Biology 442 - Human Genetics
Lecture Syllabus



Carol D. Guzé, Professor of Biology and Ph.D. Medical Geneticist, ABMG


Course Prerequisites :


Upper division cell biology and genetics


The Bio 442 Class


Dr. Carol Guzé, Professor


Genetics in Medicine 6th Edition, by Nussbaum, McInnes & Willard and Color Atlas of Genetics, 2nd edition by Passarge.
T = Thompson, P = Passarge



Chapters/Pages in Text



The The Genome, DNA, Chromosomes and Gene Structure


P 20-77, 80-83, 170-183
T Ch 1,2,3,4



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

Cell Cycle, Mitosis and Meiosis and Non Disjunction


P 112-121 T Ch 2, 9





P 184-7, 122-3, 190-5
T Ch 4, 9


Cells and tissues used and identification techniques: banding methods, high resolution banding and fluorescence in situ hybridization (FISH) and microdeletion

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



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

Quantitative Genetics


P 158-9
T Ch 7


Probability, Hardy-Weinberg and gene frequencies, risk assessment, Bayes Theorem, gene mapping (LOD scores)

Multifactorial inheritance


P 152
T Ch 15


Height, skin color, NTD, cleft lip/cleft palate, common diseases

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, Friederichs' 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, De Lange, TSD, PKU, FH, galactosemia, Marfan, achondroplasia, FGFR's, skeletal disorders, hemochromatosis, etc.

Newborn and Carrier Screening and Gene Therapy


T Ch 13, 14, 20


PKU, galactosemia, sickle cell, hypothyroidism; Tay-Sachs, hemoglobinopathies, cystic fibrosis. Enzyme replacement and gene therapy.

Teratogens and Development


T Ch 17


Phenocopies, maternal diabetes, Fetal Alcohol Syndrome (FAS/FAE), Seizure medications, viruses, hyperthermia

Linkage and Chromosome Mapping


P 144
T Ch 6, 8


Techniques past and present to locate genes on chromosomes

DNA Profiling


T Ch 6, 7


Paternity and identity testing and forensics

Course Objectives

At the end of this course you should know about:

  • Chromosome, genome structure and functions.
  • Chromosome abnormalities: how they arise, risks of occurrence and their detection
  • Prenatal tests and screening for genetic defects
  • Non-traditional inheritance: mosaicism, microdeletion syndromes, uniparental disomy, genomic imprinting, trinucleotide repeats, mitochondrial disorders
  • The events in sexual development and some genetic abnormalities
  • Several common single gene disorders, their cause, diagnosis, and recurrence risks
  • How and where new mutations arise and the possible consequences: somatic and germinal
  • Common multifactorial traits and recurrence risks
  • Common teratogens and the embryopathies they produce
  • The use of DNA fingerprinting in identification of individuals
  • The current status of prenatal testing, newborn screening, carrier testing, genetic counseling
  • How to construct a pedigree and analyze it.


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.

Pedigree and Analysis

1. Construct a pedigree of your family or the family of a friend for a single inherited trait. It can be a normal human variation (e.g., attached ear lobes, mid digital hair, tongue curling, bent little finger, dimples, cleft chin, widow's peak, big toe or index finger length) or a disorder. Use standard pedigree notations and symbols and provide a legend to explain the symbols used. Put an arrow pointing to the proband (you, if you are in the pedigree). Generations and individuals should be appropriately labeled so they can be referred to in your analysis. If you do not know a person's phenotype you must use a "?" in their box or circle, 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 relevant, may be left out. The pedigree is best drawn by hand but if you prefer, you may use your computer.

2. Describe the trait in some detail, drawings or illustrations may be useful. Define what "affected" and "unaffected" means in your pedigree. Indicate genotype when appropriate. Remember that a person with a dominant trait may have to be "D_" unless you are certain of the second allele. Discuss age of onset, any evidence of variable expressivity and/or incomplete penetrance (not all traits show these variations). Go to OMIM or other recent sources for descriptions of the trait and to find out what patterns of inheritance have been found in families with the same trait. The OMIM search page explains how to reference OMIM articles.

3. Analyze your pedigree by going through each mode of inheritance (AD, AR, XD, XR, and Y) explaining how your pedigree is consistent or not consistent with each. For those you cannot rule out, explain which is the most probable. If the mode of inheritance is known, explain how your pedigree is consistent with the known mode of inheritance. 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.

Explain how your pedigree is or is not consistent with the various pattern(s). Go through each pattern of inheritance (AD, XD, CD, AR, XR, Y, multifactorial 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 and why. If the mode of inheritance is known, you should then show how your family pedigree is consistent with the known mode.

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. A common AR trait can show a vertical pattern. 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 for the pedigree analysis are
  • Is the paper organized well? Is the paragraphing done properly? Does each paragraph have a topic sentence followed by supporting data and a closing? Are there headings and are they meaningful? Is there redundancy?
  • Is the trait clearly described? Is the age of onset clearly stated? Is there variable expressivity and/or incomplete penetrance?
  • Is there a clear and accurate legend?
  • Are the symbols used correctly? Are unknown phenotypes indicated?
  • Are the generations and individuals labeled correctly and referred to correctly in the accompanying analysis?
  • Is the inheritance pattern known? If so, does your family fit? Explain. If it is not known, what is the most likely pattern of inheritance and why? State your reasons for choosing the pattern, support the choice logically and correctly. If available, point out matings where both are "affected" and/or both are "not affected" to support your choice
  • Are all other patterns of inheritance discussed and ruled in or out using sound arguments?
  • Are the literature sources correctly identified and cited (using standard journal or OMIM format)?
  • Do you show a clear understanding of how to analyze the pedigree of a single (large or multi generational) family to confirm or suggest the mode of inheritance?

    Approximate distribution of assigned points on pedigree assignment:
    (10) Explanation/description of the trait along with known mode of inheritance or most probable mode
    (10) Title, pedigree drawn accurately (indicating known and unknown phenotypes) with a clear and appropriate legend
    (10) Analysis of the pedigree with a discussion of possible mode(s) of inheritance using specific individuals to illustrate.

Genetic Disorders or 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, Marfan, 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 . OMIM is a good place to begin your research for any single gene disorder. Gene Tests is the most complete source: after you enter the web site you click on Gene Reviews in the top banner. When it comes up put the disorder you are interested in into the box.

You can also go to PubMed to look for current articles relating to your disorder. Journal articles usually contain an encapsulated review of the disorder within the introduction of the paper so it is a good idea to read the paper, not just the abstract which is all that is given on Medline. 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 most of the chromosome disorders.

In your paper 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 (within the last year) concerning this condition.

Your grade will be based on content, accuracy, organization, command and clarity. Each paper can be divided into sections with appropriate subheadings to lead the reader through the topics/issues addressed. However, the unit of organization remains the paragraph. Each paragraph should have a topic sentence with supporting information following.

In ALL writing assignments remember the following:

• First read the background material several times then think about what you learned.
• Organize your ideas in your head or on paper before writing
• Your audience is someone eligible for this course but who has not taken it.
• Select appropriate and logical headings to guide the reader
• Write in meaningful paragraphs. Paragraphs have a topic sentence, followed by supporting statements. Do not ramble on, do not put unrelated ideas together in the same paragraph.
• Write in your own words.
• Keep it simple and write about what you learned from what you read.
• Avoid repetition.
• Do not copy material directly from the references unless it is statistical. Avoid copying tables. You may summarize or paraphrase but anything else is plagiarism. (See the University Catalog for the definition of plagiarism)
• Only primary sources (no secondary sources) go into your reference list. That means you have read each reference cited. Number the references in alphabetical order and insert the appropriate number in the text when you want to acknowledge the source.
• Use caution with Internet sources other than OMIM and Gene Tests since anyone can put anything on the Web.
• Turn in copies of all references used for your paper. Use your textbooks’ style of citing references. OMIM tells you how to cite them. Internet sources are cited as described earlier in the syllabus.
• Do not reference well known facts.
• Read your paper to yourself before you hand it in.

Approximate distribution of assigned points on chromosome and single gene assignment:
(10) Organization of the information. Proper use of headings appearing in a logical order. Choice of appropriate references approriately referred to in the paper. Use of standard format for listing references.
(10) Description of the disorder (clinical presentation), description of the inheritance pattern, the gene(s) involved. If present a discussion of variable expressivity and incomplete penetrance, locus and allelic heterogeneity, sex influence.
(10) Command of the material as seen in the ability to express yourself in your own words.

Academic Integrity

It is essential that you read those pages in the University Catalog explaining, Academic Integrity: Its Place in the University Community.
It explains academic integrity and the nature of academic dishonesty. It also describes the role of the faculty and student in promoting academic integrity.
In addition it explains the University policies and procedures for dealing with questions of academic dishonesty.