Book Reviews 499

The Principles of Human Biochemical Genetics. 3rd Revised Edition. Harry Harris. Elsevier/North-Holland Biomedical Press, Amsterdam, 1980, 554 pp. Price: $27.

Like other sturdy British transplants, Harry Harris and his book, “The Princi- ples of Human Biochemical Genetics,” are thriving in the New World. The book has grown some- understandably so, as the science it represents matures. The new parts are solid, however, and blend well with the heartwood of Doctor Harris’s earlier scholarship (second edition, 1975).

The author revised by a system of “crossing-over, deletions . . . and other re- arrangements” (Chapter 3). He realigned the discussion of hybrid proteins with top- ics in Chapter 1, deleted the chapter on “Mutations Affecting Rates of Synthesis,” and transformed the durable segment on the thalassemias with interpretations from endonuclease analysis. Other sections remain untouched, presumably because the same principles apply, like those referring to deficiency of and variation in glucose-6- phosphate dehydrogenase, or are deemphasized, like that on haptoglobin variants, now tucked away at the end of Chapter 3.

The text retains the organization of the previous edition - nine chapters and two appendixes. The first four chapters direct the reader through the complexities of genetic theory, an understanding of which is needed to sense the order and substance of clinical genetics. Two chapters relating to pathologic genetics discuss the inborn errors, which are classified by sites of biochemical defect. Doctor Harris devotes a chapter to the composition and action of blood group substances and a chapter to the occurrence of allelic variation in populations. The final chapter explains the molecu- lar basis for current genetic theory and the phenomenon of genetic heterogeneity.

Doctor Harris bases much of his revision on knowledge derived from recent ge- netic breakthroughs - the discovery of the precise molecular natures of the thalas- semias, new evidence for variable susceptibility of loci to X-inactivation, tetrahydro- biopterin’s role in atypical phenylketonuria, and the heterogeneity of urea cycle enzyme deficiency diseases, to mention a few. Throughout he acknowledges the in- sights geneticists have gained from studying tissue culture models, especially when discussing the classification of lysosomal storage diseases and the recognition, in het- erozygotes, of variable gene dosage effects.

Other new sections reflect the active sites of genetic research. The ramifications of familial hypercholesterolemia, for example, underlie a new essay on receptor defects. Recently described enzymic products coded for by the Lewis locus and a rein- terpretation of the Bombay phenotype based on newly recognized interactions among H, A, and B gene products highlight the revised chapter on blood group substances.

Doctor Harris’s revisions of the chapter on enzyme and protein diversity are ex- tensive. Introducing polymorphisms and explaining them didactically, he treats read- ers to the intellectual pleasure of developing new concepts from raw data (frequently his own). There are new segments on polymorphisms in plasma and tissue proteins, polymorphisms detectable immunologically (especially the HLA system), and poly- morphisms at the DNA level. He reviews the “selectionist” and “neutralist” positions on the evolutionary origins of allelic variation, citing new evidence from globin phylogeny, amino-acid substitution rates, and single-base substitutions.

In his final chapter Doctor Harris explains how molecular probes for DNA mapping and base-sequence determination of cloned DNA fragments have been used to identify the structural changes in DNA that occur in inherited disease, citing exam- ples from their application to the hemoglobinopathies. The addition of familial hy-

500 Book Reviews

percholesterolemia as an example of “dominance” caused by a receptor protein defect, a detailed explanation of methylmalonicacidemia heterogeneity, and a discus- sion of Wernicke-Korsakoff syndrome in chronic alcoholism complete the changes in the final chapter.

Both appendixes are longer. Appendix 1, listing disorders due to specific en- zyme deficiencies, has 19 new entries, while Appendix 2, listing enzyme and protein polymorphisms, has nearly four times the former number of entries. The reference list has also been updated.

This is an excellent book - attractive layout, crisp illustrations, frequent cross references, generous documentation - filled with the don’s stylish prose and lucid abstraction.

The price is fair ($27.00 for the soft-cover edition), considering its size. Run- ning heads, unfortunately, have been omitted, and there are a few typographic errors. The index is spare but adequate.

Recommended for research workers, graduate students, teachers, and medical geneticists; ideal for the advanced medical student.

Sally Kelly PhD, MD New York State Department

Division of Laboratories and

Albany, New York

of Health

Research