Project description:How and when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we find that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (KYA), and after no more than 8,000-year isolation period in Beringia. Native Americans diversified into two basal genetic branches around 13 KYA, one in North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians and Australo-Melanesians, the latter possibly through the ancestors of Aleutian Islanders. Putative relict populations in South America, including the historical Pericúes and Fuego-Patagonians, are not directly related to modern Australo-Melanesians.
Project description:For many decades Indigenous people, including Native Americans and Aboriginal Australians, have fought for their return of their ancient people. By sequencing ten ancient nuclear genomes of Aboriginal Australians and 27 mitogenomes from ancient pre-European Aboriginal Australians (up to 1,540 yr BP) of known provenance we demonstrate the feasibility of successfully identifying the geographic origins of unprovenanced ancestral remains using genomic methods.
Project description:Over the past few years, studies of DNA isolated from human fossils and archaeological remains have generated considerable novel insight into the history of our species. Several landmark papers have described the genomes of ancient human ancestors and have demonstrated that contemporary humans harbour genetic material from ancient close relatives, the Neanderthals and Denisovans, and that ancient human individuals are often genetically distinct from nearby extant populations whilst also showing affinities with populations from further afield. Across West Eurasia, there is growing genetic evidence of large-scale, dynamic population movements over the period between 10,000 to 2,000 years ago, such that the ancestry across present-day populations is likely to be a mixture of several ancient groups. Whilst these efforts are bringing the details of West Eurasian prehistory into increasing focus, studies aimed at understanding the processes behind the generation of the current West Eurasian genetic landscape have been limited by the number of populations sampled, or have been either too regional or global in their outlook. Here, using recently described haplotype-based techniques, we present the results of a systematic survey of recent admixture history across Western Eurasia and show that admixture is a universal property across almost all groups. Admixture in all regions except North Western Europe involved the influx of genetic material from outside of West Eurasia, which we date to specific time periods. Within Northern, Western, and Central Europe, admixture tended to occur between local groups during the period 300 to 1200CE. Comparisons of the genetic profiles of West Eurasians before and after admixture show that population movements within the last 1500 years are likely to have maintained differentiation amongst groups. Our analysis provides a timeline of the gene flow events that have generated the contemporary genetic landscape of West Eurasia. 20 individuals from Croatia included as part of an analysis of admixture in West Eurasia
Project description:Since the first reports of hepatitis of unknown aetiology occurring in UK children, over 1000 cases have been reported worldwide, including 268 cases in the UK, with the majority younger than 6 years old. Using genomic, proteomic and immunohistochemical methods, we undertook extensive investigation of 28 cases and 136 control subjects. In five cases who underwent liver transplantation, we detected high levels of adeno-associated virus 2 (AAV2) in the explanted livers. AAV2 was also detected at high levels in blood from 10/11 non-transplanted cases. Low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), both of which enable AAV2 lytic replication, were also found in the five explanted livers and blood from 15/17 and 6/9 respectively, of the 23 non-transplant cases tested. In contrast, AAV2 was detected at low titre in 6/100 whole bloods from child controls from cohorts with presence or absence of hepatitis and/or adenovirus infection. Our data show an association of AAV2 at high titre in blood or liver tissue, with unexplained hepatitis in children infected in the recent HAdV-F41 outbreak. We were unable to find evidence by electron microscopy, immunohistochemistry or proteomics of HAdV or AAV2 viral particles or proteins in explanted livers, suggesting that hepatic pathology is not due to direct lytic infection by either virus. The potential that AAV2, although not previously associated with disease, may, together with HAdV-F41 and/or HHV-6, be causally implicated in the outbreak of unexplained hepatitis, requires further investigation.
Project description:We used scRNA-seq data generated using Smart-seq2 to reconstruct the native TCR from Ag-specific T cells and then to link these with the gene expression profile of individual cells. antigen specific CD8 T cells were obtained from a subject who had previously cleared hepatitis C virus (HCV) infection. A cell line was also generated from the same subject and included in the analysis with and without antigen stimulation.
Project description:Liver-specific ten-eleven translocation methylcytosine dioxygenases 2 and 3 (Tet2 plus Tet3)-deficient hepatitis B virus (HBV) transgenic mice fail to support viral biosynthesis. The levels of viral transcription and replication intermediates are dramatically reduced. Hepatitis B core antigen (HBcAg) is only observed in a very limited number of pericentral hepatocytes in a pattern that is similar to glutamate-ammonia ligase (Glul), a -catenin target gene. HBV transcript abundance in Tet-deficient mice resembles that observed in wild-type neonatal mice. Furthermore, the RNA levels of several -catenin target genes including Glul, Lhpp, Notun, Oat, Slc1a2 and Tbx3, in Tet-deficient mice was also similar to that observed in wild-type neonatal mice. As HBV transcription is regulated by -catenin, these finding support the suggestion that neonatal Tet-deficiency might limit -catenin target gene expression, limiting viral biosynthesis. Additionally, HBV transgene DNA displays increased 5-methylcytosine (5mC) frequency at CpG sequences consistent with neonatal Tet-deficiency being responsible for decreased developmental viral DNA demethylation mediated by 5mC oxidation to 5-hydroxymethylcytosine (5hmC), a process that might be responsible for the reduction in cellular -catenin target gene expression and viral transcription and replication.
Project description:The purpose of this study is to determine if there is an association between hepatitis C infection and kidney cancer. All patients who are diagnosed with kidney cancer and who will either have a biopsy or surgery will be offered to be tested for hepatitis C. The control group will be colon cancer patients. Both groups would be of recent diagnosis (6 months).
Project description:Methylation of Hepatitis B Virus (HBV) DNA in a CpG context (5mCpG) can alter the expression patterns of viral genes related to infection and cellular transformation. Moreover, it may also provide clues to why certain infections are cleared, or persist with or without progression to cancer. The detection of 5mCpG often requires techniques that damage DNA or introduce bias through a myriad of limitations. Therefore, we developed a method for the detection of 5mCpG on the HBV genome that does not rely on bisulfite conversion or PCR. Moreover, using the developed technique, we have provided the first de novo assembly of native HBV DNA, as well as the first landscape of 5mCpG from native HBV sequences