This class will include problem sets (1/3 of the grade will be based on problem sets and classroom participation) as well as a mid-term exam (1/3 of total grade) and a final exam (1/3 of total grade).

Week One: Introduction to Models
1. (Jan. 7) Genetic models for human phenotypes - single locus, polygenic, and mixed models for dichotomous and quantitative phenotypes, classic threshold models, parameters and their relationships.
2. (Jan. 8) Optional review section on selected topics in Genetics/Biology.
3. (Jan. 9) Relationship of specific genetics models to general genetics models such as common disease/common variant of multi-equivalent risk model; implicit and explicit assumptions of models.
4. (Jan. 10) Optional review section on commands/text editing in UNIX.

Week Two: Linkage Analysis
5. (Jan. 14) Linkage Analysis - Classic parametric 2-point linkage analysis; multipoint linkage analysis; algorithms for linkage analysis; LOD scores, MOD scores, likelihood ratio tset
6. (Jan. 15) Optional review section on Statistics/Probability Theory.
7. (Jan 16) Linkage Analysis - non-parametric linkage analysis; complete discussion of implicit and explicit parameters, sensitivity of results to nuisance parameters; assessment of significance and criteria for accepting/rejecting linkage; linkage studies of type I diabetes.
8. (Jan 17) Section - Topics of Linkage Analysis; Problem set I released.

Week Three: Intro to Linkage Disequilibrium (LD)
9. (Jan. 21) Linkage Disequilibrium - simple pairwise measures; power to detect; theoretical and empirical data, case/control studies.
10. (Jan. 23) Transmission/disequilibrium test (TDT) and related approaches; population structure and methods to identify and correct for it.
11. (Jan. 24) Optional Section - Topics of LD. Problem set I due, problem set II released.

Week Four: Linkage Disequilibrium (LD) Mapping Methods
12. (Jan. 28) Haplotype frequency estimation - family data vs. data on unrelated individuals, value of haplotype data in contrast with individual loci, evolutionary perspectives in haplotype frequency estimation.
13. (Jan. 30) Haplotype block structure and genome-wide studies of LD; implications for genome wide linkage disequilibrium mapping; implicit assumptions of such mapping studies.
14. (Jan 31) Section - Hidden Markov Models (HMM), the Expectation/Maximization (EM) algorithm, the coalescent. Problem set II due.

Week Five: Mapping Methods: LD vs. Linkage
15. (Feb. 4) Multipoint LD mapping - DHS and other approaches; simultaneous estimation of linkage and linkage disequilibrium parameters.
16. (Feb. 6) Linkage mapping vs. LD mapping debates - full class participation.
17. (Feb. 7) Optional Section - review for midterm exam.

Week Six: Midterm and Variance Components Analysis
18. (Feb. 11) MIDTERM - time during class with TA available, and exam dure Tuesday, Feb. 18.
19. (Feb. 13) Linkage analysis of quantitative phenotypes - Haseman and Elston regression and related approaches, variance components approaches, and the relationships among these.
20. (Feb. 14) TA available for exam questions during section time.

Week Seven: Difficulties with Conventional Linkage Analysis
21. (Feb. 18) One million and one ways to screw up data (and how to find and fix them all) - relationship misspecification, genotyping error, random and non-random error, violations of assumptions on distributions of quantitative traits.
22. (Feb 20) Choice of study population - myth and facts, isolated populations, admixed populations, and mapping by admixture linkage disequilibrium.
23. (Feb 21) Optional Section - Population structure, topics of abberent data. Problem set III released.

Week Eight: Topics in Genome-Wide Linkage Analysis
24. (Feb. 25) Genome-wide criteria for linkage mapping and for association studies - theoretical and practical considerations.
25. (Feb. 27) Linkage and association studies allowing for gene x gene and gene x environment interactions - theory and applications.
26. (Feb. 28) Section - Example of simulations to assess genome-wide significance and the number of loci expected to meet a particular theshold in a genome-wide screen, simulations to assess significance of interaction. Problem set III due, problem set IV released.

Week Nine: Analysis of Variation to Complex Disease
27. (Mar. 4) Methods for distinguishing variants affecting susceptibility to disease in the context of positional cloning studies for complex phenotypes, accounting for the evidence for linkage.
28. (Mar. 6) Hirschsprungs disease as an example of a relatively "simple" complex disorder - complete dissection.
29. (Mar. 7) Optional Section - Review for Final Exam, problem set IV due.

Week Ten: Final Exam and Tourette Syndrome
30. (Mar. 11) Tourette Syndrome - full class debate on likely models, critique of research to date.
31. (Mar. 13) FINAL EXAM - take home, but time in class with TA availible.