Cas9-Based Local Enrichment and Genomics Sequence Revision of Megabase-Sized Shark IgNAR Loci

J Immunol. 2022 Jan 1;208(1):181-189. doi: 10.4049/jimmunol.2100844. Epub 2021 Dec 8.

Abstract

The 0.8-Mb Ig new Ag receptor (IgNAR) region of the whitespotted bamboo shark (Chiloscyllium plagiosum) is incompletely assembled in Chr_44 of the reference genome. Here we used Cas9-assisted targeting of chromosome segments (CATCH) to enrich the 2 Mb region of the Chr_44 IgNAR loci and sequenced it by PacBio and next-generation sequencing. A fragment >3.13 Mb was isolated intact from the RBCs of sharks. The target was enriched 245.531-fold, and sequences had up to 94% coverage with a 255× mean depth. Compared with the previously published sequences, 20 holes were filled, with a total length of 3508 bp. In addition, we report five potential germline V alleles of IgNAR1 from six sharks that may belong to two clusters of the IgNAR. Our results provide a new method to research the germline of large Ig gene segments, as well as provide the enhanced bamboo shark IgNAR gene loci with fewer gaps.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CRISPR-Associated Protein 9
  • CRISPR-Cas Systems
  • Fish Proteins / genetics*
  • Genetic Loci / genetics*
  • Genome
  • Genomics
  • High-Throughput Nucleotide Sequencing
  • Immunoglobulins / genetics*
  • Receptors, Antigen / genetics*
  • Sequence Analysis, DNA
  • Sharks / immunology*

Substances

  • Fish Proteins
  • Immunoglobulins
  • Receptors, Antigen
  • CRISPR-Associated Protein 9