cytidylyl-3--5--guanosine and Wiskott-Aldrich-Syndrome

The genes ARAF1, SYN1, TIMP, and PFC are clustered within 70 kb of one another, and, as reported in the accompanying paper (J. Knight et al., 1994, Genomics 21: 180-187), at least four more genes map within 400 kb: a cluster of Krüppel-type zinc finger genes (including ZNF21, ZNF41, and ZNF81) and ELK-1, a member of the ets oncogene superfamily. This gene-rich region is of particular interest because of the large number of disease genes mapping to Xp11.23: at least three eye diseases (retinitis pigmentosa type 2, congenital stationary night blindness CSNB1, and Aland Island eye disease), Wiskott-Aldrich syndrome, X-linked nephrolithiasis, and a translocation breakpoint associated with synovial sarcoma. We have constructed a 1.8-Mb YAC contig in this region, confirming the link between TIMP and OATL1 reported by Knight et al. (1994) and extending the map in the distal direction. To investigate the likelihood that more genes are located within this region, we have carried out detailed mapping of rare-cutter restriction sites in these YACs and identified seven CpG islands. At least six of these islands are located over 50 kb from any known gene locations, suggesting that the region contains at least this many as yet unidentified genes. We have also mapped the physical locations of six highly polymorphic CA repeats within the contig, thus integrating the physical, genetic, and transcriptional maps of the region and facilitating the mapping and identification of disease genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Base Sequence; Chromosome Mapping; Chromosomes, Artificial, Yeast; Cosmids; Dinucleoside Phosphates; DNA Primers; Eye Diseases; Genetic Markers; Humans; Kidney Calculi; Molecular Sequence Data; Multigene Family; Night Blindness; Polymerase Chain Reaction; Repetitive Sequences, Nucleic Acid; Retinitis Pigmentosa; Sarcoma; Synovial Membrane; Translocation, Genetic; Wiskott-Aldrich Syndrome; X Chromosome

We developed an X chromosome inactivation PCR assay, based on differential methylation of the 5' CpG island of the monoamine oxidase A gene (MAOA), close to a highly polymorphic region just downstream of the first exon. The assay provides a method to determine the carrier status of females from pedigrees with X-linked immunodeficiency diseases (XLID).

Topics: Agammaglobulinemia; Chromosome Mapping; Dinucleoside Phosphates; Dosage Compensation, Genetic; Exons; Female; Genetic Carrier Screening; Genetic Linkage; Humans; Immunologic Deficiency Syndromes; Male; Methylation; Monoamine Oxidase; Polymerase Chain Reaction; Severe Combined Immunodeficiency; Wiskott-Aldrich Syndrome; X Chromosome

The differential methylation of a CpG island 2.5 kb distant from a hypervariable region at the DXS255 locus provides the basis for a Southern blotting X chromosome inactivation analysis system. The technique enables carrier detection in about 90% of females at risk from pedigrees with Wiskott-Aldrich syndrome, X-linked severe combined immunodeficiency or X-linked agammaglobulinemia.

Topics: Agammaglobulinemia; Chromosome Mapping; Dinucleoside Phosphates; Dosage Compensation, Genetic; Female; Genetic Carrier Screening; Genetic Linkage; Humans; Immunologic Deficiency Syndromes; Male; Methylation; Repetitive Sequences, Nucleic Acid; Severe Combined Immunodeficiency; Wiskott-Aldrich Syndrome; X Chromosome