Masoud Garshasbi

Evaluation of DNMT1 gene expression profile and methylation of its promoter region in patients with ankylosing spondylitis

Ankylosing spondylitis (AS) is an autoimmune disease with a chronic inflammatory arthritis. The critical role of methylation in the biology of immunocytes has increasingly been surveyed to discover disease etiology. DNA methyltransferase 1 (DNMT1) is an enzyme, which establishes and regulates patterns of methylated cytosine residues. The aim of the current investigation was to unveil if methylation circumstances of CpG sites in DNMT1 promoter could affect the mRNA expression level of this gene in peripheral blood mononuclear cells (PBMCs) from AS patients. PBMCs were isolated from whole blood of 40 AS patients and 40 healthy individuals. Total RNA and DNA contents of leukocytes were extracted. Afterward, quantitative analysis was carried out by real-time PCR using the SYBR Green PCR Master Mix. Finally, to determine the methylation level, PCR products of bisulfite-treated DNA from patients and controls were sequenced. Compared with healthy controls, expression level of DNMT1 in AS patients was significantly downregulated. Methylation of DNMT1 promoter was significantly higher in AS patients in comparison to controls. While a negative correlation between methylation and expression level of DNMT1 was observed in AS patients, both methylation and expression level of DNMT1 did not correlate with clinical manifestations. Considering the observation that decreased expression level of DNMT1 was associated with hypermethylation of DNMT1 promoter in PBMCs from AS patients, this survey suggests that dysregulation of DNMT1 expression through altered methylation level of other target genes would probably contribute to AS development.

PTRHD1 (C2orf79) mutations lead to autosomal-recessive intellectual disability and parkinsonism.

Atypical parkinsonism is a neurodegenerative disease that includes diverse neurological and psychiatric manifestations.

Isolated Congenital Anosmia and CNGA2 Mutation

Isolated congenital anosmia (ICA) is a rare condition that is associated with life-long inability to smell. Here we report a genetic characterization of a large Iranian family segregating ICA. Whole exome sequencing in five affected family members and five healthy members revealed a stop gain mutation in CNGA2 (OMIM 300338) (chrX:150,911,102; CNGA2. c.577C > T; p.Arg193*). The mutation segregates in an X-linked pattern, as all the affected family members are hemizygotes, whereas healthy family members are either heterozygote or homozygote for the reference allele. cnga2 knockout mice are congenitally anosmic and have abnormal olfactory system physiology, additionally Karstensen et al. recently reported two anosmic brothers sharing a CNGA2 truncating variant. Our study in concert with these findings provides strong support for role of CNGA2 gene with pathogenicity of ICA in humans. Together, these results indicate that mutations in key olfactory signaling pathway genes are responsible for human disease.

Lack of association between btb domain and cnc homolog 2 polymorphism and susceptibility to rheumatoid arthritis in Iranian population

Background: Rheumatoid arthritis (RA) is an autoimmune systemic inflammatory disease, which mostly occurs in genetically susceptible individuals. Single-nucleotide polymorphism (SNP), as the major type of genetic variations, is one of the controversial issues discussed in a large portion of autoimmune disorders. BTB domain and CNC homolog 2 (BACH2), encoded by BACH2 gene, is a regulator of the immune system which reduces activation of T cells and suppresses the inflammation. In this study, we surveyed association of rs72928038 Single-nucleotide polymorphism (SNP) located in an intron region of BACH2 gene in Iranian RA population. Methods: Blood samples were collected from 623 RA patients and 412 age-, sex-, and ethnicity-matched healthy controls. In order to genotyping the rs72928038 SNP, amplification refractory mutation system-polymerase chain reaction was employed. Results: None of the alleles and genotypes of rs72928038 SNP had significantly different distributions between RA patients and healthy controls. The GA, GG, and AA genotypes were slightly frequent in patients compared with healthy controls but with no significant differences. Conclusions: This study did not show rs72928038 as a risk factor for RA in the Iranian population, which was strongly associated with other populations. This underscores genetic diversity in RA susceptibility in different populations.

Identification of a novel mutation in the APTX gene associated with ataxia-oculomotor apraxia

Hereditary ataxias are a clinically and genetically heterogeneous family of disorders defined by the inability to control gait and muscle coordination. Given the nonspecific symptoms of many hereditary ataxias, precise diagnosis relies on molecular genetic testing. To this end, we conducted whole-exome sequencing (WES) on a large consanguineous Iranian family with hereditary ataxia and oculomotor apraxia. WES in five affected and six unaffected individuals resulted in the identification of a homozygous novel stop-gain mutation in the APTX gene (c.739A>T; p.Lys247*) that segregates with the phenotype. Mutations in the APTX (OMIM 606350) gene are associated with ataxia with oculomotor apraxia type 1 (OMIM 208920).

Application and effectiveness of ontology on e-Health

With the mutual understanding of the concepts and terms and the semantic relationship, Interaction and integration between health systems, decision support systems can be easily done. Ontology is one way of overcoming the problems of interoperability. Ontology is a formal explicit description of concepts in a special domain. In this article, to review the application and effectiveness of Ontologies in e-Health, and we provided a model for the design of disease ontology. By creating an ontology for the domain Diseases, Concepts and relationships in a variety of diseases and the semantic interoperability between them can be determined. By understanding the various aspects of the Ontology application in e-Health and overcoming their weaknesses and strengths, the impact of these tools can be used in the field. However, the use of valid models of Ontology Design Disease in order to manage data and representing knowledge, creating integrated systems and interaction and Knowledge-based decision support systems in the field of e-health is very important.