Determination of candidate genes involved in schizophrenia using the whole-exome sequencing

• Published in: Bratislavské lékarské listy Vol. 119; no. 9; pp. 572 - 576
• Main Authors: Senormanci, O, Karakas Celik, S, Valipour, E, Dogan, V, Senormanci, G
• Format: Journal Article
• Language: English
• Published: Slovakia 2018
• Subjects: Adult; Amino Acid Substitution; Female; Frameshift Mutation; Humans; INDEL Mutation; Male; Middle Aged; Pedigree; Schizophrenia - genetics; Whole Genome Sequencing; genetic; whole-exome sequencing family; schizophrenia
• ISSN: 0006-9248
• DOI: 10.4149/BLL_2018_104

We used the whole-exome sequencing to evaluate several genes suspected of being involved in the pathogenesis of schizophrenia. The study sample was composed of two families. In the first family, two siblings had schizophrenia, and the parents were healthy. In the second family, two siblings had schizophrenia, while the other sibling and the parents did not. Indels were detected in some genes, including SPON1, GRIA3, SMAD5, PCLO, KMT2C, SRD5A2, SEMA3B, NCOR2, GPHB5, FAM174B, CLTCL1, and TMEM216. The insertion of three nucleotides (TGA) was detected in the sequence of the PCLO gene. The mutation resulted in the insertion of aspartic acid (Asp, D) in the amino acid sequence of the PCLO protein. Indels detected in SPON1, GRIA3, SMAD5, KMT2C, SRD5A2, SEMA3B, GPHB5, CLTCL1, and TMEM216 were shown to be frameshifting. Bioinformatics analysis showed that the indels in SPON1, GRIA3, SMAD5, KMT2C, SRD5A2, SEMA3B, NCOR2, GPHB5, FAM174B, CLTCL1, and TMEM216 had a damaging effect, while the indel in PCLO had a non-damaging effect on protein function. To the best of our knowledge, no previous studies have examined the relationship between the pathogenesis of schizophrenia and the gene mutations identified in this study (Tab. 1, Ref, 42).