Articles in 2019

A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci influencing this trait. Enrichment analyses, fine-mapping and colocalization with gene expression in 47 tissues implicate the kidney and liver as key target organs and prioritize potential causal genes.

A new study identifies germline NPM1 mutations in people with dyskeratosis congenita. These NPM1 mutations inhibit ribosomal RNA 2´-O-methylation by decreasing the binding of the rRNA methyltransferase FBL to small nucleolar RNAs. Thus, NPM1 influences ribosomal functions via epitranscriptomic regulation.

Understanding how to biologically interpret the loci identified in genome-wide association studies is a major goal of current genetics research. To achieve this goal, we need to understand where, when and how relevant genes are expressed in specific contexts, in order to explore the mechanistic links between genetic associations and diseases or complex traits.

Natural variation of the F-box protein ZmFBL41 in maize confers resistance to Rhizoctonia solani, the causal fungus for banded leaf and sheath blight in maize, through decreased interaction of ZmFBL41 with the cinnamyl alcohol dehydrogenase ZmCAD.

Analysis of iPSC-derived cardiomyocytes identifies variants associated with allele-specific effects on NKX2-5 binding. Fine-mapping and functional studies suggest that such variants underlie cardiac-specific expression quantitative trait loci and associations with electrocardiographic traits.

Whole-genome sequencing of metastatic biopsies from 442 patients with breast cancer provides insights into metastatic disease, including associations of genomic features with prior treatments and identification of therapeutic vulnerabilities.

Analysis of gene expression and open chromatin regions in up to 32 immune cell populations under resting and stimulated conditions identifies widespread chromatin remodeling and shared response elements between stimulated B and T cells.

NPM1 regulates ribosomal RNA 2′-O-methylation by binding to small nucleolar RNAs, thereby modulating translation. NPM1 mutations lead to altered 2′-O-methylation and impaired ribosomal function, resulting in bone marrow failure and leukemia susceptibility.

Postzygotic inactivating mutations in RHOA cause a mosaic neuroectodermal syndrome characterized by linear hypopigmentation, leukoencephalopathy and craniofacial anomalies, highlighting the role of RHOA in human development and disease.

Analysis of the bracteatus pineapple genome provides insight into fiber production, color formation, sugar accumulation and fruit maturation. Resequencing of 89 Ananas genomes supports the coexistence of sexual recombination and a ‘one-step operation’ during domestication.

Common genetic variants increase the risk of schizophrenia, but the downstream biological mechanisms are largely unknown. A new study demonstrates that schizophrenia risk genes cause neuronal dysfunction and have synergistic effects on gene expression.

To increase the utility of Gene Ontology (GO) annotations for interpretation of genome-wide experimental data, we have developed GO-CAM, a structured framework for linking multiple GO annotations into an integrated model of a biological system. We expect that GO-CAM will enable new applications in pathway and network analysis, as well as improve standard GO annotations for traditional GO-based applications.

Large-scale genomic analyses in wheat identify regions associated with 50 agronomic traits evaluated in South Asia, Africa and the Americas. This genotype–phenotype map can be used to enhance wheat productivity and stress resilience.

Combinatorial perturbation of schizophrenia risk loci in human induced pluripotent stem cell–derived neuronal cells demonstrates a synergistic effect converging on synaptic function.

Integration of immune-disease GWAS variants with open chromatin and enhancer profiling in T cells and macrophages stimulated with different cytokines and analyzed at different time points reveals cell-state-specific enrichments for 12 complex diseases.

Mapping long-range chromatin interactions in 27 human cell/tissue types identifies candidate target genes of 70,329 putative regulatory elements. Further analysis suggests potential regulatory function for 27,325 noncoding variants associated with 2,117 traits and diseases.

The genome of the model genetic organism Pisum sativum, or pea plant, links nineteenth-century genetics to twenty-first-century genomics, serving as a symbol of how far the genetics field has developed and how greatly technologies have advanced. Almost every student’s introduction to genetics currently involves learning Mendel’s laws; we envision that genomics and genome sequencing will become just as foundational in the education of future geneticists.

Inferring adaptation, migration and population history would be profoundly easier if we could use the genomes that we sequence to infer the true genealogical history of each locus. Two new papers bring us close to achieving this goal.