Microsatellites are polymorphic tracts of short tandem repeats with one to six base-pair (bp) motifs and are some of the most polymorphic variants in the genome. Using 6084 Icelandic parent-offspring ...trios we estimate 63.7 (95% CI: 61.9-65.4) microsatellite de novo mutations (mDNMs) per offspring per generation, excluding one bp repeats motifs (homopolymers) the estimate is 48.2 mDNMs (95% CI: 46.7-49.6). Paternal mDNMs occur at longer repeats than maternal ones, which are in turn larger with a mean size of 3.4 bp vs 3.1 bp for paternal ones. mDNMs increase by 0.97 (95% CI: 0.90-1.04) and 0.31 (95% CI: 0.25-0.37) per year of father's and mother's age at conception, respectively. Here, we find two independent coding variants that associate with the number of mDNMs transmitted to offspring; The minor allele of a missense variant (allele frequency (AF) = 1.9%) in MSH2, a mismatch repair gene, increases transmitted mDNMs from both parents (effect: 13.1 paternal and 7.8 maternal mDNMs). A synonymous variant (AF = 20.3%) in NEIL2, a DNA damage repair gene, increases paternally transmitted mDNMs (effect: 4.4 mDNMs). Thus, the microsatellite mutation rate in humans is in part under genetic control.
Malignant hyperthermia (MH) susceptibility is a rare life-threatening disorder that occurs upon exposure to a triggering agent. MH is commonly due to protein-altering variants in RYR1 and CACNA1S. ...The American College of Medical Genetics and Genomics recommends that when pathogenic and likely pathogenic variants in RYR1 and CACNA1S are incidentally found, they should be reported to the carriers. The detection of actionable variants allows the avoidance of exposure to triggering agents during anesthesia. First, we report a 10-year-old Icelandic proband with a suspected MH event, harboring a heterozygous missense variant NM_000540.2:c.6710G>A r.(6710g>a) p.(Cys2237Tyr) in the RYR1 gene that is likely pathogenic. The variant is private to four individuals within a three-generation family and absent from 62,240 whole-genome sequenced (WGS) Icelanders. Haplotype sharing and WGS revealed that the variant occurred as a somatic mosaicism also present in germline of the proband's paternal grandmother. Second, using a set of 62,240 Icelanders with WGS, we assessed the carrier frequency of actionable pathogenic and likely pathogenic variants in RYR1 and CACNA1S. We observed 13 actionable variants in RYR1, based on ClinVar classifications, carried by 43 Icelanders, and no actionable variant in CACNA1S. One in 1450 Icelanders carries an actionable variant for MH. Extensive sequencing allows for better classification and precise dating of variants, and WGS of a large fraction of the population has led to incidental findings of actionable MH genotypes.
Despite the important role that monozygotic twins have played in genetics research, little is known about their genomic differences. Here we show that monozygotic twins differ on average by 5.2 early ...developmental mutations and that approximately 15% of monozygotic twins have a substantial number of these early developmental mutations specific to one of them. Using the parents and offspring of twins, we identified pre-twinning mutations. We observed instances where a twin was formed from a single cell lineage in the pre-twinning cell mass and instances where a twin was formed from several cell lineages. CpG>TpG mutations increased in frequency with embryonic development, coinciding with an increase in DNA methylation. Our results indicate that allocations of cells during development shapes genomic differences between monozygotic twins.
The spread of SARS-CoV-2 is dependent on several factors, both biological and behavioural. The effectiveness of nonpharmaceutical interventions can be attributed largely to changes in human ...behaviour, but quantifying this effect remains challenging. Reconstructing the transmission tree of the third wave of SARS-CoV-2 infections in Iceland using contact tracing and viral sequence data from 2522 cases enables us to directly compare the infectiousness of distinct groups of persons.
The transmission tree enables us to model the effect that a given population prevalence of vaccination would have had on the third wave had one of three different vaccination strategies been implemented before that time. This allows us to compare the effectiveness of the strategies in terms of minimizing the number of cases, deaths, critical cases, and severe cases.
We found that people diagnosed outside of quarantine (Rˆ=1.31) were 89% more infectious than those diagnosed while in quarantine (Rˆ=0.70) and that infectiousness decreased as a function of time spent in quarantine before diagnosis, with people diagnosed outside of quarantine being 144% more infectious than those diagnosed after ≥3 days in quarantine (Rˆ=0.54). People of working age, 16 to 66 years (Rˆ=1.08), were 46% more infectious than those outside of that age range (Rˆ=0.74).
We found that vaccinating the population in order of ascending age or uniformly at random would have prevented more infections per vaccination than vaccinating in order of descending age, without significantly affecting the expected number of deaths, critical cases, or severe cases.
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Abstract
A pressing concern in the SARS-CoV-2 epidemic and other viral outbreaks, is the extent to which the containment measures are halting the viral spread. A straightforward way to assess this is ...to tally the active cases and the recovered ones throughout the epidemic. Here, we show how epidemic control can be assessed with molecular information during a well characterized epidemic in Iceland. We demonstrate how the viral concentration decreased in those newly diagnosed as the epidemic transitioned from exponential growth phase to containment phase. The viral concentration in the cases identified in population screening decreased faster than in those symptomatic and considered at high risk and that were targeted by the healthcare system. The viral concentration persists in recovering individuals as we found that half of the cases are still positive after two weeks. We demonstrate that accumulation of mutations in SARS-CoV-2 genome can be exploited to track the rate of new viral generations throughout the different phases of the epidemic, where the accumulation of mutations decreases as the transmission rate decreases in the containment phase. Overall, the molecular signatures of SARS-CoV-2 infections contain valuable epidemiological information that can be used to assess the effectiveness of containment measures.
We construct two functors from the submodule category of a representation-finite self-injective algebra Λ to the module category of the stable Auslander algebra of Λ. These functors factor through ...the module category of the Auslander algebra of Λ. Moreover they induce equivalences from the quotient categories of the submodule category modulo their respective kernels and said kernels have finitely many indecomposable objects up to isomorphism. Their construction uses a recollement of the module category of the Auslander algebra induced by an idempotent and this recollement determines a characteristic tilting and cotilting module. If Λ is taken to be a Nakayama algebra, then said tilting and cotilting module is a characteristic tilting module of a quasi-hereditary structure on the Auslander algebra. We prove that the self-injective Nakayama algebras are the only algebras with this property.
Quiver-graded Richardson orbits Eiríksson, Ögmundur; Sauter, Julia
Communications in algebra,
10/2019, Letnik:
47, Številka:
10
Journal Article
Recenzirano
Odprti dostop
In Lie theory, a dense orbit in the nilpotent radical of a parabolic group under the operation of the parabolic is called a Richardson orbit. We define a quiver-graded version of Richardson orbits ...generalizing the classical definition in the case of the general linear group. We define a quasi-hereditary algebra called the nilpotent quiver algebra whose isomorphism classes of Δ-filtered modules correspond to orbits in our generalized setting. We translate the existence of a Richardson orbit into the existence of a rigid Δ-filtered module of a given dimension vector. We study an idempotent recollement of this algebra whose associated intermediate extension functor can be used to produce Richardson orbits in some situations. This can be explicitly calculated in examples. We also give examples where no Richardson orbit exists.
We construct two functors from the submodule category of a self-injective representation-finite algebra \(\Lambda\) to the module category of the stable Auslander algebra of \(\Lambda\). These ...functors factor through the module category of the Auslander algebra of \(\Lambda\). Moreover they induce equivalences from the quotient categories of the submodule category modulo their respective kernels and said kernels have finitely many indecomposable objects up to isomorphism. Their construction uses a recollement of the module category of the Auslander algebra induced by an idempotent and this recollement determines a characteristic tilting and cotilting module. If \(\Lambda\) is taken to be a Nakayama algebra, then said tilting and cotilting module is a characteristic tilting module of a quasi-hereditary structure on the Auslander algebra. We prove that the self-injective Nakayama algebras are the only algebras with this property.
In Lie theory, a dense orbit in the unipotent radical of a parabolic group under the adjoint action is called a Richardson orbit. We define a quiver-graded version of Richardson orbits generalising ...the classical definition in the case of the general linear group. In our setting a product of parabolic subgroups of general linear groups acts on a closed subvariety of the representation space of a quiver. Such dense orbits do not exist in general. We define a quasi-hereditary algebra called the nilpotent quiver algebra whose isomorphism classes of \(\Delta\)-filtered modules correspond to orbits in our generalised setting. We translate the existence of a Richardson orbit into the existence of a rigid \(\Delta\)-filtered module of a given dimension vector. We study an idempotent recollement of this algebra whose associated intermediate extension functor can be used to produce Richardson orbits in some situations. This can be explicitly calculated in examples. We also give examples where no Richardson orbit exists.
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