Plasmodium falciparum histidine rich protein 2 (pfhrp2): an additional genetic marker suitable for anti-malarial drug efficacy trials

Background Genotyping of the three Plasmodium falciparum polymorphic genes, msp1, msp2 and glurp, has been adopted as a standard strategy to distinguish recrudescence from new infection in drug efficacy clinical trials. However, the suitability of a particular gene is compromised in areas where its allelic variants distribution is significantly skewed, a phenomenon that might occur in isolated parasite populations or in areas of very low transmission. Moreover, observation of amplification bias has diminished the value of glurp as a marker. Methods The suitability of the polymorphic P. falciparum histidine-rich protein 2 (pfhrp2) gene was assessed to serve as an alternative marker using a PCR-sequencing or a PCR–RFLP protocol for genotyping of samples in drug efficacy clinical trials. The value of pfhrp2 was validated by side-by-side analyses of 5 admission-recrudescence sample pairs from Yemeni malaria patients. Results The outcome of the single pfhrp2 gene discrimination analysis has been found consistent with msp1, msp2 and glurp pool genotyping analysis for the differentiation of recrudescence from new infection. Conclusion The findings suggest that under the appropriate circumstances, pfhrp2 can serve as an additional molecular marker for monitoring anti-malarials efficacy. However, its use is restricted to endemic areas where only a minority of P. falciparum parasites lack the pfhrp2 gene.

Haplotype Analysis of Varroa destructor and Deformed Wing Virus Using Long Reads

As a phoretic parasite and virus vector, the mite Varroa destructor and the associated Deformed wing virus (DWV) form a lethal combination to the honey bee, Apis mellifera. Routine acaricide treatment has been reported to reduce the diversity of mites and select for tolerance against these treatments. Further, different DWV strains face selective pressures when transmitted via mites. In this study, the haplotypes of Varroa mites and associated DWV variants were quantified using long reads. A single haplotype dominated the mite mitochondrial gene cytochrome oxidase subunit I, reflecting an ancient bottleneck. However, highly polymorphic genes were present across the mite genome, suggesting the diversity of mites could be actively maintained at a regional level. DWV detected in both mites and honey bees show a dominant variant with only a few low-frequency alternate haplotypes. The relative abundances of DWV haplotypes isolated from honey bees and mites were highly consistent, suggesting that some variants are favored by ongoing selection.

Genetic differentiation of Coregonus muksun in natural populations and broodstocks of fish rearing farms “Forvat” and “Sobsky” in relation to the problem of restoring the species population in Western Siberia

With regard to the problem of restoring the muksun (Coregonus muksun) population in Western Siberia by means of artificial regeneration, the genetic differentiation of natural populations and broodstocks of fish rearing farms “Forvat” and “Sobsky” was studied. Eighty-four sequences of mtDNA (3,006 bp) containing the highly polymorphic genes ND1 and ND2 were analysed. The differences between the populations of Western and Eastern Siberia were revealed. These findings must be taken into account when attempting to restore the species population in each particular region. The genetic closeness of the muksun from fish rearing farms “Forvat” and “Sobsky” with muksun from the Ob-Taz basin gives grounds for using these broodstocks for seeding the Ob and Taz rivers.

Haplotype analysis of polymorphic genes of lipid metabolism and its association with an increased risk of the first non-cardioembolic ischemic stroke

Aim We studied the effect of haplotype variations in lipid metabolism genes on the risk of first non-cardioembolic ischemic stroke in 206 patients and 206 controls. Material and methods The alleles frequencies and genotypes assessed for 5 mono-nucleotide polymorphic gene variants (APOB (rs1042031), APOEB (rs676210), APOC-IV (rs1132899), APOE (rs 7412), APOE (rs 429358), LP(a) (rs41267817)) in 206 patients, who had first non-cardioembolic ischemic stroke, and 206 persons with no stroke, comparable with age, gender, place of living and ethnicity. Genotyping of polymorphisms was done with the prepared TaqMan probes. Haplotype analysis was performed using the online tool SNPStat. Results Haplotype analysis revealed that CTGATT, CTGACT and CCAGTT, haplotypes of lipid metabolism genes polymorphisms are associated with risk of first non-cardioembolic ischemic stroke after multivariate adjustment. Conclusions These results show that haplotype of lipid metabolism genes polymorphisms are signifcantly associated with increased the development of the first non-cardioembolic ischemic stroke In the studied groups. FUNDunding Acknowledgement Type of funding sources: None.

Genetic Polymorphisms and Pesticide-Induced DNA Damage: A Review

The drastic increase in pesticide applications makes human exposure inevitable either through environment or occupation. Pesticide toxicity causes many adverse health effects through a number of pathways leading to DNA damage, mutations and cancers. Nevertheless, there is heterogeneity in the degree of toxicity among individuals due to the influence of genetic polymorphisms on xenobiotic metabolizing enzymes (XMEs) that modulate the biological process. Thus, study of the most common polymorphic genes coding for the enzymes involved in pesticide metabolism (such as cytochrome P450, Glutathione S-transferases, N-acetyltransferase and paraoxonase) may help determine individual’s susceptibility to pesticide toxicity. In this review, we give an overview of some recent developments in the field of genetic polymorphism and pesticide-related DNA damage, including probable biomarkers that may uncover genome susceptibility to pesticide toxicity. We have tried to create a connection between DNA polymorphism and cancer onslaught globally. It is envisaged that knowledge on this line would improve our understanding of facilitating the association between genotype and phenotype in cancer biology.

INFLUENCE OF POLYMORPHIC GENES ON QUALITATIVE INDICATORS OF MEAT PRODUCTS

Проблема и цель. Целью данной работы являлось генотипирование животных по генам CAST и CAPN1 c выявлением частот генотипов и аллелей, а также тестирование продукции этих животных, выраженное в оценке выдержанного в течение 8 суток мяса, на показатели, составляющие нежность, сочность, органолептическую оценку вкуса. Методология. Объектом исследований являлись бычки кроссов брединского мясного типа симменталов, полученные от использования выдающихся быков-производителей канадских мясных симменталов на отечественных матках различных линий. Для осуществления полимеразной цепной реакции (ПЦР) по тиражированию участка генома, составляющего ген CAPN1316 и ген CAST2857, использовались праймеры, найденные в открытой печати и синтезированные в фирме «Синтол». Проводилась оценка мяса на нежность (сопротивление усилию на разрез прибором Уорнера-Братцлера + органолептическая оценка варёного и жареного мяса), сочность (p/h, с использованием прокалывающего электрода LoT406-M6-DXK-S7/25 + влагоудерживающая способность). Результаты. В результате показатели мяса бычков, имеющих сочетание генотипов TT* по CAST и СС* по CAPN1, имели превосходство над средними показателями общей выборки (P< 0,001); а также над имеющей наибольшее распространение в выборке группой животных с желательным генотипом СС по гену CAPN1 на 1,22 балла или 15,4 % (P< 0,01) по нежности; на 1,44 балла или 18,2 % (P< 0,05) по сочности; на 1,56 балла или 19,2 % (P< 0,001) по вкусу. Заключение. Таким образом, исследования подтвердили влияние полиморфного состояния гомозиготы СС гена CAPN1 само по себе, а также генов CAST и CAPN1 на нежность говядины в той её части, когда сочетание генотипов ТТ в гене CAST и СС в гене CAPN1 даёт положительный эффект по нежности говядины, вероятно связанный с активизацией деятельности μ-кальпаина в связи с ослаблением влияния кальпастатина как ингибитора на μ-кальпаин. Problem and purpose.The aim of this work was to genotype animals for the CAST and CAPN1 genes with identifying the frequencies of genotypes and alleles, as well as testing the products of these animals, expressed in assessing meat aged for 8 days, for indicators that make up tenderness, juiciness, and organoleptic taste assessment.Methodology. The object of research was the bulls of the breeds of the Bredy meat type of simmentals obtained from the use of outstanding bulls-producers of Canadian meat simmentals on domestic females of various lines. To carry out the polymerase chain reaction (PCR) for replicating a region of the genome constituting the CAPN1316 gene and the CAST2857 gene, primers found in the open press and synthesized by Syntol were used. The meat was evaluated for tenderness (resistance to cutting force with a Warner-Bratzler device + sensory evaluation of cooked and fried meat), juiciness (p/h, using a piercing electrode LoT406-M6-DXK-S7/25 + water-holding capacity). Results. As a result, the meat indicators of bulls with a combination of TT * genotypes for CAST and CC * for CAPN1 were superior over the average indicators of the total sample (P <0.001), as well as over the most common group of animals in the sample with the desired CC genotype for the CAPN1 gene by 1.22 points or 15.4% (P <0.01) for tenderness, 1.44 points or 18.2% (P <0.05) for juiciness, 1.56 points or 19.2% (P <0.001) for taste. Conclusion. Thus, the studies have confirmed the influence of the polymorphic state of the CC homozygote of the CAPN1 gene itself, as well as of the CAST and CAPN1 genes, on the tenderness of beef in that part of it when the combination of TT genotypes in the CAST gene and CC in the CAPN1 gene has a positive effect on the tenderness of beef, probably associated with the activation of the activity of μ-calpain due to the weakening of the effect of calpastatin as an inhibitor on μ-calpain.

SIRT1 gene polymorphism and its plasma concentration in men with no signs of cardiovascular pathology, residents of Podilia region of Ukraine

Annotation. The aim of the work – on the basis of scientific literature to consider the current state of prediction and diagnosis of hypertension using biomarkers. A review analysis of literature sources of domestic and foreign authors on the polymorphism of the SIRT1 gene and the possibility of using data of the biomarker SIRT1 in the diagnosis and treatment of patients with cardiovascular pathology and the concentration of SIRT1 in the blood plasma of 79 practically healthy men, 40-60 years old, residents of the Podilia region of Ukraine with carriers of polymorphic SIRT1 genes, genotype GG, CC and CG was studied. The concentration of SIRT1 in the blood plasma of the examined men was determined by enzyme-linked immunosorbent assay. Genotyping of the SIRT1 gene was performed by polymerase chain reaction. Processing of the obtained results was performed using STATISTICA 6.0. Practically healthy men from the Podilia region of Ukraine are dominated by variants of the CC and CG genotypes. The concentration of SIRT1 in the blood plasma of men, residents of the Podilia region of Ukraine without signs of cardiovascular pathology is not associated with polymorphism of variants of the coding gene SIRT1. It is planned to use the obtained results for further study of SIRT1 concentration in carriers of polymorphic genes in men with stage I and II hypertension, which may have diagnostic value.

Bioinformatic HLA Studies in the Context of SARS-CoV-2 Pandemic and Review on Association of HLA Alleles with Preexisting Medical Conditions

After the announcement of a new coronavirus in China in December 2019, which was then called SARS-CoV-2, this virus changed to a global concern and it was then declared as a pandemic by WHO. Human leukocyte antigen (HLA) alleles, which are one of the most polymorphic genes, play a pivotal role in both resistance and vulnerability of the body against viruses and other infections as well as chronic diseases. The association between HLA alleles and preexisting medical conditions such as cardiovascular diseases and diabetes mellitus is reported in various studies. In this review, we focused on the bioinformatic HLA studies to summarize the HLA alleles which responded to SARS-CoV-2 peptides and have been used to design vaccines. We also reviewed HLA alleles that are associated with comorbidities and might be related to the high mortality rate among COVID-19 patients. Since both genes and patients’ medical conditions play a key role in both severity of the disease and the mortality rate in COVID-19 patients, a better understanding of the connection between HLA alleles and SARS-CoV-2 can provide a wider perspective on the behavior of the virus. Such understanding can help scientists, especially in terms of protecting healthcare workers and designing effective vaccines.

Comparative analysis of genome-wide sequences of the seed lot of the vaccine strain of Mycobacterium bovis BCG-1 (Russia) and daughter isolates obtained from children with BCG osteitis

The objective of the study: a comparative analysis of genome-wide sequences of seed lot (SL) 361 "sh" M. bovis BCG-1 (Russia) and its daughter isolates obtained from children with manifestations of BCG osteitis.Subjects and methods: genotyping; bioinformational analysis of genome-wide sequences of PS 361 "sh” vaccine BCG-1 (Russia) and its daughter isolates.Results. PS 361 "sh" BCG-1 (Russia) was heterogeneous in 7 coding sequences with different ratios of single nucleotide substitutions inherited by 2 of 6 daughter BCG isolates. At the same time, polymorphisms did not violate the genomic stability and viability of the BCG vaccine during long-term existence in vivo. In isolates of BCG 2925 and 5448, accumulation (hypothetically, under the pressure of selection in the vaccinated organism) of nonsynonymous substitutions in 4 out of 7 polymorphic genes was noted, including the genes ppsC, eccD5, and eccA5 associated with mycobacterial virulence. Evaluation of the significance of genomic variations in BCG isolates relating to the association with the development of post-vaccination osteitis requires more detailed information about the immune status of patients. Genome-wide analysis of production strains, seed lots, finished vaccine lots and daughter clinical isolates makes the contemporary approach to understanding the molecular basis of the efficacy and complications of BCG vaccination.