This is a competing continuation application for years 21-25 of a project to develop and implement models and methodology for the likelihood analysis of pedigree data and to distribute the resultant software to the research community. Each aspect of the proposal involves PAP (Pedigree Analysis Package). Parametric genetic analysis, the primary strength of PAP, should play a role in the multi-pronged approach needed to tackle the difficult task of characterizing and localizing genes for complex diseases, which result from complicated interactions of multiple genes and environmental factors. Non-parametric linkage analysis will also become available in PAP upon completion of extensions proposed in this application. Although there exist a number of other software packages for the analysis of family data, none matches the versatility of PAP. The extension of PAP more efficiently produces software for diverse genetic analysis than does the development of new software for that purpose. In addition, PAP has a track record for having been wellsupported over the years. During the previous funding period, a graphical user interface in Java was developed to facilitate the use of PAP. During the remaining year of funding the conversion of the source code will be completed, thereby making PAP very portable and convenient to install while maintaining all the analysis versatility. Nevertheless, PAP remains impractical for multipoint linkage analysis, because of the memory and computer time requirements. Therefore, this application proposes to remedy that shortcoming by implementing Markov chain Monte Carlo (MCMC) methods for the analysis of multi-locus marker data. MCMC methods sample, rather than exhaustively enumerate, the possible combinations of genotypes within a pedigree, therefore effecting an enormous saving of computer time. With the availability of MCMCproduced probabilities, multipoint linkage analysis will become feasible for either variance components models or using any of the extensive selection of major gene models already available in PAP. Nevertheless, the current application also proposes to develop new genetic models of disease risk, including a mode-of-inheritance free method. In addition, this application proposes to implement changes to increase computational speed, allow data exploration, and facilitate data handling and analysis, while continuing to distribute and support PAP.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD017463-24
Application #
7383893
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Coulombe, James N
Project Start
1999-09-15
Project End
2010-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
24
Fiscal Year
2008
Total Cost
$192,679
Indirect Cost
Name
University of Utah
Department
Genetics
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
de Haan, Hugoline G; Bezemer, Irene D; Vossen, Carla Y et al. (2014) Genetic variants in Cell Adhesion Molecule 1 (CADM1): a validation study of a novel endothelial cell venous thrombosis risk factor. Thromb Res 134:1186-92
Meltzer, M E; Hasstedt, S J; Vossen, C Y et al. (2011) Genome scan of clot lysis time and its association with thrombosis in a protein C-deficient kindred. J Thromb Haemost 9:1383-90
Hunt, Steven C; Hasstedt, Sandra J; Xin, Yuanpei et al. (2011) Polymorphisms in the NPY2R gene show significant associations with BMI that are additive to FTO, MC4R, and NPFFR2 gene effects. Obesity (Silver Spring) 19:2241-7
Hasstedt, Sandra J; Hanis, Craig L; Das, Swapan K et al. (2011) Pleiotropy of type 2 diabetes with obesity. J Hum Genet 56:491-5
Hasstedt, Sandra J; Thomas, Alun (2011) Detecting pleiotropy and epistasis using variance components linkage analysis in jPAP. Hum Hered 72:258-63
Hasstedt, Sandra J; Hanis, Craig L; Elbein, Steven C et al. (2010) Univariate and bivariate linkage analysis identifies pleiotropic loci underlying lipid levels and type 2 diabetes risk. Ann Hum Genet 74:308-15
Hasstedt, Sandra J; Xin, Yuanpei; Hopkins, Paul N et al. (2010) Two-dimensional, sex-specific autosomal linkage scan of the number of sodium pump sites. J Hypertens 28:740-7
Hasstedt, Sandra J; Bezemer, Irene D; Callas, Peter W et al. (2009) Cell adhesion molecule 1: a novel risk factor for venous thrombosis. Blood 114:3084-91
Hasstedt, Sandra J; Scott, Bruce T; Rosendaal, Frits R et al. (2007) Exclusion of the alpha2 subunit of platelet-activating factor acetylhydrolase 1b (PAFAH1B2) as a prothrombotic gene in a protein C-deficient kindred and population-based case-control sample. Thromb Haemost 98:587-92