S. Povey

Summary Five of the most variable loci detected in human DNA by hybridization with DNA fingerprint probes have been cloned and characterized. Each locus consists of a tandem‐repetitive minisatellite, with repeat units ranging in length from 9 to 45 base pairs depending on the locus. All of these cloned minisatellites act as locus‐specific hybridization probes, and detect extremely variable Mendelian loci with heterozygosities ranging from 90 to 99%. These five hypervariable loci, together with a previously‐isolated minisatellite designated pΛg3, are dispersed over four autosomes (chromosomes 1, 5, 7 and 12). Syntenic pairs on chromosomes 1 and 7 show no detectable pair‐wise linkage, and thus these hypervariable loci show no evidence of clustering within the genome and should provide valuable markers for mapping inherited disease. The locus‐specific minisatellites act as very sensitive hybridization probes, and can be pooled to detect several hypervariable loci simultaneously. The applications of these probes in individual identification, paternity testing and analysis of cell chimaerism are discussed, and are illustrated by an analysis of forensic specimens from two victims who had been sexually assaulted and murdered. We are very grateful to Professor J. Dausset and Dr H. Cann at the Human Polymorphism Study Centre, Paris. for the generous provision of DNA samples from the panel of CEPH families, to Dr Mary Davis for providing DNA from the JDA hybrids, and also to the following people who kindly allowed us to use their hybrids. Dr Ellen Solomon. Dr Nigel Spurr. Dr P. Goodfellow, Dr Denise Sheer, Dr John Cowell and Dr Ben Carritt. We also thank Anabel Kearney who did the enzyme analysis on the hybrids, and Lynne West who did the karyotyping. We are also grateful to the Leicestershire Constabulary for their permission to cite details of the forensic analysis. A.J.J. is a Lister Institute Research Fellow, and this work was supported by a grant to A.J.J. from the Medical Research Council. The minisatellite probes are the subject of Patent Applications, and commercial enquiries should be addressed to the Lister Institute of Preventive Medicine, Brockley Hill, Stanmore. Middlesex, H A7 4JD, U.K.

SUMMARY 1. The elctrophoretic pattern of phosphohexose isomerase has been examine in the blood of 3397 unrelated individuals from several different populations groups. 2. Eight variant phenotypes were identinfied and these were designated PHI 2‐1, 3‐1, 4‐1, 5‐11 6‐1, 7‐1, 8‐1, 9‐1. All of these were rare in the populations studied except the variant designated PHI 3‐1, which was observed with a frequency of about 1% in a mixed population of Asiatic Indians. 3. Studies of selected families indicated that the variants occured in individuals who are heterozygous for one or another of a series of rare alleles at an autosomal locus. 4. Studies on the family of a patient that the patient was heterozygous for two different rare alleles at the PHI locus, each associated with reduced PHI activity. The patinet's mother showed the PHI 9‐1 phenotype and his father showed a new phenotype designated PHI 10‐1. The patient's phenotype has been designeated PHI 9‐10. 5. The enzyme appears to be a dimer and in heterozygotes isozymes of hybrid submit compostion as well as isozymes of like subunit compostion are apparently formed.

The HUGO Gene Nomenclature Committee (HGNC) aims to assign a unique and ideally meaningful name and symbol to every human gene. The HGNC database currently comprises over 24 000 public records containing approved human gene nomenclature and associated gene information. Following our recent relocation to the European Bioinformatics Institute our homepage can now be found at http://www.genenames.org, with direct links to the searchable HGNC database and other related database resources, such as the HCOP orthology search tool and manually curated gene family webpages.

Twenty-two continuous cell lines derived from normal and neoplastic urothelium, maintained under identical culture conditions, were characterized in terms of isozyme phenotype, tumorigenicity, and xenograft morphology following xenotransplantation to nude mice, cytological appearance, in vitro growth rate, labelling index, and colony-forming efficiency, in parallel with separate studies of in vitro drug sensitivities and monoclonal antibody reactivities. Three groups were identified: (a) distinct lines with differing isozyme patterns, a broad spectrum of growth characteristics, and xenograft morphologies similar to the histopathology of the parent tumors after periods of up to 17 yr following establishment in vitro; (b) cross-contaminated sublines (maintained separately in different laboratories for periods of up to 10 yr), with identical isozyme patterns and similar growth characteristics, but differing markedly in tumorigenicity and xenograft morphology; and (c) lines derived from normal urothelium which were nontumorigenic and had an isozyme pattern usually only encountered in untransformed cells. These data indicate that cell lines representative of human transitional cell carcinomas can be selected on the basis of xenograft morphology and isozyme patterns, and that a panel of lines derived from normal and neoplastic urothelium could provide a model system to study the biology and treatment of this disease.