Construction and analysis of high-density linkage map using high-throughput sequencing data

PLoS One. 2014 Jun 6;9(6):e98855. doi: 10.1371/journal.pone.0098855. eCollection 2014.

Abstract

Linkage maps enable the study of important biological questions. The construction of high-density linkage maps appears more feasible since the advent of next-generation sequencing (NGS), which eases SNP discovery and high-throughput genotyping of large population. However, the marker number explosion and genotyping errors from NGS data challenge the computational efficiency and linkage map quality of linkage study methods. Here we report the HighMap method for constructing high-density linkage maps from NGS data. HighMap employs an iterative ordering and error correction strategy based on a k-nearest neighbor algorithm and a Monte Carlo multipoint maximum likelihood algorithm. Simulation study shows HighMap can create a linkage map with three times as many markers as ordering-only methods while offering more accurate marker orders and stable genetic distances. Using HighMap, we constructed a common carp linkage map with 10,004 markers. The singleton rate was less than one-ninth of that generated by JoinMap4.1. Its total map distance was 5,908 cM, consistent with reports on low-density maps. HighMap is an efficient method for constructing high-density, high-quality linkage maps from high-throughput population NGS data. It will facilitate genome assembling, comparative genomic analysis, and QTL studies. HighMap is available at http://highmap.biomarker.com.cn/.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Carps / genetics
  • Chromosome Mapping*
  • Genetic Markers / genetics
  • Genomics / methods*
  • Genotyping Techniques
  • High-Throughput Nucleotide Sequencing*

Substances

  • Genetic Markers

Grants and funding

This work was supported by a National Program on Key Basic Research Projects [the 973 Program: 2012CB113906 and 2012CB113900]; a National High Technology Research and Development Program of China [the 863 Program, No. 2012AA100101]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.