Wellcome Trust Centre for Human Genetics

About: Wellcome Trust Centre for Human Genetics is a facility organization based out in Oxford, United Kingdom. It is known for research contribution in the topics: Population & Genome-wide association study. The organization has 2122 authors who have published 4269 publications receiving 433899 citations.

The UTX gene escapes X inactivation in mice and humans

Abstract: We recently have identified a ubiquitously transcribed mouse Y chromosome gene, Uty , which encodes a tetratricopeptide repeat (TPR) protein. A peptide derived from the UTY protein confers H-Y antigenicity on male cells. Here we report the characterization of a widely transcribed X-linked homologue of Uty , called Utx , which maps to the proximal region of the mouse X chromosome and which detects a human X-linked homologue at Xp11.2. Given that Uty is ubiquitously transcribed, we assayed for Utx expression from the inactive X chromosome (Xi) in mice and found that Utx escapes X chromosome inactivation. Only Smcx and the pseudoautosomal Sts gene on the mouse X chromosome have been reported previously to escape inactivation. The human UTX gene was also found to be expressed from Xi. We discuss the significance of these data for our understanding of dosage compensation of X-Y homologous genes in humans and mice.

Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells

Abstract: The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34(+) cells from MDS patients with SF3B1 mutations using RNA sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared with wild-type cases include genes that are involved in MDS pathogenesis (ASXL1 and CBL), iron homeostasis and mitochondrial metabolism (ALAS2, ABCB7 and SLC25A37) and RNA splicing/processing (PRPF8 and HNRNPD). Many genes regulated by a DNA damage-induced BRCA1-BCLAF1-SF3B1 protein complex showed differential expression/splicing in SF3B1 mutant cases. This is the first study to determine the target genes of SF3B1 mutation in MDS CD34(+) cells. Our data indicate that SF3B1 has a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processes/pathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link.

The global distribution of Crimean-Congo hemorrhagic fever

Abstract: Background: Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne infection caused by a virus (CCHFV) from the Bunyaviridae family. Domestic and wild vertebrates are asymptomatic reservoirs for the virus, putting animal handlers, slaughter-house workers and agricultural labourers at highest risk in endemic areas, with secondary transmission possible through contact with infected blood and other bodily fluids. Human infection is characterized by severe symptoms that often result in death. While it is known that CCHFV transmission is limited to Africa, Asia and Europe, definitive global extents and risk patterns within these limits have not been well described. Methods: We used an exhaustive database of human CCHFoccurrence records and a niche modeling framework to map the global distribution of risk for human CCHF occurrence. Results: A greater proportion of shrub or grass land cover was the most important contributor to our model, which predicts highest levels of risk around the Black Sea, Turkey, and some parts of central Asia. Sub-Saharan Africa shows more focalized areas of risk throughout the Sahel and the Cape region. Conclusions:These newrisk maps provide avaluable starting point for understanding the zoonotic niche of CCHF, its extent and the risk it poses to humans.