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Short tandem repeats (STRs) are a class of rapidly mutating genetic elements typically characterized by repeated units of 1-6 bp. We leveraged whole-genome sequencing data for 152 recombinant inbred (RI) strains from the BXD family of mice to map loci that modulate genome-wide patterns of new mutations arising during parent-to-offspring transmission at STRs. We defined quantitative phenotypes describing the numbers and types of germline STR mutations in each strain and performed quantitative trait locus (QTL) analyses for each of these phenotypes. We identified a locus on Chromosome 13 at which strains inheriting the C57BL/6J (B) haplotype have a higher rate of STR expansions than those inheriting the DBA/2J (D) haplotype. The strongest candidate gene in this locus is Msh3, a known modifier of STR stability in cancer and at pathogenic repeat expansions in mice and humans, as well as a current drug target against Huntington's disease. The D haplotype at this locus harbors a cluster of variants near the 5' end of Msh3, including multiple missense variants near the DNA mismatch recognition domain. In contrast, the B haplotype contains a unique retrotransposon insertion. The rate of expansion covaries positively with Msh3 expression-with higher expression from the B haplotype. Finally, detailed analysis of mutation patterns showed that strains carrying the B allele have higher expansion rates, but slightly lower overall total mutation rates, compared with those with the D allele, particularly at tetranucleotide repeats. Our results suggest an important role for inherited variants in Msh3 in modulating genome-wide patterns of germline mutations at STRs.

Short tandem repeats (STRs) are units of 1-6 bp that repeat in a tandem fashion in DNA. Along with single nucleotide polymorphisms and large structural variations, they are among the major genomic variants underlying genetic, and likely phenotypic, divergence. STRs experience mutation rates that are orders of magnitude higher than other well-studied genotypic variants. Frequent copy number changes result in a wide range of alleles, and provide unique opportunities for modulating complex phenotypes through variation in repeat length. While classical studies have identified key roles of individual STR loci, the advent of improved sequencing technology, high-quality genome assemblies for diverse species, and bioinformatics methods for genome-wide STR analysis now enable more systematic study of STR variation across wide evolutionary ranges. In this review, we explore mutation and selection processes that affect STR copy number evolution, and how these processes give rise to varying STR patterns both within and across species. Finally, we review recent examples of functional and adaptive changes linked to STRs.

Tandem repeats (TRs) represent one of the largest sources of genetic variation in humans and are implicated in a range of phenotypes. Here we present a deep characterization of TR variation based on high coverage whole genome sequencing from 3550 diverse individuals from the 1000 Genomes Project and H3Africa cohorts. We develop a method, EnsembleTR, to integrate genotypes from four separate methods resulting in high-quality genotypes at more than 1.7 million TR loci. Our catalog reveals novel sequence features influencing TR heterozygosity, identifies population-specific trinucleotide expansions, and finds hundreds of novel eQTL signals. Finally, we generate a phased haplotype panel which can be used to impute most TRs from nearby single nucleotide polymorphisms (SNPs) with high accuracy. Overall, the TR genotypes and reference haplotype panel generated here will serve as valuable resources for future genome-wide and population-wide studies of TRs and their role in human phenotypes.

The problem of static analysis of a circular cylindrical shell located on the elastic base of the Winkler and reinforced by longitudinal ribs is considered. The stiffeners have a rectangular cross section. The external action is represented by forces evenly distributed along the longitudinal axis, acting on the ribs from the upper structure. It is assumed that at the ends of the shell there are flat vertical walls, which give the contour absolute rigidity in the transverse direction and do not interfere with the longitudinal movement of the shell points. The General moment theory of a circular cylindrical shell is used to solve the problem. A computer program has been developed to implement the proposed algorithm. With the help of the program, a number of examples of calculation are made In the given examples, the influence of such factors as the relative length and thickness, the slope angle of the solution shell, the relative stiffness of the onboard elements on the stress state of the shell is analyzed.

The aim of this paper is to determine the trends of the main indicators of life expectancy in Russia in the 1950s to 2000s. For this purpose, life tables for Russia (former -- RSFSR) from 1959 to 2014 for one-year age intervals were analyzed. The main indicators under review are the modal age at death and the standard deviation of life expectancy from the modal value for all ages and the mode. As a result, it is concluded that in Russia the modal age at death and the indicator of life expectancy have stagnated over the past 60 years, and definite trends can be traced only in short periods of time, namely after 2009 when all basic life expectancy indicators were steadily increasing. Life expectancy is far behind those of the developed countries by about half a century. [ABSTRACT FROM AUTHOR]

The equation of symmetric equilibrium of an isothermal gas with an unknown boundary in the field of a body force is considered. Conditions for solvability and insolvability of the problem as well as for uniqueness and nonuniqueness of solutions are presented. Examples of finite, countable, or continual sets of solutions are constructed including equipotential ones. Static stability of solutions is analyzed too. [ABSTRACT FROM AUTHOR]

Lasso peptides are a class of ribosomally-synthesized and posttranslationally-modified natural products with diverse bioactivities. This review describes the structure and function of all known lasso peptides (as of mid-2012) and covers our current knowledge about the biosynthesis of those molecules. The isolation and characterization of lasso peptides are also covered as are bioinformatics strategies for the discovery of new lasso peptides from genomic sequence data. Several studies on the engineering of new or improved function into lasso peptides are highlighted, and unanswered questions in the field are also described.