Genotyping and Genetic Epidemiology. The CIP Genetics Core (CIPGC) has been active in both the generation of genotypic data and in the statistical, bioinformatic and epidemiological analysis of the genetic data. In particular, the work of the Genetics Core over the past year has been used by CIP principal investigators to establish findings for 7 published manuscripts. The CIPGC participated in the study of genetic factors involved in the control of HIV viral load. Manuscripts identified genomic locations in the human genome of major effects in such control. In particular, a region of the 3 untranslated region of the HLA-C gene is targeted by a microRNA resulting in reduced expression of the gene and higher human immunodeficiency virus (HIV) viral loads. We are supporting research investigating the mechanism by which polymorphism in the target site of the microRNA arise and how this affects outcomes in HIV disease and also initiating efforts into possible roles for this polymorphism in transplantation outcomes. We have been involved in analysis of HLA-C genomic sequences that enabled us to identify the polymorphisms of the binding site and the donor sequence involved in gene conversion at the site. Another host genome effect in HIV infection was characterized as a reduction in viral loads associated with the DRB1*1303 gene. Ongoing work into the role of the human IL28B gene in control of hepatitis C virus (HCV) infection has resulted in one publication indicating that none of the suspected polymorphisms of the gene is causal for higher rates of spontaneous clearance of HCV. Other published work has involved the characterization of the role of transporter genes in multidrug resistance in cancer stem cells.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Scientific Cores Intramural Research (ZIC)
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National Cancer Institute Division of Basic Sciences
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Ramsuran, Veron; Hernández-Sanchez, Pedro G; O'hUigin, Colm et al. (2017) Sequence and Phylogenetic Analysis of the Untranslated Promoter Regions for HLA Class I Genes. J Immunol 198:2320-2329
Lou, Hong; Villagran, Guillermo; Boland, Joseph F et al. (2015) Genome Analysis of Latin American Cervical Cancer: Frequent Activation of the PIK3CA Pathway. Clin Cancer Res 21:5360-70
Ramsuran, Veron; Kulkarni, Smita; O'huigin, Colm et al. (2015) Epigenetic regulation of differential HLA-A allelic expression levels. Hum Mol Genet 24:4268-75
Rizvi, Syed Monem; Salam, Nasir; Geng, Jie et al. (2014) Distinct assembly profiles of HLA-B molecules. J Immunol 192:4967-76
Dean, Michael; Bendfeldt, Giovana; Lou, Hong et al. (2014) Increased incidence and disparity of diagnosis of retinoblastoma patients in Guatemala. Cancer Lett 351:59-63
Bashirova, Arman A; Martin-Gayo, Enrique; Jones, Des C et al. (2014) LILRB2 interaction with HLA class I correlates with control of HIV-1 infection. PLoS Genet 10:e1004196
Petersdorf, Effie W; Gooley, Theodore A; Malkki, Mari et al. (2014) HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation. Blood 124:3996-4003
Dean, Michael; Lou, Hong (2013) Genetics and genomics of prostate cancer. Asian J Androl 15:309-13
Ranasinghe, Srinika; Cutler, Sam; Davis, Isaiah et al. (2013) Association of HLA-DRB1-restricted CD4? T cell responses with HIV immune control. Nat Med 19:930-3
Jiménez-Morales, Silvia; Martínez-Aguilar, Nora; Gamboa-Becerra, Roberto et al. (2013) Polymorphisms in metalloproteinase-9 are associated with the risk for asthma in Mexican pediatric patients. Hum Immunol 74:998-1002

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