130 kb of DNA sequence reveals two new genes and a regional duplication distal to the human iduronate-2-sulfate sulfatase locus.

Deficiency of IDs activity results in Hunter Syndrome (mucopolysaccharidosis type II), a fatal X-linked recessive disorder. We report characterization of 28 cosmids around the IDS locus in Xq28. Four overlapping cosmids have been sequenced in their entirety generating a 130-kb contig. These studies show the fine structure of the IDS gene and identify an IDS pseudogene-like structure located 20 kb distal to the active gene. Two novel genes have also been identified in this sequence, and one of these genes is also locally duplicated. Both homologs are expressed, and a number of alternative transcript products have been characterized. The presence of a highly conserved pseudogene-like structure within a larger duplicated region close to the IDS gene has significant implications for the study of mutations at this locus.

[1]  Jerzy Jurka,et al.  Censor - a Program for Identification and Elimination of Repetitive Elements From DNA Sequences , 1996, Comput. Chem..

[2]  J. Hughes,et al.  The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains , 1995, Nature Genetics.

[3]  W J Kleijer,et al.  Inversion of the IDS gene resulting from recombination with IDS-related sequences is a common cause of the Hunter syndrome. , 1995, Human molecular genetics.

[4]  R. Gibbs,et al.  Adaptor-based uracil DNA glycosylase cloning simplifies shotgun library construction for large-scale sequencing. , 1994, Analytical biochemistry.

[5]  R. Gibbs,et al.  PCR Based Strategies for Gap Closure in Large-scale Sequencing Projects , 1994 .

[6]  M. Adams,et al.  Automated DNA sequencing and analysis. , 1994 .

[7]  C. P. Morris,et al.  Sequence of the human iduronate 2-sulfatase (IDS) gene. , 1993, Genomics.

[8]  D. Bentley,et al.  Determination of the organisation of coding sequences within the iduronate sulphate sulphatase (IDS) gene. , 1993, Human molecular genetics.

[9]  R. Gibbs,et al.  A simple protocol for the automation of DNA cycle sequencing reactions and polymerase chain reactions. , 1992, DNA sequence : the journal of DNA sequencing and mapping.

[10]  E. Uberbacher,et al.  Locating protein-coding regions in human DNA sequences by a multiple sensor-neural network approach. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[11]  G. Suthers.  Estimation of an approximate confidence interval for FRAXA location by using linkage data from many pedigrees. , 1991, American Journal of Human Genetics.

[12]  R. Staden,et al.  A sequence assembly and editing program for efficient management of large projects. , 1991, Nucleic acids research.

[13]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[14]  W. Ansorge,et al.  A simple and rapid preparation of M13 sequencing templates for manual and automated dideoxy sequencing. , 1987, Nucleic acids research.

[15]  J. Nathans,et al.  Molecular genetics of human color vision: the genes encoding blue, green, and red pigments. , 1986, Science.