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
N1 - Publisher Copyright:
© 2014 Xing et al.
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.
AB - 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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U2 - 10.1371/journal.pone.0112531
DO - 10.1371/journal.pone.0112531
M3 - Article
C2 - 25393624
AN - SCOPUS:84911885365
SN - 1932-6203
VL - 9
JO - PloS one
JF - PloS one
IS - 11
M1 - 0112531
ER -