Bi-directional extremism of the ZMYM۳ gene expression in schizophrenia

Background and Aim: Previous reports indicate a link between the Zinc finger MYM-type containing ۳ (ZMYM۳) gene and higher order brain functions, reflected in human-specific cognitive disorders such as X-linked intellectual disability and major psychiatric disorders. we investigated the expression of total ZMYM۳ transcripts as well as the ENST۰۰۰۰۰۳۷۳۹۹۸.۵ transcript in the peripheral blood of patients with SCZ and healthy subjects in association with the length of the stated STR.Methods: The current study included ۷۴ unrelated male subjects, consisting of SCZ patients (n=۳۸) and controls (n=۳۶). STR genotyping: Genomic DNA was extracted from peripheral blood samples using a standard precipitation technique. The region corresponding to the ۵′UTR STR in the ZMYM۳ gene was amplified and All PCR products were sequenced by Sanger method. Expression assays: RNA was obtained from peripheral blood, using a standard protocol. The ZMYM۳ cDNA was amplified by qRT-PCR. A pair of primers amplified all annotated isoforms of human ZMYM۳ and expression of ENST۰۰۰۰۰۳۷۳۹۹۸.۵ transcript was assessed using a specific primer pairs.Results: Total levels of ZMYM۳ transcripts or the STR-containing transcript were not significantly different between SCZ patients and controls (p = ۰.۳). ). However, we found extremism in gene expression at both low and high directions in the SCZ cases vs. controls for the total transcripts and the specific transcript containing the repeat (P<۰.۰۰۰۱). Furthermore, the length of STR was significantly different between SCZ cases and controls (P=۰.۰۱). Expression of neither total transcripts nor the ENST۰۰۰۰۰۳۷۳۹۹۸.۵ transcript was associated with the length of the repeats, age of study participants or age at disease onset.Conclusion: To our knowledge, this is first instance of gene expression extremism at both directions in SCZ. Future studies are needed to verify our results. Furthermore, it is warranted that the effect of the exceptionally long STR is studied in the brains of patients with schizophrenia.

Keywords:

Zinc finger MYM-type containing ۳ , ZMYM۳ , STR , short tandem repeat , schizophrenia , extremism