Draft genome of neurotropic nematode parasite Angiostrongylus cantonensis, causative agent of human eosinophilic meningitis

Angiostrongylus cantonensis is a bursate nematode parasite that causes eosinophilic meningitis (or meningoencephalitis) in humans in many parts of the world. The genomic data from A. cantonensis will form a useful resource for comparative genomic and chemogenomic studies to aid the development of diagnostics and therapeutics. We have sequenced, assembled and annotated the genome of A. cantonensis. The genome size is estimated to be ~260. Mb, with 17,280 genomic scaffolds, 91X coverage, 81.45% for complete and 93.95% for partial score based on CEGMA analysis of genome completeness. The number of predicted genes of ≥300. bp was 17,482. A total of 7737 predicted protein-coding genes of ≥50 amino acids were identified in the assembled genome. Among the proteins of known function, kinases are the most abundant followed by transferases. The draft genome contains 34 excretory-secretory proteins (ES), a minimum of 44 Nematode Astacin (NAS) metalloproteases, 12 Homeobox (HOX) genes, and 30 neurotransmitters. The assembled genome size (260. Mb) is larger than those of Pristionchus pacificus, Caenorhabditis elegans, Necator americanus, Caenorhabditis briggsae, Trichinella spiralis, Brugia malayi and Loa loa, but smaller than Haemonchus contortus and Ascaris suum. The repeat content (25%) is similar to H. contortus. The GC content (41.17%) is lower compared to P. pacificus (42.7%) and H. contortus (43.1%) but higher compared to C. briggsae (37.69%), A. suum (37.9%) and N. americanus (40.2%) while the scaffold N50 is 42,191. This draft genome will facilitate the understanding of many unresolved issues on the parasite and the disorder it causes

Genome-Wide Analysis of Copy Number Variation Identifies Candidate Gene Loci Associated with the Progression of Non-Alcoholic Fatty Liver Disease

<div><p>Between 10 and 25% of individuals with non-alcoholic fatty liver disease (NAFLD) develop hepatic fibrosis leading to cirrhosis and hepatocellular carcinoma (HCC). To investigate the molecular basis of disease progression, we performed a genome-wide analysis of copy number variation (CNV) in a total of 49 patients with NAFLD [10 simple steatosis and 39 non-alcoholic steatohepatitis (NASH)] and 49 matched controls using high-density comparative genomic hybridization (CGH) microarrays. A total of 11 CNVs were found to be unique to individuals with simple steatosis, whilst 22 were common between simple steatosis and NASH, and 224 were unique to NASH. We postulated that these CNVs could be involved in the pathogenesis of NAFLD progression. After stringent filtering, we identified four rare and/or novel CNVs that may influence the pathogenesis of NASH. Two of these CNVs, located at 13q12.11 and 12q13.2 respectively, harbour the exportin 4 (<i>XPO4</i>) and phosphodiesterase 1B (<i>PDE1B</i>) genes which are already known to be involved in the etiology of liver cirrhosis and HCC. Cross-comparison of the genes located at these four CNV loci with genes already known to be associated with NAFLD yielded a set of genes associated with shared biological processes including cell death, the key process involved in ‘second hit’ hepatic injury. To our knowledge, this pilot study is the first to provide CNV information of potential relevance to the NAFLD spectrum. These data could prove invaluable in predicting patients at risk of developing NAFLD and more importantly, those who will subsequently progress to NASH.</p></div

Size range distribution of the CNVs.

<p>The CNVs ranged in size from 5.77</p

Rare and novel CNVs in NASH.

<p>Start = first base-pair location in the copy number region, End = last base-pair location in the copy number region.</p

qPCR validation performed on selected genomic regions.

<p>(<b>A</b>) Results for the region 11q11. (<b>B</b>) Results for the region 13q12.11. A copy number of around 2 was deemed to be indicative of wild-type status (i.e. no CNV), a copy number of 1 was indicative of one copy lost, whereas a copy number of 3 or above was held to indicate copy number gain(s). The error bars represent the standard error among four replicates.</p

Enriched GO terms associated with NASH.

<p>GO_BP, Gene Ontology biological process; GO_CC, Gene Ontology cellular component.</p><p>*Modified Fisher’s Exact test, <i>P</i>-Value ≤0.05.</p

Top regions of copy number gains and losses in NASH.

<p>Start = first base-pair location in the copy number region, End = last base-pair location in the copy number region.</p

Array CGH based identification of amplified chromosome 8p11.23-11.22 region encompassing ADAM9 gene.

<p>Array CGH based identification of amplified chromosome 8p11.23-11.22 region encompassing ADAM9 gene.</p

Array CGH based identification of amplified chromosome 7q34 region encompassing MGAM gene.

<p>Array CGH based identification of amplified chromosome 7q34 region encompassing MGAM gene.</p