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Univ. of Pennsylvania Penn's Neurobiology of Disease Curriculum

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BEHAVIORAL GENETICS - INSC 600-008/INSC 578 - 2008
Course meets Tuesdays beginning January 22 from 1:30 to 4:30 pm in the Barchi library (140 John Morgan Bldg.)

Course Summary

Overview:
This course focuses on the use of genetic techniques to study the molecular and cellular bases of behavior. Particular emphasis will be given to the role of genetic approaches in understanding the biological processes underlying learning, memory storage, circadian rhythms and drug abuse. Reverse genetic approaches utilizing gene knockout and transgenic technology and forward genetic approaches using mutagenesis and quantitative genetic techniques will be discussed, as well as application of these studies to different model organisms (fly, zebrafish, mouse). Genetic approaches to behavior and complex disease in humans will be illustrated with the series of lectures on, bipolar disorder and schizophrenia (Module 1) and neurodevelopmental and neurodegenerative disorders, such as mental retardation, autism and Asperger syndrome, Alzheimer's disease and tauopathies (Module 2).

Course Format:
This course meets once a week for three hours. Half of this time will be devoted to a lecture that will provide a general overview of the topic to be discussed and the approaches used in these studies. A discussion will follow the lecture. Discussions after the second and third lecture will involve solving genetic problems. In subsequent lectures, the discussion will be based on primary readings from the literature and will be led by students who have been given primary responsibility for presenting these papers. All students are required to turn in one discussion question for each paper at the beginning of each class to either Maja or Ted. These questions will then be used to guide the discussion. It is critically important that everyone participates in the discussion. We will be discussing cutting edge research that is often complex and controversial!

Grading:
There are four components that will be used in determining grades for this course:
  1. Class participation (10%): Ask critical questions and participate actively in discussions
  2. Paper presentations (30%): Each paper presentation is a maximum of 15 minutes long, including a maximum of five overheads or Powerpoint slides. A major purpose of these presentations is to initiate discussion.
  3. Midterm Exam (30%): A midterm take home exam.
  4. Final Exam (30%): A take home final exam will be given during finals period.

Lectures - Spring 2008

LECTURE VIDEOS: This year the videos of these lectures are not being made available outside of the University of Pennsylvania. Students in the course, or others with a Penn ID, can access the videos here.

Lecture Title Lecturer Date Papers assigned
INTRODUCTION INTO BEHAVIORAL GENETICS; GENE MAPPING AND NATURE OF MUTATIONS Ted Abel, PhD January 22, 2008

Readings
Chapter 8, "Linkage, crossing over, and chromosome mapping in eukaryotes" from Principles of Genetics, Third Edition, D. P. Snustad and M. J. Simmons, J. Wiley and Sons, 2003, pp. 156-177.
As necessary, review basic genetic principles using a textbook such as Principles of Genetics, Third Edition, D. P. Snustad and M. J. Simmons, J. Wiley and Sons.
Chapter 3, "Genes and behavior" from Principles of Neural Science, Fourth Edition, E. R. Kandel, J. H. Schwartz and T. M. Jessell, McGraw-Hill, 2000, pp. 36-62.

REVERSE AND FORWARD GENETICS AND POSITIONAL CLONING Maja Bucan, PhD January 29, 2008

Readings
same as for January 22, 2008 plus:
Bucan, M. and Abel, T. 2002. The mouse: Genetics meets behavior. Nature Reviews Genetics. 3: 114-123.

ANALYSIS OF QUANTITATIVE TRAIT LOCI Ted Brodkin, MD February 5, 2008

Readings
Chapter 5, "Inheritance of complex traits" from Principles of Genetics, Third Edition, D. P. Snustad and M. J. Simmons, J. Wiley and Sons, 2003, pp. 90-113.
Flint, J. and Mott, R. 2001. Finding the molecular basis of quantitative traits: successes and pitfalls. Nature Reviews Genetics. 2: 437-45.
Primary papers to be discussed:
Yalcin et al 2004 Genetic dissection of a behavioral quantitative trait locus shows that Rgs2 modulates anxiety in mice. Nature Genetics 36:1197-1202
Singer JB, Hill AE, Nadeau JH, Lander ES. (2005) Mapping quantitative trait loci for anxiety in chromosome substitution strains of mice. Genetics. 169:855-62.

INTRODUCTION TO STATISTICAL AND LINKAGE ANALYSIS Mingyao Li February 12, 2008

Reviews:
Chapter 7, "Linkage analysis" from Statistical Methods in Genetic Epidemiology, D. C. Thomas, Oxford University Press, 2004, pp. 167-226.
Primary papers to be discussed:
Lander E.S., Schork N.J. 1994. Genetic dissection of complex traits. Science 265:2037-2048.
Balding D.J. 2006. A tutorial on statistical methods for population association studies. Nature Review Genetics 7:781-791.

GENETIC APPROACHES TO LEARNING AND MEMORY Ted Abel, PhD February 19, 2008

Reviews:
Kandel, E. R. (2001) The molecular biology of memory storage: A dialogue between genes and synapses. Science. 294: 1030-1038.
Levenson JM, Sweatt JD. (2005) Epigenetic mechanisms in memory formation. Nat Rev Neurosci. 6: 108-18.
Primary papers to be discussed:
Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH. (2007) Recovery of learning and memory is associated with chromatin remodelling. Nature. 447: 178-82.
Vecsey CG, Hawk JD, Lattal KM, Stein JM, Fabian SA, Attner MA, Cabrera SM, McDonough CB, Brindle PK, Abel T, Wood MA. (2007) Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation. J Neurosci. 27: 6128-40.

MOLECULAR BASIS OF CIRCADIAN BEHAVIOR Amita Sehgal February 26, 2008

Reviews:
Gallego M, Virshup DM. (2007) Post-translational modifications regulate the ticking of the circadian clock. Nat Rev Mol Cell Biol. 8:139-48.
Primary papers to be discussed:
Liu AC, Welsh DK, Ko CH, Tran HG, Zhang EE, Priest AA, Buhr ED, Singer O, Meeker K, Verma IM, Doyle FJ 3rd, Takahashi JS, Kay SA. (2007) Intercellular coupling confers robustness against mutations in the SCN circadian clock network. Cell. 129: 605-16.
Stoleru D, Peng Y, Nawathean P, Rosbash M. (2005) A resetting signal between Drosophila pacemakers synchronizes morning and evening activity. Nature. 438:238-42.

NARCOLEPSY AND SLEEP DISORDER Sigrid Veasey March 4, 2008

Reviews:
Pace-Schott, E. F. Hobson, J. A. 2002. The neurobiology of sleep: genetics, cellular physiology and subcortical networks. Nature Reviews Neuroscience. 3: 591-605.
Chabas, D., Taheri, S., Renier, C. and Mignot, E. 2003. The genetics of narcolepsy. Annu Rev Genomics Hum Genet. 4: 459-483.
Primary papers to be discussed:
Chemelli, R. M., Willie, J. T., Sinton, C. M., Elmquist, J. K., Scammell, T., Lee, C., Richardson, JA, Williams, S. C., Xiong, Y., Kisanuki, Y., Fitch, T. E., Nakazato, M., Hammer, R. E., Saper, C. B., Yanagisawa, M. (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98: 437-451.
Maret S, Franken P, Dauvilliers Y, Ghyselinck NB, Chambon P, Tafti M. (2005) Retinoic acid signaling affects cortical synchrony during sleep. Science 310:111-3.

Spring Break   March 11, 2008  
GENETIC STUDIES OF PSYCHIATRIC DISORDERS Wade Berrettini, MD, PhD March 18, 2008

Reviews:
Owen MJ et al (2007) The genetic deconstruction of psychoses. Schizophrenia Bull 33: 905-11.
Pomerleau OF, Burmeister M, Madden P, Long JC, Swan GE, Kardia SL. (2007) Genetic research on complex behaviors: an examination of attempts to identify genes for smoking. Nicotine Tob Res. 9: 883-901.
Primary papers to be discussed:
Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447; 661-78.
Berrettini WH, Yuan X, Tozzi F, Song K, Chilcoat H, Francks C, Waterworth D, Muglia P, Mooser V: Alpha-5/Alpha-3 Nicotinic Receptor Subunit Alleles Increase Risk for Heavy Smoking. Molecular Psychiatry, in press.