0000000000542969
AUTHOR
Davids Fridmanis
First Report on the Latvian SARS-CoV-2 Isolate Genetic Diversity
Remaining a major healthcare concern with nearly 29 million confirmed cases worldwide at the time of writing, novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused more than 920 thousand deaths since its outbreak in China, December 2019. First case of a person testing positive for SARS-CoV-2 infection within the territory of the Republic of Latvia was registered on 2nd of March 2020, 9 days prior to the pandemic declaration by WHO. Since then, more than 277,000 tests were carried out confirming a total of 1,464 cases of coronavirus disease 2019 (COVID-19) in the country as of 12th of September 2020. Rapidly reacting to the spread of the infection, an ongoing sequenci…
Additional file 1: Table S1. of Next-generation-sequencing-based identification of familial hypercholesterolemia-related mutations in subjects with increased LDLâ C levels in a latvian population
All variants found in study group. (DOC 611Â kb)
Unusual genomic structure: melanocortin receptors in Fugu.
The melanocortin (MC) receptors are found in five subtypes in mammals and chicken, while recent studies have shown that the Fugu (Takifugu rubripes) genome has only four MC receptors and the zebrafish genome has six subtypes. The MC3 receptor seems to be missing from the two closely related pufferfishes, Fugu and Tetraodon (Tetraodon nigroviridis). The MC2 and MC5 receptors in the pufferfish have introns. Moreover, these two receptors are found in a tandem that is remarkably conserved in several vertebrate species. Here, we speculate about the genomic origin of the MC receptors.
High affinity agonistic metal ion binding sites within the melanocortin 4 receptor illustrate conformational change of transmembrane region 3.
We created a molecular model of the human melanocortin 4 receptor (MC4R) and introduced a series of His residues into the receptor protein to form metal ion binding sites. We were able to insert micromolar affinity binding sites for zinc between transmembrane region (TM) 2 and TM3 where the metal ion alone was able to activate this peptide binding G-protein-coupled receptor. The exact conformation of the metal ion interactions allowed us to predict the orientation of the helices, and remodeling of the receptor protein indicated that Glu100 and Ile104 in TM2 and Asp122 and Ile125 in TM3 are directed toward a putative area of activation of the receptor. The molecular model suggests that a rot…
Stronger Association of Common Variants in TCF7L2 Gene with Nonobese Type 2 Diabetes in the Latvian Population
Polymorphisms in the gene coding for transcription factor 7 like 2 (TCF7L2) are recognized as the strongest common genetic risk factors for type 2 diabetes (T2D) across multiple ethnicities. This study was conducted to evaluate an association between TCF7L2 variants and diabetes susceptibility in the population of Latvia. We genotyped 4 single nucleotide polymorphisms (SNP) rs7901695, rs7903146, rs11196205 and rs12255372 in 1 093 controls and 1 043 diabetic subjects. Association with T2D was found for 3 SNPs rs7901695, rs7903146 and rs12255372 in the whole sample (under an additive genetic model, the adjusted odds ratios (OR) were 1.26, 95% CI [1.08-1.48], P=0.003; OR=1.32, 95% CI [1.12-1.5…
Origin of the prolactin-releasing hormone (PRLH) receptors: evidence of coevolution between PRLH and a redundant neuropeptide Y receptor during vertebrate evolution.
We present seven new vertebrate homologs of the prolactin-releasing hormone receptor (PRLHR) and show that these are found as two separate subtypes, PRLHR1 and PRLHR2. Analysis of a number of vertebrate sequences using phylogeny, pharmacology, and paralogon analysis indicates that the PRLHRs are likely to share a common ancestry with the neuropeptide Y (NPY) receptors. Moreover, a micromolar level of NPY was able to bind and inhibit completely the PRLH-evoked response in PRLHR1-expressing cells. We suggest that an ancestral PRLH peptide started coevolving with a redundant NPY binding receptor, which then became PRLHR, approximately 500 million years ago. The PRLHR1 subtype was shown to have…