Title: Fast and Cheap Genome wide Haplotype Construction via Optical Mapping (NYU-CS-TR852) Authors: Thomas Anantharaman, Venkatesh Mysore, and Bud Mishra Abstract: We describe an efficient algorithm to construct genome wide haplotype restriction maps of an individual by aligning single molecule DNA fragments collected with Optical Mapping technology. Using this algorithm and small amount of genomic material, we can construct the parental haplotypes for each diploid chromosome for any individual, one from the father and the other from the mother. Since such haplotype maps reveal the polymorphisms due to single nucleotide differences (SNPs) and small insertions and deletions (RFLPs), they are useful in association studies, studies involving genomic instabilities in cancer, and genetics. For instance, such haplotype restriction maps of individuals in a population can be used in association studies to locate genes responsible for genetics diseases with relatively low cost and high throughput. If the underlying problem is formulated as a combinatorial optimization problem, it can be shown to be NP-complete (a special case of K-population problem). But by effectively exploiting the structure of the underlying error processes and using a novel analog of the Baum-Welch algorithm for HMM models, we devise a probabilistic algorithm with a time complexity that is linear in the number of markers. The algorithms were tested by constructing the first genome wide haplotype restriction map of the microbe T. Pseudoana, as well as constructing a haplotype restriction map of a 120 Megabase region of Human chromosome 4. The frequency of false positives and false negatives was estimated using simulated data. The empirical results were found very promising.