Linear-time reconstruction of zero-recombinant Mendelian inheritance on pedigrees without mating loops.

Abstract

With the launch of the international HapMap project, the haplotype inference problem has attracted a great deal of attention in the computational biology community recently. In this paper, we study the question of how to efficiently infer haplotypes from genotypes of individuals related by a pedigree without mating loops, assuming that the hereditary process was free of mutations (i.e. the Mendelian law of inheritance) and recombinants. We model the haplotype inference problem as a system of linear equations as in [10] and present an (optimal) linear-time (i.e. O(mn) time) algorithm to generate a particular solution (A particular solution of any linear system is an assignment of numerical values to the variables in the system which satisfies the equations in the system.) to the haplotype inference problem, where m is the number of loci (or markers) in a genotype and n is the number of individuals in the pedigree. Moreover, the algorithm also provides a general solution (A general solution of any linear system is denoted by the span of a basis in the solution space to its associated homogeneous system, offset from the origin by a vector, namely by any particular solution. A general solution for ZRHC is very useful in practice because it allows the end user to efficiently enumerate all solutions for ZRHC and performs tasks such as random sampling.) in O(mn2) time, which is optimal because the size of a general solution could be as large as Theta(mn2). The key ingredients of our construction are (i) a fast consistency checking procedure for the system of linear equations introduced in [10] based on a careful investigation of the relationship between the equations (ii) a novel linear-time method for solving linear equations without invoking the Gaussian elimination method. Although such a fast method for solving equations is not known for general systems of linear equations, we take advantage of the underlying loop-free pedigree graph and some special properties of the linear equations.