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Browsing by Subject "Mosaicism"
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Item Analysis of integration sites of transgenic sheep generated by lentiviral vectors using next-generation sequencing technology(2014-07-31) Chen, Yu-Hsiang; Malkova, Anna; Cornetta, Kenneth; Randall, Stephen Karl, 1953-; Atkinson, SimonThe development of new methods to carry out gene transfer has many benefits to several fields, such as gene therapy, agriculture and animal health. The newly established lentiviral vector systems further increase the efficiency of gene transfer dramatically. Some studies have shown that lentiviral vector systems enhance efficiency over 10-fold higher than traditional pronuclear injection. However, the timing for lentiviral vector integration to occur remains unclear. Integrating in different stages of embryogenesis might lead to different integration patterns between tissues. Moreover, in our previous study we found that the vector copy number in transgenic sheep varied, some having one or more copies per cells while other animals having less than one copy per cell suggesting mosaicism. Here I hypothesized that injection of a lentiviral vector into a single cell embryo can lead to integration very early in embryogenesis but can also occur after several cell divisions. In this study, we focus on investigating integration sites in tissues developing from different germ layers as well as extraembryonic tissues to determine when integration occurs. In addition, we are also interested in insertional mutagenesis caused by viral sequence integration in or near gene regions. We utilize linear amplification-mediated polymerase chain reaction (LAM-PCR) and next- generation sequencing (NGS) technology to determine possible integration sites. In this study, we found the evidence based on a series of experiments to support my hypothesis, suggesting that integration event also happens after several cell divisions. For insertional mutagenesis analysis, the closest genes can be found according to integration sites, but they are likely too far away from the integration sites to be influenced. A well-annotated sheep genome database is needed for insertional mutagenesis analysis.Item Cytogenetic studies of mosaicism(1987) Higgins, Michael D.Item Hormonal suppression of mini-puberty in a neonate with mosaic 45X/46XY disorder of sexual development(Elsevier, 2020-05-03) Kaefer, Martin; Eugster, Erica; Medicine, School of MedicineDisorders of Sex Development (DSD) are some of the most controversial and challenging conditions that pediatric urologists treat. This may be especially true in mosaic 45X/46XY DSD, due to the inability to ascertain in the neonatal period which gender identity will best suit a given child with this condition. It has therefore been proposed to forgo any irreversible surgical interventions. In order to address the concern of early testosterone production in a nonsurgical manner we describe a case in which we treat a patient with a GnRH agonist to block the early physiologic rise in testosterone during the neonatal mini-puberty.Item Maternal mosaicism in long QT syndrome due to a pathogenic variant in KCNH2(Elsevier, 2020-11-16) Sawyer, Briana L.; Tristani-Firouzi, Martin; Wells, Layne E.; Vatta, Matteo; Etheridge, Susan P.; Medical and Molecular Genetics, School of Medicine