University of Oregon

 

Psychology 607 Seminar: GENES AND INDIVIDUAL DIFFERENCES

Spring 2001

 

Leader/Instructor: Gerard Saucier, Ph.D.

Office: 312 Straub

Internet: gsaucier@oregon.uoregon.edu Phone: 346-4927 with voice mail

Office Hours: Tuesdays 3-3:30 pm, Wednesdays 1-2:30 pm, or by appointment

Readings: Available from instructor, except for readings from the following text which includes some of the readings for sessions 2-5, and which is available on 24-hour reserve at the Science Library:

Cummings, M. R. (2000). Human heredity (5th ed.). Pacific Grove, CA: Brooks/Cole.

 

Seminar Objectives (or, what's the purpose of this seminar?)

 

Genetics has become an extremely important part of biology, and its place in psychology is also rapidly expanding. Genetics (even human genetics alone) is a huge domain, and no attempt is made to cover it completely in this seminar. The primary goal of this seminar is to help students gain a critical understanding of methodologies used in genetic studies of psychological characteristics in humans, so as to be able to make use of (by first making sense of) this literature. This is a first step, of course, in being able to actually use genetics in research. Along the way, the seminar should provide students with increased understanding of those molecular biological factors that make methodologies of genetic studies distinct from those more familiar in psychology.

 

The emphasis is, however, jointly methodological and substantive. Although the sequence of topics in seminar sessions moves generally from one methodology to another, at each point we will critically review recent work on specific genetic influences, especially influences on psychiatric disorders (e.g., bipolar and schizophrenic disorders, depression, substance abuse), personality, and 'intelligence.' Examples will relate how genes might work on these psychological phenotypes with how they work on other phenotypes like blood types, globins, Huntington's disease, Alzheimer's, and cancer. The seminar stresses psychological characteristics, human genetics, and research methodologies, and thus is not interchangeable with biology offerings in genetics.

 

Requirements of the seminar

 

1. Discussion questions based on readings. You are responsible for turning in sets of discussion questions based on the readings by the beginning of six different class meetings (of the nine after the first session). However, because discussion questions turned in well in advance of the class meeting aid the leader/instructor in preparation, a "discount program" is available. For each two sets of discussion program that you turn in (both) by Friday at high noon of the previous week, you get credit for having turned in three sets. Discussion questions are turned in via e-mail to gsaucier@oregon. Discussion questions, to be worthwhile and to count, should (a) be indicative of your having done the reading and (b) be instances to some degree of critical or insightful thinking. In case you ever develop a "block" about coming up with some, you might consider GS's list of favorite types of questions: Why is this issue important? How are you defining _____? Aren't you assuming _____? Isn't it debatable whether _____? Does the evidence really support the notion that _____? Aren't you leaving out _____? Isn't there a limitation with regard to _____ caused by using that methodology?

 

2. A paper. The topic is up to you. In general, a paper ought to be on how behavioral and/or molecular genetics relates to areas of psychology of interest to the student. The paper may be a literature review, a research proposal, or a conceptual/theoretical piece. First draft is due at noon on Friday, May 18 (7th week of term); the purpose of the first draft is to enable you to get early feedback and suggestions. The final draft is due some four weeks later at the assigned final exam time for the course to the leader/instructor's office (10:15 am - 1 pm, Tuesday June 12). With regard to length of the paper, Gracián wrote in 1647 that "good things, when short, are twice as good." Parsimony -- refined high-quality thinking briefly stated -- is valued, and keeping the text under 10 pages, double-spaced, will be a good idea. Keep in mind that, in general, the best index for gene-related searches is often not PsycLit but rather Medline (PubMed, etc.).

 

3. A summary presentation based on the paper (or at least on early drafts of the paper) during sessions 9 or 10. These presentations will be allotted about 10-15 minutes each (maybe more if the number of seminar participants permits).



It is important that you come to the seminar having read the assigned readings and prepared to discuss them. The readings vary in difficulty; some of them are from an excellent introductory text on human genetics by Michael R. Cummings; students with previous well-imprinted coursework specifically in genetics will probably be able to skip the M. R. Cummings readings.



The only other work involved in the course is a free-form informal essay written during 20 minutes in the last session, summarizing and reflecting on your learning experience in the seminar, for which no advance preparation is necessary.



Overall, work in the seminar is graded on a pass/fail basis. The final grade is based on the following: 20% is based on turning in discussion questions and a generally acceptable level of general in-class contribution, 10% for the initial rough draft, 15% for the presentation, 50% for the final draft of the project, and 5% for the free-form informal essay at the last session. The seminar leader's general scheme for assigning grades from percentage of possible credit is as follows: A 90, B 80, C 67, D 50, F < 50, with pluses or minuses being based on being in either the top or bottom third of the range of percentages for that grade. For graduate students, a D does not confer credit for having completed the course. Converting this into a pass/fail system: You need 2/3 or higher of all possible credit to pass. Anyone in danger of not passing will be discreetly notified and advised as soon as possible in order to maximize desired outcomes.



In a collaborative environment like this seminar, lateness can wreak havoc on everyone involved, and, in terms of final grade, up to 50% of credit for an assignment can be lost, at 10% per calendar day.



Readings and Course Calendar



Session 1: April 3

* Common myths and misconceptions about genetics and gene influences, and problems with various isms that have sprung up concerning genes



Session 2: April 11

* More molar (not quite molecular) approaches I: Chromosomal transmission

Dawkins, R. (1989). The selfish gene (2nd ed.). Oxford: Oxford University Press. (Chapter 3, "Immortal coils", only)

Cummings text (Only chapter 2 and pp. 60-69 of chapter 3)

Migeon, B. R. (1994). X-chromosome inactivation: Molecular mechanisms and genetic consequences. Trends in Genetics, 10, 230-235.

Jobling, M. A., & Tyler-Smith, C. (2000). New uses for haplotypes: The human Y chromosome, disease, and selection. Trends in Genetics, 16, pp. 356-362.



Session 3: April 18

* Molar (not quite molecular) approaches II: Behavior genetics (twin and adoption studies, additive and epistatic influences)

Cummings text, chapters 4 and 5 on pedigree analysis, polygenes and multifactorial inheritance

Bouchard, T. J., Lykken, D. T., McGue, M., Segal, N. L., & Tellegen, A. (1990). Sources of human psychological differences: The Minnesota study of twins reared apart. Science, 250, 223-228.

Rose, R. J. (1995). Genes and human behavior. Annual Review of Psychology, 46, 625-654.

McGue, M., & Bouchard, T. J. (1998). Genetic and environmental influences on human behavioral differences. Annual Review of Neuroscience, 21, 1-24.

Turkheimer, E. (2000). Three laws of behavioral genetics and what they mean. Current Directions in Psychological Science.



Session 4: April 25

* Overview of DNA and of gene expression

Cummings text, chapters 8 and 9: "DNA structure and chromosome organization" and "Gene expression: How proteins are made") and pp. 241-243 of chapter 10 on proteins and metabolic pathways (read further in chapter 10 for relevant examples)

Ostrer, H. (1998). Non-mendelian genetics in humans. New York: Oxford University Press. (Only chapter 2: "The molecular basis of mendelian disease")

Weiss, K. M. (1995). Genetic variation and human disease: Principles and evolutionary approaches. Cambridge, UK: Cambridge University Press. Chapters 1 and 2 (appendix 2.1 is optional).



Session 5: May 2

* DNA technology: DNA fingerprinting, different types of genetic polymorphisms, RFLPs, PCR, and applications to understanding human evolution and human diversity

Cummings text, chapters 12 and 13: "Recombinant DNA technology" and "Applications of recombinant DNA technology"

Kaessmann, H., Wiebe, V., Weiss, G., & Pääbo, S. (2001). Great ape DNA sequences reveal a reduced diversity and an expansion in humans. Nature Genetics, 27, 155-156.

Krings, M., et al. (2000). A view of Neandertal genetic diversity. Nature Genetics, 26, 144-146.

Renfrew, C., Forster, P., & Hurles, M. (2000). The past within us. Nature Genetics, 26, 253-254.

Underhill, P. A., et al. (2000). Y chromosome sequence variation and the history of human populations. Nature Genetics, 26, 358-361.

Pääbo, S. (2001). The human genome and our view of ourselves. Science, 291, 1219-1220.



Session 6: May 9

* Linkage analysis; the experience with the genetics of schizophrenia; newer approaches to searching for major genes

Weiss, K. M. (see above) chapters 7 and 8 (appendix 7.1 is optional)

Plomin, R., & Crabbe, J. (2000). DNA. Psychological Bulletin, 126, 806-828.

Weeks, D. E., & Lathrop, G. M. (1995). Polygenic disease: Methods for mapping complex disease traits. Trends in Genetics, 11, 513-519.

Baron, M. (2001). Genetics of schizophrenia and the new millenium: Progress and pitfalls. American Journal of Human Genetics, 68, 299-312.

Antonarakis, S. E., & McKusick, V. A. (2000). OMIM passes the 1,000 disease-gene mark. Nature Genetics, 25, 11.

Kruglyak, L., & Nickerson, D. A. (2001). Variation is the spice of life. Nature Genetics, 27, 234-236.

Boehnke, M. (2000). A look at linkage disequilibrium. Nature Genetics, 25, 246-247.

Weiss, K. M., & Terwilliger, J. D. (2000). How many diseases does it take to map a gene with SNPs? Nature Genetics, 26, 151-157.

MacGregor, A. J., Snieder, H., Schork, N. J., & Spector, T. D. (2000). Twins: Novel uses to study complex traits and genetic diseases. Trends in Genetics, 16, pp. 131-134.

Eaves, L., & Meyer, J. (1994). Locating human quantitative trait loci: Guidelines for the selection of sibling pairs for genotyping. Behavior Genetics, 24, 443-455.

Freeman, B., Powell, J., Ball, D., Hill, L., Craig, I., & Plomin, R. (1997). DNA by mail: An inexpensive and noninvasive method for collecting DNA samples from widely dispersed populations. Behavior Genetics, 27, 251-257.



Session 7: May 16

* Debate over future methodological directions for studying the genetics of complex behaviors; neuroendocrine genetics

Peltonen, L., & McKusick, V. A. (2001). Dissecting human disease in the postgenomic era. Science, 291, 1224-1229.

Thomson, G. & Esposito, M. S. (1999). The genetics of complex diseases. Trends in Genetics, 15, p. M17-M20.

Risch, N. J. (2000). Searching for genetic determinants in the new millenium. Nature, 405, 847-856.

Weiss, K. M. (see above) chapter 12

Comings, D. E. (1998). Polygenic inheritance and micro/minisatellites. Molecular Psychiatry, 3, 21-31.

Wahlsten, D. (1999). Single-gene influences on brain and behavior. Annual Review of Psychology, 50, 599-624.

Bale, T. L., et al. (2000). Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress. Nature Genetics, 24, 410-414.

Ferguson, J. N., Young, L. J., Hearn, E. F., Matzuk, M. M., Insel, T. R., & Winslow, J. T. (2000). Social amnesia in mice lacking the oxytocin gene. Nature Genetics, 25, 284-288.



Session 8: May 23

* Catecholamines; impulsive and addictive behaviors; population-sampling issues

Shih, J. C., Chen, K., & Ridd, M. J. (1999). Monoamine oxidase: From genes to behavior. Annual Review of Neuroscience, 22, 197-217.

Ebstein, R. P., & Belmaker, R. H. (1997). Saga of an adventure gene: Novelty seeking, substance abuse and the dopamine D4 receptor (D4DR) exon III repeat polymorphism. Molecular Psychiatry, 2, 381-384.

Waldman, I. D., et al. (1998). Association and linkage of the dopamine transporter gene and attention-deficit hyperactivity disorder in children: Heterogeneity owing to diagnostic subtype and severity. American Journal of Human Genetics, 63, 1767-1776.

Kang, A. M., Palmatier, M. A., & Kidd, K. K. (1999). Global variation of a 40-bp VNTR in the 3'-untranslated region of the dopamine transporter gene (SLC6A3). Biological Psychiatry, 46, 151-160.

Nestler, E. J. (2000). Genes and addiction. Nature Genetics, 26, 277-281.

Osier, M., et al. (1999). Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism. American Journal of Human Genetics, 64, 1147-1157.

Goedde, H. W., et al. (1992). Distribution of ADH2 and ALDH2 genotypes in different populations. Human Genetics, 88, 344-346.

Farrar, L. A., et al. (1997). Effects of age, sex, and ethnicity on the association between Apolipoprotein E genotype and Alzheimer disease. Journal of the American Medical Association, 278, 1349-1356.



Session 9: May 30

Readings TBA; session will include some presentations



Session 10: June 6

* Use of genetic knowledge, genetic screening, and ethical issues; presentations

Marks, J. (1993). Historiography of eugenics. American Journal of Human Genetics, 52, 650-652.

Brosius, J., & Kreitman, M. (2000). Eugenics - evolutionary nonsense? Nature Genetics, 25, 253.

Parker, L. S. (1995). Ethical concerns in the research and treatment of complex disease. Trends in Genetics,11, 520-523.

Reilly, P. R., & Page, D. C. (1998). We're off to see the genome. Nature Genetics, 20, 15-17.

Davison, C. (1996). Predictive genetics: The cultural implications of supplying probable futures. In T. Marteau & M. Richards (Eds.), The troubled helix: Social and psychological implications of the new human genetics (pp. 317-330).



Interesting sites for Internet surfing (optional)



Cells alive www.cellsalive.com

Nanoworld www.uq.oz.au/nanoworld/images_1.html

Frank Potter's science gems www-sci.lib.uci.edu/SEP/life.html#4

MIT Biology textbook esg_www.mit.edu:8001/esgbio/7001main.html

Classical genetics papers www.esp.org/

Natural history of genes raven.umnh.utah.edu/

US Dept of Energy primer on molecular genetics www.bis.med.jhmi.edu/Dan/DOE/intro.html

Dog genome project mendel.berkeley.edu/dog.html

Human genome project www.ornl.gov/TechResources/Human_Genome/home.html

Institute for Genomic Research www.tigr.org/tdb/

Human transcript map www.ncbi.nlm.nih/gov/science96/

OMIM www.hgmp.mrc.ac.uk/omim/searchomim.html

Human gene mutation database www.uwcm.ac.uk/uwcm/mg/hgmd0.html

RFLP tutorial www.wadsworth.org/rflp/Tutorials/RFLP_Tutorial.html

Your genes, your choices ehrweb.aaas.org/ehr/books/index.html

Ethical, legal, social issues www.ornl.gov/hgmis/resource/elsi.html

Many interesting web sources amica.csustan.edu/index.html (click genetics) OR TRY www.wadsworth.com/biology

Your name and ID# ______________________________________________

Your e-mail address ______________________________________________



What are your interests?



Indicate your degree of interest in learning more about each of the following by writing a number in the blank before each item, using a 0 to 10 scale, where 0 indicates no interest and 10 indicates extremely high interest. Be aware that these possible interest areas vary widely with respect to how much research has been done with them.



"Psychological phenotypes"

____ Schizophrenia

____ Bipolar disorder (manic-depr.)

____ Depression

____ Anxiety and/or phobias

____ Alcoholism

____ Drug abuse/dependence

____ Smoking

____ Impulsive, risk-taking behavior

____ Irritability, hostility, anger-proneness

____ Aggression and violence

____ Criminal behavior

____ Integrity, virtue

____ Agreeableness, warmth, empathy

____ Extraversion, sociability

____ Dominance, assertiveness

____ Narcissism

____ Conscientiousness (order, ambition, dependability, effortful control, etc.)

____ Memory

____ 'Intelligence'

____ Mental retardation

____ Social attitudes (religiousness, spirituality, conservatism, etc.)

____ Other (list) _____________________



"Other phenotypes" that can provide useful examples in genetics

____ Cancer

____ Alzheimer's disease

____ Aging and longevity

____ Diabetes

____ Hypertension

____ Phenylketonuria

____ Cystic fibrosis

____ Huntington's disease

____ Immune system (HLA antigens, etc.)

____ ABO blood types

____ Hemoglobins (thalassemia, sickle-cell, etc.)

____ Cholesterol/lipid metabolism

____ Handedness (left, right)

____ Homosexuality

____ Salient physical features (hair color, eye color, etc.)

____ Obesity

____ Other (list) _____________________



Psychobiological factors (including neurotransmitters, hormones) that interest you:











Have you had a course in genetics before? ___________

If so, when? __________

Was it a course in human genetics specifically? ________



What else do you want to say about your interests and/or concerns with respect to the seminar? (Please use back of sheet)



Notes for first session:



Introduce self and explain interests and background

1. Clinical experience (1983-1993)

2. Personality (1989- )

3. Genetics (course in 1976, collab since 1994, several articles in preparation, co-author on many already published): I'm best on the psychiatric stuff and the methodologies, weakest on the real nano-nanostuff and the biochemistry (I missed a critical period in high school when I was rebelling against all grading systems!). Likely to affect response latencies.

4. Social attitudes (isms)



Explain potential problems with several isms re genetics



"Hereditarianism" : Heredity -- genetic transmission of characteristics -- is the primary factor determining intelligence and behavior

1. Much that is genetic is not really hereditary (epistasis, cancer)

2. Even, then, too strong: Genes could never be primary because they must be expressed in an environment and that environment affects the expression



Same (2) problem with "Environmentalism" : The main influence on intellectual growth and cultural development is the environment rather than heredity



"Social darwinism" : Individuals or human groups achieve advantage over others as a result of genetic or biological superiority

1. Advantage with regard to what? Economic? Reproductive? Health? Nutrition? Quality of life? Stress-avoidence or stress-resilience?

2. On what set of the many possible phenotypic traits would superiority be defined? Would this form of superiority be superior across times and situations?

3. Given the many, many 1000s of ways in which genes vary, how will you define superiority at the molecular level (we all carry lethal alleles!)

4. Where do you draw the boundary around a "human group"? (Race is not viable because of blending between populations; the geographic Y -- with isolated pops as warts -- in genetic distances)

5. Again, much that is genetic is not really hereditary



Common misconceptions about genetics:



1. All that is genetic is strictly hereditary



2. Whatever is genetic is static and inflexible

(the gene as an all-your-life 24-hour-running machine pumping out product, rather than part of a complex system)



3. One gene, one trait

(especially invalid with respect to psychological phenotypes, where a single gene is likely to be a small risk factor)



4. Studying genes interferes with profitably studying environment



5. Human populations differ widely in what genes (or rather, alleles of genes) they carry, as if there were a genetic basis for so-called "races"







Isms on genes



"Hereditarianism" : Heredity -- genetic transmission of characteristics -- is the primary factor determining intelligence and behavior



"Environmentalism" : The main influence on intellectual growth and cultural development is the environment rather than heredity



"Social darwinism" : Individuals or human groups achieve advantage over others as a result of genetic or biological superiority













Grouping psychol phenotypes as groups of correlating constructs



Agreeableness and (-) aggression



Impulsivity and (-) conscientiousness (and + extrav.)



(But another indep aspect of extrav would be assertiveness?)



Neuroticism and depression and anxiety

 

Intelligence and mental retardation



The psychoses (bipolar, schizophrenia)