Gene Mapping at the Crossroads Peroxidase-Catalysed Iodination and Corre by Mary Lindley Lated the Presence of Fibronectin with Chromosome 8

12 Nature Vol. 281 6 September 1979

labelled surface proteins by lacto Gene mapping at the crossroads peroxidase-catalysed iodination and corre by Mary Lindley lated the presence of fibronectin with chromosome 8. The disagreement arises THE human gene map is said to be poised translocation. again in the results of a similar study by M. for rapid expansion, during the next few The application of 'restriction mapping' Smith (Mount Sinai School of Medicine, years, as the techniques of molecular to increasing numbers of genes now New York) and colleagues who found that biology and immunology take firm root in depends on the rate at which cloned probes hybrid cells could be positive for fibro this traditional domain of geneticists and can be producd and characterised. F.H. nectin while lacking glutathione reductase cell biologists. At a recent reunion in Ruddle (Yale University) predicted that which is associated with chromosome 8. Edinburgh •, 150 of the aficionados agreed restriction mapping will become the The genetics of fibronectin it seems may be that they have now identified the positions predominant method for mapping genes, complex, and possibly may involve genes of about 350 genes on the human and that the major part of the human gene on various chromosomes. On the other chromosomes. Although the current rate map could be known by the end of this hand, the discrepancy may be resolved by of increase is a mere two or three genes per century. the application of more refined techniques. month, the atmosphere was full of Speed, convenience and scope for fine Another promising area is represented confidence that this will accelerate rapidly, resolution should give restriction mapping by two reports of genes that influence the making a complete human gene map a an advantage over in situ hybridisation, expression of oncornaviruses. Using possibility within the lifetime of some of which has recently revealed further human-mouse cell hybrids, C.E. Wright the younger members of the gene mapping information about the arrangement of the and T.B. Shows (Roswell Park Memorial fraternity. histone genes on chromosome 7. Using Institute, Buffalo) have found a gene on One of the most promising strategies labelled pn)bes of complementary RNA, human chromosome 11 that induces the involves the combination of some of the prepared from cloned sea urchin genes, expression of a mouse xenotropic oncorna familiar tools of cytogenetics with D.M. Steffensen (University of Illinois, virus and another on chromosome 15 techniques developed to investigate the fine Urbana) and J .J. Yunis and M.E. involved in the induction of endogenous structure of both prokaryotic and Chandler (University of Minnesota mouse N-tropic oncornavirus. They call eukaryotic genes. By such methods the Medical School) have both localised the these genes B VIX and B V1N, respectively, 13-globin gene, already believed to be on five human histone genes to the long arm of and have found that they are carried on chromosome 11, has been localised more this chromosome. Their results, however, human chromosomes homologous to precisely by D. Housman (Massachusetts do not indicate precisely the same mouse chromosome regions that also carry Institute of Technology) and colleagues. positions, with the latter group placing the genes affecting the expression of oncorna They used cells from hybrid clones each of cluster of genes nearer to the end of the viruses. which contained the Chinese hamster long arm (Chandler et at. Science, in the This suggestion of genetic conservation genome together with a section of human press). The difference may be due to the during evolution is just one of many chromosome 11. To identify the section difficulty of interpreting the pattern of examples that are emerging as gene maps carrying the 13-globin gene they extracted silver grains in the final, autoradiographic are developed for different mammalian the DNA from cells of each clone, treated it stage of this procedure. species. As well as those of mouse, rabbit with a restriction endonuclease and Another promising line of enquiry for and various primates, genes are now being separated the resulting fragments on the future is provided by cell surface mole assigned to the chromosomes of cow, agarose gel. The separated fragments were cules which can be recognised by bio sheep, pig, cat, dog and horse. As would be transferred onto nitrocellulose filters and chemical and immunological techniques expected, these are providing further hybridised to a radioactively labelled and correlated with the presence of evidence of the conservation of the X cloned human 13-globin DNA probe. The particular chromosomes. A. de Ia Chapelle chromosome during evolution. It is also pattern of hybridisation revealed by (Folkhalser Institute of Genetics, Helsinki) becoming increasingly clear that other link autoradiography showed that the gene for and colleagues have followed up previous age groups have been strongly conserved, human 13-globin is carried on a section of studies which indicated an association especially between the great apes and man. the short arm of chromosome 11 . Because between monosomy for chromosome 7 and Yunis and Chandler, for example, have the gene for 13-globin is known to be linked defective granulocyte chemotaxis (Rutuu et extended their in situ hybridisation study to to those for y, 6, and E globins, all four a/. Nature 265, 146; 1977). Treating the chimpanzee, gorilla and orangutan and genes must be carried on this chromosomal defective monosomic granuloctyes with a localised the histone genes on homologous region. radioactive label specific for glycoproteins, regions of the counterparts of human By a similar procedure, B.R. Migeon the Helsinki group has shown that these chromosome 7. and colleagues (Johns Hopkins University blood cells have much less than the normal Similarly J.J. Garver (State University, School of Medicine, Baltimore) have used amount of one particular glycoprotein. Leiden) and colleagues have localised the hybrid cells containing the mouse genome This suggests that a gene on chromosome 7 major histocompatibility complexes of and a human chromosome resulting from a codes for a glycoprotein associated with chimpanzee and rhesus monkey on a translocation between chromosome 11 and chemotaxis. The same chromosome may chromosome homologous with human the X chromosome (Proc. natn. Acad. also be involved in the expression of chromosome 6, which carries the HLA Sci. U.S.A. in the press). They were able to receptors for epidermal growth factor, complex. P.A. Lalley and colleagues (Oak select for the presence or absence of the according to N. Shimizu and colleagues Ridge National Laboratory) have found human chromosome because it carried a (University of Arizona, Tucson). They that some genes on human chromosomes I functioning gene for the enzyme have correlated the presence of this and 6 are correspondingly linked in the hypoxanthine guanine phosphoribosyl chromosome in hybrid cells with the ability baboon, indicating conservation. On the transferase, which the mouse cells lacked. to bind epidermal growth factor. other hand, they interpret their study of the These experiments have further confirmed Indirect immunofluorescence, used by baboon counterpart of human chromo that the Band 6-globin genes are carried on C.K. Eun and H.P. Klinger (Albert some 2, as a sign that extensive chromo human chromosome 11, and show that Einstein College of Medicine, New York), somal rearrangements have occurred they are not on the segment involved in the has suggested that the expression of during the evolution of this chromosome. fibronectin on cell surfaces is affected by Many more such insights should come as •The fifth International Workshop on Human Gene Mapping was held in Edinburgh on 9-13 July 1979. 11 wa s organised by chromosome 11. This contrasts with the the various gene maps develop. 0 H.J. Evans. MRC Clinical and Population Cytogenetics Uni! . suggestion of Owerbach et at. (Proc. natn. Edinburgh. The abstracts and committee reports will be published in Cytog~n~tics and Cell Genetics. Acad. Sci. U.S.A. 15, 5640; 1978), who Mary Lindley is an Assistant Editor of Nature.