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Inactivation of pyruvate dehydrogenase A1 (PDHA1), a subunit of the pyruvate dehydrogenase complex (PDC) regulating mitochondrial metabolism, inhibits lipid biosynthesis and prostate cancer development in mouse and human xenograft tumor models.
Depletion of easiRNAs (epigenetically activated small interfering RNAs) relieves the triploid block reproduction barrier mediated by increased paternal ploidy in Arabidposis. Loss of RNA Pol IV blocks easiRNA formation and rescues triploid seeds.
Reconstructing the genome of an ancestor: 788 Icelanders are descended from a man who arrived there in 1802. 38% of his African mother’s genome has now been reconstructed from their pedigree and the genomes and genotypes of current Icelanders up to 8 generations later.
This study shows that inactivation of Pml in the mouse prostate turns indolent Pten-null tumors into lethal metastatic disease. The authors identify an aberrant SREBP prometastatic lipogenic program and show that a high-fat diet induces lipid accumulation in prostate tumors and is sufficient to drive metastasis.
A pan-genome dataset of the Oryza sativa–Oryza rufipogon species complex generated through deep sequencing and de novo genome assembly of 66 divergent accessions will be helpful in pinpointing new causal variants underlying complex traits and in promoting evolutionary and functional studies in rice.
MC4R colocalizes with ADCY3 at primary cilia in hypothalamic neurons, and MC4R mutations associated with human obesity impair this localization. Inhibition of adenylyl cyclase signaling at primary cilia of neurons leads to increased body weight in mice.
Genetic analysis of children with severe obesity identifies mutations in the ADCY3 gene (encoding adenylate cyclase 3). These variants are rare in public databases and affect the functional activity of the protein, indicating that ADCY3 is a potential pharmacological target for obesity treatment.
Individuals from a Greenlandic Inuit population with homozygous loss-of-function variants in ADCY3 (adenylate cyclase 3) have increased risk for obesity and type 2 diabetes. Carriers of rare ADCY3 variants in trans-ancestry populations also show increased association with type 2 diabetes.
MTAG is a new method for joint analysis of summary statistics from genome-wide association studies of different traits. Applying MTAG to summary statistics for depressive symptoms, neuroticism and subjective well-being increased discovery of associated loci as compared to single-trait analyses.
