Cisco Science: Using Omics To Answer A Range Of Key Questions

Coregonines, including cisco (Coregonus artedi), kiyi (Coregonus kiyi), and bloater (Coregonus hoyi), are a focus for prey fish conservation and restoration efforts throughout the Laurentian Great Lakes. However, fundamental questions about coregonine ecology and genetics remain. For example, we know little about how the early life stages of coregonines respond to environmental change at either the genotypic or phenotypic level. We also have limited knowledge about how to identify different species at the larval stage and the genetic relationships among species, which makes the different species difficult to study at the larval stage. To increase the probability for success in restoration efforts, current and future research need to integrate traditional and novel approaches to better understand what leads to current and future coregonine successes. We used DNA and RNA omics tools, genomics and transcriptomics to boost our comprehension of current coregonine populations and to help understand how C. artedi may respond to environmental change. During the winter of 2017, we conducted a pilot experiment to evaluate how C. artedi eggs may respond to increased light exposure resulting from current and expected reductions in annual ice and snow cover due to global warming. We used transcriptomics to assess differences in gene expression between a continuous light and continuous dark treatment. Our results indicate that light is an environmental factor that could lead to earlier hatch dates, smaller yolk sacs, changes in mortality and differential gene expression in metabolic related and other functionally important genes. In 2018, we sampled larval coregonines in the Apostle Islands of Lake Superior each week from hatch in May until late July. We used genomic sequencing to genetically identify 197 larvae to species: C. artedi, C. hoyi, and C. kiyi. The larval demographic characteristics of each species was assessed and revealed that length ranges, growth rates, yolk sac condition, and effective population size varied among species. Larvae of all three species were found throughout the entirety of the Apostle Islands and the genetic diversity within each species appears high. The results from our pilot experiment and field observations help advance our understanding of the important early life stages of coregonines and how changes in light exposure or growth rates could affect their success or failure in a changing climate

Examination of the rumen bacteria and methanogenic archaea of wild impalas (Aepyceros melampus melampus) from Pongola, South Africa

Although the rumen microbiome of domesticated ruminants has been evaluated, few studies have explored the rumen microbiome of wild ruminants, and no studies have identified the rumen microbiome in the impala (Aepyceros melampus melampus). In the present study, next-generation sequencing and real-time polymerase chain reaction were used to investigate the diversity and density of the bacteria and methanogenic archaea residing in the rumen of five adult male impalas, culled during the winter dry season in Pongola, South Africa. A total of 15,323 bacterial 16S rRNA gene sequences (from five impala), representing 3,892 different phylotypes, were assigned to 1,902 operational taxonomic units (OTUs). A total of 20,124 methanogen 16S rRNA gene sequence reads (from four impala), of which 5,028 were unique, were assigned to 344 OTUs. From the total sequence reads, Bacteroidetes, Proteobacteria, and Firmicutes were the most abundant bacterial phyla. While the majority of the bacterial genera found were unclassified, Prevotella and Cupriavidus were the most abundant classified genera. For methanogens, the genera Methanobrevibacter and Methanosphaera represented 94.3 % and 4.0 % of the classified sequences, respectively. Most notable was the identification of Methanobrevibacter thaueri-like 16S rRNA gene sequence reads in all four impala samples, representing greater than 30 % of each individual’s total sequences. Both data sets are accessible through NCBI’s Sequence Read Archive (SRA), under study accession number SRP [048619]. The densities of bacteria (1.26×1010–3.82×1010 cells/ml whole rumen contents) and methanogens (4.48×108–7.2×109 cells/ml of whole rumen contents) from five individual impala were similar to those typically observed in domesticated ruminants.http://link.springer.com/journal/2482016-04-30hb201

Workplace-Linked Pensions for an Aging Demographic

Pensions and population aging intersect in two ways. First, demographic change threatens the sustainability of traditional pay-as-you-go social security pensions, leaving workplace-linked pensions with a greater role in retirement provision. Second, as the Baby Boom generation enters retirement, new challenges arise around its retirement support. This chapter reviews some of the implications of population aging for workplace pensions in this new environment, outlines market considerations important for workplace-related pension design for the future, and discusses how governments can create an environment supportive of workplace-related pensions, should they wish to do so. We conclude that workplace-linked retirement saving systems will be asked to do even more than in the past, given the financial stress that pay-as-you-go governmentrun Social Security plans are confronting in the face of an aging demographic. This will require further product innovation and additional research

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants

TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport

Tiina Paunio on työryhmän UK10K jäsen.The analysis of individuals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanied by destabilization of the retrograde IFT dynein motor. We thus define TCTEX1D2 as an integral component of the evolutionarily conserved retrograde IFT machinery. In complex with several IFT dynein light chains, it is required for correct vertebrate skeletal formation but may be functionally redundant under certain conditions.Peer reviewe

Whole-genome sequence-based analysis of thyroid function

Tiina Paunio on työryhmän UK10K Consortium jäsen.Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project (N = 2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF >= 1%) associated with TSH and FT4 (N = 16,335). For TSH, we identify a novel variant in SYN2 (MAF = 23.5%, P = 6.15 x 10(-9)) and a new independent variant in PDE8B (MAF = 10.4%, P = 5.94 x 10(-14)). For FT4, we report a low-frequency variant near B4GALT6/ SLC25A52 (MAF = 3.2%, P = 1.27 x 10(-9)) tagging a rare TTR variant (MAF = 0.4%, P = 2.14 x 10(-11)). All common variants explain >= 20% of the variance in TSH and FT4. Analysis of rare variants (MAFPeer reviewe

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)