Mouse SNP Miner: an annotated database of mouse functional single nucleotide polymorphisms

BACKGROUND: The mapping of quantitative trait loci in rat and mouse has been extremely successful in identifying chromosomal regions associated with human disease-related phenotypes. However, identifying the specific phenotype-causing DNA sequence variations within a quantitative trait locus has been much more difficult. The recent availability of genomic sequence from several mouse inbred strains (including C57BL/6J, 129X1/SvJ, 129S1/SvImJ, A/J, and DBA/2J) has made it possible to catalog DNA sequence differences within a quantitative trait locus derived from crosses between these strains. However, even for well-defined quantitative trait loci (<10 Mb) the identification of candidate functional DNA sequence changes remains challenging due to the high density of sequence variation between strains. DESCRIPTION: To help identify functional DNA sequence variations within quantitative trait loci we have used the Ensembl annotated genome sequence to compile a database of mouse single nucleotide polymorphisms (SNPs) that are predicted to cause missense, nonsense, frameshift, or splice site mutations (available at ). For missense mutations we have used the PolyPhen and PANTHER algorithms to predict whether amino acid changes are likely to disrupt protein function. CONCLUSION: We have developed a database of mouse SNPs predicted to cause missense, nonsense, frameshift, and splice-site mutations. Our analysis revealed that 20% and 14% of missense SNPs are likely to be deleterious according to PolyPhen and PANTHER, respectively, and 6% are considered deleterious by both algorithms. The database also provides gene expression and functional annotations from the Symatlas, Gene Ontology, and OMIM databases to further assess candidate phenotype-causing mutations. To demonstrate its utility, we show that Mouse SNP Miner successfully finds a previously identified candidate SNP in the taste receptor, Tas1r3, that underlies sucrose preference in the C57BL/6J strain. We also use Mouse SNP Miner to derive a list of candidate phenotype-causing mutations within a previously uncharacterized QTL for response to morphine in the 129/Sv strain

Asymmetric and non-uniform evolution of recently duplicated human genes

<p>Abstract</p> <p>Background</p> <p>Gene duplications are a source of new genes and protein functions. The innovative role of duplication events makes families of paralogous genes an interesting target for studies in evolutionary biology. Here we study global trends in the evolution of human genes that resulted from recent duplications.</p> <p>Results</p> <p>The pressure of negative selection is weaker during a short time immediately after a duplication event. Roughly one fifth of genes in paralogous gene families are evolving asymmetrically: one of the proteins encoded by two closest paralogs accumulates amino acid substitutions significantly faster than its partner. This asymmetry cannot be explained by differences in gene expression levels. In asymmetric gene pairs the number of deleterious mutations is increased in one copy, while decreased in the other copy as compared to genes constituting non-asymmetrically evolving pairs. The asymmetry in the rate of synonymous substitutions is much weaker and not significant.</p> <p>Conclusions</p> <p>The increase of negative selection pressure over time after a duplication event seems to be a major trend in the evolution of human paralogous gene families. The observed asymmetry in the evolution of paralogous genes shows that in many cases one of two gene copies remains practically unchanged, while the other accumulates functional mutations. This supports the hypothesis that slowly evolving gene copies preserve their original functions, while fast evolving copies obtain new specificities or functions.</p> <p>Reviewers</p> <p>This article was reviewed by Dr. Igor Rogozin (nominated by Dr. Arcady Mushegian), Dr. Fyodor Kondrashov, and Dr. Sergei Maslov.</p

Application of system approach to the analysis of socially caused psychological peculiarities of a person during his occupational activity

It is shown that the loss of social work human homeostatic mechanisms operate less efficiently, which prompts him to change the type of activity. Job vocation allows higher quality, less tired. If the necessary knowledge, skills are an employee, the «emotional intellect» helps to achieve a unique highquality productsПоказано, что при потере работы социальные гомеостатические механизмы человека функционируют менее эффективно, что подталкивает его менять вид деятельности. Работа по призванию позволяет производить больше, с более высоким качеством, меньше уставать. Если необходимые знания, навыки имеются у работника, то эмоциональный ителлект помогает добиться уникально высокого качества продукци

Interaction between continuous education and the state-formed system of long-term care for elderly people

Created a state system of long-term care for the elderly will allow them to implement passive adaptation. Active adaptation through continuous education occurs when the representatives of the older independently or with a special organization, volunteer free find suitable jobs for them, are retrained carry out feasible public meaningful, paid work. For economic reasons, it is advisable to use distance education methodsСоздаваемая государством система долговременного ухода за пожилыми людьми позволит им осуществить пассивную адаптацию. Активная адаптация путем непрерывного образования происходит, если представители старшего возраста самостоятельно или с помощью специальной организации, добровольно находят сво-бодные, подходящие для них рабочие места, проходят профессиональную переподго-товку, выполняют посильный общественно значимый, оплачиваемый труд. По эконо-мическим соображениям целесообразно использовать дистанционные методы образо-вани

Application of professional standards for the organization of training of pensioners at the level of secondary vocational education

Применение профессиональных стандартов позволит повысить эффективность трудоустройства и работы пенсионеров, которые часто занимают должности, соответствующие уровню подготовки СПО. Этот процесс имеет характерные черты аттракторовThe professional standards allows to increase the effectiveness of employment and working pensioners, who often occupy positions corresponding to the level of training of secondary vocational education. This process has the characteristic features of attractor

Questions of reliability and validity of professional standards in the event of the solution problem of professional education

Решаются вопросы оценки надежности и валидности профессиональных стандартов, применяемых для выбора ответственными лицами наиболее перспективных кандидатур из числа желающих занять вакантное рабочее местоThe issues of assessing the reliability and validity of professional standards applicable to the selection of responsible persons the most promising candidates from among those wishing to occupy the vacant job

A retrocopy of a gene can functionally displace the source gene in evolution

The e(y)2 gene of Drosophila melanogaster encodes the ubiquitous evolutionarily conserved co-activator of RNA polymerase II that is involved in transcription regulation of a high number of genes. The Drosophila e(y)2b gene, paralogue of the e(y)2 has been found. The analysis of structure of the e(y)2, e(y)2b and its orthologues from other species reveals that the e(y)2 gene derived as a result of retroposition of the e(y)2b during Drosophila evolution. The mRNA-derived retrogenes lack introns or regulatory regions; most of them become pseudogenes whereas some acquire tissue-specific functions. Here we describe the different situation: the e(y)2 retrogene performs the general function and is ubiquitously expressed, while the source gene is functional only in a small group of male germ cells. This must have resulted from retroposition into a transcriptionally favorable region of the genome

Simplifying the mosaic description of DNA sequences

By using the Jensen-Shannon divergence, genomic DNA can be divided into compositionally distinct domains through a standard recursive segmentation procedure. Each domain, while significantly different from its neighbours, may however share compositional similarity with one or more distant (non--neighbouring) domains. We thus obtain a coarse--grained description of the given DNA string in terms of a smaller set of distinct domain labels. This yields a minimal domain description of a given DNA sequence, significantly reducing its organizational complexity. This procedure gives a new means of evaluating genomic complexity as one examines organisms ranging from bacteria to human. The mosaic organization of DNA sequences could have originated from the insertion of fragments of one genome (the parasite) inside another (the host), and we present numerical experiments that are suggestive of this scenario.Comment: 16 pages, 1 figure, Accepted for publication in Phys. Rev.