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 5 published manuscripts. The CIPGC participated in the study of enhanced anti-HIV functional activity associated with Gag-specific CD8 T cell responses. This CIPGC epidemiological research indicated that it is the magnitude and functional capacity of CD8 T-cell responses to certain conserved proteins, like Gag, which predict effective antiviral HIV-specific CD8 T-cell function. The CIPGC undertook epidemiological analysis for a study of effects of IL28B polymorphism on hepatitis B virus and HIV. The study results indicate that an IL28B polymorphism previously shown to be associated with HCV clearance is not associated with hepatitis B virus (HBV) and human immunodeficiency virus-1 (HIV) outcomes. Epidemiological approaches were used to determine the consistency of HLA-B allelic effects in AIDS induced by HIV-1 in different disease transmission cohorts. It could be shown that HLA-B polymorphisms that affect the risk of AIDS, may also alter HIV-1 infectivity, but do not appear to protect against infection. The CIPGC undertook the sequencing and analysis of somatic mutations in the ctnnb1 and kras genes of MyD88 knockout and control mice to determine whether genetic backgrounds influenced the outcome of carcinogenic treatments. By quantifying the number of such somatic mutations found in a portion of the ctnnb1 gene of colon polyps, the GC was able to assist in the demonstration indicating that somatic mutations occurred at higher levels in the control mice and that the MyD88 knockout was protective. The epidemiological analyses that show the role of KIR and HLA on HIV-2 infection and progression was undertaken by the CIPGC. HLA-B*1503 was shown to be associated with poor prognosis after HIV-2 infection. It was shown that alleles strongly associated with HIV-1 disease show no effect in HIV-2 disease, emphasizing the dependence of host factors effects upon the identity of the pathogen.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICBC011237-02
Application #
8158375
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2010
Total Cost
$979,020
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
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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