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

Jingrui Xing, Chenyao Wang, Hiroki Kimura, Yuto Takasaki, Shohko Kunimoto, Akira Yoshimi, Yukako Nakamura, Takayoshi Koide, Masahiro Banno, Itaru Kushima, Yota Uno, Takashi Okada, Branko Aleksic, Masashi Ikeda, Nakao Iwata, Norio Ozaki

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 39UTR 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 39UTR 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.

Original languageEnglish
Article number0112531
JournalPloS one
Volume9
Issue number11
DOIs
Publication statusPublished - 13-11-2014

Fingerprint

Schizophrenia
Genes
missense mutation
Missense Mutation
genes
mutation
Polymorphism
Mutation
neurodevelopment
Genome-Wide Association Study
Screening
Animals
Proteins
Nucleotides
Gene Frequency
single nucleotide polymorphism
gene frequency
Single Nucleotide Polymorphism
linkage (genetics)
Animal Models

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Xing, Jingrui ; Wang, Chenyao ; Kimura, Hiroki ; Takasaki, Yuto ; Kunimoto, Shohko ; Yoshimi, Akira ; Nakamura, Yukako ; Koide, Takayoshi ; Banno, Masahiro ; Kushima, Itaru ; Uno, Yota ; Okada, Takashi ; Aleksic, Branko ; Ikeda, Masashi ; Iwata, Nakao ; Ozaki, Norio. / Resequencing and association analysis of PTPRA, a possible susceptibility gene for schizophrenia and autism spectrum disorders. In: PloS one. 2014 ; Vol. 9, No. 11.
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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 39UTR 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 39UTR 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.",
author = "Jingrui Xing and Chenyao Wang and Hiroki Kimura and Yuto Takasaki and Shohko Kunimoto and Akira Yoshimi and Yukako Nakamura and Takayoshi Koide and Masahiro Banno and Itaru Kushima and Yota Uno and Takashi Okada and Branko Aleksic and Masashi Ikeda and Nakao Iwata and Norio Ozaki",
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Xing, J, Wang, C, Kimura, H, Takasaki, Y, Kunimoto, S, Yoshimi, A, Nakamura, Y, Koide, T, Banno, M, Kushima, I, Uno, Y, Okada, T, Aleksic, B, Ikeda, M, Iwata, N & Ozaki, N 2014, 'Resequencing and association analysis of PTPRA, a possible susceptibility gene for schizophrenia and autism spectrum disorders', PloS one, vol. 9, no. 11, 0112531. https://doi.org/10.1371/journal.pone.0112531

Resequencing and association analysis of PTPRA, a possible susceptibility gene for schizophrenia and autism spectrum disorders. / Xing, Jingrui; Wang, Chenyao; Kimura, Hiroki; Takasaki, Yuto; Kunimoto, Shohko; Yoshimi, Akira; Nakamura, Yukako; Koide, Takayoshi; Banno, Masahiro; Kushima, Itaru; Uno, Yota; Okada, Takashi; Aleksic, Branko; Ikeda, Masashi; Iwata, Nakao; Ozaki, Norio.

In: PloS one, Vol. 9, No. 11, 0112531, 13.11.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Resequencing and association analysis of PTPRA, a possible susceptibility gene for schizophrenia and autism spectrum disorders

AU - Xing, Jingrui

AU - Wang, Chenyao

AU - Kimura, Hiroki

AU - Takasaki, Yuto

AU - Kunimoto, Shohko

AU - Yoshimi, Akira

AU - Nakamura, Yukako

AU - Koide, Takayoshi

AU - Banno, Masahiro

AU - Kushima, Itaru

AU - Uno, Yota

AU - Okada, Takashi

AU - Aleksic, Branko

AU - Ikeda, Masashi

AU - Iwata, Nakao

AU - Ozaki, Norio

PY - 2014/11/13

Y1 - 2014/11/13

N2 - 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 39UTR 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 39UTR 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.

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