Institut fur Humangenetik der Philipps-Universitiit, 0-35037 Marburg, Germany (M. G., A. K.), Ludwig Institute for Cancer Research and Department of Medicine, University of California at San Diego, La l olla, California 92093-0660 (K.A., W.c. ) , Cross Cancer Institute, Edmonton, Alberta, Canada (P.G. ), Division of HematologylOncology, Children's Hospital, Department of Pediatrics, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02 11 5 (S.O.), Division of Pediatric Oncology, Dana Farber Cancer Institute and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02 115 (S.5.), Division of Urology, Department of Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02 115 (c. P., S. R. , l. M.), Dana-Farber Cancer Institute , Boston, Massachusetts 02115 (F. L.) , and Genetics Division, Children's Hospital and Dept. of Pediatrics , Harvard Medical School, Boston, Massachusetts 021 15 (0. B.); Fax: 49-93 I -888-4150

Complete and simple analytical expressions for the partial structure factors of the ternary hard sphere mixture are obtained within the Percus-Yevick approximation and presented as functions of relative packing fractions and relative hard sphere diameters. These solutions follow from the Laplace transform method as applied to multicomponent systems by Lebowitz [Phys. Rev. 133, A895 (1964)]. As an important application, we examine effective interactions in hard sphere liquid mixtures using the microscopic information contained in their partial structure factors. Thus the ensuring pair potential for an effective one-component system is obtained from the correlation functions by using an approximate inversion, and examples of effective potentials for three-component hard sphere mixtures are given. These mixtures may be of particular interest for the study of the packing aspects of melts that form glasses or quasicrystals, since noncrystalline solids often emerge from melts with at least three atomic constituents.

The space-group symmetry of a crystal has a simple form in Fourier space, which provides a natural language for the basic facts about x-ray extinctions and band sticking in nonsymmorphic crystals.

The traditional crystallographic symmetry elements of screw axes and glide planes are subdivided into those that are removable and those that are essential. A simple real-space criterion, depending only on Bravais class, determines which types can be present in any space group. This terminological refinement is useful in expressing the complementary relation between the real-space and Fourier-space formulations of crystal symmetry, particularly in the case of the two nonsymmorphic space groups that have no systematic extinctions (I212121 and I213). A simple analysis in Fourier space demonstrates the nonsymmorphicity of these two space groups, which finds its physical expression not in a characteristic absence of Bragg peaks, but in a characteristic presence of electronic level degeneracies.

The theory of space-group representations is extended to aperiodic crystals by reformulating it as the theory of symmetry-required degeneracies of electronic levels that emerges from the Fourier-space approach to crystal symmetry. As an illustration it is shown that the nonvanishing of a simple linear combination of phase functions belonging to commuting elements from the little group of q requires the degeneracy of all levels with generalized Bloch wave vector q. This condition is applied to all cubic and icosahedral centrosymmetric nonsymmorphic space groups, and to the two nonsymmorphic space groups of periodic crystals that have no systematic extinctions.

The WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) deletion region on chromosome 11p13 has been extensively characterized by deletion analysis and long-range restriction mapping. A dense probe set is available for this genomic region, which harbors a number of disease gene loci, some of which still are not cloned. The identification of candidates for these genes would be greatly facilitated by a complete gene map for this chromosomal segment. As an initial step toward this goal, we have isolated the entire region in 58 overlapping YAC clones. The contig spanning 8 Mb from RAG1 to KCNA4 has been assembled by STS and probe content mapping for 76 loci with an average spacing of about 100 kb. A subset of clones has been analyzed by PFG analysis to position these within the known physical map. Common microsatellite markers permit an alignment of the YAC contig with the genetic and radiation hybrid maps of chromosome 11. Ten known genes, some with much more refined map positions, are placed in the contig. The severalfold coverage of 11p13-p14.1 provides a reliable resource for the future development of a complete gene map of this region.

A NotI end fragment library has been constructed for human Chromosome (Chr) 11p. Seventy-two clones were mapped to chromosomal subregions by use of somatic cell hybrids. The clones detect 44 different CpG islands, and we have isolated cosmid contigs for 36 of them. Extrapolation from the known 11p13 NotI restriction map suggests that every second CpG island from 11p containing a Not site is already represented in the clone collection. By sequence analysis all of the 11p13 clones exhibit typical features of CpG islands, and cross-species hybridization has been detected with at least one fragment in most cases. The cosmids serve as valuable linking clones for long-range restriction mapping. They also provide excellent starting material for transcript isolation procedures to identify genes on chromosome 11p associated with developmental anomalies and various tumor types. Several transcribed sequences have already been isolated with some of these clones.

Homozygous deletions in Wilms' tumor DNA have been a key step in the identification and isolation of the WT1 gene. Several additional loci are also postulated to contribute to Wilms' tumor formation. To assess the frequency of WT1 alterations we have analyzed the WT1 locus in a panel of 77 Wilms' tumors. Eight tumors showed evidence for large deletions of several hundred or thousand kilobasepairs of DNA, some of which were also cytogenetically detected. Additional intragenic mutations were detected using more sensitive SSCP analyses to scan all 10 WT1 exons. Most of these result in premature stop codons or missense mutations that inactivate the remaining WT1 allele. The overall frequency of WT1 alterations detected with these methods is less than 15%. While some mutations may not be detectable with the methods employed, our results suggest that direct alterations of the WT1 gene are present in only a small fraction of Wilms' tumors. Thus, mutations at other Wilms' tumor loci or disturbance of interactions between these genes likely play an important role in Wilms' tumor development.

The direct involvment of the Wilm's tumor suppressor gene (WT1) in Denys-Drash syndrome through mutations within exons 8 or 9 has recently been established. The absence of such alterations in three patients with Frasier syndrome provides a molecular basis for distinguishing these two syndromes that are associated with streak gonads, pseudohermaphroditism and renal failure.

Wilms' tumor is a childhood nephroblastoma that is postulated to arise through the inactivation of a tumor suppressor gene by a two-hit mechanism. A candidate 11p13 Wilms' tumor gene, WT1, has been cloned and shown to encode a zinc finger protein. Patients with the WAGR syndrome (Wilms' tumor, aniridia, genitourinary abnormalities, and mental retardation) have a high risk of developing Wilms' tumor and they carry constitutional deletions of one chromosome 11 allele encompassing the WT1 gene. Analysis of the remaining WT1 allele in a Wilms' tumor from a WAGR patient revealed the deletion of a single nucleotide in exon 7. This mutation likely played a key role in tumor formation, as it prevents translation of the DNA-binding zinc finger domain that is essential for the function of the WT1 polypeptide as a transcriptional regulator. (C) 1993 Wiley-Liss, Inc.

Journal Article Further evidence that imbalance of WT1 isoforms may be involved in Denys – Drash syndrome Get access Anja Konlg, Anja Konlg Search for other works by this author on: Oxford Academic PubMed Google Scholar Sybille Jakubiczka, Sybille Jakubiczka 1Institut fur Humangenetik, Medizinische Hochschule Hannover, D-3000 Hannover 61 and Frauenklink der Medizinischen Hochschule Hannover, Oststadtkrankenhaus, D-3000 HannoverGermany Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter Wleacker, Peter Wleacker 1Institut fur Humangenetik, Medizinische Hochschule Hannover, D-3000 Hannover 61 and Frauenklink der Medizinischen Hochschule Hannover, Oststadtkrankenhaus, D-3000 HannoverGermany Search for other works by this author on: Oxford Academic PubMed Google Scholar Hans W. Schlosser, Hans W. Schlosser 2Frauenklink der Medizinischen Hochschule Hannover, Oststadtkrankenhaus, D-3000 HannoverGermany Search for other works by this author on: Oxford Academic PubMed Google Scholar Manfred Gessler Manfred Gessler * * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Molecular Genetics, Volume 2, Issue 11, November 1993, Pages 1967–1968, https://doi.org/10.1093/hmg/2.11.1967 Published: 01 November 1993 Article history Received: 07 July 1993 Revision received: 13 August 1993 Accepted: 13 August 1993 Published: 01 November 1993

The Wilms tumor gene WT1, a proposed tumor suppressor gene, has been identified based on its location within a homozygous deletion found in tumor tissue. The gene encodes a putative transcription factor containing a Cys/His zinc finger domain. The critical homozygous deletions, however, are rarely seen, suggesting that in many cases the gene may be inactivated by more subtle alterations. To facilitate the search for smaller deletions and point mutations we have established the genomic organization of the WT1 gene and have determined the sequence of all 10 exons and flanking intron DNA. The pattern of alternative splicing in two regions has been characterized in detail. These results will form the basis for future studies of mutant alleles at this locus.