Resequencing and association analysis of PTPRA, a possible susceptibility gene for schizophrenia and autism spectrum disorders

PLoS One. 2014 Nov 13;9(11):e112531. doi: 10.1371/journal.pone.0112531. eCollection 2014.

Abstract

Background: The PTPRA gene, which encodes the protein RPTP-α, is critical to neurodevelopment. Previous linkage studies, genome-wide association studies, controlled expression analyses and animal models support an association with both schizophrenia and autism spectrum disorders, both of which share a substantial portion of genetic risks.

Methods: We sequenced the protein-encoding areas of the PTPRA gene for single nucleotide polymorphisms or small insertions/deletions (InDel) in 382 schizophrenia patients. To validate their association with the disorders, rare (minor allele frequency <1%), missense mutations as well as one InDel in the 3'UTR region were then genotyped in another independent sample set comprising 944 schizophrenia patients, 336 autism spectrum disorders patients, and 912 healthy controls.

Results: Eight rare mutations, including 3 novel variants, were identified during the mutation-screening phase. In the following association analysis, L59P, one of the two missense mutations, was only observed among patients of schizophrenia. Additionally, a novel duplication in the 3'UTR region, 174620_174623dupTGAT, was predicted to be located within a Musashi Binding Element.

Major conclusions: No evidence was seen for the association of rare, missense mutations in the PTPRA gene with schizophrenia or autism spectrum disorders; however, we did find some rare variants with possibly damaging effects that may increase the susceptibility of carriers to the disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adolescent
  • Adult
  • Aged
  • Case-Control Studies
  • Child
  • Child Development Disorders, Pervasive / genetics*
  • Computational Biology
  • Evolution, Molecular
  • Exons
  • Female
  • Genetic Linkage
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Mutation, Missense
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4 / genetics*
  • Schizophrenia / genetics*
  • Sequence Analysis, DNA
  • Young Adult

Substances

  • 3' Untranslated Regions
  • PTPRA protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4

Grants and funding

Funding for this study was provided by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Ministry of Health, Labor and Welfare of Japan; Grant-in-Aid for “Integrated research on neuropsychiatric disorders” carried out under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan; Grant-in-Aid for Scientific Research on Innovative Areas, “Glial assembly: a new regulatory machinery of brain function and disorders”; and Grant-in-Aid for Scientific Research on Innovative Areas (Comprehensive Brain Science Network) from the Ministry of Education, Science, Sports and Culture of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.