title: Sixty-nine kilobases of contiguous human genomic sequence containing the alpha-galactosidase A and Bruton's tyrosine kinase loci.
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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Oeltjen
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: R C
authors.initials: RC
authors.lastname: Allen
authors.forename: D
authors.initials: D
authors.lastname: Muzny
authors.forename: J W
authors.initials: JW
authors.lastname: Belmont
authors.forename: R A
authors.initials: RA
authors.lastname: Gibbs
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000595:Amino Acid Sequence; D001483:Base Sequence; D003360:Cosmids; D000795:Fabry Disease / Q000235:genetics; D015723:Gene Library; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D014960:X Chromosome; D000519:alpha-Galactosidase / Q000235:genetics*
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D000519:alpha-Galactosidase