Population specific analysis of Yakut exomes.

We studied the genetic diversity of the Yakut population using exome sequencing. We performed comparative analysis of the Yakut population and the populations that are included in the "1000 Genomes" project and we identified the alleles specific to the Yakut population. We showed, that the Yakuts population is a separate cluster between Europeans and East Asians.

A common polymorphism in the ABCB1 gene is associated with side effects of PGP-dependent antidepressants in a large naturalistic Dutch cohort.

The drug efflux transporter permeability glycoprotein (PGP) and cytochrome P450 (CYP) 2C19 are important for eliminating antidepressants from the brain and body. The ABCB1 gene, encoding for PGP, and CYP2C19 gene have several variants that could influence enzyme function and thereby the effect of PGP- and 2C19-dependent antidepressants. We investigated the association of antidepressant side effect and common genetic variation in 789 antidepressant users. In PGP-dependent antidepressant users, the A-allele of the rs2032588 single-nucleotide polymorphism (SNP) was associated with a lower number of side effects after adjusting for gender, age, dosage and duration of use, (B=-0.44, q=4.6 × 10(-3)). This association was different from and absent in non-PGP-dependent antidepressant users. Other SNP associations as well as an interaction analysis between the rs2032588 SNP and the CYP2C19 SNPs were not statistically significant after adjusting for covariates and multiple comparisons. The association of rs2032588 with antidepressant side effects suggests the involvement of the ABCB1 genotype in the clinical pharmacology of PGP-dependent antidepressants.

Exome sequencing is a useful diagnostic tool for complicated forms of hereditary spastic paraplegia.

Hereditary spastic paraplegias constitute a heterogeneous group of neurodegenerative diseases encompassing pure and complicated forms, for which at least 52 loci and 31 causative genes have been identified. Although mutations in the SPAST gene explain approximately 40% of the pure autosomal dominant forms, molecular diagnosis can be challenging for the sporadic and recessive forms, which are often complicated and clinically overlap with a broad number of movement disorders. The validity of exome sequencing as a routine diagnostic approach in the movement disorder clinic needs to be assessed. The main goal of this study was to explore the usefulness of an exome analysis for the diagnosis of a complicated form of spastic paraplegia. Whole-exome sequencing was performed in two Spanish siblings with a neurodegenerative syndrome including upper and lower motor neuron, ocular and cerebellar signs. Exome sequencing revealed that both patients carry a novel homozygous nonsense mutation in exon 15 of the SPG11 gene (c.2678G>A; p.W893X), which was not found in 584 Spanish control chromosomes. After many years of follow-up and multiple time-consuming genetic testing, we were able to diagnose these patients by making use of whole-exome sequencing, showing that this is a cost-efficient diagnostic tool for the movement disorder specialist.

The New Coronavirus COVID-19 Infection.

In December 2019, the first cases of pneumonia of unknown etiology were found in Wuhan (China). Later, the pneumonia was associated with a new coronavirus; in February 2020, the World Health Organization (WHO) gave the name COVID-19 to the new disease, while the International Committee on Taxonomy of Viruses (ICTV) gave the name SARS-CoV-2 to the virus causing it. By March 11, 2020, when the virus had spread to 114 countries, the number of diagnosed patients had reached 118 thousand and the number of deaths was 4000, the WHO declared the outbreak of the disease a pandemic. In this review, we summarize the relevant information about the origin and spread of SARS-CoV-2, its epidemiology and diagnostics, and the clinical course and treatment of COVID-19.

Associations with tight junction genes PARD3 and MAGI2 in Dutch patients point to a common barrier defect for coeliac disease and ulcerative colitis.

BACKGROUND: Coeliac disease (gluten-sensitive enteropathy; GSE) and inflammatory bowel disease (IBD) are common gastrointestinal disorders. Both display enhanced intestinal permeability, initiated by gluten exposure (GSE) or bacterial interactions (IBD). Previous studies showed the association of both diseases with variants in MYO9B, presumably involved in epithelial permeability. AIM: It was hypothesised that genetic variants in tight junction genes might affect epithelial barrier function, thus contributing to a shared pathogenesis of GSE and IBD. METHODS: This hypothesis was tested with a comprehensive genetic association analysis of 41 genes from the tight junction pathway, represented by 197 tag single nucleotide polymorphism (SNP) markers. RESULTS: Two genes, PARD3 (two SNPs) and MAGI2 (two SNPs), showed weak association with GSE in a Dutch cohort. Replication in a British GSE cohort yielded significance for one SNP in PARD3 and suggestive associations for two additional SNPs, one each in PARD3 and MAGI2. Joint analysis of the British and Dutch data further substantiated the association for both PARD3 (rs10763976, p = 6.4 x 10(-5); OR 1.23, 95% CI 1.11 to 1.37) and MAGI2 (rs6962966, p = 7.6 x 10(-4); OR 1.19, 95% CI 1.08 to 1.32). Association was also observed in Dutch ulcerative colitis patients with MAGI2 (rs6962966, p = 0.0036; OR 1.26, 95% CI 1.08 to 1.47), and suggestive association with PARD3 (rs4379776, p = 0.068). CONCLUSIONS: These results suggest that coeliac disease and ulcerative colitis may share a common aetiology through tight junction-mediated barrier defects, although the observations need further replication.

[Transformation of Mycoplasma hominis by plasmid pAM120 using electroporation]. / Transformatsiia Mycoplasma hominis plazmidoi pAM120 s pomoshch'iu élektroporatsii.

Mycoplasma hominis was transformed by electroporation with plasmid pAM120 containing the transposon Tn916 that carried the tetM gene responsible for the resistance to tetracycline. The frequency of transformation was 10(-7)-10(-8) colony-forming units (CFU) per 10 micrograms of plasmid DNA. The PCR analysis of transformed DNA confirmed the transposon integration into the mycoplasma genome.

[Cytotoxic activity of melittin expressed by recombinant vectors in Acholeplasma laidlawii and Mycoplasma hominis cells]. / Tsitotoksicheskaia aktivnost' melitina, ékspressiruemogo rekombinantnymi vektorami, v kletkakh Acholeplasma laidlawii i Mycoplasma hominis.

Recombinant plasmids containing the mellitin gene under the control of the lac and the tetM gene promoters were used for studying cytotoxic activity of mellitin in cells of mollicutes (mycoplasmas) and Escherichia coli. After transformation of Acholeplasma laidlawii and Mycoplasma hominis cells with recombinant plasmid DNAs by electroporation, cell growth was suppressed. The expression of the mellitin gene in A. laidlawii and M. hominis cells was demonstrated using the reverse transcription polymerase chain reaction (RT-PCR). The possibility of using the mellitin gene in the recombinant vector as a potential antimycoplasmic gene-therapeutic agent with its selective expression in target cells is discussed.