MMAPPR – Mutation Mapping Analysis Pipeline for Pooled RNA-seq

Forward genetic screens in model organisms are vital for identifying novel genes essential for developmental or disease processes. One drawback of these screens is the labor-intensive and sometimes inconclusive process of mapping the causative mutation.

In order to leverage high-throughput techniques to improve this mapping process, scientists at the University of Utah have developed a Mutation Mapping Analysis Pipeline for Pooled RNA-seq (MMAPPR) that works without parental strain information, without the requirement of a pre-existing snp map of the organism, and adapts to differential recombination frequencies across the genome. MMAPPR accommodates the considerable amount of noise in RNA-seq datasets, calculates allelic frequency by Euclidean distance followed by Loess regression analysis, identifies the region where the mutation lies and generates a list of putative coding region mutations in the linked genomic segment. MMAPPR can exploit RNA-seq datasets from isolated tissues or whole organisms that are utilized for gene expression and transcriptome analysis in novel mutants.

The researchers tested MMAPPR on two known mutant lines in zebrafish , nkx2.5 and tbx1, and used it to map two novel ENU-induced cardiovascular mutants, with mutations found in the ctr9 and cds2. MMAPPR can be directly applied to other model organisms, such as Drosophila and C. elegans, that are amenable to both forward genetic screens and pooled RNA-seq experiments. Thus, MMAPPR is a rapid, cost-efficient, and highly automated online pipeline, available to perform mutant mapping in any organism with a well assembled genome.

MMAPPR

Availability – MMAPPR is available at: http://yost.genetics.utah.edu/software.php

  • Hill JT, Demarest BL, Bisgrove BW, Gorsi B, Su YC, Yost HJ. (2013)  MMAPPR: Mutation Mapping Analysis Pipeline for Pooled RNA-seq. Genome Res [Epub ahead of print]. [abstract]