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Nature Papers Examine Molecular Pathways in Alzheimer's Disease, Diploid Potato Assembly, More

Using a combination of transcriptomics, proteomics, and epigenomics to analyze post-mortem brains from Alzheimer's disease (AD) patients, a team led by scientists from the University of Pennsylvania have uncovered new molecular pathways involved in the disease. As reported in Nature Genetics, RNA sequencing analysis of the samples revealed upregulation of transcription- and chromatin-related genes including the histone acetyltransferases for H3K27ac and H3K9ac, which were further implicated in the disease through proteomic screening and epigenomic profiling. Experiments in a Drosophila model of AD showed that increasing H3K27ac and H3K9ac genome-wide worsened neurodegeneration. "Overall, these multi-omic analyses have identified H3K27ac and H3K9ac as potential epigenetic drivers of AD, which spur disease pathways through dysregulation of transcription and chromatin-gene feedback loops," the study's authors write. "Our findings provide mechanistic insights on AD progression and highlight alternative avenues for potential intervention." GenomeWeb has more on this, here.

The de novo assembly and haplotype determination of the heterozygous diploid potato is presented in Nature Genetics this week. The potato is an economically important tuber and projects are underway to transform it from a tuber-propagated, tetraploid crop into a seed-propagated, inbred-line-based diploid crop. To support such efforts, a group led by scientists from the Chinese Academy of Agricultural Sciences used circular consensus sequencing and other sequencing technologies to generate the 1.67-Gb haplotype-resolved assembly of a diploid potato. Findings from the work include the identification of deleterious mutations and differentially expressed alleles dispersed throughout both haplotypes, which could complicate efforts to eradicate deleterious alleles or stack beneficial alleles via meiotic recombination, the study's authors write. 

A whole-genome sequence analysis of indigenous African cattle is published in Nature Genetics this week. Despite the importance of cattle pastoralism to humans in Africa, its underlying genetics are poorly understood. To gain insights, a group of South Korean and African scientists sequenced the genomes of 114 cattle that belong to 12 indigenous African cattle populations and two African buffalo. They combined these with the previously sequenced genomes of 58 cattle from four additional African populations to create a collection representative of the main African cattle groups. A study of the genomes uncovers a major taurine/indicine cattle admixture event dated to around 750 to 1,050 years ago, as well as 16 loci linked to African environmental adaptations including ones associated with immunity, heat-tolerance, and reproduction.