Allele Imputation and Haplotype Determination from Databases Composed of Nuclear Families

Abstract

The alleHap package is designed for imputing genetic missing data and reconstruct nonrecombinant haplotypes from pedigree databases in a deterministic way. When genotypes of related individuals are available in a number of linked genetic markers, the program starts by identifying haplotypes compatible with the observed genotypes in those markers without missing values. If haplotypes are identified in parents or offspring, missing alleles can be imputed in subjects containing missing values. Several scenarios are analyzed: family completely genotyped, children partially genotyped and parents completely genotyped, children fully genotyped and parents containing entirely or partially missing genotypes, and founders and their offspring both only partially genotyped. The alleHap package also has a function to simulate pedigrees including all these scenarios. This article describes in detail how our package works for the desired applications, including illustrated explanations and easily reproducible examples. This paper presents new improvements and a detailed description for the R package alleHap (Medina-Rodríguez et al., 2014). Our program is capable of imputing missing alleles and identifying haplotypes from non-recombinant regions considering the mechanism of heredity and the genetic information present in parents and offspring. The algorithm is deterministic in the sense that haplotypes are identified from the existing genotypes guaranteeing compatibility between parents and children. When a haplotype can not be identified (due to genotyping errors, or recombination events in the genetic region), the procedure does not infer more haplotypes in the corresponding family members. The following sections will describe the implemented methods as well as some functional examples.