~]OOK []~EVIEWS

The studies of human disorders involving chromosomal instability are, unfortunately, limited primarily to phenomenological observations of complex and poorly understood in vitro systems. Suggestions that chromosome breakage can be relied upon for prenatal diagnosis of ataxia-telangiectasia (AT) should be viewed with extreme caution, especially in light of the near-term promise of direct genetic testing. Similarly, Sanford and Parshad report the impressive differences between AT homozygotes and heterozygotes when measuring chromosomal gaps and breaks induced by X-irradiation in G2 while, on the other hand, they see similar differences with dysplastic nevus syndrome, XP, retinoblastoma, familial polyposis, and more than a dozen other clinical entities associated with cancer susceptibility, making it unlikely that these differences reflect the effects of any single gene. It will be interesting to learn how these results correlate with mutations in the recently cloned genes for retinoblastoma and familial polyposis. (Unfortunately, references to almost all recent reports on the isolation

and sequencing of cancer genes are missing from this volume.)

An overwhelming amount of information is available on the in vitro mutagenic effects of a variety of agents. Such effects on the organism and its progeny are yet to be extrapolated con- clusively. In an example of the complex picture of cause and effect, Wolff et al. demonstrate that human lymphocytes can show an 'adaptive response' when challenged with some DNA-damaging agents. On the other hand, investigators are still attempting to interpret one of the few in vivo examples of radiation effects in A-bomb survivors of Hiroshima and Nagasaki. Reassessment of data shows a linear increase in the number of chromosome aberrations as dose increases; however, a wide variety of aberrations occurs within a dose range. This may be due to errors in original exposure estimates or individual differ- ences in response to DNA damage. Adler shows clearly that, when trying to predict the heritable effects of mutagens in germ cells, the stage of differentiation is a significant factor in determining susceptibility to aberration. It seems that

a comprehensive assessment of muta- genic effects must necessarily consider both hereditary predisposition and lifestyle. A logical first step, as Ishidate suggests, requires standardization of mutagen-testing protocols on an international level.

All in all, ChromosomalAberrations has many commendable features. The formating and quality of figures is excellent. Referencing is not extensive but should be useful in locating key articles up to 1989. However, despite the broad coverage of cytogenetic topics, this is not a textbook, and the individual articles in this book are likely to be more useful to specialists than the general reader.

FeyruzR~sool

Section of Hematology/Oncology, Department of Medicine, University of Chicago,

IL 60637, USA.

Richard Gatti Department of Pathology, UCLA School of Medicine, Los Angeles, CA 90024, USA.

] ~ Pulsed fields and empty pockets Advanced Techniques in Chromosome Research edited by Kenneth W. Adolph

Marcel Dekker, 1991. $145.00 (USA and Canada), $166.75 (elsewhere) (xi + 462 pages) ISBN 0 8247 8430 8

Molecular and cell biological approaches to the behaviour, organization and structure of chromosomes have become increasingly popular and interesting in recent years (the December 1990 issue of T/G was a special issue devoted to this subject). In part this is due to developments in methods; imaging tech- niques have allowed chromosomes and chromosome movements in the nucleus to be visualized in a variety of systems, and in mammalian cells antisera from CREST patients have been useful tools for the analysis of chromosomal proteins. Moreover, the revitalization of in situ hybridization by the use of fluorescently labelled probes, yeast artificial chromosome (YAO cloning and genome mapping programs have all raised the awareness of investigators to chromosomes as a level of DNA organization. Genetic approaches in Drosophila and yeast have led to the identification - and in some cases tt{e isolation and analysis - of chromosomal elements such as telomeres, origins of replication and centromeres, and of chromosomal components such as the

molecular motors dynein and kinesin. An encouragingly high degree of conservation of some of these structures has emerged, particularly of telomeres, and has been used to apply ideas or information from one species to others.

Chromosomes are more than just strings of genes, and a better under- standing of them at the molecular and cellular level is highly desirable. Perhaps the major problem in their analysis is the fact that the paradigms available for genes (promoters, terminators, etc.), which provide the impetus for the inten- sive searches for transcription factors, are not available for chromosomal phenomena such as pairing, position effects and banding. We have some ideas about which features of chromo- somes are important (YACs are an example of how a good working under- standing of the structure and function of yeast chromosomes has been exploited), but there are many features, such as bands and replication patterns, that may prove to have little or no biological significance.

With the increasing interest in chromosomes, a book on techniques in chromosome research could be useful. Unfortunately, I don't think this one is. The major reason is that 'chromosome research' is taken to encompass every- thing from YAC cloning to mutagen testing with 'High base-sequence- resolution extraction of DNA fragments

"rig MARCH 1992 VOL. 8 NO. 3

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by immobilized probe for high efficiency gene cloning' (Editor - what happened?). The division of the contents into three sections - molecular, cyto- genetic and cellular - to cover this breadth of material has resulted in a rather arbitrary chapter order. Cytogenetic analysis in malignancies is discussed in two chapters in different sections. The selection of articles is odd. Pulsed field gel electrophoresis is covered in three chapters, and some obvious areas are absent. Fluorescent in situ hybridization, one of the most important new methods, is covered in a limited manner, with discussion restricted to repetitive probes. Homologous recombination in mammalian systems is not represented and the human genome mapping effort and the polymerase chain reaction only touched upon.

I could go on, but although some articles are good - those on linkage stand out - it is difficult to see the point of this book. The choice of topics seems eccentric, and the format of the contri- butions varies: some are reviews, others research reports and still others methods articles. But it is not a methods book of the Maniatis style (Molecular Cloning: A Laboratory Manual) and neither is it a focused view of a particular area. Incidentally, have you noticed the price!

Howard Cooke

MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.