Platelets in myeloproliferative neoplasms have a distinct transcript signature in the presence of marrow fibrosis.

Marrow fibrosis is a significant complication of myeloproliferative neoplasms (MPN) that affects up to 20% of patients and is associated with a poor prognosis. The pathological processes that lead to fibrotic progression are not well understood, but megakaryocytes have been implicated in the process. The aim of this study was to determine whether platelets, derived from megakaryocytes, have transcriptomic alterations associated with fibrosis.

Whole-exome sequencing in multiplex preeclampsia families identifies novel candidate susceptibility genes.

Objective: Preeclampsia is a common and serious heritable disorder of human pregnancy. Although there have been notable successes in identification of maternal susceptibility genes a large proportion of the heritability of preeclampsia remains unaccounted for. It is has been postulated that rare variation may account for some of this missing heritability.

Megakaryocytes in Myeloproliferative Neoplasms Have Unique Somatic Mutations.

Myeloproliferative neoplasms (MPNs) are a group of related clonal hemopoietic stem cell disorders associated with hyperproliferation of myeloid cells. They are driven by mutations in the hemopoietic stem cell, most notably JAK2, CALR, and MPL. Clinically, they have the propensity to progress to myelofibrosis and transform to acute myeloid leukemia.

Archival Isolates Confirm a Single Topotype of West Nile Virus in Australia.

West Nile virus is globally wide-spread and causes significant disease in humans and animals. The evolution of West Nile virus Kunjin subtype in Australia (WNVKUN) was investigated using archival samples collected over a period of 50 years. Based on the pattern of fixed amino acid substitutions and time-stamped molecular clock analyses, a single long-term lineage (or topotype) was inferred.

Comparison of faecal microbiota in Blastocystis-positive and Blastocystis-negative irritable bowel syndrome patients.

Background: We investigated whether the carriage of Blastocystis in IBS patients was associated with differences in the faecal microbiota. Forty patients with diarrhoea-predominant IBS (26 Blastocystis-positive and 14 Blastocystis-negative) and 57 healthy controls (HC) (42 Blastocystis-positive and 15 Blastocystis-negative) submitted faecal samples for metataxonomic analysis of the 16S ribosomal RNA gene. Differences in the relative abundance of bacteria in these IBS and HC groups were evaluated from phylum to genus level.

Isolation and characterization of 13 microsatellites for the rare endemic shrub Tetratheca erubescens (Elaeocarpaceae).

Premise Of The Study: Microsatellite markers were developed for the rare Tetratheca erubescens (Elaeocarpaceae) to assess genetic diversity and spatial structuring.

Methods And Results: We generated ca. 2.

Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients.

HIV-associated sensory neuropathy (HIV-SN) is the most common neurological condition associated with HIV. HIV-SN has characteristics of an inflammatory pathology caused by the virus itself and/or by antiretroviral treatment (ART). Here, we assess the impact of single-nucleotide polymorphisms (SNPs) in a cluster of three genes that affect inflammation and neuronal repair: P2X7R, P2X4R and CAMKK2.

Combined DNA, toxicological and heavy metal analyses provides an auditing toolkit to improve pharmacovigilance of traditional Chinese medicine (TCM).

Globally, there has been an increase in the use of herbal remedies including traditional Chinese medicine (TCM). There is a perception that products are natural, safe and effectively regulated, however, regulatory agencies are hampered by a lack of a toolkit to audit ingredient lists, adulterants and constituent active compounds. Here, for the first time, a multidisciplinary approach to assessing the molecular content of 26 TCMs is described.

Next generation sequencing in a large cohort of patients presenting with neuromuscular disease before or at birth.

Background: Fetal akinesia/hypokinesia, arthrogryposis and severe congenital myopathies are heterogeneous conditions usually presenting before or at birth. Although numerous causative genes have been identified for each of these disease groups, in many cases a specific genetic diagnosis remains elusive. Due to the emergence of next generation sequencing, virtually the entire coding region of an individual's DNA can now be analysed through "whole" exome sequencing, enabling almost all known and novel disease genes to be investigated for disorders such as these.

Mutations of GPR126 are responsible for severe arthrogryposis multiplex congenita.

Arthrogryposis multiplex congenita is defined by the presence of contractures across two or more major joints and results from reduced or absent fetal movement. Here, we present three consanguineous families affected by lethal arthrogryposis multiplex congenita. By whole-exome or targeted exome sequencing, it was shown that the probands each harbored a different homozygous mutation (one missense, one nonsense, and one frameshift mutation) in GPR126.

Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma.

Malignant mesothelioma (MM) is a uniformly fatal tumour caused predominantly by exposure to asbestos. It is not known why some exposed individuals get mesothelioma and others do not. There is some epidemiological evidence of host susceptibility.

Australian bat lyssavirus infection in two horses.

In May 2013, the first cases of Australian bat lyssavirus infections in domestic animals were identified in Australia. Two horses (filly-H1 and gelding-H2) were infected with the Yellow-bellied sheathtail bat (YBST) variant of Australian bat lyssavirus (ABLV). The horses presented with neurological signs, pyrexia and progressing ataxia.

Novel CHKB mutation expands the megaconial muscular dystrophy phenotype.

Introduction: Mutations in the choline kinase beta (CHKB) gene are associated with a congenital muscular dystrophy with giant mitochondria at the periphery of muscle fibers.

Methods: We describe a patient of Italian origin in whom whole-exome sequencing revealed a novel homozygous nonsense mutation, c.648C>A, p.

SPEG interacts with myotubularin, and its deficiency causes centronuclear myopathy with dilated cardiomyopathy.

Centronuclear myopathies (CNMs) are characterized by muscle weakness and increased numbers of central nuclei within myofibers. X-linked myotubular myopathy, the most common severe form of CNM, is caused by mutations in MTM1, encoding myotubularin (MTM1), a lipid phosphatase. To increase our understanding of MTM1 function, we conducted a yeast two-hybrid screen to identify MTM1-interacting proteins.

Production and analytic bioinformatics for next-generation DNA sequencing.

The bioinformatics requirements within the clinical environment are very specific, and analytic techniques need to be fit for purpose, robust, and predictable. At the same time, the bewildering amount of information produced during these analyses needs to be carefully managed, used and interpreted correctly. The challenge for clinical laboratories now is to implement production analytical processes that are capable of handling different experimental approaches on current equipment, as well as to incorporate ways for these systems to evolve to take account of developments likely to make impacts in the near future.

Scrapheap challenge: a novel bulk-bone metabarcoding method to investigate ancient DNA in faunal assemblages.

Highly fragmented and morphologically indistinct fossil bone is common in archaeological and paleontological deposits but unfortunately it is of little use in compiling faunal assemblages. The development of a cost-effective methodology to taxonomically identify bulk bone is therefore a key challenge. Here, an ancient DNA methodology using high-throughput sequencing is developed to survey and analyse thousands of archaeological bones from southwest Australia.

Identification of KLHL41 Mutations Implicates BTB-Kelch-Mediated Ubiquitination as an Alternate Pathway to Myofibrillar Disruption in Nemaline Myopathy.

Nemaline myopathy (NM) is a rare congenital muscle disorder primarily affecting skeletal muscles that results in neonatal death in severe cases as a result of associated respiratory insufficiency. NM is thought to be a disease of sarcomeric thin filaments as six of eight known genes whose mutation can cause NM encode components of that structure, however, recent discoveries of mutations in non-thin filament genes has called this model in question. We performed whole-exome sequencing and have identified recessive small deletions and missense changes in the Kelch-like family member 41 gene (KLHL41) in four individuals from unrelated NM families.

Microsatellite markers from the Ion Torrent: a multi-species contrast to 454 shotgun sequencing.

The development and screening of microsatellite markers have been accelerated by next-generation sequencing (NGS) technology and in particular GS-FLX pyro-sequencing (454). More recent platforms such as the PGM semiconductor sequencer (Ion Torrent) offer potential benefits such as dramatic reductions in cost, but to date have not been well utilized. Here, we critically compare the advantages and disadvantages of microsatellite development using PGM semiconductor sequencing and GS-FLX pyro-sequencing for two gymnosperm (a conifer and a cycad) and one angiosperm species.

Detection of variations and identifying genomic breakpoints for large deletions in the LDLR by Ion Torrent semiconductor sequencing.

Objectives: The aims of this study were to 1) compare LDLR variant detection between Ion Torrent Personal Genome Machine (PGM) sequencing and conventional methods used for familial hypercholesterolaemia (FH) diagnosis i.e. exon-by-exon sequence analysis and multiplex ligation-dependent probe amplification (MLPA) and 2) identify genomic breakpoints for 12 cases of large deletions in LDLR previously identified by MLPA.

Mutations in CYC1, encoding cytochrome c1 subunit of respiratory chain complex III, cause insulin-responsive hyperglycemia.

Many individuals with abnormalities of mitochondrial respiratory chain complex III remain genetically undefined. Here, we report mutations (c.288G>T [p.

Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy.

Nemaline myopathy (NEM) is a common congenital myopathy. At the very severe end of the NEM clinical spectrum are genetically unresolved cases of autosomal-recessive fetal akinesia sequence. We studied a multinational cohort of 143 severe-NEM-affected families lacking genetic diagnosis.

Whole exome sequencing in foetal akinesia expands the genotype-phenotype spectrum of GBE1 glycogen storage disease mutations.

The clinically and genetically heterogenous foetal akinesias have low rates of genetic diagnosis. Exome sequencing of two siblings with phenotypic lethal multiple pterygium syndrome identified compound heterozygozity for a known splice site mutation (c.691+2T>C) and a novel missense mutation (c.

Investigation of NOTCH4 coding region polymorphisms in sporadic inclusion body myositis.

The NOTCH4 gene, located within the MHC region, is involved in cellular differentiation and has varying effects dependent on tissue type. Coding region polymorphisms haplotypic of the sIBM-associated 8.1 ancestral haplotype were identified in NOTCH4 and genotyped in two different Caucasian sIBM cohorts.