MMAPPR

MMAPPR maps causative mutations from pooled RNA-seq data to identify linked genomic regions and putative coding-region mutations for forward genetic screens in model organisms.

Key Features:

• Parental Strain Independence: Operates without requiring sequencing data from parental strains.
• No Pre-existing SNP Map Required: Does not rely on a pre-established single nucleotide polymorphism (SNP) map of the organism.
• Adaptation to Differential Recombination Frequencies: Accommodates varying recombination frequencies across genomic regions.
• Noise Accommodation in RNA-seq Data: Handles inherent noise present in RNA-seq datasets.
• Allelic Frequency Calculation: Calculates allelic frequency using Euclidean distance followed by Loess regression analysis.
• Identification of Putative Coding Region Mutations: Generates a list of potential coding-region mutations within linked genomic segments.

Scientific Applications:

• Forward Genetic Screens: Identification of genes essential for developmental processes or disease mechanisms using pooled RNA-seq.
• Mutation Mapping from RNA-seq: Mapping mutations using high-throughput RNA-seq data from isolated tissues or whole organisms.
• Zebrafish Case Studies: Applied to zebrafish mutants including nkx2.5 and tbx1 and to ENU-induced cardiovascular mutants with mutations identified in ctr9 and cds2.
• Applicability to Other Model Organisms: Directly applicable to pooled RNA-seq forward genetic screens in Drosophila and Caenorhabditis elegans.

Methodology:

Uses pooled RNA-seq datasets for gene expression and transcriptome analysis in novel mutants; calculates allelic frequencies using Euclidean distance and Loess regression and identifies linked genomic regions to output putative coding-region mutations.