A genome‐wide search for local adaptation in a terrestrial‐breeding frog reveals vulnerability to climate change

2019 ◽  
Vol 25 (9) ◽  
pp. 3151-3162 ◽  
Author(s):  
Deanne Cummins ◽  
W. Jason Kennington ◽  
Tabitha Rudin‐Bitterli ◽  
Nicola J. Mitchell
Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1984
Author(s):  
Majid Nikpay ◽  
Sepehr Ravati ◽  
Robert Dent ◽  
Ruth McPherson

Here, we performed a genome-wide search for methylation sites that contribute to the risk of obesity. We integrated methylation quantitative trait locus (mQTL) data with BMI GWAS information through a SNP-based multiomics approach to identify genomic regions where mQTLs for a methylation site co-localize with obesity risk SNPs. We then tested whether the identified site contributed to BMI through Mendelian randomization. We identified multiple methylation sites causally contributing to the risk of obesity. We validated these findings through a replication stage. By integrating expression quantitative trait locus (eQTL) data, we noted that lower methylation at cg21178254 site upstream of CCNL1 contributes to obesity by increasing the expression of this gene. Higher methylation at cg02814054 increases the risk of obesity by lowering the expression of MAST3, whereas lower methylation at cg06028605 contributes to obesity by decreasing the expression of SLC5A11. Finally, we noted that rare variants within 2p23.3 impact obesity by making the cg01884057 site more susceptible to methylation, which consequently lowers the expression of POMC, ADCY3 and DNAJC27. In this study, we identify methylation sites associated with the risk of obesity and reveal the mechanism whereby a number of these sites exert their effects. This study provides a framework to perform an omics-wide association study for a phenotype and to understand the mechanism whereby a rare variant causes a disease.


Hypertension ◽  
2000 ◽  
Vol 35 (6) ◽  
pp. 1291-1296 ◽  
Author(s):  
Pankaj Sharma ◽  
Jennie Fatibene ◽  
Franco Ferraro ◽  
Haiyan Jia ◽  
Sue Monteith ◽  
...  

2022 ◽  
Author(s):  
Tiago da Silva Ribeiro ◽  
José A Galván ◽  
John E Pool

Local adaptation can lead to elevated genetic differentiation at the targeted genetic variant and nearby sites. Selective sweeps come in different forms, and depending on the initial and final frequencies of a favored variant, very different patterns of genetic variation may be produced. If local selection favors an existing variant that had already recombined onto multiple genetic backgrounds, then the width of elevated genetic differentiation (high FST) may be too narrow to detect using a typical windowed genome scan, even if the targeted variant becomes highly differentiated. We therefore used a simulation approach to investigate the power of SNP-level FST (specifically, the maximum SNP FST value within a window) to detect diverse scenarios of local adaptation, and compared it against whole-window FST and the Comparative Haplotype Identity statistic. We found that SNP FST had superior power to detect complete or mostly complete soft sweeps, but lesser power than window-wide statistics to detect partial hard sweeps. To investigate the relative enrichment and nature of SNP FST outliers from real data, we applied the two FST statistics to a panel of Drosophila melanogaster populations. We found that SNP FST had a genome-wide enrichment of outliers compared to demographic expectations, and though it yielded a lesser enrichment than window FST, it detected mostly unique outlier genes and functional categories. Our results suggest that SNP FST is highly complementary to typical window-based approaches for detecting local adaptation, and merits inclusion in future genome scans and methodologies.


2014 ◽  
Vol 23 (03) ◽  
pp. 1460008
Author(s):  
Kevin Byron ◽  
Jason T. L. Wang ◽  
Dongrong Wen

Developing effective artificial intelligence tools to find motifs in DNA, RNA and proteins poses a challenging yet important problem in life science research. In this paper, we present a computational approach for finding RNA tertiary motifs in genomic sequences. Specifically, we predict genomic coordinate locations for coaxial helical stackings in 3-way RNA junctions. These predictions are provided by our tertiary motif search package, named CSminer, which utilizes two versatile methodologies: random forests and covariance models. A coaxial helical stacking tertiary motif occurs in a 3-way RNA junction where two separate helical elements form a pseudocontiguous helix and provide thermodynamic stability to the RNA molecule as a whole. Our CSminer tool first uses a genome-wide search method based on covariance models to find a genomic region that may potentially contain a coaxial helical stacking tertiary motif. CSminer then uses a random forests classifier to predict whether the genomic region indeed contains the tertiary motif. Experimental results demonstrate the effectiveness of our approach.


Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1217-1226 ◽  
Author(s):  
Yun Chen ◽  
David H. Gorski

Abstract Angiogenesis is critical to tumor progression. The homeobox gene GAX inhibits angiogenesis in vascular endothelial cells (ECs). We have identified a microRNA (miR-130a) that regulates GAX expression and hypothesized that it plays a major role in modulating GAX activity in ECs. A 280-bp fragment from the GAX 3′-untranslated region (3′-UTR) containing 2 miR-130a targeting sites was observed to be required for the rapid down-regulation of GAX expression by serum and proangiogenic factors, whereas the activity of the GAX promoter did not vary with exposure to serum or proangiogenic factors. This same 280-bp sequence in the GAX 3′-UTR cloned into the psiCHECK2-Luciferase vector mediated serum-induced down-regulation of the reporter gene when placed 3′ of it. Finally, forced expression of miR-130a inhibits GAX expression through this specific GAX 3′-UTR sequence. A genome-wide search for other possible miR-130a binding sites revealed an miR-130a targeting site in the 3′-UTR of the antiangiogenic homeobox gene HOXA5, the expression and antiangiogenic activity of which are also inhibited by miR-130a. From these data, we conclude that miR-130a is a regulator of the angiogenic phenotype of vascular ECs largely through its ability to modulate the expression of GAX and HOXA5.


BMC Genomics ◽  
2013 ◽  
Vol 14 (1) ◽  
pp. 648 ◽  
Author(s):  
Jeroen Crappé ◽  
Wim Van Criekinge ◽  
Geert Trooskens ◽  
Eisuke Hayakawa ◽  
Walter Luyten ◽  
...  

1999 ◽  
Vol 5 (4) ◽  
pp. 271-278 ◽  
Author(s):  
Yuanhong Ma ◽  
Jeffrey D. Ohmen ◽  
Zhiming Li ◽  
Gordon L. Bentley ◽  
Colleen McElree ◽  
...  

BMC Genetics ◽  
2005 ◽  
Vol 6 (Suppl 1) ◽  
pp. S55 ◽  
Author(s):  
Albert Rosenberger ◽  
Nico Janicke ◽  
Karola Köhler ◽  
Katrin Korb ◽  
Bettina Kulle ◽  
...  

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