Abstract

The neighboring human complement C4 and steroid 21-hydroxylase(CYP21) genes are flanked by novel genes RP and Gene X. RP-C4-CYP21-Gene X form a modular structure termed RCCX in the major histocompatability complex(MHC). There is a variation in the number and structure of RCCX modules in the population. Deficiencies of the functional genes in RCCX may lead to genetic and/or autoimmune defects. Three groups of mobile genetic elements have been found by us at the RCCX modules: an endogenous retrovirus HERV-K(C4) which mediates the size variation of C4 genes, eight Alu elements, and a novel group of composite repetitive DN forming a discrete genetic unit, the SVA element, in the RP1 gene. It is proposed here to fully characterize the RCCX modular structures in the population, to analyze the 180 Kb DNA sequence spanning more than ten human genes by mapping the disease markers and mutations. This research will be extended to the 38 members of HERV-K(C4), and the composite SVA in the human genome. The common theme is to elucidate the mechanisms leading to genetic instabilities of the MHC. Determination of DNA sequences, analysis of sequences through multiple sequence alignments and database searching are the most important component of this research. The facilities and software of PSC enable us to analyze the complex structures of RCCX and large amounts of sequence information effectively.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR006009-10
Application #
6221056
Study Section
Project Start
1999-08-01
Project End
2000-07-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
10
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Mellon Pitts Corporation (Mpc Corp)
Department
Type
DUNS #
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213

  Publications

Simakov, Nikolay A; Kurnikova, Maria G (2018) Membrane Position Dependency of the pKa and Conductivity of the Protein Ion Channel. J Membr Biol 251:393-404
Yonkunas, Michael; Buddhadev, Maiti; Flores Canales, Jose C et al. (2017) Configurational Preference of the Glutamate Receptor Ligand Binding Domain Dimers. Biophys J 112:2291-2300
Hwang, Wonmuk; Lang, Matthew J; Karplus, Martin (2017) Kinesin motility is driven by subdomain dynamics. Elife 6:
Earley, Lauriel F; Powers, John M; Adachi, Kei et al. (2017) Adeno-associated Virus (AAV) Assembly-Activating Protein Is Not an Essential Requirement for Capsid Assembly of AAV Serotypes 4, 5, and 11. J Virol 91:
Subramanian, Sandeep; Chaparala, Srilakshmi; Avali, Viji et al. (2016) A pilot study on the prevalence of DNA palindromes in breast cancer genomes. BMC Med Genomics 9:73
Ramakrishnan, N; Tourdot, Richard W; Radhakrishnan, Ravi (2016) Thermodynamic free energy methods to investigate shape transitions in bilayer membranes. Int J Adv Eng Sci Appl Math 8:88-100
Zhang, Yimeng; Li, Xiong; Samonds, Jason M et al. (2016) Relating functional connectivity in V1 neural circuits and 3D natural scenes using Boltzmann machines. Vision Res 120:121-31
Lee, Wei-Chung Allen; Bonin, Vincent; Reed, Michael et al. (2016) Anatomy and function of an excitatory network in the visual cortex. Nature 532:370-4
Murty, Vishnu P; Calabro, Finnegan; Luna, Beatriz (2016) The role of experience in adolescent cognitive development: Integration of executive, memory, and mesolimbic systems. Neurosci Biobehav Rev 70:46-58
Jurkowitz, Marianne S; Patel, Aalapi; Wu, Lai-Chu et al. (2015) The YhhN protein of Legionella pneumophila is a Lysoplasmalogenase. Biochim Biophys Acta 1848:742-51

Showing the most recent 10 out of 292 publications