5 research outputs found
Forensic evaluation of the Asia Pacific ancestry-informative MAPlex assay
DNA intelligence, and particularly the inference of biogeographical ancestry (BGA) is increasing in interest, and relevance within the forensic genetics community. The majority of current MPS-based forensic ancestry-informative assays focus on the differentiation of major global populations. The recently published MAPlex (Multiplex for the Asia Pacific) panel contains 144 SNPs and 20 microhaplotypes and aims to improve the differentiation of populations in the Asia Pacific region. This study reports the first forensic evaluation of the MAPlex panel using AmpliSeq technology and Ion S5 sequencing. This study reports on the overall performance of MAPlex including the assay’s sequence coverage distribution and stability, baseline noise and description of problematic SNPs. Dilution series, artificially degraded and mixed DNA samples were also analysed to evaluate the sensitivity of the panel with challenging or compromised forensic samples. As the first panel to combine biallelic SNPs, multiple-allele SNPs and microhaplotypes, the MAPlex assay demonstrated an enhanced capacity for mixture detection, not easily performed with common binary SNPs. This performance evaluation indicates that MAPlex is a robust, stable and highly sensitive assay that is applicable to forensic casework for the prediction of BGAMdlP is supported by a postdoctoral fellowship awarded by the Consellería de Cultura, Educación e Ordenación Universitaria and the Consellería de Economía, Emprego e Industria from Xunta de Galicia (Modalidade A, ED481B 2017/088). CP, AFA, AMM, MdlP, MVL are supported by MAPA, Multiple Allele Polymorphism Analysis (BIO2016-78525-R), a research project funded by the Spanish Research State Agency (AEI), and co-financed with ERDF funds. AFA is supported by a post-doctorate grant funded by the Consellería de Cultura, Educación e Ordenación Universitaria e da Consellería de Economía, Emprego e Industria from Xunta de Galicia, Spain (Modalidade B, ED481B 2018/010). The 1000 Genomes high coverage sequence data were generated at the New York Genome Center with funds provided by NHGRI Grant 3UM1HG008901-03S1S
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Virus-host Cophylogeny Motivated Viral Detection and Discovery Using Viral Microarrays and High-throughput Sequencing
The emergence of high-throughput genomic technologies has markedly accelerated virus detection, virus discovery, and viral metagenomics. DNA viral microarrays and high-throughput sequencing platforms allow for the unbiased detection of all pathogens in parallel. In this dissertation, the capacity for a novel or unexpected viral etiology in a number of idiopathic diseases is investigated. More specifically, serum from individuals with acute liver failure, ocular fluids from patients with uveitis, and bronchoalveolar lavage from individuals experiencing an acute exacerbation of idiopathic pulmonary fibrosis are analyzed for all viruses. An alternative to the syndromic approach to virus discovery is also taken in tandem, where a hypothesized gap in virus phylogeny is targeted specifically. Overlaying viral hosts onto a phylogenetic tree of a conserved herpesvirus gene reveals a clade of herpesviruses found in a number of primates, with a distinct gap suggesting a homologous herpesvirus in human hosts. Attributes of this gap, such as sequence similarity, viral lifestyle, and tropism, are used to design a set of discovery projects. Saliva samples from patients with full-blown AIDS were collected and banked in an era before antiretroviral therapy, and tonsils, a lymphocyte rich tissue, from adolescents with recurrent tonsillitis was collected and treated with a chemical known to induce the herpesvirus lytic gene cascade. These samples were analyzed with the pan-viral microarray and high-throughput sequencing for the presence of a novel human herpesvirus. This method of targeted analysis of a hypothesized virus gap is then generalized to all viruses in an effort to precipitate hypotheses of discovery targets, or gaps, in virus trees when they are overlaid onto their corresponding host trees. The propensity for viruses to coevolve with their hosts motivates a framework for translating host homology to homology between known viruses and their suggested orthologs (gap-recognition). These proposed gaps present insight into viral diversity and evolution, and can also be used to motivate targeted microarray-based and high throughput sequencing-based virus discovery efforts. With the rapid advances in massively parallel genomic platforms, there is a clear demand for more informed and targeted molecular and bioinformatic strategies of detection
Viral Infection in Acute Exacerbation of Idiopathic Pulmonary Fibrosis
Rationale: Idiopathic pulmonary fibrosis is a progressive, uniformly fatal interstitial lung disease. An acute exacerbation of idiopathic pulmonary fibrosis is an episode of acute respiratory worsening without an identifiable etiology. Occult viral infection has been proposed as a possible cause of acute exacerbation
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Associations of autozygosity with a broad range of human phenotypes
Abstract: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding