This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have developed a generalized EM algorithm (Quade et al. 2005) for estimating population haploytpe frequences that can accomodate a wide variety of types of data, including unrelated individuals, pedigrees, and measues of allele frequencies in pooled data, or any combination of the above. Autosomal and X-linked markers can be considered. Haplotype frequencies can be estimated separately for subsets of the data (e.g., cases, controls, or different populations). A likelihood ratio test and a permutation test have been implemented to compare the distribution of haploytpes among groups. In addition, the program can provide a list of all possible haplotypes (for nonrecombinanat regions) and the most likely haplotype(s) for each unit. We are currently extending this approach to facilitate the use of the program for whole genome association studies. This will include adding filters to automatically remove problematic markers or individuals, and adding a moving window feature to automate scanning through the genome. The moving window feature will haplotype adjacent markers with window sizes specified either using a constant number of markers, or by defining haplotype blocks. We are currently exploring an approach for clustering similar haplotypes to determine if this will improve the performance of the method. We anticipate that this algorithm will be useful in the context of association studies and fine mapping projects.
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