Reviews & Analysis

A new study reports the genome of common bean (Phaseolus vulgaris) and genome-wide resequencing data from both wild and domesticated accessions. These data confirm that common bean was domesticated at least twice, in Mesoamerica and South America, and also provide a framework to identify genes that contributed to the phenotypic changes associated with domestication.

Elucidating the molecular mechanisms responsible for changes in gene expression is important for understanding the evolution of morphological traits. A new study identifies the molecular basis of the association between KITLG and blond hair color, presenting an intriguing example of how a single DNA base-pair change in an upstream regulatory element can cause relatively large and specific downstream changes in phenotype.

Although silent transposons in plants can be reactivated by stress or during development, their potential deleterious effects are prevented by transposon-derived epigenetically activated small interfering RNAs (easiRNAs). A new study shows how serendipitous interactions between reactivated transposons and endogenous microRNAs might initiate easiRNA biogenesis, establishing an unexpected link between these two classes of silencing small RNAs.

Proper control of cyclin-dependent kinases ensures coordinated cell cycle progression and guards against tumorigenesis. A new study identifies the PARK2 E3 ubiquitin ligase as an important coordinator of G1/S-phase cyclin turnover and explains how mutations targeting this key cell cycle regulatory node contribute to a range of cancers.

Prader-Willi syndrome (PWS) is caused by loss of paternally expressed genes at an imprinted locus on chromosome 15, including the long noncoding RNA IPW. A new study identifies a critical role for IPW in modulating the expression of maternally expressed genes in trans, which has important implications for the understanding of imprinted gene networks.

Many inherited human DNA repair deficiency syndromes involve pronounced neurological dysfunction, although the DNA lesions responsible are generally unknown. A new study shows that the phosphodiesterase TDP2 has a key role in protecting the nervous system by preventing DNA breaks induced by aberrant topoisomerase II activity.

Pediatric diffuse gliomas are rare but aggressive brain tumors for which effective therapies are unavailable. New studies identify recurrent mutations of the ACVR1 gene in these tumors, identify molecular subtypes and highlight differences between gliomas affecting children and adults.

A new study shows that gain-of-function mutations in IFIH1, which encodes the cytosolic double-stranded RNA sensor MDA5, lead to upregulated type I interferon responses. Individuals with these mutations exhibit phenotypes consistent with autoimmune diseases, including Aicardi-Goutières syndrome and systemic lupus erythematosus.

Genome-wide association studies have previously identified variants in SLC30A8, encoding the zinc transporter ZnT8, associated with diabetes risk. A rare variant association study has now established the direction of effect, surprisingly showing that loss-of-function mutations in SLC30A8 are protective against diabetes.

Peripheral T cell lymphomas are rare but aggressive non-Hodgkin lymphomas derived from mature T lymphocytes or natural killer (NK) cells. New studies identify recurrent dominant-negative mutation of the RHOA GTPase gene in these lymphomas.

A new study explores the ancient oral microbiome from the well-preserved dental calculus samples of four human individuals who lived during medieval times, using a suite of genomic, proteomic and microscopic approaches. The authors investigate the evolution of dental pathogens by reconstructing the genome of the periodontal pathogen Tannerella forsythia and also identify antibiotic resistance genes, bacterial virulence factors and host immune defense proteins.

Sex chromosomes in mammals, birds, reptiles and fish represent many independent evolutionary events, but there is spectacular convergence and stunning parallels. A new study details the early stages of ZW differentiation and sex determination in a flatfish and the establishment of dosage compensation and sex reversal by epigenetic mechanisms including DNA methylation.

Cell fate regulation is a central component of maintaining tissue homeostasis, yet the mechanisms instructing cell division diversity in tissue-specific stem cells have not been well understood. A new study uncovers a central role for microtubule motor–regulating protein Lis1 in hematopoietic stem cell fate determination and in leukemogenesis.

Clear cell renal cell carcinoma (CCRCC) is characterized by mutation of the VHL gene and loss of a segment of chromosome 3. A new study using multi-region exome sequencing has identified substantial intratumoral heterogeneity within large primary CCRCCs, which has profound implications for understanding tumor evolution and for developing effective therapies.

A new study shows that HOXB13 is preferentially recruited to the risk allele of a prostate cancer–associated SNP, enhancing the expression of RFX6, a driver of prostate cancer cell migration and predictor of disease progression. The work illustrates how a single risk locus contributes both to prostate cancer incidence and, through functional follow-up, to disease progression.

Genomic aberrations affecting genes in B cell differentiation are hallmarks of B-precursor acute lymphoblastic leukemia (ALL). A new whole-genome sequencing study of ETV6-RUNX1–positive ALL has now identified RAG-mediated recombination, which specifically targets genes and regulatory elements active during B cell differentiation, as the underlying mechanism.

Although dozens of common variants have been associated with increased risk of type 2 diabetes (T2D), the mechanisms by which these variants increase disease susceptibility are largely unknown. A new study mapping the human pancreatic islet cistrome provides a roadmap for exploring the effects of these variants and suggests that altered enhancer function might be a common contributor to the genetic risk of T2D.

Alkes Price, Peter Visscher and colleagues provide recommendations on the application of mixed-linear-model association methods across a range of study designs.