The Rabbit Genome, Immune System and Ig Genetics

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

Rabbits are the only or best animal model for several infectious diseases. The sequence of the rabbit genome is currently unfinished at 2x, but deeper 7x coverage started in 2007. A 2006 NHGRI recommendation that rabbit be sequenced more deeply, describes the NIAID allotype-defined rabbits as a valuable resource for future SNP discovery. They have polymorphisms of a variety of immune system genes including allelic allotypes of the VH, CH, and CL regions of antibody molecules. The colony also contained descendants of rabbits formerly at the Basel Institute for Immunology, including mutant and wild-type parental of VH1a2-deleted Alicia, CK1 splicing defective Basilea, and several VH-CH recombinant heavy chain types. These rabbits were made available to interested individuals, particularly to sites where breeding colonies could be established. A 4D relational database contains more than 45 years of breeding records and other information about animals in the colony. The mutant ali animals have a deletion of a key variable region gene in the immunoglobulin heavy chain locus that is present in related 2R1 wild type rabbits. The mutants may be more susceptibe to infectious disease because they have abnormal delayed development of humoral immunity. In part as the result of a White Paper I coauthored in 2005 proposing deep sequencing of the rabbit genome, 7x coverage was completed In July 2008 at Broad Institute MIT and Harvard. Assembly of the deep coverage is anticipated in early 2009. The sequences we have been able to find and use in the incomplete 2x trace archive, and in the 7x trace archive have already proven useful for various studies. As a result of my efforts, two websites are now available one maintained by the National Center for Biotechnology Information (NCBI) http://www.ncbi.nlm.nih.gov/projects/genome/guide/rabbit/ -- and one by NIAID on Rabbit in Immunology & Infectious Disease (http://www3.niaid.nih.gov/research/resources/ri/. The latter site offers a summary of an NIAID workshop on Rabbit Models of Human Infectious diseases held in 2005 that I helped the extramural NIAID DMID to program and chair.