Physical mapping of the bovine immunoglobulin heavy chain constant region gene locus.
Bovine antibodies have recently attracted increasing attention, as they have been shown to exhibit prophylactic and therapeutic properties in selected infectious diseases in humans. In the present study, we have isolated bacterial artificial chromosomes and cosmid clones containing the bovine JH, mu, delta, gamma 1, gamma 2, gamma 3, epsilon, and alpha genes, which allowed us to make a contig of the genes within the bovine IGHC locus. The genes are arranged in a 5'-JH-7 kb-mu-5 kb-delta-33 kb-gamma 3-20 kb-gamma 1-34 kb-gamma 2-20 kb-epsilon- 13 kb-alpha-3' order, spanning approximately 150 kb DNA. Examination of the bovine germline JH locus revealed six JH segments, two of which, JH1 and JH2, were shown to be functional although there was a strong preference for expression of the former. Sequence alignment of the bovine 5' E mu enhancer core region with those of other mammals, demonstrated an absence of the mu E3 motif and a shortened spacer between the mu A and mu B sites within the bovine E mu enhancer core region. Furthermore, the essential sequence element for class switching, switch mu, spanning approximately 3-kb repetitive sequence and abundant in the switch region motifs CTGGG (187 repeats) and CTGAG (127 repeats), was identified immediately upstream of the mu gene. A further sequence comparison revealed that the bovine IGHC genes display an extensive polymorphism leading to expression of multiple antibody allotypes.
Zhao
Yaofeng
Y
Center for Biotechnology, Department of Bioscience at Novum, Karolinska, Institutet, SE-14157, Huddinge, Sweden.
Kacskovics
Imre
I
Rabbani
Hodjattallah
H
Hammarstrom
Lennart
L
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D022202:Chromosomes, Artificial, Bacterial; D003001:Cloning, Molecular; D016521:Electrophoresis, Gel, Pulsed-Field; D005803:Genes, Immunoglobulin; D014644:Genetic Variation; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011817:Rabbits; D051381:Rats; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D012756:Sheep
D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains