Identifying the favored mutation in a positive selective sweep.

Most approaches that capture signatures of selective sweeps in population genomics data do not identify the specific mutation favored by selection. We present iSAFE (for "integrated selection of allele favored by evolution"), a method that enables researchers to accurately pinpoint the favored mutation in a large region (∼5 Mbp) by using a statistic derived solely from population genetics signals. iSAFE does not require knowledge of demography, the phenotype under selection, or functional annotations of mutations

Simulation of Thermal Stratification and Salinity Using the Ce-Qual-W2 Model (Case Study: Mamloo Dam)

Due to the shortage of fresh water, the quality of stored water in reservoirs has become increasingly important. Thermal regime and salinity are factors that affect the quality of water reservoirs. These two parameters were studied in Mamloo Dam in Tehran province. This dam has recently started to be uses as a source of drinking water for Tehran and thus its water quality is of increased importance. In this regard, the hydrodynamic model for 2014 to 2015 was built and calibrated by the CE-QUAL-W2 model and the model was used to simulate the thermal regime and salinity up to 2020. Two main scenarios were studied in this period, the continuation of the current situation or a 2.5% increase in water requirements and 5% decrease in discharge. The results show that the reservoir will experience thermal stratification in the summer and vertical mixing in the winter. Dased on these results Mamloo reservoir is in branch of warm Monomictic lake. Also results showed that thermal stratification and ssalinity stratification dominates simultaneity. Besides this issue with 2.5% increase in water requirements and 5% decrease in discharge, duration of summer thermal stratification will decrease although intensity of thermal stratification will increase

Reduction in Renal Function After Renal Arteriography and After Renal Artery Angioplasty

AbstractObjective: to investigate the incidence and risk factors for renal function deterioration after renal angiography and angioplasty or stenting.Methods: a retrospective study of 85 consecutive patients undergoing selective renal artery arteriography (n=53) or renal artery angioplasty % (PTRA) stenting (n=32) for renal artery stenosis. Multivariate logistic regression analysis was used to determine independent predictors of deterioration of renal function, defined as an increase of serum creatinine by at least one third within 24h.Results: deterioration of renal function occurred in 13 patients (15%), [8/53 (15%) after angiography and 5/32 (16%) after PTRA/stenting]. Only pre-existing renal impairment (se-creatinine≥177μmol/l) (Odds ratio: 40; 95% confidence interval 1.2–72, p=0.02) and administered dosage of contrast agent (more than 225ml) (OR 67; 95% CI1 1.8–100, p=0.02) were independently associated with renal function deterioration.Conclusion: transient renal dysfunction after renal artery angiography or PTRA/stenting occurs in about 15% of patients, but persistent renal failure is uncommon. Pre-existing renal impairment and amount of contrast agent are independent risk factors. Endovascular treatment of renal artery stenosis is not associated with a higher risk of renal deterioration compared to selective renal angiography

Evaluation of sperm chromatin integrity using aniline blue and toluidine blue staining in infertile and normozoospermic men

Background: Male infertility is defined as a man lost his ability to fertilize a fertile female naturally. Diagnosis of male infertility cannot be made just according to basic semen analysis. It is necessity to have specific tests for evaluation of chromatin integrity. In this study, an attempt was made to evaluate the sperm chromatin quality in fertile men and infertile subgroup. Methods: Among 1386 couples, 342 men were categorized into normospermia and 1044 were infertile and they were referred to Yazd Research and Clinical Center for infertility treatment. Standard semen analysis and sperm nuclear maturity tests including aniline blue (AB) and toluidine blue (TB) staining were done. Data were analyzed by SPSS software. The p=0.05 was considered statistically significant. Results: The mean value of TB staining was significantly higher in infertile group compared to normospermic group (p=0.005). Mean of sperm normal morphology was lower in idiopathic infertile men in comparison with normozoospermic men (p= 0.001). The highest negative correlation was obtained between sperm count and AB staining. Progressive motility was negatively correlated with AB and TB staining in both groups but there was no significant difference between AB staining and progressive motility in men normospermia group. Conclusion: Sperm chromatin staining using AB and TB showed a negative association between sperm chromatin condensation with sperm count, normal morphology and progressive motility. It seems that the AB and TB test may be useful for the assessment of male fertility potential. © 2019 Avicenna Research Institute. All rights reserved

Genome-wide scans provide evidence for positive selection of genes implicated in Lassa fever

Rapidly evolving viruses and other pathogens can have an immense impact on human evolution as natural selection acts to increase the prevalence of genetic variants providing resistance to disease. With the emergence of large datasets of human genetic variation, we can search for signatures of natural selection in the human genome driven by such disease-causing microorganisms. Based on this approach, we have previously hypothesized that Lassa virus (LASV) may have been a driver of natural selection in West African populations where Lassa haemorrhagic fever is endemic. In this study, we provide further evidence for this notion. By applying tests for selection to genome-wide data from the International Haplotype Map Consortium and the 1000 Genomes Consortium, we demonstrate evidence for positive selection in LARGE and interleukin 21 (IL21), two genes implicated in LASV infectivity and immunity. We further localized the signals of selection, using the recently developed composite of multiple signals method, to introns and putative regulatory regions of those genes. Our results suggest that natural selection may have targeted variants giving rise to alternative splicing or differential gene expression of LARGE and IL21. Overall, our study supports the hypothesis that selective pressures imposed by LASV may have led to the emergence of particular alleles conferring resistance to Lassa fever, and opens up new avenues of research pursuit

Extreme Evolutionary Disparities Seen in Positive Selection across Seven Complex Diseases

Positive selection is known to occur when the environment that an organism inhabits is suddenly altered, as is the case across recent human history. Genome-wide association studies (GWASs) have successfully illuminated disease-associated variation. However, whether human evolution is heading towards or away from disease susceptibility in general remains an open question. The genetic-basis of common complex disease may partially be caused by positive selection events, which simultaneously increased fitness and susceptibility to disease. We analyze seven diseases studied by the Wellcome Trust Case Control Consortium to compare evidence for selection at every locus associated with disease. We take a large set of the most strongly associated SNPs in each GWA study in order to capture more hidden associations at the cost of introducing false positives into our analysis. We then search for signs of positive selection in this inclusive set of SNPs. There are striking differences between the seven studied diseases. We find alleles increasing susceptibility to Type 1 Diabetes (T1D), Rheumatoid Arthritis (RA), and Crohn's Disease (CD) underwent recent positive selection. There is more selection in alleles increasing, rather than decreasing, susceptibility to T1D. In the 80 SNPs most associated with T1D (p-value <7.01×10−5) showing strong signs of positive selection, 58 alleles associated with disease susceptibility show signs of positive selection, while only 22 associated with disease protection show signs of positive selection. Alleles increasing susceptibility to RA are under selection as well. In contrast, selection in SNPs associated with CD favors protective alleles. These results inform the current understanding of disease etiology, shed light on potential benefits associated with the genetic-basis of disease, and aid in the efforts to identify causal genetic factors underlying complex disease

Gene Expression Levels Are a Target of Recent Natural Selection in the Human Genome

Changes in gene expression may represent an important mode of human adaptation. However, to date, there are relatively few known examples in which selection has been shown to act directly on levels or patterns of gene expression. In order to test whether single nucleotide polymorphisms (SNPs) that affect gene expression in cis are frequently targets of positive natural selection in humans, we analyzed genome-wide SNP and expression data from cell lines associated with the International HapMap Project. Using a haplotype-based test for selection that was designed to detect incomplete selective sweeps, we found that SNPs showing signals of selection are more likely than random SNPs to be associated with gene expression levels in cis. This signal is significant in the Yoruba (which is the population that shows the strongest signals of selection overall) and shows a trend in the same direction in the other HapMap populations. Our results argue that selection on gene expression levels is an important type of human adaptation. Finally, our work provides an analytical framework for tackling a more general problem that will become increasingly important: namely, testing whether selection signals overlap significantly with SNPs that are associated with phenotypes of interest

Mining data from 1000 genomes to identify the causal variant in regions under positive selection

The human genome contains hundreds of regions in which the patterns of genetic variation indicate recent positive natural selection, yet for most of these the underlying gene and the advantageous mutation remain unknown. We recently reported the development of a method, Composite of Multiple Signals (CMS), that combines tests for multiple signals of natural selection and increases resolution by up to 100-fold