Biology subjects

Meng, J.

Publications and source records attributed to Meng, J..

4 recordsLinked to original sources

bioRxiv2018

Genome-wide selection footprints and deleterious variations in young Asian allotetraploid rapeseed

Brassica napus (AACC, 2n=38), is an important oilseed crop grown worldwide. However, little is known about the population evolution of this species, the genomic difference between its major genetic clusters, such as European and Asian rapeseed, and impacts of historical large-sale introgression events in this young tetraploid. In this study, we reported the de novo assembly of the genome sequences of an Asian rapeseed (B. napus), Ningyou 7 and its four progenitors and carried out de novo assembly-based comparison, pedigree and population analysis with other available genomic data from diverse European and Asian cultivars. Our results showed that Asian rapeseed originally derived from European rapeseed, but it had subsequently significantly diverged, with rapid genome differentiation after intensive local breeding selection. The first historical introgression of B. rapa dramatically broadened the allelic pool of Asian B. napus, but decreased their deleterious variations. The secondary historical introgression of European rapeseed (canola-quality) has reshaped Asian rapeseed into two groups, accompanied by an increase in genetic load. This study demonstrates distinctive genomic footprints by recent intra- and inter-species introgression events for local adaptation, and provide novel insights for understanding the rapid genome evolution of a young allopolyploid crop.

genomics↗

bioRxiv2018

A database of simulated tumor genomes towards accurate detection of somatic small variants in cancer

BackgroundSomatic mutations promote the transformation of normal cells to cancer. Accurate identification of such mutations facilitates cancer diagnosis and treatment. A number of callers have been developed to predict them from paired tumor/normal or unpaired tumor sequencing data. However, the small size of currently available experimentally validated somatic sites limits evaluation and then improvement of callers. Fortunately, NIST reference material NA12878 genome has been well-characterized with publicly available high-confidence genotype calls.\n\nResultsWe used BAMSurgeon to create simulated tumors by introducing somatic small variants (SNVs and small indels) into homozygous reference or wildtype sites of NA12878. We generated 135 simulated tumors from 5 pre-tumors/normals. These simulated tumors vary in sequencing and subsequent mapping error profiles, read length, the number of sub-clones, the VAF, the mutation frequency across the genome and the genomic context. Furthermore, these pure tumor/normal pairs can be mixed at desired ratios within each pair to simulate sample contamination.\n\nConclusionsThis database (a total size of 15 terabytes) will be of great use to benchmark somatic small variant callers and guide their improvement.\n\nContact informationjing.mengrabbit@gmail.com

bioinformatics↗

bioRxiv2017

Excitatory Motor Neurons Function As Central Pattern Generators In An Anatomically Compressed Motor Circuit For Reverse Locomotion

Central pattern generators are cell- or network-driven oscillators that underlie motor rhythmicity. The existence and identity of C. elegans CPGs are unknown. Through cell ablation, electrophysiology, and calcium imaging, we identified oscillators for C. elegans reverse locomotion. We show that the cholinergic and excitatory class A motor neurons exhibit intrinsic and oscillatory activity, and such an activity can drive reverse locomotion without premotor interneurons. Regulation of their oscillatory activity, either through effecting the P/Q/N high voltage-activated calcium channel, an endogenous constituent of their intrinsic oscillation, or, via the dual regulation by descending premotor interneurons, determines the propensity, velocity, and sustention of reverse locomotion. Thus, the reversal motor neuron themselves serve as distributed local oscillators; regulation of their intrinsic activity controls the reversal motor state. These findings exemplify anatomic and functional compression: motor executors integrate the role of rhythm generation in a locomotor network that is constrained by small cell numbers.\n\nHighlightsO_LIThe class A motor neurons (A-MNs) intrinsically oscillate.\nC_LIO_LIHigh voltage-activated calcium channel is a constituent of A-MN oscillation.\nC_LIO_LIRegulation of A-MN oscillation by interneurons determines the reversal state.\nC_LIO_LIA-MNs integrate the role of multiple neuron types in large locomotor networks.\nC_LI

neuroscience↗

bioRxiv2017

Zebrafish models for human ALA-dehydratase-deficient porphyria (ADP) and hereditary coproporphyria (HCP) generated with TALEN and CRISPR-Cas9

Defects in the enzymes involved in heme biosynthesis result in a group of human metabolic genetic disorders known as porphyrias. Using a zebrafish model for human hepatoerythropoietic porphyria (HEP), caused by defective uroporphyrinogen decarboxylase (Urod), the fifth enzyme in the heme biosynthesis pathway, we recently have found a novel aspect of porphyria pathogenesis. However, no hereditable zebrafish models with genetic mutations of alad and cpox, encoding the second enzyme delta-aminolevulinate dehydratase (Alad) and the sixth enzyme coproporphyrinogen oxidase (Cpox), have been established to date. Here we employed site-specific genome-editing tools transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) to generate zebrafish mutants for alad and cpox. These zebrafish mutants display phenotypes of heme deficiency, hypochromia, abnormal erythrocytic maturation and accumulation of heme precursor intermediates, reminiscent of human ALA-dehydratase-deficient porphyria (ADP) and hereditary coproporphyrian (HCP), respectively. Further, we observed altered expression of genes involved in heme biosynthesis and degradation and particularly down-regulation of exocrine pancreatic zymogens in ADP (alad-/-) and HCP (cpox-/-) fishes. These two zebrafish porphyria models can survive at least 7 days and thus provide invaluable resources for elucidating novel pathological aspects of porphyrias, evaluating mutated forms of human ALAD and CPOX, discovering new therapeutic targets and developing effective drugs for these complex genetic diseases. Our studies also highlight generation of zebrafish models for human diseases with two versatile genome-editing tools.

genetics↗