Investigation of the Relationship between MBP Gene Polymorphisms and Delayed Encephalopathy after Acute Carbon Monoxide Poisoning

Background Increasing evidence reveals that delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) results from the combined effects of environmental and genetic factors. The main pathological feature of DEACMP was generalized demyelination of cerebral white matter. Myelin basic protein (MBP) levels in cerebrospinal fluid (CSF) and serum samples from DEACMP patients were elevated.Objectives This study investigated the association of MBP single nucleotide polymorphisms(SNPs) (rs470555, rs470724, rs4890785, rs595997, rs76452994, and rs921336) with DEACMP. Methods We genotyped 416 DEACMP patients and 785 age, educational level, and sex-matched ACMP patients for rs470555, rs470724, rs4890785, rs595997, rs76452994, and rs921336 SNPs using the Agena MassArray. Results There were no significant differences in the allele frequency distribution, four genetic models, and genotype distributions between the DEACMP and ACMP groups for rs470555, rs470724, rs4890785, and rs595997. However, significant differences were observed for rs76452994 and rs921336.Conclusions This study revealed that the MBP polymorphisms, rs470555, rs470724, rs4890785, and rs595997, were not associated with DEACMP. Based on the codominant, dominant, and overdominant genetic inheritability patterns, the MBP rs76452994 and rs921366 polymorphisms were associated with DEACMP. Furthermore, the G allele of rs76452994 and T allele of rs921336 could lead to higher DEACMP risk.

Revisiting the number of self-incompatibility alleles in finite populations: from old models to new results

Under gametophytic self-incompatibility (GSI), plants are heterozygous at the self-incompatibility locus (S-locus) and can only be fertilized by pollen with a different allele at that locus. The last century has seen a heated debate about the correct way of modeling the allele diversity in a GSI population that was never formally resolved. Starting from an individual-based model, we derive the deterministic dynamics as proposed by Fisher (1958), and compute the stationary S-allele frequency distribution. We find that the stationary distribution proposed by Wright (1964) is close to our theoretical prediction, in line with earlier numerical confirmation. Additionally, we approximate the invasion probability of a new S-allele, which scales inversely with the number of resident S-alleles. Lastly, we use the stationary allele frequency distribution to estimate the population size of a plant population from an empirically obtained allele frequency spectrum, which complements the existing estimator of the number of S-alleles. Our expression of the stationary distribution resolves the long-standing debate about the correct approximation of the number of S-alleles and paves the way to new statistical developments for the estimation of the plant population size based on S-allele frequencies.

Association study of a genetic variant in the long intergenic noncoding RNA (linc01080) with schizophrenia in Han Chinese

Background Schizophrenia is currently considered to be a polygene-related disease with unknown etiology. This research will verify whether the single nucleotide polymorphism (SNP) of the long intergenic noncoding RNA01080 (linc01080) contributes to the susceptibility and phenotypic heterogeneity of schizophrenia, with a view to providing data support for the prevention and individualized treatment of this disease. Method The SNP rs7990916 in linc01080 were genotyped in 1139 schizophrenic and 1039 controls in a Southern Chinese Han population by the improved multiplex ligation detection reaction (imLDR) technique. Meanwhile, we assessed and analyzed the association between this SNP and schizophrenics’ clinical symptoms, and the cognitive function. Result There was no significant difference in genotype distribution, allele frequency distribution, gender stratification analysis between the two groups. However, the SNP of rs7990916 was significantly associated with the age of onset in patients with schizophrenia (P = 8.22E-07), patients with T allele had earlier onset age compared with CC genotype carriers. In terms of cognitive function, patients with T allele scored lower than CC genotype carriers in the Tower of London score and symbol coding score in the Brief assessment of Cognition (BACS), and the difference was statistically significant (P = 0.014, P = 0.022, respectively). Conclusion Our data show for the first time that linc01080 polymorphism may affect the age of onset and neurocognitive function in patients with schizophrenia.

Estimation of linkage disequilibrium levels and allele frequency distribution in crossbred Vrindavani cattle using 50K SNP data

The objective of this study was to calculate the extent and decay of linkage disequilibrium (LD) in 96 crossbred Vrindavani cattle genotyped with Bovine SNP50K Bead Chip. After filtering, 43,821 SNPs were retained for final analysis, across 2500.3 Mb of autosome. A significant percentage of SNPs was having minor allele frequency of less than 0.20. The extent of LD between autosomal SNPs up to 10 Mb apart across the genome was measured using r2 statistic. The mean r2 value was 0.43, if pairwise distance of marker was less than10 kb and it decreased further to 0.21 for 25–50 kb markers distance. Further, the effect of minor allele frequency and sample size on LD estimate was investigated. The LD value decreased with the increase in inter-marker distance, and increased with the increase of minor allelic frequency. The estimated inbreeding coefficient and effective population size were 0.04, and 46 for present generation, which indicated small and unstable population of Vrindavani cattle. These findings suggested that a denser or breed specific SNP panel would be required to cover all genome of Vrindavani cattle for genome wide association studies (GWAS).

Frequency of HLA Alleles in a Group of Severe COVID‐19 Irani-an Patients

Background: Human Leukocyte Antigen (HLA) system composed of a group of related proteins with important functions in the immune system. Several studies have reported that there is a significant association between specific HLA alleles and the susceptibility to different infectious diseases. This study aimed to detect the specific HLA alleles that cause higher susceptibility to COVID-19, we analyzed the HLA allele frequency distribution in Iranian patients with a severe form of COVID-19. Methods: Overall, 48 severe cases of COVID-19 that were hospitalized and required intensive care unit (ICU) admission between Oct and Dec 2020 were included in this study. Genomic DNA was extracted from the peripheral blood samples and HLA typing (Locus A, B, and DR) was performed for the patients. Results: After analyzing and comparing the results with a reference group of 500 Iranian individuals, a significant association was found for HLA-B*38, HLA-A*68, HLA-A*24, and HLA-DRB1*01. Conclusion: These results may be valuable for studying the potential association of specific HLA alleles with susceptibility to COVID-19 and mortality due to the disease.

Modeling minimum viable population size with multiple genetic problems of small populations

An important goal for conservation is to define minimum viable population (MVP) sizes for long-term persistence. Although many MVP size estimates focus on ecological processes, with increasing evidence for the role of genetic problems in population extinction, conservation practitioners have also increasingly started to incorporate inbreeding depression (ID). However, small populations also face other genetic problems such as mutation accumulation (MA) and loss of genetic diversity through genetic drift that are usually factored into population viability assessments only via verbal arguments. Comprehensive quantitative theory on interacting genetic problems is missing. Here we develop eco-evolutionary quantitative models that track both population size and levels of genetic diversity. Our models assume a biallelic multilocus genome whose loci can be under either a single or interacting genetic forces. In addition to mutation-selection-drift balance (for loci facing ID and MA), we include three forms of balancing selection (for loci where variation is lost through genetic drift). We define MVP size as the lowest population size that avoids an eco-evolutionary extinction vortex after a time sufficient for an equilibrium allele frequency distribution to establish. Our results show that MVP size decreases rapidly with increasing mutation rates for populations whose genomes are only under balancing selection, while for genomes under mutation-selection-drift balance, the MVP size increases rapidly. MVP sizes also increase rapidly with increasing number of loci under the same or different selection mechanisms until a point is reached at which even arbitrarily large populations cannot survive anymore. In the case of fixed number of loci under selection, interaction of genetic problems did not necessarily increase MVP sizes. To further enhance our understanding about interaction of genetic problems, there is need for more empirical studies to reveal how different genetic processes interact in the genome.

Analysis of bone metabolism mechanisms in postmenopausal females with type 2 diabetes and DKK1 gene polymorphisms and the effects of polymer nanomaterials on wound infection in patients

Diabetic patients are prone to abnormal bone metabolism. Menopausal women exhibit reduced estrogen secretion and bone absorption exceeds the rate of bone formation. Therefore, postmenopausal women with diabetes are even more likely to suffer from osteoporosis. Identifying the specific mechanism of abnormal bone metabolism in diabetic menopausal women will help reduce the risk of bone fractures. This study explored the specific mechanisms of bone metabolism disorders in menopausal women with type 2 diabetes in relation to genetic polymorphisms. We found that the distribution frequency of the CA genotype and A allele at the rs1373004 locus of the DKK1 gene in menopausal women with diabetes and abnormal bone mass were significantly lower compared with that in normal bone. The distribution of the GG genotype at the rs1528877 locus was also less frequent compared with those exhibiting normal bone mass. This suggests that the genotype and allele frequency distribution in the DKK1 gene at rs1373004 and RS1528877 in postmenopausal T2DM women is associated with glucose metabolism and bone metabolism. To analyze the efficacy of polylactic acid (PLA)/gelatin nanofibers on T2DM patients with infectious fractures, we compared various aspects of wound healing in patients treated with conventional therapy versus PLA/gelatin nanofibers. The results indicated that the number of days required for wound healing and the frequency of incisions in patients treated with PLA/gelatin nanofibers were significantly lower compared with those treated with conventional therapy (P < 0.05). The wound healing rate of patients treated with PLA/gelatin nanofibers was significantly higher compared with that of patients treated with conventional therapy on days 7, 14, 21, and 28 of treatment. Our findings indicate that PLA/gelatin nanofiber treatment can significantly promote fracture wound healing.

X-chromosomal STR based genetic polymorphisms and demographic history of Sri Lankan ethnicities and their relationship with global populations

A new 16 X-short tandem repeat (STR) multiplex PCR system has recently been developed for Sr Lankans, though its applicability in evolutionary genetics and forensic investigations has not been thoroughly assessed. In this study, 838 unrelated individuals covering all four major ethnic groups (Sinhalese, Sri Lankan Tamils, Indian Tamils and Moors) in Sri Lanka were successfully genotyped using this new multiplex system. The results indicated a high forensic efficiency for the tested loci in all four ethnicities confirming its suitability for forensic applications of Sri Lankans. Allele frequency distribution of Indian Tamils showed subtle but statistically significant differences from those of Sinhalese and Moors, in contrast to frequency distributions previously reported for autosomal STR alleles. This suggest a sex biased demographic history among Sri Lankans requiring a separate X-STR allele frequency database for Indian Tamils. Substantial differences observed in the patterns of LD among the four groups demand the use of a separate haplotype frequency databases for each individual ethnicity. When analysed together with other 14 world populations, all Sri Lankan ethnicities except Indian Tamils clustered closely with populations from Indian Bhil tribe, Bangladesh and Europe reflecting their shared Indo-Aryan ancestry.

Genomic and Phenotypic Diversity of Cultivated and Wild Tomatoes with Varying Levels of Heat Tolerance

Assessment of genetic variability in heat-tolerant tomato germplasm is a pre-requisite to improve yield and fruit quality under heat stress. We assessed the population structure and diversity in a panel of three Solanum pimpinellifolium (wild tomatoes) and 42 S. lycopersicum (cultivated tomatoes) lines and accessions with varying heat tolerance levels. The DArTseq marker was used for the sequencing and 5270 informative single nucleotide polymorphism (SNP) markers were retained for the genomic analysis. The germplasm was evaluated under two heat stress environments for five yield and flower related traits. The phenotypic evaluation revealed moderate broad-sense heritabilities for fruit weight per plant and high broad-sense heritabilities for fruit weight, number of inflorescences per plant, and number of flowers per inflorescence. The hierarchical clustering based on identity by state dissimilarity matrix and UPGMA grouped the germplasm into three clusters. The cluster analysis based on heat-tolerance traits separated the germplasm collection into five clusters. The correlation between the phenotypic and genomic-based distance matrices was low (r = 0.2, p < 0.05). The joint phenotypic and genomic-based clustering grouped the germplasm collection into five clusters well defined for their response to heat stress ranging from highly sensitive to highly tolerant groups. The heat-sensitive and heat-tolerant clusters of S. lycopersicum lines were differentiated by a specific pattern of minor allele frequency distribution on chromosome 11. The joint phenotypic and genomic analysis revealed important diversity within the germplasm collection. This study provides the basis for efficient selection of parental lines to breed heat-tolerant varieties.

Common Treatment, Common Variant: Evolutionary Prediction of Functional Pharmacogenomic Variants

Pharmacogenomics holds the promise of personalized drug efficacy optimization and drug toxicity minimization. Much of the research conducted to date, however, suffers from an ascertainment bias towards European participants. Here, we leverage publicly available, whole genome sequencing data collected from global populations, evolutionary characteristics, and annotated protein features to construct a new in silico machine learning pharmacogenetic identification method called XGB-PGX. When applied to pharmacogenetic data, XGB-PGX outperformed all existing prediction methods and identified over 2000 new pharmacogenetic variants. While there are modest pharmacogenetic allele frequency distribution differences across global population samples, the most striking distinction is between the relatively rare putatively neutral pharmacogene variants and the relatively common established and newly predicted functional pharamacogenetic variants. Our findings therefore support a focus on individual patient pharmacogenetic testing rather than on clinical presumptions about patient race, ethnicity, or ancestral geographic residence. We further encourage more attention be given to the impact of common variation on drug response and propose a new ‘common treatment, common variant’ perspective for pharmacogenetic prediction that is distinct from the types of variation that underlie complex and Mendelian disease. XGB-PGX has identified many new pharmacovariants that are present across all global communities; however, communities that have been underrepresented in genomic research are likely to benefit the most from XGB-PGX’s in silico predictions.