Combination of G72 Genetic Variation and G72 Protein Level to Detect Schizophrenia: Machine Learning Approaches.

The D-amino acid oxidase activator (DAOA, also known as G72) gene is a strong schizophrenia susceptibility gene. Higher G72 protein levels have been implicated in patients with schizophrenia. The current study aimed to differentiate patients with schizophrenia from healthy individuals using G72 single nucleotide polymorphisms (SNPs) and G72 protein levels by leveraging computational artificial intelligence and machine learning tools. A total of 149 subjects with 89 patients with schizophrenia and 60 healthy controls were recruited. Two G72 genotypes (including rs1421292 and rs2391191) and G72 protein levels were measured with the peripheral blood. We utilized three machine learning algorithms (including logistic regression, naive Bayes, and C4.5 decision tree) to build the optimal predictive model for distinguishing schizophrenia patients from healthy controls. The naive Bayes model using two factors, including G72 rs1421292 and G72 protein, appeared to be the best model for disease susceptibility (sensitivity = 0.7969, specificity = 0.9372, area under the receiver operating characteristic curve (AUC) = 0.9356). However, a model integrating G72 rs1421292 only slightly increased the discriminative power than a model with G72 protein alone (sensitivity = 0.7941, specificity = 0.9503, AUC = 0.9324). Among the three models with G72 protein alone, the naive Bayes with G72 protein alone had the best specificity (0.9503), while logistic regression with G72 protein alone was the most sensitive (0.8765). The findings remained similar after adjusting for age and gender. This study suggests that G72 protein alone, without incorporating the two G72 SNPs, may have been suitable enough to identify schizophrenia patients. We also recommend applying both naive Bayes and logistic regression models for the best specificity and sensitivity, respectively. Larger-scale studies are warranted to confirm the findings.

A novel PEPP homeobox gene, TOX, is highly glutamic acid rich and specifically expressed in murine testis and ovary.

The homeobox gene superfamily has been highly conserved throughout evolution. These genes act as transcription factors during several important developmental processes. To explore the functional roles of homeobox genes in spermatogenesis, we performed a degenerate oligonucleotide polymerase chain reaction (PCR) screening of a testis cDNA library and isolated a novel mouse homeobox gene. This gene, which we named Tox, encodes a homeodomain protein distantly related to members of the Paired/Pax (Prd/Pax) family. A phylogenetic analysis revealed Tox to be a member of the recently defined PEPP subfamily of Paired-like homeobox genes. Tox was mapped to chromosome X, with its homeodomain organized into three exons. A special feature of Tox is that the encoded protein sequence contains two poly-glutamic acid (poly E) stretches, which make Tox highly acidic. Tox transcripts were detected predominately in the testis and ovary of mice. Tox expression in testes was initiated soon after birth, mainly in Sertoli cells and spermatogonia; however, in adult mice, Tox expression shifts to the spermatids and spermatozoa. Tox expression in ovaries was detected in somatic cells of follicles, early on in theca cells, and in both granulosa and theca cells at the later stages of follicular development. Based on these results, Tox may play an important role during gametogenesis.

Expression of a novel TGIF subclass homeobox gene, Tex1, in the spermatids of mouse testis during spermatogenesis.

The homeobox gene superfamily is highly conserved during evolution. These genes act as transcription factors during several important developmental processes through their 60 amino acid homeodomains that recognize and bind to the regulatory region of their target genes. We isolated a novel homeobox gene designated Tex1 from a mouse testis cDNA library by degenerate oligonucleotide polymerase chain reaction (PCR) screening. Three extra amino acid residues, AYP, are inserted between the first and second helices of the homeodomain, which makes Tex1 a TGIF subclass homeobox gene. Tex1 was expressed specifically in the testis as seen by both Northern blot and RT-PCR analysis. Tex1 expression is initiated at around day 20 of testes. Furthermore, the results of in situ hybridization analysis reveal that the expression of Tex1 in testis is restricted in the germ cells at spermatid stage. Based on these data, it is suggested that Tex1, a novel testis homeobox gene, may play a crucial role during spermatogenesis.