Topics suggested Fall 2004

One overarching approach that people are suggesting is to look at some real studies, both human and non-human. It would be useful for each topic area to make sure we include one or more such real study.

• Choose a study of a complex trait (e.g., Alzheimer study in AJHG, or Abkevitch Utah study) and back up to the background methods (couple of weeks) etc. needed to work up to study (week 3). Could do this for a couple of rather different types of study.
• Results of experimentation on non-human animals (e.g., varying mutation rates, recombination hotspots, evidence of selection, evidence of how mutation works, etc.) because human data are sparse and what applies to other animals may be found in humans, but we need to know what to look for.
• Insights from experiments on "experimental species", e.g., Drosophila.

Association studies

• real example and data
• haplotype-based methods for disease gene mapping
• Admixture mapping

Introducing LD into linkage analysis

Methods using haplotypes, update on and perspectives for the HapMap project, TagSNPs, etc.

Haplotype estimation/reconstruction

Recombination hot spot detection

Trait models

• for human disease
• for longitudinal data
• complex disease
• incorporating environmental influences in linkage analysis
• missing data

Maybe some quantitative genetics.

Mapping functions

Modelling IBD processes

Review current ideas for mapping genes involved in complex traits

• nonparametric analysis statistics - S_pairs, S_all, Kong-Cox lod, etc.
• linkage analysis methods - comparing several such methods?

Measures of information in gene mapping

• What are they?
• What do they measure?

Problems, errors about genetical data

Phylogeography

• Y-chromosome work (Underhill)
• mt DNA (Avisa)

Natural selection with coalescent (Neuhauser)

Coalescent model

Using the coalescent to do gene mapping

Reproducibility of genetic tests (sensitivity, specificity, predictive value)

Specific papers:

• Montana & Pritchard (2004) Statistical tests for admixture mapping with case-control and case-only data. Am J Hum Genet 75:771-789.
• Wasser et al (2004) Assigning African elephant DNA to geographic region of origin: applications to the ivory trade. PNAS Sep 30 [Epub]
• Bias toward the null: IBD estimation and use in linkage analysis by Schork & Greenwood 2004 AJHG 74:306-316; Cordell 2004 AJHG 74:1294-1302; and the several following letters in Oct 2004 issue of AJHG 74:716-726.
• Fine Mapping of a Quantitative Trait Locus for Twinning Rate Using Combined Linkage and Linkage Disequilibrium Mapping. Meuwissen et al. Genetics 2002 May;161(1):373-9.
• Fridman et al (2004) Zooming in on a quantitative trait for tomato yield using interspecific introgressions. Science 305:1786-1789. (and some papers leading up to this). It would be interesting to contrast this paper to similar work in drosophila, probably by Trudy Mackay's group.
• Bailey-Wilson et al (2004) A major lung-cancer susceptibility locus maps to chromosome 6q23-25. Am J Hum Genet 75:460-474.
• Orzack et al (2003) Analysis and exploration of the use of rule-based algorithms and consensus methods for the inferral of haplotypes. Genetics 165:915-928.
• Hu X et al. (2004) Selecting Tagging SNPs for Association Studies Using Power Calculations from Genotype Data. Human Heredity 57:156-170.
• Lu X et al (2003) Haplotype Information and Linkage Disequilibrium Mapping for Single Nucleotide Polymorphisms. Genome Research 13:2112-2117.
• Becker and Knapp (2004) Maximum-likelihood estimation of haplotype frequencies in nuclear families. Genetic Epidemiology 27:21-32.
• Perez-Enciso M (2003) Fine mapping of complex trait genes combining pedigree and linkage disequilibrium in formation: A Bayesian unified framework. Genetics 163:1497-1510
• Clark et al (2003) Linkage disequilibrium and inference of ancestral recombination in 538 single-nucleotide polymorphisms clusters across the genome. Am J Hum Genet 73:285-300