identity testing and forensics
Quantitative Genetics: P 158-9 T Ch 7 Probability, Hardy-Weinberg and gene frequencies, risk assessment, Bayes Theorem, gene mapping (LOD scores)
COURSE GOALS AND OBJECTIVES
At the end of this course you should know about
| EVALUATION | POINTS | Approximate DATE |
| Weekly quizzes | 100 | Weekly |
| Mitosis and Meiosis diagram | 20 | February 20 (Wednesday) |
| Chromosome Abnormality Paper | 50 | March 20 (Wednesday) |
| Midterm exam | 150 | April 3 (Wednesday) |
| Pedigree and Analysis | 30 | April 29 (Monday) |
| Genetic Disorder Paper | 50 | May 15 (Wednesday) |
| Poster (Either chromosome or single gene disorder) | bonus up to 30 | May 15 |
| Final exam | 150 | May 22 |
| Total points | 550 |
Occasionally extra points can be earned by attending specific lectures or workshops. Up to 20 extra points can be earned.
GRADES:
| A 100-92% | B+ 89-87 | C + 79-77 | D+ 69-66 |
| A- 91-90 | B 86-83 | C 76-73 | D 65-60 |
| B- 82-80 | C- 72-70 | F < 60 |
QUIZZES. In general, quizzes will be given weekly. The total points will be equal to one midterm but the percentage correct will be normalized using the highest percent earned.
DISCUSSION SECTIONS. The teaching assistants will be arranging study sessions. I will also post the regular meetings on my Web site once they have been decided upon.
ASSIGNMENTS
Grading on assignments and test essay questions is based on your command and control of the subject matter, the organization, clarity, accuracy, your ability to express yourself clearly in standard written English, and whether you have appropriately written at the level of your audience. Your audience is a biology major with the prerequisites to this course.
Unless the information you include is yours or common knowledge, cite the sources. All references used should appear alphabetically at the end of your papers and should be written in standard journal format. Use the format that is used by your textbook when it lists references. Number the references and place the number of the reference within the text of your paper. When you cite information from a book give the page number(s) from which the information came. Ask me or go to a biological journal to see how journal articles include references within the text. For example, do not put the reference at the end of the paragraph, instead say, "Vickers (1999) found that........." or after a statement refer to the source. READ a journal article to see how it is done.
Style manuals can show you how to cite non standard references such as those from the Internet. Be cautious in the use of Internet sources. Anyone can say anything they want and there is no peer review! The correct way to cite Internet sources is described in the newer Style Manuals. The basic entry should include the following elements: Author. The author's name, last name first. Date of publication. The year of Internet publication or the year of the most recent update in parentheses followed by a period. Title. The title of the document or subject line of the message, in quotation marks. End with a period inside the quotation marks. Address. The URL, in angle brackets, or other retrieval information. Date of access. In parentheses, followed by a period: An example: Shade, LR (1993). Gender issues in computer networking. <http://www.mit.edu:8001/people/sorokin/women/lrs.html> (1996, May 28).
The correct way to cite an OMIM reference is described in detail under "Citing OMIM in the literature." You can get there by going to the OMIM home page. The title of the page is included as seen in the following example: Online Mendelian Inheritance in Man, OMIM. TM. Johns Hopkins University, Baltimore, MD. MIM Number:130050:1996. Ehlers-Danlos syndrome, Type IV, autosomal dominant. World Wide Web URL: http://www.ncbi.nlm.nih.gov/omim/
Also, be sure you read the University Catalog's statement on Academic Integrity and Plagiarism to clearly understand what is meant by original work. Plagiarism will result in a grade of F in the course. Rewording is still plagiarism. Merely stating the source of material you have copied is not sufficient. If you want to quote material directly, single space the information and indent on both margins. Keep this to a minimum.
BEFORE you begin to compose or write, read the material you have collected many times so you really understand it. Then think it over and talk it over with your family, friends and/or colleagues to be certain you can convey the information to them. After you have thought the information over and distilled it to its essence, organize it in your head in a logical sequence. Then make a rough draft or layout. Your audience is undergraduate biology majors. Most of all, remember to KEEP IT SIMPLE. Do not use complex words or sentences when simple ones will do. Select only relevant information. Do not overwrite and do not repeat yourself. Do not have run on sentences with too many ideas. Remember to break the information down into paragraphs and that a paragraph has a central idea to convey with supporting evidence. Use headers to direct the readers attention to each section of information. Some examples are: Description of the Syndrome (Phenotype); Etiology (Genetic Basis, Pattern of Inheritance, Age of onset, Variable Expressivity, Incomplete Penetrance, etc.); Genetic Testing (Prenatal Diagnosis, Newborn Screening, Carrier Testing); Treatment; etc. The headings depend on the subject and the type of disorder described.
Check your spelling. Use your computer's spell check and a dictionary. Read what you have written and revise it. You should have classmates read your paper critically. Never turn in a paper or project that has not been though more than one draft.
Unless prearranged, all assignments must be turned in at the time specified and all quizzes and exams must be taken at the time announced. Special arrangements for a late paper or project or a make-up quiz or exam may be made if you contact me well in advance of the due date or time of the quiz or exam. Grades for assignments will be reduced by 20% for each day it is late.
Except for the poster, THE AUDIENCE FOR ALL ASSIGNMENTS IS A BIOLOGY MAJOR WHO HAS THE PREREQUISITES FOR THIS COURSE. That means you must thoroughly understand the material you include and that the contents be unambiguous and accurate. Know more than you write about. The audience for the poster, however, is the people that will be looking at them in the NSM hallways so they should be written as for a newspaper...simply.
1. Meiosis and Mitosis Homework. Draw a cell 2n = 6 in metaphase of mitosis and in metaphase I of meiosis. The pairs of chromosomes are telocentric, metacentric and acrocentric. Distinguish between the maternally and paternally derived chromosomes by using two different colors. Show one pair of the meiotic chromosomes with a completed cross over. Label all parts of the drawing, including the cell membrane, centrioles, spindle microtubules, each type of chromosome, chromatids, homologous chromosomes, etc.
2. Pedigree. Construct a pedigree of your family or the family of a friend which includes a single inherited trait. You must use standard pedigree notations and symbols. Analysis of a trait not found in the literature (this would be unusual) should include an explanation of the most probable mode of inheritance and how other patterns can be ruled out or would be less probable. This analysis should be based SOLELY on the pedigree and not from prior knowledge of how the trait is actually inherited.
After you have selected a trait or disorder found in this family (a normal trait is fine), 1. describe the trait (phenotype), search OMIM to see if there is a similar entry, 2. explain how your family/pedigree does or doesn't support the pattern(s) of inheritance given, and 3. explain what patterns of inheritance can or cannot be excluded based solely on your pedigree and how you reached that conclusion. Be sure to refer to individuals in your pedigree by generation and number, e.g. III-1 when using them as examples of how to rule out a particular pattern of inheritance. The title should include the name of the trait and should be at the top of the pedigree and the accompanying analysis paper.
When analyzing a single family pedigree, remember that the generalizations made about inheritance patterns may not apply. The pedigree should be drawn with standard symbols and a legend should explain their use. Legends must be understandable by anyone. Generations and individuals should be appropriately labeled and referred to in your discussion. If you do not know a person's phenotype you must use a "?" in their symbol, because a blank symbol means they definitely do not have the trait studied. If a person does not have children use the appropriate symbol. If the trait is not usually present at birth and has a later age of onset, you must indicate the ages on the pedigree of those not affected. Spouses, if not directly related, can be left out if they are not of interest.
The pedigree is best drawn by hand but if you prefer, you may use your computer. Describe the trait in some detail, use drawings or illustrations to make it clear. Define what "affected" and "unaffected" means in your pedigree. Indicate genotype when appropriate. Discuss age of onset, any evidence of variable expressivity and/or incomplete penetrance.
Go to OMIM or other recent sources to find out what patterns of inheritance have been found in families with the same trait. Explain how your pedigree is or is not consistent with the pattern(s) in the literature. Go through each pattern of inheritance (AD, XD, CD, AR, XR, Y and mitochondrial) and explain how you can or cannot rule out each pattern. Either start or end your analysis with what pattern of inheritance best explains your pedigree.
Remember that one does not find every possible feature of any one pattern in one pedigree. For example, an AD disorder will not always result in 50% of the children of an affected person being affected. Nor can you rule out AR because the trait appears in every generation or because there is no consanguinity. When analyzing pedigrees, it is best to identify AD by the fact that those affected have an affected parent, that both males and females are affected and both can pass the gene on to their offspring. But even an AD can be sex limited and, therefore, non penetrant in one sex so be careful.
Grading criteria are:
3. Genetic Conditions. Each person writes her/his own paper but you should help one another by proofreading and editing. The paper should be no more than 4-6 double spaced pages.
The first paper due will be on a chromosome abnormality and the second on a single gene defect (see lists below). After reading about the disorder (and related cases) in your textbooks, go to OMIM for the single gene disorders (OMIM will have information on microdeletion syndromes but has little or nothing on the the chromosome aneuploidies) and elsewhere to get more background. You would be well advised to ask me and the teaching assistants to guide you.
Chromosome Abnormalities
Choose one of the common autosomal trisomies (21, 18, 13) or sex chromosome abnormalities (Turner, Triple X, Klinefelter, XXY, Cri du Chat, Wolff-Hirschhorn). Start the paper with a general description of the disorder (include the original description in the literature if you can find it), move next to the genetic basis and its origin, include testing, and treatment (if any). Depending on the subject, you may have additional sections of your paper. It should be limited to four double spaced pages. This may require several rewrites!!
Single Gene Disorders
Examples to select from are NF 1, Huntington, Tay-Sachs, Phenylketonuria, Osteogenesis Imperfecta, Sickle Cell Disease; Duchenne/Becker Muscular Dystrophy, Cystic Fibrosis, Marfans, Androgen Insensitivity, Prader Willi/Angelman, Myotonic Dystrophy, Fragile X. This paper should begin with a general description of the disorder and pattern of inheritance. Then move into the genetic basis, testing and treatments.
After reading your textbook on the disorder go to Online Mendelian Inheritance is Man http://www.ncbi.nlm.nih.gov/Omim . OMIM is a good place to begin your research for any single gene disorder, however, there are many others sources. Gene Tests is an excellent source: http://www.genetests.org You can also go to PubMed to look for current articles relating to your disorder. Paper usually contain an encapsulated review of the disorder within the introduction to the paper so it is a good idea to read the paper, not just the abstract which is all that is given on Medine. Medline (PubMed) can be accessed from the same Web address as OMIM (PubMed) by substituting "PubMed" for "OMIM." You may decide to spend one or two days in the Biomed Library at UCLA to look at textbooks in human genetics and articles of interest that you have found on PubMed. Incidentally, OMIM does not have the chromosome disorders.
In your paper (and on a poster) you will need to give a clinical description (phenotype) of the disorder or condition. If appropriate, you may wish to include a "typical" pedigree of the single gene disorder if one is given in the literature and it is interesting.. If it is a disorder involving a single gene, include mention of any clinical variability; the mode(s) of inheritance; any genetic heterogeneity (locus and/or allelic); what is known about the gene(s) involved including the chromosomal locus/loci; the function of the gene(s) at the cellular level; molecular or other detection methods useful for prenatal or carrier detection. For the single gene disorder paper, you should also include information from a recent paper concerning this condition.
Your grade will be based on content, accuracy, organization, command and clarity. Each paper should be divided into sections with appropriate subheadings to lead the reader through the topics/issues addressed.
4. Poster. You will prepare a poster on either the chromosome or single gene disorder. The poster should be simple and readable for someone casually walking by in the NSM hallway. Keep it simple and interesting. Do not try to put everything on the poster that you have in your paper!