HAPLOPOOL: improving haplotype frequency estimation through DNA pools and phylogenetic modeling.
BACKGROUND
The search for genetic variants that are linked to complex diseases such as cancer, Parkinson's;, or Alzheimer's; disease, may lead to better treatments. Since haplotypes can serve as proxies for hidden variants, one method of finding the linked variants is to look for case-control associations between the haplotypes and disease. Finding these associations requires a high-quality estimation of the haplotype frequencies in the population. To this end, we present, HaploPool, a method of estimating haplotype frequencies from blocks of consecutive SNPs.


RESULTS
HaploPool leverages the efficiency of DNA pools and estimates the population haplotype frequencies from pools of disjoint sets, each containing two or three unrelated individuals. We study the trade-off between pooling efficiency and accuracy of haplotype frequency estimates. For a fixed genotyping budget, HaploPool performs favorably on pools of two individuals as compared with a state-of-the-art non-pooled phasing method, PHASE. Of independent interest, HaploPool can be used to phase non-pooled genotype data with an accuracy approaching that of PHASE. We compared our algorithm to three programs that estimate haplotype frequencies from pooled data. HaploPool is an order of magnitude more efficient (at least six times faster), and considerably more accurate than previous methods. In contrast to previous methods, HaploPool performs well with missing data, genotyping errors and long haplotype blocks (of between 5 and 25 SNPs).
Kirkpatrick
Bonnie
B
Department of Electrical Engineering and Computer Sciences, UC Berkeley, CA, , USA.
Armendariz
Carlos Santos
CS
Karp
Richard M
RM
Halperin
Eran
E
D003198:Computer Simulation; D004247:DNA / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics*; D005788:Gene Pool; D014644:Genetic Variation / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D008957:Models, Genetic; D010802:Phylogeny; D017422:Sequence Analysis, DNA / Q000379:methods*
D004247:DNA