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In 2020, we reported MICA allele frequencies from a cohort of over one million German individuals. This study identified MICA*008 (42%), MICA*002 (12%), and MICA*009 (9%) as the most common MICA alleles at protein resolution. Additionally, we discovered novel alleles with a cumulative frequency of 0.3%. To reduce this fraction of unnamed sequences, we aimed to fully characterize the most frequent novel alleles using both long- and short-read sequencing. As a result, we submitted 603 sequences to the IPD-IMGT/HLA Database: 406 novel alleles and 197 sequence extensions and confirmations. Among the novel alleles, 199 encoded for distinct novel MICA proteins. Following the inclusion of these sequences into the IPD-IMGT/HLA Database, we genotyped 93,814 individuals from an independent cohort. In the German subset (n=48,618), our previous findings on MICA allele frequencies were confirmed. As anticipated, the cumulative frequency of novel alleles decreased significantly from 0.3% to 0.03%, reflecting the expanded reference database. The most frequent of the previously novel alleles were MICA*107N (0.02%), MICA*141 (0.01%), MICA*119 (0.01%), MICA*089 (0.01%), and MICA*247 (0.01%). While allele frequencies in other European and the South African White population were similar to those in Germany, greater variation was observed in the South African Black, non-indigenous Chilean, and Turkish populations. Notably, some of the novel alleles appeared to be population-specific; for example, MICA*258 was exclusively identified in samples from the Black or Colored populations of South Africa. In conclusion, the extensive characterization of novel MICA alleles has substantially reduced the fraction of unknown sequences in MICA donor genotyping, which will support future biomedical and population genetic studies.

The brain's response to external events depends on its internal arousal states, which are dynamically governed by neuromodulatory systems and have recently been linked to coordinated spike timing cascades in widespread brain networks. At rest, both arousal fluctuations and spiking cascades are evident throughout the forebrain and play out over multisecond time scales. Here, by analyzing large‐scale neural recording data collected by the Allen Institute, it is demonstrated that these intrinsic processes persist across the mouse brain even during periods of continuous visual stimulation. In the stationary animal, each quasi‐periodic cascade cycle systematically influenced 1) the efficacy of encoding in visually responsive brain areas and 2) the incidence of memory‐related hippocampal ripples. During this cycle, the phase of high arousal is marked by high efficiency in visual encoding whereas the phase of low arousal is marked by the occurrence of hippocampal ripples. However, during bouts of active locomotion, this cycle is abolished and brain maintained a state of elevated visual coding efficiency, with ripples being nearly absent. It is hypothesized that the infra‐slow cascade dynamics reflect an adaptive cycle of alternating exteroceptive sensory sampling and internal mnemonic function that persistently pervades the forebrain, only stopping during active exploration of the environment. This study reveals widespread, coordinated brain activity during passive visual stimulation in mice. Sensory coding, phase‐locked with the periodic dynamics, shows an inverse relationship to hippocampal ripples. The results suggest that periodic brain activity spurs alteration between two distinct operational modes of brain, facilitating exteroceptive sensory sampling and internal mnemonic processes, respectively.

Lynch syndrome is characterised by heterozygous germline mutations in the MisMatch Repair (MMR) genes and an increased risk of cancer. Previous population estimates based on cohorts with colorectal cancer suggest one in 300 people have a disease-causing variant. This study calculated the population frequency of Lynch syndrome from Predicted pathogenic variants in MMR genes in the general population. MLH1, MSH2, MSH6 and PMS2 variants were downloaded from gnomAD v.2.1, and annotated in ANNOVAR. Our population frequencies of heterozygous Predicted pathogenic variants were calculated from the sum of structural, null, rare computationally-damaging missense changes, and founder variants. Population frequencies were also derived from the proposed ClinGen variant specifications, and from pathogenic variants in the ClinVar, LOVD or InSiGHT websites. Predicted pathogenic variants were found in one in 94 people in gnomAD v.2.1.1 using our strategy, and one in 122, 203, 199 or 594 using the proposed ClinGen specifications, and the ClinVar, LOVD or InSiGHT databases, respectively. The frequencies derived from ClinVar (one in 203) and LOVD (one in 199) were based on accurate assessments of penetrant variants since they were largely derived from patient testing, but were underestimates because not all gnomAD variants had been assessed. Our strategy and that of the proposed ClinGen specifications examined each variant in gnomAD and resulted in more common population frequencies but some assessments may have been inaccurate, and variants incompletely penetrant. The number of Predicted pathogenic MMR gene variants in the general population suggests that Lynch syndrome is more common than reported previously.

In genetic disease assessment centers, DNA sequencing can produce results irrelevant to the genetic examination’s purpose. The American College of Medical Genetics and Genomics (ACMG) recommends evaluating and reporting 81 genes discovered using clinical genomic sequencing. While population studies on large cohorts can provide statistics on the prevalence of secondary findings (SFs), no studies have been published yet on large cohorts in Turkiye. We investigated ACMG SF by evaluating clinical exome sequencing data in 1600 individuals from different regions in Turkiye. We detected SF variants reported in ClinVar in 86 individuals (5.375%). Of the SFs, 30% were cardiovascular, 26% were cancer, 16% were neonatal metabolic disorders, and 28% were variants associated with various genetic diseases. In addition, we identified 212 different variants in 226 individuals and 45 different genes, which were not reported in ClinVar. When our results are compared with the Turkish National Genome and Bioinformatics Project database and studies in the literature, the studies vary in terms of participant characteristics, sequencing techniques, and versions of the ACMG SF list. Our findings highlight the importance of expanding and tailoring SF reporting guidelines in populations with high consanguinity and limited cohort-based data.

MICA is a stress-induced ligand of the NKG2D receptor that stimulates NK and T cell responses and was identified as a key determinant of anti-tumor immunity. The MICA gene is located inside the MHC complex and is in strong linkage disequilibrium with HLA-B . While an HLA-B*48 -linked MICA deletion-haplotype was previously described in Asian populations, little is known about other MICA copy number variations. Here, we report the genotyping of more than two million individuals revealing high frequencies of MICA duplications (1%) and MICA deletions (0.4%). Their prevalence differs between ethnic groups and can rise to 2.8% (Croatia) and 9.2% (Mexico), respectively. Targeted sequencing of more than 70 samples indicates that these copy number variations originate from independent nonallelic homologous recombination events between segmental duplications upstream of MICA and MICB . Overall, our data warrant further investigation of disease associations and consideration of MICA copy number data in oncological study protocols.

Background Exome and genome sequencing is becoming the method of choice for rare disease diagnostics. One of the key challenges remaining is distinguishing the disease causing variants from the benign background variation. After analysis and annotation of the sequencing data there are typically thousands of candidate variants requiring further investigation. One of the most effective and least biased ways to reduce this number is to assess the rarity of a variant in any population. Currently, there are a number of reliable sources of information for major population frequencies when considering single nucleotide variants (SNVs) and small insertion and deletions (INDELs), with gnomAD as the most prominent public resource available. However, local variation or frequencies in sub-populations may be underrepresented in these public resources. In contrast, for structural variation (SV), the background frequency in the general population is more or less unknown mostly due to challenges in calling SVs in a consistent way. Keeping track of local variation is one way to overcome these problems and significantly reduce the number of potential disease causing variants retained for manual inspection, both for SNVs and SVs. Results Here, we present loqusdb, a tool to solve the challenge of keeping track of any type of variant observations from genome sequencing data. Loqusdb was designed to handle a large flow of samples and unlike other solutions, samples can be added continuously to the database without rebuilding it, facilitating improvements and additions. We assessed the added value of a local observations database using 98 samples annotated with information from a background of 888 unrelated individuals. Conclusions We show both how powerful SV analysis can be when filtering for population frequencies and how the number of apparently rare SNVs/INDELs can be reduced by adding local population information even after annotating the data with other large frequency databases, such as gnomAD. In conclusion, we show that a local frequency database is an attractive, and a necessary addition to the publicly available databases that facilitate the analysis of exome and genome data in a clinical setting.

Population frequency has been one of the most widely used criteria to help assign pathogenicity to newly described mitochondrial DNA variants. However, after sequencing this molecule in thousands of healthy individuals, it has been observed that a very large number of genetic variants have a very low population frequency, which has raised doubts about the utility of this criterion. By analyzing the genetic variation of mitochondrial DNA-encoded genes for oxidative phosphorylation subunits in 195,983 individuals from HelixMTdb that were not sequenced based on any medical phenotype, we show that rare variants are deleterious and, along with other criteria, population frequency is still a useful criterion to assign pathogenicity to newly described variants.

Conservation agriculture is increasingly recognized as a sustainable alternative to conventional farming in temperate regions due to its benefits in terms of reducing soil erosion, enhancing water retention, and mitigating climate change. Despite these benefits, these practices are not broadly adopted, partially due to perceived weed management challenges in conservation systems. This paper explores how a conservation system that uses cover crops and non-inversion tillage (chiselling) influences the weed flora abundance and evolution before cover crop termination and over a complete rotation cycle (sunflower–winter wheat–maize–sunflower) in southeastern Romania when compared to conventional tillage (ploughing). Overall, the conservation system significantly reduced weed density by 31%, preserving a higher diversity and evenness (H′ = 0.75, E = 0.46) by the end of the rotation cycle and an evenly distributed weed community compared to the conventional system, where the opportunistic species Veronica hederifolia exhibited dominance.

Despite the general belief that the Southern Ocean harbors low fish biodiversity, the Weddell Sea hosts one of the richest fish communities in the region. Parallelly, the Weddell Sea is also known for the presence of dense and diverse macrobenthos. Most macrobenthic invertebrates, such as gorgonians, sponges and bryozoans, are considered ecosystem engineers as they generate a three-dimensional structure that increases habitat heterogeneity. This structural complexity serves as a refuge against predators as well as a nursery ground for many organisms, including fish species. By analyzing video transects recorded by a Remotely Operated Vehicle, we investigated density, spatial distribution and size-frequency of populations of the demersal fish species inhabiting macrobenthic communities in the southernmost part of the Weddell Sea. We also attempted to unveil whether there is any relationship between benthic and fish communities and substrate, as well as some fish behavioral patterns. The dominance of juveniles in the surveyed fish assemblages provides evidence that, at this life stage, some fish species appear to be positively associated with complex benthic communities conformed by bryozoans, sponges and gorgonians which are more common in sand matrix with sparse rocks substrates. Moreover, about 37% of all specimens recorded were resting on benthic invertebrates or were using them to hide, implying that Antarctic benthic communities might offer suitable habitat. As such, it can be concluded that there was an apparent relationship between certain species of fish and the different benthic communities, yet the exact triggers and/or factors behind such an association remain partially elusive.

The study of the geographic distribution of the allelic variant of the OAS1 gene associated with severe form of the infections caused by RNA viruses was carried out using the rs10774671 polymorphic locus. The mutant allele encoding the p42 protein isoform was most prevalent in the Russian populations. A comparative analysis of the prevalence of the mutant allele in world populations showed that its frequency is 0.9 among the inhabitants of Northern Eurasia, while the allele encoding the p46 protein isoform is widespread among the population of West Central Africa. A cartographic analysis of the relationship between the population—frequency characteristics of the marker alleles and the geographical remoteness of the populations showed that the mutant allele is most often observed in the indigenous populations of the Far East, which suggests its East Asian origin.