cytidylyl-3--5--guanosine and Syndrome

Topics: Animals; Centromere; Chromosome Aberrations; Chromosome Disorders; CpG Islands; Dinucleoside Phosphates; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases; DNA Methylation; DNA Methyltransferase 3A; DNA Methyltransferase 3B; DNA, Satellite; Drosophila; Embryonic and Fetal Development; Face; Humans; Immunologic Deficiency Syndromes; Mice; Mice, Knockout; Stem Cells; Syndrome

McLeod syndrome, characterized by acanthocytosis and the absence of a red-blood-cell Kell antigen (Kx), is a multisystem disorder involving a late-onset myopathy, splenomegaly, and neurological defects. The locus for this syndrome has been mapped, by deletion analysis, to a region between the loci for Duchenne muscular dystrophy (DMD) and chronic granulomatous disease (CGD). In this study, we describe a new marker, 3BH/R 0.3 (DXS 709), isolated by cloning the deletion breakpoint of a DMD patient. A long-range restriction map of Xp21, encompassing the gene loci for McLeod and CGD, was constructed, and multiple CpG islands were found clustered in a 700-kb region. Using the new marker, we have limited the McLeod syndrome critical region to 150-380-kb. Within this interval, two CpG-rich islands which may represent candidate sites for the McLeod gene were identified.

Topics: Blotting, Southern; Chromosome Fragility; Chromosome Mapping; Dinucleoside Phosphates; DNA; Electrophoresis, Gel, Pulsed-Field; Genetic Linkage; Genetic Markers; Granulomatous Disease, Chronic; Humans; Kell Blood-Group System; Male; Muscular Dystrophies; Nucleic Acid Hybridization; Restriction Mapping; Syndrome; X Chromosome

We have isolated a DNA segment absent from all the constitutionally deleted chromosomes 11 of our patients with Wilms tumor. This marker separates two balanced translocations that break in band 11p13: the distal one associated with aniridia (AN2), and the proximal one with genitourinary dysplasia (GUD). The GUD breakpoint maps within the smallest region of overlap (SRO) for the Wilms tumor (WT) gene locus, thus strengthening the previous suggestion of an association between Wilms tumor and other abnormalities of the genitourinary system. The 11p13 translocation breakpoint associated with T-cell acute lymphatic leukemia (T-ALL) is centromeric to the SRO and separated from the WT locus by at least one known gene. This region of the human genome (11p13) is rich in CpG islands that potentially identify genes, some of which may be involved in the various phenotypes associated with the WAGR syndrome. This is consistent with the proposition that the majority of human genes are in G-negative bands.

Topics: Animals; Aniridia; Blotting, Southern; Chromosome Mapping; Chromosomes, Human, Pair 11; Dinucleoside Phosphates; DNA; Genes; Humans; Hybrid Cells; Kidney Neoplasms; Mice; Restriction Mapping; Syndrome; Translocation, Genetic; Urogenital Abnormalities; Wilms Tumor