**1. Introduction**

Next generation sequencing (NGS) technology has been broadly used in biomedical research. The most valuable application of this technology is genome and transcriptome sequencing, which form a bridge to link fundamental discoveries in research using disease model systems

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to clinical application. Aquatic animal models are widely used in genomics, development biology, toxicology, pathology, and cancer research (for a recent review, see [1]). The genomes of several aquatic models had been sequenced using NGS technology over the past few years [2, 3]. NGS technology has been trending toward reduced cost with greater sequencing length and accuracy. While this has facilitated the sequencing process, sequence assembly remains a significant challenge for bench-top scientists, and especially for species with complicated genomes.

In this chapter, we will focus on the application of NGS in aquatic genome and transcriptome assemblies. Although our focus will be on the genome sequencing of aquatic models, the associated techniques, problems, concerns, and solutions can also be applied to genome sequencing of other model systems. Using *Xiphophorus maculatus* (*X. maculatus*), *X. couchia‐ nus*, and *X. hellerii* genome sequencing as examples, we will discuss the technical details of NGS, data processing, and genome assembly using guided approaches. We will also discuss the problems encountered in genome sequencing of several feral fish models (ice fish, blind cave fish, etc.) and alternative approaches to sequence and assemble these genomes. Some problems remain and these are causing a bottleneck to broadening the representation of aquatic models with genome assemblies. These problems are summarized and methods to address them in the next five years are proposed.
