Coexistence of Multiple Functional Variants and Genes Underlies Genetic Risk Locus 11p11.2 of Alzheimer's Disease.

Background: Genome-wide association studies have identified dozens of genetic risk loci for Alzheimer's disease (AD), yet the underlying causal variants and biological mechanisms remain elusive, especially for loci with complex linkage disequilibrium and regulation.

Methods: To fully untangle the causal signal at a single locus, we performed a functional genomic study of 11p11.2 (the CELF1/SPI1 locus).

Direct evidence of CRISPR-Cas9-mediated mitochondrial genome editing.

Pathogenic mitochondrial DNA (mtDNA) mutations can cause a variety of human diseases. The recent development of genome-editing technologies to manipulate mtDNA, such as mitochondria-targeted DNA nucleases and base editors, offer a promising way for curing mitochondrial diseases caused by mtDNA mutations. The CRISPR-Cas9 system is a widely used tool for genome editing; however, its application in mtDNA editing is still under debate.

Rheb-regulated mitochondrial pyruvate metabolism of Schwann cells linked to axon stability.

The metabolic coupling of Schwann cells (SCs) and peripheral axons is poorly understood. Few molecules in SCs are known to regulate axon stability. Using SC-specific Rheb knockout mice, we demonstrate that Rheb-regulated mitochondrial pyruvate metabolism is critical for SC-mediated non-cell-autonomous regulation of peripheral axon stability.

Mapping leprosy-associated coding variants of interleukin genes by targeted sequencing.

Previous genotyping-based assays have identified non-coding variants of several interleukins (ILs) being associated with genetic susceptibility to leprosy. However, understanding of the involvement of coding variants within all IL family genes in leprosy was still limited. To obtain the full mutation spectrum of all ILs in leprosy, we performed a targeted deep sequencing of coding regions of 58 ILs genes in 798 leprosy patients (age 56.

Exploring the Genetic Association of the ABAT Gene with Alzheimer's Disease.

Accumulating evidence demonstrated that GABAergic dysfunction contributes to the pathogenesis of Alzheimer's disease (AD). The GABA aminotransferase (ABAT) gene encodes a mitochondrial GABA transaminase and plays key roles in the biogenesis and metabolism of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. In this study, we performed an integrative study at the genetic and expression levels to investigate the potential genetic association between the ABAT gene and AD.