Genetics publications

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Browsing Genetics publications by Author "Adelson, D."

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    Copy number variation in the horse genome
    (Public Library of Science, 2014) Ghosh, S.; Qu, Z.; Das, P.; Fang, E.; Juras, R.; Cothran, E.; McDonell, S.; Kenney, D.; Lear, T.; Adelson, D.; Chowdhary, B.; Raudsepp, T.; Barsh, G.
    We constructed a 400K WG tiling oligoarray for the horse and applied it for the discovery of copy number variations (CNVs) in 38 normal horses of 16 diverse breeds, and the Przewalski horse. Probes on the array represented 18,763 autosomal and X-linked genes, and intergenic, sub-telomeric and chrY sequences. We identified 258 CNV regions (CNVRs) across all autosomes, chrX and chrUn, but not in chrY. CNVs comprised 1.3% of the horse genome with chr12 being most enriched. American Miniature horses had the highest and American Quarter Horses the lowest number of CNVs in relation to Thoroughbred reference. The Przewalski horse was similar to native ponies and draft breeds. The majority of CNVRs involved genes, while 20% were located in intergenic regions. Similar to previous studies in horses and other mammals, molecular functions of CNV-associated genes were predominantly in sensory perception, immunity and reproduction. The findings were integrated with previous studies to generate a composite genome-wide dataset of 1476 CNVRs. Of these, 301 CNVRs were shared between studies, while 1174 were novel and require further validation. Integrated data revealed that to date, 41 out of over 400 breeds of the domestic horse have been analyzed for CNVs, of which 11 new breeds were added in this study. Finally, the composite CNV dataset was applied in a pilot study for the discovery of CNVs in 6 horses with XY disorders of sexual development. A homozygous deletion involving AKR1C gene cluster in chr29 in two affected horses was considered possibly causative because of the known role of AKR1C genes in testicular androgen synthesis and sexual development. While the findings improve and integrate the knowledge of CNVs in horses, they also show that for effective discovery of variants of biomedical importance, more breeds and individuals need to be analyzed using comparable methodological approaches.
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    Derivation of an endogenous small RNA from double-stranded Sox4 sense and natural antisense transcripts in the mouse brain
    (Elsevier, 2016) Ling, K.; Brautigan, P.; Moore, S.; Fraser, R.; Cheah, P.; Raison, J.; Babic, M.; Lee, Y.; Daish, T.; Mattiske, D.; Mann, J.; Adelson, D.; Thomas, P.; Hahn, C.; Scott, H.
    Abstract not available
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    Discovery of a novel long terminal repeat (LTR2i-SS) in Sus Scrofa
    (Wiley, 2014) Lim, S.; Kortschak, R.; Adelson, D.
    Long terminal repeat (LTR) retrotransposons are transposable elements flanked by 5'/3' LTRs. They have a structure similar to endogenous retroviruses, but they lack the envelope (env) gene making them non-infectious. Long terminal repeats are motif-rich sequences and can act as bidirectional promoters or enhancers to regulate or inactivate genes by insertion. In this study, we identified a new chimeric LTR subfamily, LTR2i_SS, in the pig genome. This chimeric LTR family appears to be the ancestral form of the previously described LTR2_SS family. LTR2_SS appears to have deleted ~300 bp of un-annotated, ancestral sequence from LTR2i_SS. We identified no functional provirus sequences for either of these LTR types. LTR2i_SS sequences have been exapted into the untranslated regions of two protein-coding gene mRNAs. Both of these genes lie within previously mapped pig quantitative trait loci.
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    HENMT1 and piRNA stability are required for adult male germ cell transposon repression and to define the spermatogenic program in the mouse
    (Public Library of Science, 2015) Lim, S.; Qu, Z.; Kortschak, R.; Lawrence, D.; Geoghegan, J.; Hempfling, A.; Bergmann, M.; Goodnow, C.; Ormandy, C.; Wong, L.; Mann, J.; Scott, H.; Jamsai, D.; Adelson, D.; O'Bryan, M.; Frye, M.
    piRNAs are critical for transposable element (TE) repression and germ cell survival during the early phases of spermatogenesis, however, their role in adult germ cells and the relative importance of piRNA methylation is poorly defined in mammals. Using a mouse model of HEN methyltransferase 1 (HENMT1) loss-of-function, RNA-Seq and a range of RNA assays we show that HENMT1 is required for the 2' O-methylation of mammalian piRNAs. HENMT1 loss leads to piRNA instability, reduced piRNA bulk and length, and ultimately male sterility characterized by a germ cell arrest at the elongating germ cell phase of spermatogenesis. HENMT1 loss-of-function, and the concomitant loss of piRNAs, resulted in TE de-repression in adult meiotic and haploid germ cells, and the precocious, and selective, expression of many haploid-transcripts in meiotic cells. Precocious expression was associated with a more active chromatin state in meiotic cells, elevated levels of DNA damage and a catastrophic deregulation of the haploid germ cell gene expression. Collectively these results define a critical role for HENMT1 and piRNAs in the maintenance of TE repression in adult germ cells and setting the spermatogenic program.
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    Modelling predictors of molecular response to frontline imatinib for patients with chronic myeloid leukaemia
    (PloSOne, 2017) Banjar, H.; Ranasinghe, D.; Brown, F.; Adelson, D.; Kroger, T.; Leclercq, T.; White, D.; Hughes, T.; Chaudhri, N.; Speletas, M.
    BACKGROUND: Treatment of patients with chronic myeloid leukaemia (CML) has become increasingly difficult in recent years due to the variety of treatment options available and challenge deciding on the most appropriate treatment strategy for an individual patient. To facilitate the treatment strategy decision, disease assessment should involve molecular response to initial treatment for an individual patient. Patients predicted not to achieve major molecular response (MMR) at 24 months to frontline imatinib may be better treated with alternative frontline therapies, such as nilotinib or dasatinib. The aims of this study were to i) understand the clinical prediction 'rules' for predicting MMR at 24 months for CML patients treated with imatinib using clinical, molecular, and cell count observations (predictive factors collected at diagnosis and categorised based on available knowledge) and ii) develop a predictive model for CML treatment management. This predictive model was developed, based on CML patients undergoing imatinib therapy enrolled in the TIDEL II clinical trial with an experimentally identified achieving MMR group and non-achieving MMR group, by addressing the challenge as a machine learning problem. The recommended model was validated externally using an independent data set from King Faisal Specialist Hospital and Research Centre, Saudi Arabia. PRINCIPLE FINDINGS: The common prognostic scores yielded similar sensitivity performance in testing and validation datasets and are therefore good predictors of the positive group. The G-mean and F-score values in our models outperformed the common prognostic scores in testing and validation datasets and are therefore good predictors for both the positive and negative groups. Furthermore, a high PPV above 65% indicated that our models are appropriate for making decisions at diagnosis and pre-therapy. Study limitations include that prior knowledge may change based on varying expert opinions; hence, representing the category boundaries of each predictive factor could dramatically change performance of the models.
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    The sheep genome illuminates biology of the rumen and lipid metabolism
    (American Association for the Advancement of Science, 2014) Jiang, Y.; Xie, M.; Chen, W.; Talbot, R.; Maddox, J.; Faraut, T.; Wu, C.; Muzny, D.; Li, Y.; Zhang, W.; Stanton, J.; Brauning, R.; Barris, W.; Hourlier, T.; Aken, B.; Searle, S.; Adelson, D.; Bian, C.; Cam, G.; Chen, Y.; et al.
    Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of wool and represent a distinct class of animals that have a specialized digestive organ, the rumen, that carries out the initial digestion of plant material. We have developed and analyzed a high-quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution. We also identified genes involved in lipid metabolism that had been amplified and/or had altered tissue expression patterns. This may be in response to changes in the barrier lipids of the skin, an interaction between lipid metabolism and wool synthesis, and an increased role of volatile fatty acids in ruminants compared with nonruminant animals.