Genetic research in psychopathology is fast moving. Although evidence for heredity's role has been consistent and replicable over this past century, attempts to locate genes has not been exceptionally successful. Current literature reviews on linkage and association studies are quite confusing and full of null results. Hence, this course will focus on teaching the principles and tools of genetics rather than summarizing all the empirical literature. It is hoped that with the skills gained in the course, students will be able to follow the genetic literature and apply the principles in clinical practice.

(1) Consistent class attendance and participation.

(2) "Case presentation" (without a patient, of course) of the type that would be done in genetics rounds or psychiatric rounds in a medical research center. The presentation should focus on a known Mendelian or chromosomal disorder that has important behavioral consequences. A 5 to 10 scholarly write-up of the disorder will be due one week after the presentation.

(3) A major research paper reviewing the literature on the genetics of a disorder in psychopathology. The paper should be of "publishable quality" in the sense that it could serve as a rough draft for an article that you would, with some extra spit and polishing, send away to a respectable journal. This paper will be due at the end of the semester.

(4) Attendance at a case conference in the genetics' counseling center at Children's Hospital. We will arrange this later in the semester.

1. Introductory propaganda and b.s.
2. The Cell
   1. Introduction
   2. Intracellular Processes
      1. Cell Structure
      2. Metabolism in the Cell
      3. Transportation
      4. Storage
   3. Intercellular Processes: Cell Communication
   4. The Nerve Cell
      1. Structure of the Nerve Cell
      2. Neuronal Communication
      3. Genes and the Nerve Cell
3. DNA and the Genetic Code
   1. Introduction
   2. DNA
      1. Structure of DNA
      2. DNA replication
      3. Chromosomes: Packaged DNA
      4. RNA: DNAÃs first cousin
   3. The Genetic Code
      1. General Perspectives
      2. Proteins and Enzymes Revisited
      3. The Process of Protein Synthesis
         1. Transcription
         2. Editing
         3. Transportation
         4. Translation
         5. Final Assembly
   4. Hemoglobin: An Example of DNA, the Genetic Code, and Protein Synthesis
4. Genetic Regulation and Development
   1. Introduction
   2. Lyonization: X Chromosome Inactivation
   3. Genomic Imprinting
   4. Transcriptional Control
      1. Introduction
      2. Lactose metabolism in E. Coli
   5. A Behavioral Example: Genes, Stress, and Cortisol
   6. Developmental Genetics
      1. General Development
      2. Hemoglobin Again
      3. Sexual Differentiation
      4. Intelligence: A Behavioral Example
   7. Why Such Complexity?
5. Chromosomes
   1. Cytogenetics
      1. An Historical Curiosity
      2. Staining & Microscopy
         1. A Conventional Karyotype
      3. Chromosomal Mutations
         1. Common Types
         2. Scientific Notation
   2. Chromosomal Anomalies and Behavior
      1. DownÃs Syndrome
      2. Prader-WilliÃs Syndrome and Angelman's Syndrome
      3. William's Syndrome
      4. Sex Chromosome Anomalies
         1. TurnerÃs Syndrome
         2. XYY Syndrome
6. Mendelian Genetics
   1. MendelÃs Laws
      1. Segregation
      2. Independent Assortment
      3. Dominance
   2. Offspring RiskÃs
      1. Punnett Rectangle
         1. Punnett Rectangle for X-linked Loci
7. Mendelian Disorders and Behavior
   1. Introduction
   2. Phenylketonuria (PKU)
      1. Clinical Description
      2. Mode of Transmission
      3. Molecular Genetics
      4. Treatment
      5. Implications for the Behavioral Scientist
   3. Fragile X Syndrome
      1. as per PKU
   4. Congenital Adrenal Hyperplasia
      1. as per PKU
   5. Mendelian Disorders and Ethnicity: The Sickle Cell Anemia Story
      1. as per PKU
      2. World wide association with malaria
      3. Lessons on genetic screening
   6. All Western Europeans have a Mendelian Disorder
      1. The metabolism of alcohol
      2. Alcohol dehydrogenase and aldehyde dehydrogenase
   7. MendelÃs Law of Dominance revisited and Molecular Genetics
      1. Why the Asian ALDH-2 allele is dominant
      2. Why PKU is recessive
8. Disorders with complex genetics
   1. Introduction: Disorders with complex genetics versus complex genetic disorders
   2. The Breast Cancer Story
      1. BRCA1
      2. BRCA2
      3. The other 95%
   3. AlzheimerÃs Disease
      1. chromosome 21 loci
      2. APO-E4 locus
   4. The Great Unknown: Polygenic Contributions
      1. Polygenic, oligogenic, and who-cares-a-genic
      2. Liability-threshold model
   5. Genetic Heterogeneity Revisited
      1. Strong Heterogeneity
         1. Example: albinism
      2. Weak Heterogeneity
         1. Example: mental retardation
9. How do we find genes?
   1. Introduction
   2. Polymorphisms
      1. Definition
      2. Methods to detect polymorphisms:
         1. Electrophoresis: the Genetic Word Processor
         2. PCR technology
         3. Restriction Endonuclease Technology
         4. Genomic stuttering: SSRs, STRPs, VNTRs
   3. Genetic Fingerprinting
   4. Linkage
      1. Inductive approach with sample pedigrees
         1. linkage with A (oebig Aî)
         2. linkage with a (oelittle aî)
         3. why A (oebig Aî) and why a (oelittle aî)?
      2. Definition of Linkage
         1. Definition of marker loci
         2. Cosegregation of marker and trait
         3. Why are linkage studies on behavior so messy?
   5. Association Design
      1. APO-E4 revisited
      2. Alcohol dehydrogenase and aldehyde dehydrogenase revisited
      3. Methodological issues
         1. Population based association studies
         2. Within family association studies
10. Behavioral Genetics: Methods
    1. Galton, family studies, and the first behavioral genetic mistake
       1. Recurrence risks and their calculation
    2. Twin Design
       1. Logic
       2. Logical Problems
       3. Empirical data example
    3. Adoption Design
       1. Logic
       2. Logical Problems
       3. Empirical data example
    4. Methods for psychopathology
       1. Epidemiology
       2. Age correction
       3. Survival analysis
11. Psychopathology
    1. The genetics of all disorders of psychopathology have two things in common:
       1. heritability in the moderate range
       2. environmentability in the moderate range
          1. MZ twins are not 100% concordant for any disorder studied so far
    2. Schizophrenia as a prototypical example
       1. twin studies:
          1. Gottesman and Shields
          2. selected case histories of concordant and discordant MZ twins
          3. cotwin control studies
       2. adoption studies
          1. Heston
          2. Kety
    3. Fine, Everything is heritable. Now what do we do?
       1. Finding genes
          1. Linkage
             1. Rice et al. (1997) as an example of the linkage literature
          2. Association
             1. Schizophrenia and dopamine receptors
             2. the DRD2 - substance abuse story
          3. Role of animal models
             1. synteny of the mouse genome
             2. suitable candidate genes
       2. Genetic analysis of comorbidity
          1. Kendler et al. article on the female Virginia twins
       3. Tracing pathways
          1. religion as a protective factor (Kendler)
          2. IQ and antisocial behavior
             1. Caspi and Moffit hypothesis
             2. empirical data
          3. personality as a filtering mechanism
             1. with anxiety and depression (Australian twin data)
             2. with antisocial behavior (ASA data)
12. Open seminar: genetics and the clinical psychologist
    1. how to express information about genetics to patients
       1. etiological information
       2. how to get better information
       3. popular misconceptions
    2. the family history
       1. how to take a good family history
       2. what to do with the information
    3. counseling about reproductive decisions
       1. does genetics even matter here?
    4. will the clinical psychologist ever order genetic testing?

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