Sixty-nine kilobases of contiguous human genomic sequence containing the alpha-galactosidase A and Bruton's tyrosine kinase loci.

TitleSixty-nine kilobases of contiguous human genomic sequence containing the alpha-galactosidase A and Bruton's tyrosine kinase loci.
Publication TypeJournal Article
Year of Publication1995
AuthorsOeltjen, JC, Liu, X, Lu, J, Allen, RC, Muzny, DM, Belmont, JW, Gibbs, RA
JournalMamm Genome
Volume6
Issue5
Pagination334-8
Date Published1995 May
ISSN0938-8990
KeywordsAgammaglobulinaemia Tyrosine Kinase, alpha-Galactosidase, Amino Acid Sequence, Base Sequence, Cosmids, Fabry Disease, Gene Library, Humans, Introns, Molecular Sequence Data, Protein-Tyrosine Kinases, Repetitive Sequences, Nucleic Acid, X Chromosome
Abstract

Several disease loci have been mapped to the Xq21.3-Xq22 region of the human X Chromosome (Chr) including X-linked agammaglobulinemia (XLA), Fabry disease, Alport syndrome, and Pelizaeus Merzbacher disease. Upon cloning of the XLA gene, Bruton's tyrosine kinase (btk), both Fabry disease and XLA were mapped within the same 50- to 70-kb interval. In order to investigate the genomic organization of the region surrounding btk and the Fabry disease gene, alpha-galactosidase A (gla), we constructed a 6-cosmid contig spanning the region from 5' of gla to 3' of btk. Two of these cosmids spanning most of the coding sequence and the upstream region of btk and gla, U237D10 and U230D1, were sequenced by a random shotgun strategy combined with automated sequencing, resulting in 69 kb of contiguous genomic sequence. Sequencing of U237D10 showed btk to be comprised of 19 exons spanning over 35 kb. Sequencing of U230D1 showed that the 3' end of gla is 9 kb from the 5' end of btk and also demonstrated the presence of two additional genes in the region immediately 5' to btk. The surprisingly high gene density is similar to that seen previously only in the human major histocompatibility locus.

Alternate JournalMamm. Genome
PubMed ID7626884
Grant ListR01H151232 / / PHS HHS / United States
R01H900823 / / PHS HHS / United States