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


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.
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Jingrui
J
Xing
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Chenyao
C
Wang
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hiroki
H
Kimura
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yuto
Y
Takasaki
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Shohko
S
Kunimoto
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Akira
A
Yoshimi
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yukako
Y
Nakamura
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Takayoshi
T
Koide
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Masahiro
M
Banno
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Itaru
I
Kushima
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yota
Y
Uno
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Takashi
T
Okada
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Branko
B
Aleksic
Department of Psychiatry, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan.
Masashi
M
Ikeda
Department of Psychiatry, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan.
Nakao
N
Iwata
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Norio
N
Ozaki
D020413:3' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D019295:Computational Biology; D019143:Evolution, Molecular; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4 / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult
D020413:3' Untranslated Regions; C516841:PTPRA protein, human; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4