Genes and Weightlifting Performance

A recent case-control study identified 28 DNA polymorphisms associated with strength athlete status. However, studies of genotype-phenotype design are required to support those findings. The aim of the present study was to investigate both individually and in combination the association of 28 genetic markers with weightlifting performance in Russian athletes and to replicate the most significant findings in an independent cohort of Japanese athletes. Genomic DNA was collected from 53 elite Russian (31 men and 22 women, 23.3 ± 4.1 years) and 100 sub-elite Japanese (53 men and 47 women, 21.4 ± 4.2 years) weightlifters, and then genotyped using PCR or micro-array analysis. Out of 28 DNA polymorphisms, LRPPRC rs10186876 A, MMS22L rs9320823 T, MTHFR rs1801131 C, and PHACTR1 rs6905419 C alleles positively correlated (p < 0.05) with weightlifting performance (i.e., total lifts in snatch and clean and jerk in official competitions adjusted for sex and body mass) in Russian athletes. Next, using a polygenic approach, we found that carriers of a high (6–8) number of strength-related alleles had better competition results than carriers of a low (0–5) number of strength-related alleles (264.2 (14.7) vs. 239.1 (21.9) points; p = 0.009). These findings were replicated in the study of Japanese athletes. More specifically, Japanese carriers of a high number of strength-related alleles were stronger than carriers of a low number of strength-related alleles (212.9 (22.6) vs. 199.1 (17.2) points; p = 0.0016). In conclusion, we identified four common gene polymorphisms individually or in combination associated with weightlifting performance in athletes from East European and East Asian geographic ancestries.

Investigation of Mitochondrial Transfer between Human Erythroblasts

<p>The increasingly studied phenomenon of mitochondria transferring between cells contrasts the popular belief that mitochondria reside permanently within their cells of origin. Research has identified this process occurring in many tissues such as brain, lung and more recently within the bone marrow. This project aimed to investigate if mitochondria could be transferred between human erythroblasts, a context not previously studied. Tissue microenvironments can be modelled using co-culture systems. Fluorescence activated cell sorting and a highly sensitive Allele-Specific-Blocker qPCR assay were used to leverage mitochondrial DNA polymorphisms between co-cultured populations. Firstly, HL-60ρ₀ bone marrow cells, without mitochondrial DNA, deprived of essential nutrients pyruvate and uridine were co-cultured in vitro with HEL cells, a human erythroleukemia. Secondly, HEL cells treated with deferoxamine or cisplatin, were cocultured with parental HL-60 cells in vitro. Lastly, ex vivo co-cultures between erythroblasts differentiated from mononuclear cells in peripheral blood were conducted, where one population was treated with deferoxamine. Co-culture was able to improve recovery when HL-60ρ₀ cells were deprived of pyruvate and uridine. Improved recovery was similarly detected for HEL cells treated with deferoxamine after co-culture with HL-60 cells. Transfer of mitochondrial DNA did not occur at a detectable level in any co-culture condition tested. The high sensitivity of the allele-specific-blocker qPCR assay required completely pure populations to analyse, however this was not achieved using FACS techniques. In conclusion, results have not demonstrated but cannot exclude the possibility that erythroid cells transfer mitochondria to each other.</p>

Investigation of Mitochondrial Transfer between Human Erythroblasts

<p>The increasingly studied phenomenon of mitochondria transferring between cells contrasts the popular belief that mitochondria reside permanently within their cells of origin. Research has identified this process occurring in many tissues such as brain, lung and more recently within the bone marrow. This project aimed to investigate if mitochondria could be transferred between human erythroblasts, a context not previously studied. Tissue microenvironments can be modelled using co-culture systems. Fluorescence activated cell sorting and a highly sensitive Allele-Specific-Blocker qPCR assay were used to leverage mitochondrial DNA polymorphisms between co-cultured populations. Firstly, HL-60ρ₀ bone marrow cells, without mitochondrial DNA, deprived of essential nutrients pyruvate and uridine were co-cultured in vitro with HEL cells, a human erythroleukemia. Secondly, HEL cells treated with deferoxamine or cisplatin, were cocultured with parental HL-60 cells in vitro. Lastly, ex vivo co-cultures between erythroblasts differentiated from mononuclear cells in peripheral blood were conducted, where one population was treated with deferoxamine. Co-culture was able to improve recovery when HL-60ρ₀ cells were deprived of pyruvate and uridine. Improved recovery was similarly detected for HEL cells treated with deferoxamine after co-culture with HL-60 cells. Transfer of mitochondrial DNA did not occur at a detectable level in any co-culture condition tested. The high sensitivity of the allele-specific-blocker qPCR assay required completely pure populations to analyse, however this was not achieved using FACS techniques. In conclusion, results have not demonstrated but cannot exclude the possibility that erythroid cells transfer mitochondria to each other.</p>

Genetic Diversity and Population Structure of Myanmar Rice (Oryza sativa L.) Varieties Using DArTseq-Based SNP and SilicoDArT Markers

Myanmar is well known as a primary center of plant genetic resources for rice. A considerable number of genetic diversity studies have been conducted in Myanmar using various DNA markers. However, this is the first report using DArTseq technology for exploring the genetic diversity of Myanmar rice. In our study, two ultra-high-throughput diversity array technology markers were employed to investigate the genetic diversity and population structure of local rice varieties in the Ayeyarwady delta, the major region of rice cultivation. The study was performed using 117 rice genotypes with 7643 SNP and 4064 silicoDArT markers derived from the DArT platform. Genetic variance among the genotypes ranged from 0 to 0.753 in SNPs, and from 0.001 to 0.954 in silicoDArT. Two distinct population groups were identified from SNP data analysis. Cluster analysis with both markers clearly separated traditional Pawsan varieties and modern high-yielding varieties. A significant divergence was found between populations according to the Fst values (0.737) obtained from the analysis of molecular variance, which revealed 74% genetic variation at the population level. These findings support rice researchers in identifying useful DNA polymorphisms in genes and pinpointing specific genes conferring desirable phenotypic traits for further genome-wide association studies and parental selection for recombination breeding to enhance rice varietal development and release.

DNA Polymorphisms as Potential Biomarkers of Thrombophilic Prognosis for COVID-19 Patients

Coronavirus disease 2019 (COVID-19) is a major issue of our times. Many aspects and features of this new and complex disease are being described on a daily basis. Major endpoints are systemic inflammation, markedly characterized by the cytokine storm, respiratory failure, and coagulation disorders, such as thrombophilia. In its terms, thrombophilia has a major impact on the COVID-19 prognosis. With regard to this, paying attention on molecular variants, such as DNA polymorphisms, epigenetic factors, and other biomarkers, could be an important approach to optimizing and personalizing the treatment of patients according to their inherited thrombotic features. This chapter brings an overview on the three major DNA polymorphisms associated with thrombophilia and proposes that these same biomarkers could be used in pretreatment screenings of patients with COVID-19 to seek the most appropriate therapy for each individual molecular profile.

Assessment of Genetic Diversity of Rheum species (Endangered Medicinal Herb of Indian Himalayan Region) using Molecular Markers

The Rheum species are important medicinal plants that are facing extinction due to their unplanned development and overexploitation by pharmaceutical industries. DNA polymorphisms are not prone to environmental modifications, thus they are widely used for the identification and characterization of plants. The use of different molecular markers has enabled the researchers for the valuation of genetic variability and diversity in its natural zone of distribution. The conventional approach may take several years to yield this information. For the estimation of molecular and genetic variations in geographical zone of distribution, various molecular markers technique are available like RAPD (Randomly Amplified Polymorphic DNA), RFLP (Restriction fragment length polymorphism), ISSR (Inter-Simple Sequence Repeats), SSR and AFLP. The uses of different molecular markers for the study of genetic diversity have been discussed in the review.

Genomic Heritability: A Ragged Diagonal Between Bias and Variance

Many important traits in plants, animals, and microbes are polygenic and are therefore difficult to improve through traditional marker?assisted selection. Genomic prediction addresses this by enabling the inclusion of all genetic data in a mixed model framework. The main method for predicting breeding values is genomic best linear unbiased prediction (GBLUP), which uses the realized genomic relationship or kinship matrix (K) to connect genotype to phenotype. The use of relationship matrices allows information to be shared for estimating the genetic values for observed entries and predicting genetic values for unobserved entries. One of the key parameters of such models is genomic heritability (h2g), or the variance of a trait associated with a genome-wide sample of DNA polymorphisms. Here we discuss the relationship between several common methods for calculating the genomic relationship matrix and propose a new matrix based on the average semivariance that yields accurate estimates of genomic variance in the observed population regardless of the focal population quality as well as accurate breeding value predictions in unobserved samples. Notably, our proposed method is highly similar to the approach presented by Legarra (2016) despite different mathematical derivations and statistical perspectives and only deviates from the classic approach presented in VanRaden (2008) by a scaling factor. With current approaches, we found that the genomic heritability tends to be either over- or underestimated depending on the scaling and centering applied to the marker matrix (Z), the value of the average diagonal element of K, and the assortment of alleles and heterozygosity (H) in the observed population and that, unlike its predecessors, our newly proposed kinship matrix KASV yields accurate estimates of h2g in the observed population, generalizes to larger populations, and produces BLUPs equivalent to common methods in plants and animals.

A high-frequency single nucleotide polymorphism in the MtrB sensor kinase in clinical strains of Mycobacterium tuberculosis alters its biochemical and physiological properties

The DNA polymorphisms found in clinical strains of Mycobacterium tuberculosis drive altered physiology, virulence, and pathogenesis in them. Although the lineages of these clinical strains can be traced back to common ancestor/s, there exists a plethora of difference between them, compared to those that have evolved in the laboratory. We identify a mutation present in ~80% of clinical strains, which maps in the HATPase domain of the sensor kinase MtrB and alters kinase and phosphatase activities, and affects its physiological role. The changes conferred by the mutation were probed by in-vitro biochemical assays which revealed changes in signaling properties of the sensor kinase. These changes also affect bacterial cell division rates, size and membrane properties. The study highlights the impact of DNA polymorphisms on the pathophysiology of clinical strains and provides insights into underlying mechanisms that drive signal transduction in pathogenic bacteria.