Low genetic heterogeneity of copy number variations (CNVs) in the genes encoding the human deoxyribonucleases 1-like 3 and II potentially relevant to autoimmunity

PLoS One. 2019 Apr 25;14(4):e0215479. doi: 10.1371/journal.pone.0215479. eCollection 2019.

Abstract

Deoxyribonucleases (DNases) might play a role in prevention of autoimmune conditions such as systemic lupus erythematosus through clearance of cell debris resulting from apoptosis and/or necrosis. Previous studies have suggested that variations in the in vivo activities of DNases I-like 3(1L3) and II have an impact on autoimmune-related conditions. The genes for these DNases are known to show copy number variations (CNVs) whereby copy loss leads to a reduction of the in vivo activities of the enzymes, thereby possibly affecting the pathophysiological background of autoimmune diseases. Using a simple newly developed quantitative real-time PCR method, we investigated the distributions of the CNVs for DNASE1L3 and DNASE2 in Japanese and German populations. It was found that only 2 diploid copy numbers for all of these DNASE CNVs was distributed in both of the study populations; no copy loss or gain was evident for any of the autoimmune-related DNase genes. Therefore, it was demonstrated that these human autoimmune-related DNase genes show low genetic diversity of CNVs resulting in alterations of the in vivo levels of DNase activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases
  • Autoimmunity / genetics*
  • DNA Copy Number Variations*
  • Deoxyribonucleases / genetics*
  • Endodeoxyribonucleases / genetics*
  • Genetic Heterogeneity*
  • Germany
  • Humans
  • Japan

Substances

  • DNASE1L3 protein, human
  • Deoxyribonucleases
  • Endodeoxyribonucleases
  • DNASE2 protein, human

Grants and funding

This work was supported in part by Grants-in-Aid from Japan Society for the Promotion of Science (16H05272 to TY, 26713025 to JF, 16K19295 to KK-K and 16K15403 to HT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.