Abstract

A person's genetic background plays an important role in their susceptibility to cancer, disease progression, and response to therapy. Genetic variations can be used as markers to understand complex diseases including cancer and AIDS. Variants in the estrogen receptor gene (ESR1) are associated with a reduced risk of breast cancer, and we are analyzing data from 500,000 SNPs typed in breast cancer cases and controls to identify additional genes.The TRIM5 gene encodes a protein involved in the protection of cells from HIV infection. We have identified regions of the human TRIM5 gene that appear to have undergone selection, perhaps in response to previous infection. Other TRIM family sequences in the human genome also appear to have been infected and may be involved in the protection to infection by other viruses. A cow TRIM5-related gene was identified that plays role in infection from bovine lentivrus sequences. By studying variants in the complement B and C2 (BF, C2) genes we have identified association in this gene in patients with age-related macular degeneration (AMD). AMD is the leading cause of blindness in the elderly and is estimated to effect as many as of 10 million Americans. By examining the genetic variants in the BF and C2 genes significantly protective haplotypes were identified. The complement pathway is important in the response to pathogens causative for cancer. Further study of this important component of the innate immune response could lead to insight into human disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC005652-16
Application #
7337754
Study Section
(LGD)
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2006
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

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
Garrido, Claudia; Santizo, Veronica Giron; Müllers, Petra et al. (2013) Frequency of thiopurine S-methyltransferase mutant alleles in indigenous and admixed Guatemalan patients with acute lymphoblastic leukemia. Med Oncol 30:474
Boland, Joseph F; Chung, Charles C; Roberson, David et al. (2013) The new sequencer on the block: comparison of Life Technology's Proton sequencer to an Illumina HiSeq for whole-exome sequencing. Hum Genet 132:1153-63
Meyer-Lindenberg, A; Kolachana, B; Gold, B et al. (2009) Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans. Mol Psychiatry 14:968-75
Torimiro, Judith N; Javanbakht, Hassan; Diaz-Griffero, Felipe et al. (2009) A rare null allele potentially encoding a dominant-negative TRIM5alpha protein in Baka pygmies. Virology 391:140-7
Allikmets, Rando; Dean, Michael (2008) Bringing age-related macular degeneration into focus. Nat Genet 40:820-1
Lou, H; Dean, M (2007) Targeted therapy for cancer stem cells: the patched pathway and ABC transporters. Oncogene 26:1357-60
Remsberg, Jarrett R; Lou, Hong; Tarasov, Sergey G et al. (2007) Structural analogues of smoothened intracellular loops as potent inhibitors of Hedgehog pathway and cancer cell growth. J Med Chem 50:4534-8
O'Brien, Thomas R; Kachapati, Kritika; Zhang, Mingdong et al. (2007) HCV infection clearance with functional or non-functional caspase-12. Scand J Gastroenterol 42:416-7
Li, Xing; Gold, Bert; O'hUigin, Colm et al. (2007) Unique features of TRIM5alpha among closely related human TRIM family members. Virology 360:419-33

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