Browse Articles

Whole-exome and genome sequencing in consanguineous families with unsolved lipodystrophy identified biallelic pathogenic loss-of-function variants in the phospholipase gene PLAAT3. Multi-omics and functional analyses in human and mouse PLAAT3-deficient adipose tissue and adipose stem cells revealed an adipocyte differentiation defect that is mediated by an altered gene network downstream of the adipogenesis master regulator PPARγ.

Homozygous loss-of-function variants in phospholipase A/acyltransferase 3 (PLAAT3) underlie a new lipodystrophy syndrome. Functional studies link PLAAT3 loss with peroxisome proliferator-activated receptor gamma (PPARγ)-mediated defects in white adipose tissue differentiation and function.

Single-haplotype genome assemblies from five cat species shed light on the dynamics of structural variations during felid radiation and resolve sensory gene repertoires associated with adaptation and domestication.

Genome-wide analyses identify 43 loci associated with forearm fracture, including some influencing bone quality parameters. Follow-up work shows that Tac4 knockout mice exhibit reduced mechanical bone strength with no effect on bone mineral density.

Analysis of GTEx RNA-seq samples identifies hundreds of mosaic chromosomal alterations (mCAs). Considerable inter-tissue variability and excess incidence of mCAs across malignancies suggest a complex relationship with tumorigenesis.

This Review discusses how embryonic transcriptional programs, such as epithelial–mesenchymal plasticity and stemness, may be harnessed in adult tissues to drive processes and diseases such as regeneration and cancer.

A method that allows for the detection of mosaic chromosomal alterations from blood whole-genome sequencing data highlights ancestry-specific differences in the distribution of common and rare germline susceptibility variants.

Genome-wide association analyses of migraine and its subtypes identify new susceptibility loci, including rare variants with large effects implicating PRRT2, SCN11A and KCNK5.

Analysis of the somatic mutations landscape of 111 patients with psoriasis vulgaris shows that the disease is unlikely to be driven by clonal expansions caused by somatic mutations in keratinocytes. A mutational footprint associated with psoralen treatment was observed and characterized.

Brain somatic mosaicism is linked to several neurological disorders and is thought to arise post-zygotically. A study suggests that pre-zygotic aneuploidy followed by post-zygotic partial reversion leads to a recurrent form of brain mosaicism-related epilepsy.

Mosaic copy number gains arising from an extra parentally derived chromosome 1q allele are found in brain tissue from five individuals with focal epilepsy. These copy number gains are strongly enriched in astrocytes, indicating somatic rescue in other tissues during development.

The mechanisms of many disease-associated variants are uncertain because of limited power to detect their modest effects on gene expression. This study finds that natural selection leads to preferential detection of disease-associated versus expression-associated variants.

Mouse lineage tracing in regenerating bone marrow after myeloablation shows a dynamic dedifferentiation of mature adipocytes into bone marrow stromal cells. Lipolysis disruption obstructs adipocyte dedifferentiation and hematopoietic stem cell regeneration.

Epigenomic profiling and massively parallel reporter assays identify 892 functional differentially-active single-nucleotide variants (daSNVs) linked to ten neuropsychiatric diseases. CRISPRi and gene editing approaches show magnesium transport dysfunction as a common genetic pathomechanism.

This study seeks to explain the poor overlap of genome-wide association study and cis-expression quantitative trait locus variants using a model of differential selective constraint, suggesting that these two study types have biases towards different functional classes of variants.

Genome and transcriptome analyses of 376 Gossypium hirsutum accessions uncover the regulation of gene expression during fiber development in allotetraploid cotton and highlight the potential for fiber quality improvement.

Genome-wide association meta-analysis of AAA identifies 121 independent risk loci and highlights potential therapeutic targets such as proprotein convertase, subtilisin/kexin-type 9 (PCSK9).

In single-cell studies, combining healthy reference atlases and designed control datasets allows more precise identification of disease-associated cell states.