
pmid: 16597253
A commonly used tool in disease association studies is the search for discrepancies between the haplotype distribution in the case and control populations. In order to find this discrepancy, the haplotypes frequency in each of the populations is estimated from the genotypes. We present a new method HAPLOFREQ to estimate haplotype frequencies over a short genomic region given the genotypes or haplotypes with missing data or sequencing errors. Our approach incorporates a maximum likelihood model based on a simple random generative model which assumes that the genotypes are independently sampled from the population. We first show that if the phased haplotypes are given, possibly with missing data, we can estimate the frequency of the haplotypes in the population by finding the global optimum of the likelihood function in polynomial time. If the haplotypes are not phased, finding the maximum value of the likelihood function is NP-hard. In this case, we define an alternative likelihood function which can be thought of as a relaxed likelihood function. We show that the maximum relaxed likelihood can be found in polynomial time and that the optimal solution of the relaxed likelihood approaches asymptotically to the haplotype frequencies in the population. In contrast to previous approaches, our algorithms are guaranteed to converge in polynomial time to a global maximum of the different likelihood functions. We compared the performance of our algorithm to the widely used program PHASE, and we found that our estimates are at least 10% more accurate than PHASE and about ten times faster than PHASE. Our techniques involve new algorithms in convex optimization. These algorithms may be of independent interest. Particularly, they may be helpful in other maximum likelihood problems arising from survey sampling.
Likelihood Functions, Models, Statistical, Genotype, Models, Genetic, Genetic Linkage, Genetics, Population, Gene Frequency, Haplotypes, Humans, Computer Simulation, Algorithms
Likelihood Functions, Models, Statistical, Genotype, Models, Genetic, Genetic Linkage, Genetics, Population, Gene Frequency, Haplotypes, Humans, Computer Simulation, Algorithms
| selected citations These citations are derived from selected sources. This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 10 | |
| popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Average | |
| influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Top 10% | |
| impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 10% |
