Exon-intron organization of the human dystrophin gene.

Analysis of the exon-intron organization of the human dystrophin gene has been hampered by its enormous size. By using a YAC-based exon mapping approach and long PCR, we have succeeded in defining the size of the gene and its organization. Our results, compared with data on the distribution of deletion breakpoints by intron, elucidate the topography of the intragenic deletion-prone regions. Within the central high-frequency deletion region, the small, 6.6-kb, intron 49 shows a much higher density of deletion breakpoints than intron 44, which was previously believed to coincide with the most mutable zone of the gene. On the other hand, in the proximal part of the gene, deletion breakpoints do not preferentially occur in a few introns, but are spread over a large DNA segment containing introns 2 to 42.

[1]  H. Klamut,et al.  Identification of a transcriptional enhancer within muscle intron 1 of the human dystrophin gene. , 1996, Human molecular genetics.

[2]  L. Vitiello,et al.  Genomic organization of the human dystrophin gene across the major deletion hot spot and the 3' region. , 1995, Genomics.

[3]  P. Ray,et al.  A novel dystrophin isoform is required for normal retinal electrophysiology. , 1995, Human molecular genetics.

[4]  L. Kunkel,et al.  Dp140: a novel 140 kDa CNS transcript from the dystrophin locus. , 1995, Human molecular genetics.

[5]  D. Bentley,et al.  Exon structure of the human dystrophin gene. , 1993, Genomics.

[6]  D. Bentley,et al.  Vertical integration of cosmid and YAC resources for interval mapping on the X-chromosome. , 1993, Genomics.

[7]  A. Monaco,et al.  Expression of four alternative dystrophin transcripts in brain regions regulated by different promoters. , 1992, Human molecular genetics.

[8]  D. Bentley,et al.  Determination of the exon structure of the distal portion of the dystrophin gene by vectorette PCR. , 1992, Genomics.

[9]  Z. Levy,et al.  A 71-kilodalton protein is a major product of the Duchenne muscular dystrophy gene in brain and other nonmuscle tissues. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[10]  K. Davies,et al.  Characterization of a 4.8kb transcript from the Duchenne muscular dystrophy locus expressed in Schwannoma cells. , 1992, Human molecular genetics.

[11]  A. Monaco,et al.  A yeast artificial chromosome contig containing the complete Duchenne muscular dystrophy gene. , 1992, Genomics.

[12]  D. Bentley,et al.  Construction of a 2.6-Mb contig in yeast artificial chromosomes spanning the human dystrophin gene using an STS-based approach. , 1992, Genomics.

[13]  H Sugita,et al.  Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies. , 1991, American journal of human genetics.

[14]  C. van Broeckhoven,et al.  242 breakpoints in the 200-kb deletion-prone P20 region of the DMD gene are widely spread. , 1991, Genomics.

[15]  L. Kunkel,et al.  Dystrophin is transcribed in brain from a distant upstream promoter. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[16]  M. W. Thompson,et al.  Duplicational mutation at the Duchenne muscular dystrophy locus: its frequency, distribution, origin, and phenotypegenotype correlation. , 1990, American journal of human genetics.

[17]  S. Gangopadhyay,et al.  Molecular and functional analysis of the muscle-specific promoter region of the Duchenne muscular dystrophy gene , 1990, Molecular and cellular biology.

[18]  C. van Broeckhoven,et al.  Topography of the Duchenne muscular dystrophy (DMD) gene: FIGE and cDNA analysis of 194 cases reveals 115 deletions and 13 duplications. , 1989, American journal of human genetics.

[19]  K. Fischbeck,et al.  Familial X‐linked myalgia and cramps , 1989, Neurology.

[20]  L. Kunkel,et al.  The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. , 1989, American journal of human genetics.

[21]  M. W. Thompson,et al.  Frame-shift deletions in patients with Duchenne and Becker muscular dystrophy. , 1988, Science.

[22]  Peter Beighton,et al.  de la Chapelle, A. , 1997 .

[23]  A. Monaco,et al.  An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. , 1988, Genomics.