MegaMapper

MegaMapper performs positional cloning by analyzing whole genome sequencing data to identify causative mutations in model organisms such as zebrafish.

Key Features:

• Two Strategic Approaches: Implements Bulk Segregant Linkage (BSFseq), which identified mutations in lmx1b and jagged1b, and Homozygosity Mapping (HMFseq), which validated disruption of cdh23, identified a candidate lesion in lhfpl5a, and obviates map crosses in contexts of high intrastrain polymorphism.
• Database of Sequence Variants: Uses a database of over 15 million sequence variants to subtract known SNPs from a mutant's critical region, often reducing candidates to a single SNP after filtering.

Scientific Applications:

• Positional cloning in high-diversity organisms: Enables mapping of causative mutations in species with high intrastrain polymorphism such as zebrafish.
• Characterization of mutants from forward genetic screens: Facilitates identification of genetic lesions responsible for observed phenotypes in forward screens.
• Gene function and disease modeling: Supports discovery of mutations relevant to human disease modeling and functional analysis of genes implicated by mapped lesions.

Methodology:

Analyzes whole genome sequencing data using bulk segregant linkage (BSFseq) and homozygosity mapping (HMFseq), compares those approaches, and filters variants against a database of >15 million known SNPs to identify candidate causative mutations.