We performed a whole-genome scan of genetic variants in splicing regulatory elements (SREs) and evaluated the extent to which natural selection has shaped extant patterns of variation in SREs. We investigated the degree of differentiation of single nucleotide polymorphisms (SNPs) in SREs among human populations and applied long-range haplotype- and multilocus allelic differentiation-based methods to detect selection signatures. We describe an approach, sampling a large number of loci across the genome from functional classes and using the consensus from multiple tests, for identifying candidates for selection signals. SRE SNPs in various SNP functional classes show different patterns of population differentiation compared with their non-SRE counterparts. Intronic regions display a greater enrichment for extreme population differentiation among the potentially tissue-dependent transcript ratio quantitative trait loci (trQTLs) than SRE SNPs in general and includ outlier trQTLs for cross-population composite likelihood ratio, suggesting that incorporation of context annotation for regulatory variation may lead to improved detection of signature of selection on these loci. The proportion of extremely rare SNPs disrupting SREs is significantly higher in European than in African samples. The approach developed here will be broadly useful for studies of function and disease-associated variation in the human genome.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519721PMC
http://dx.doi.org/10.1038/s41598-017-05744-9DOI Listing

Publication Analysis

Top Keywords

human populations
8
functional classes
8
sre snps
8
population differentiation
8
loci
5
evidence selection
4
selection splicing-associated
4
splicing-associated loci
4
loci human
4
populations relevance
4

Similar Publications

Introduction: Dolutegravir (DTG) + lamivudine (3TC) demonstrated high rates of virologic suppression (VS) and low rates of virologic failure (VF), discontinuation, and drug resistance in randomized trials. Real-world evidence can support treatment effectiveness, safety, and tolerability in clinical practice and aid in treatment decisions.

Methods: A systematic literature review (SLR) was conducted to identify studies using DTG + 3TC (January 2013-March 2024).

View Article and Find Full Text PDF

Objectives: As one of the most common complications of laryngopharyngeal reflux or gastroesophageal reflux disease, dental erosion presents a significant association with laryngopharyngeal reflux. This study aimed to elucidate the role of laryngopharyngeal reflux and gastroesophageal reflux disease on the severity and occurrence of dental erosion in adult populations.

Methods: A comprehensive search was performed in the databases of PubMed/MEDLINE, Web of Science, Cochrane Library, and Scopus for English literature published from July 1999 to June 2024.

View Article and Find Full Text PDF

Purpose Of Review: Male breast cancer (MBC) is a rare entity which often arises in elderly people. Aim of this review is to evaluate the principal issues related to MBC in elderly, because the therapeutic management of disease is not only related to the biological behavior of the tumor, but also to the comorbidities and frailty of older population. A scoping literature review was performed on Pubmed and Cochrane Database using the following keywords: therapeutic management/ male/ breast cancer/ elderly patients.

View Article and Find Full Text PDF

Background: Interleukin-1 receptor-associated kinase1 (IRAK1) plays a considerable role in the inflammatory signaling pathway. The current study aimed to identify any association between (rs1059703) single nucleotide polymorphism (SNP) and vulnerability to rheumatological diseases in the pediatric and adult Egyptian population.

Patients And Methods: The current study included four patient groups: adult Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), juvenile systemic lupus erythematosus (JSLE), and juvenile idiopathic arthritis (JIA).

View Article and Find Full Text PDF

Association between estrogen and kidney function: population based evidence and mutual bidirectional Mendelian randomization study.

Clin Exp Nephrol

January 2025

Department of Nephrology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background: Previous studies have suggested a potential role of estrogen in the pathophysiology of chronic kidney disease (CKD); however, the association and causality between estrogen and kidney function remain unclear.

Methods: The cross-sectional correlation between serum estradiol concentration and estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) was analyzed using data from the National Health and Nutrition Examination Survey 2013-2016. Causality was tested using mutual bidirectional Mendelian randomization (MR) approaches based on six large-scale GWAS studies.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!