Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
The FAIR data principles are simple guidelines for ensuring that machines can find and use data, supporting data reuse by individuals. More—and better—research can be generated by designing data and algorithms to be findable, accessible, interoperable and reusable, together with the tools and workflows that led to these data.
Teleosts have emerged as important model organisms, yet their ancestrally duplicated genomes sometimes complicate developmental genetic analyses and comparisons to humans. A new genome sequence of spotted gar, a fish related to teleosts but lacking a duplicated genome, now helps to bridge human and teleost biology.
A new study compares DNA methylation profiles in developing zebrafish, Xenopus tropicalis and mice and suggests roles for Tet proteins in demethylating conserved gene enhancers during the phylotypic period of early development. These findings provide an epigenetic underpinning for the 'hourglass' model.
Polymorphism of haptoglobin in human serum was first discovered over 60 years ago. A new paper characterizes the complex structural variation at the HP locus in detail and, by using imputation from flanking SNP genotype data, shows that it affects blood cholesterol levels.
Varun Aggarwala and Benjamin Voight analyze human polymorphism data and develop an expanded sequence context model that explains >81% of variability in substitution probabilities, highlighting mutation-promoting motifs. Using their model, they present substitution intolerance scores for genes and a new intolerance score for amino acids, and demonstrate clinical use of the model in neuropsychiatric diseases.
David Solit and colleagues report that inactivating CDH1 mutations are found in 84% of plasmacytoid bladder cancer samples tested and are not found in other bladder cancer subtypes. CRISPR/Cas9-mediated knockout of CDH1 in cell lines leads to enhanced cellular migration.
Steven McCarroll and colleagues present a detailed study of copy number variation of exons within the human HP (haptoglobin) gene. They show that HP exons undergo recurring deletions that, together with local SNP variation, influence LDL and total cholesterol levels in human populations.
Jun Yang and colleagues perform targeted sequencing of NUDT15 and identify loss-of-function variants associated with thiopurine intolerance. Functionally, they show that NUDT15 inactivates thiopurine metabolites, providing a mechanism to explain the association between NUDT15 loss-of-function variants and thiopurine toxicity.
Alison Dunning, Stacey Edwards and colleagues analyze 3,872 common variants across the ESR1 locus in 118,816 women. They find five independent variants within regulatory regions that associate with different breast cancer–related phenotypes and regulate the expression of ESR1, RMND1 and CCDC170.
Thomas Whitington and colleagues present a detailed characterization of gene regulatory mechanisms underlying prostate cancer susceptibility. Their analysis highlights key mechanisms altered by disease-associated SNPs, including widespread disruption of ternary complexes involving AR, FOXA1 and HOXB13.
Sergey Nikolaev, Stylianos Antonarakis and colleagues analyze the genetic architecture of 293 basal cell carcinomas (BCCs) and characterize their mutational landscape. They observe UV signature mutations and identify new driver mutations in MYCN, PTPN14 and LATS1 in BCC.
Raphael Bueno, Eric Stawiski, Somasekar Seshagiri and colleagues present a comprehensive genomic analysis of malignant pleural mesothelioma. They identify four distinct molecular subtypes using RNA-seq data and highlight recurrent somatic mutations, gene fusions and splicing alterations.
Ozren Bogdanović, Ryan Lister, José Luis Gómez-Skarmeta, Michiel Vermeulen and colleagues report widespread DNA demethylation at developmental enhancers during the phylotypic period in zebrafish, Xenopus and mouse embryos. Their findings suggest a conserved role for Tet proteins and active DNA demethylation in the regulation of phylotypic enhancers.
Ingo Braasch, John Postlethwait and colleagues report the genome of the spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before genome duplication. Their data provide insights into the evolution of genes involved in immunity, mineralization and development and facilitate the comparison of cis-regulatory elements between teleosts and humans.
David Bertioli and colleagues report the genomes of Arachis duranensis and Arachis ipaensis, the diploid ancestors of cultivated peanut, Arachis hypogaea. Their analyses are a first step in understanding the evolution of the peanut's tetraploid genome.
Bin Han and colleagues present a genome-wide association analysis of grain size and shape in cultivated rice and identify a major locus for grain size encoding the transcription factor OsSPL13. They find that the large-grain allele in tropical japonica cultivars was introgressed from indica varieties during selection for improved grain yield.
Friedhelm Hildebrandt and colleagues identify mutations in NUP93, NUP205 or XPO5 in patients with steroid-resistant nephrotic syndrome. They show that NUP93 and XPO5 interact with SMAD4 and that NUP93 mutations interfere with BMP7-SMAD4 signaling in podocytes.
Andy Dahl and colleagues present a method for imputing missing phenotype data in genetic studies with multiple correlated phenotypes where samples can have any level of relatedness. They apply their method to simulated and real data sets and show that it improves the sensitivity to detect association signals.
