Semi-automated assembly of high-quality diploid human reference genomes

The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has benefitted society. However, it still has many gaps and errors, and does not represent a biological genome as it is a blend of multiple individuals. Recently, a high-quality telomere-to-telomere reference, CHM13, was generated with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a nearly homozygous genome. To address these limitations, the Human Pangenome Reference Consortium formed with the goal of creating high-quality, cost-effective, diploid genome assemblies for a pangenome reference that represents human genetic diversity. Here, in our first scientific report, we determined which combination of current genome sequencing and assembly approaches yield the most complete and accurate diploid genome assembly with minimal manual curation. Approaches that used highly accurate long reads and parent-child data with graph-based haplotype phasing during assembly outperformed those that did not. Developing a combination of the top-performing methods, we generated our first high-quality diploid reference assembly, containing only approximately four gaps per chromosome on average, with most chromosomes within ±1% of the length of CHM13. Nearly 48% of protein-coding genes have non-synonymous amino acid changes between haplotypes, and centromeric regions showed the highest diversity. Our findings serve as a foundation for assembling near-complete diploid human genomes at scale for a pangenome reference to capture global genetic variation from single nucleotides to structural rearrangements

A draft human pangenome reference

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample

Effects of megasphaera elsdenii on ruminal pH, ruminal concentrations of organic acids, and bacterial genomes following a grain challenge

Upon arrival in feedlots, cattle normally must be adapted to high-concentrate diets. The microbial population in the rumen of incoming cattle normally is suited to digestion of forages, and when cattle are transitioned onto concentrate diets, opportunistic bacteria that produce lactic acid can proliferate rapidly, leading to excesses of lactic acid in the rumen. High levels of lactic acid in the rumen may cause mild to severe acidosis. Megasphaera elsdenii is a lactate-utilizing bacterium that normally is present in rumens of cattle that have been adapted to high-grain diets, but numbers of the organism are relatively low during the step-up phase. Increasing the numbers of lactate-utilizing bacteria in newly arrived cattle by orally dosing with M. elsdenii may be a useful means of reducing the risk of ruminal acidosis in feedlot cattle. Our objectives were to evaluate ruminal parameters and determine efficacy of increasing ruminal populations of lactateutilizing bacteria in cattle following an abrupt diet change and administration of 10 mL (low dose), 100 mL (medium dose), or 1000 mL (high dose) of a culture containing 1.62 × 108 CFU/mL of live M. elsdenii compared with a control group given a placebo without live Megasphaera

Optimizing spectral quality with quantum dots to enhance crop yield in controlled environments

Bioregenerative life-support systems (BLSS) involving plants will be required to realize self-sustaining human settlements beyond Earth. To improve plant productivity in BLSS, the quality of the solar spectrum can be modified by lightweight, luminescent films. CuInS2/ZnS quantum dot (QD) films were used to down-convert ultraviolet/blue photons to red emissions centered at 600 and 660 nm, resulting in increased biomass accumulation in red romaine lettuce. All plant growth parameters, except for spectral quality, were uniform across three production environments. Lettuce grown under the 600 and 660 nm-emitting QD films respectively increased edible dry mass (13 and 9%), edible fresh mass (11% each), and total leaf area (8 and 13%) compared with under a control film containing no QDs. Spectral modifications by the luminescent QD films improved photosynthetic efficiency in lettuce and could enhance productivity in greenhouses on Earth, or in space where, further conversion is expected from greater availability of ultraviolet photons. © 2021, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]