Beatrice Sellinger

Characterization of 10p Deletions Suggests Two Nonoverlapping Regions Contribute to the DiGeorge Syndrome Phenotype

We thank Giuseppe Monaco and Tony Lipson for providing cell lines from patients CH92-304 and CH95-199, respectively. We thank Kathy Call and Jen-i Mao (Genome Therapeutics) for providing physical-map data in the early stages of these experiments. These studies were supported in part by NIH grants HL51533 (to M.L.B. and B.S.E.) and DC02027 (to M.L.B., D.A.D., and B.S.E.).

Conserved gene structure and genomic linkage for D-dopachrome tautomerase (DDT) and MIF

Abstract. Macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT) are small proteins, which are related both by sequence and by in vitro enzyme activity. Here we show that the gene for DDT in human and mouse is identical in exon structure to MIF. Both genes have two introns that are located at equivalent positions, relative to a twofold repeat in protein structure. Although in similar positions, the introns are in different phases relative to the open reading frame. Other members of this superfamily exist in nematodes and a plant, and a related gene in C. elegans shares an intron position with MIF and DDT. In addition to similarities in structure, the genes for DDT and MIF are closely linked on human Chromosome (Chr) 22 and mouse Chr 10.

Isolation and regional localization of 35 unique anonymous DNA markers for human chromosome 22

Thirty-five new, unique, DNA probes have been isolated and each has been assigned to one of five regions on chromosome 22. The distribution of probes along the chromosome is what would be expected based on the estimated size of each region with the exception of the short arm (22p). RFLP analysis was performed using 13 different restriction enzymes and over 50% of the probes were found to have useful polymorphisms. Probes mapping to 22q11 were further characterized by pulsed-field gel analysis and it has been possible to link several on large restriction fragments. These 35 new probes will be useful reagents for producing genetic and physical maps of chromosome 22.

Localization of the rhabdomyosarcoma t(2;13) breakpoint on a physical map of chromosome 13.

Previous investigations of the pediatric soft tissue tumor alveolar rhabdomyosarcoma have identified a characteristic translocation t(2;13)(q35;q14). We have employed a physical mapping strategy to localize the site of this translocation breakpoint on chromosome 13. Using a panel of somatic cell hybrid and lymphoblast cell lines with deletions and unbalanced translocations involving chromosome 13, we have mapped numerous probes from the 13q12-q14 region and demonstrate that this region is divisible into five physical intervals. These probes were then mapped with respect to the t(2;13) rhabdomyosarcoma breakpoint by quantitative Southern blot analysis of an alveolar rhabdomyosarcoma cell line with two copies of the derivative chromosome 13 and one copy of the derivative chromosome 2. Our findings demonstrate that the t(2;13) breakpoint is localized within a map interval delimited by the proximal deletion breakpoints in lymphoblast lines GM01484 and GM07312. Furthermore, the breakpoint is most closely flanked by loci D13S29 and TUBBP2 within this map interval. These findings will facilitate chromosomal walking strategies for cloning the regions disrupted by the alveolar rhabdomyosarcoma translocation. In addition, this physical map will permit rapid determination of the proximity of new cloned sequences to the translocation breakpoint.

Characterization of CDC45L: a gene in the 22q11.2 deletion region expressed during murine and human development

Division of Human Genetics and Molecular Biology, The Children’s Hospital of Philadelphia, 1002 Abramson Research Center, 34th Street and Civic Center Blvd., Philadelphia, Pennsylvania 19104, USA Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, USA Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA