# Mapping challenging mutations by whole-genome sequencing

## TL;DR

This paper introduces new methods to identify complex mutations using whole-genome sequencing in a model organism.

## Contribution

The study presents novel strategies for mapping challenging mutation types like dominant alleles and multigenic traits using whole-genome sequencing.

## Key findings

- New strategies for identifying complex mutations were developed and validated in Caenorhabditis elegans.
- An alternative method for mutation identification from recombinant crosses was introduced.
- A solution was proposed for sequencing challenges in sterile or arrested strains.

## Abstract

Whole-genome sequencing provides a rapid and powerful method for identifying mutations on a global scale, and has spurred a renewed enthusiasm for classical genetic screens in model organisms. The most commonly characterized category of mutation consists of monogenic, recessive traits, due to their genetic tractability. Therefore, most of the mapping methods for mutation identification by whole-genome sequencing are directed toward alleles that fulfill those criteria (i.e., single-gene, homozygous variants). However, such approaches are not entirely suitable for the characterization of a variety of more challenging mutations, such as dominant and semi-dominant alleles or multigenic traits. Therefore, we have developed strategies for the identification of those classes of mutations, using polymorphism mapping in Caenorhabditis elegans as our model for validation. We also report an alternative approach for mutation identification from traditional recombinant crosses, and a solution to the technical challenge of sequencing sterile or terminally arrested strains where population size is limiting. The methods described herein extend the applicability of whole-genome sequencing to a broader spectrum of mutations, including classes that are difficult to map by traditional means.