American Journal of Medical Genetics 10:205-206 (1981)

Book Review The Principles of Human Biochemical Genetics. 3rd, revised edition, Harry Harris, ElseviedNorth-Holland Biomedical Press, Amsterdam, 1980, 554 pages $27.00.

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

rearrangements” (chapter 3). He realigned the discussion of hybrid proteins with topics in chapter 1, deleted the chapter on “Mutations Affecting Rates of Synthesis,” and transformed the durable segment on the thalassemias with in- terpretations from endonuclease analysis. Other sections remain untouched, presumably because the same principles apply (such as those refemng to defi- ciency of and variation in glucose-6-phosphate dehydrogenase) or are de- emphasized (such as that on haptoglobin variants, now tucked away at the end of chapter 3).

The text retains the organization of the previous edition - 9 chapters and 2 appendixes. The first 4 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 dis- cuss the inborn errors, which are classified by sites of biochemical defect. Dr. Harris devotes a chapter to the composition and action of blood group sub- stances and a chapter to the occurrence of allelic variation in populations. The final chapter explains the molecular basis for current genetic theory and the phenomenon of genetic heterogeneity.

genetic advances - the discovery of the precise molecular natures of the thalassemias, new evidence for variable susceptibility of loci to X-inactivation, tetrahydrobiopterin’s role in atypical phenylketonuria, and the heterogeneity of urea cycle enzyme deficiency diseases to mention a few. Throughout, he ac- knowledges the insights geneticists have gained from studying tissue-culture models, especially when discussing the classification of lysosomal storage dis- eases and the recognition, in heterozygotes, of variable gene-dose effects.

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

The author revised by a system of “crossing-over, deletions . . . and other

Dr. Harris bases much of his revision on knowledge derived from recent

0148-7299/81/1002-0205 $01.00 0 1981 Alan R. Liss, Inc.

206 Kelly

Dr. Harris’s revisions of the chapter on enzyme and protein diversity are extensive. Introducing polymorphisms and explaining them didactically, he treats readers 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 (espe- cially the HLA system), and polymorphisms at the DNA level. He reviews the “selectionist” and “neutralist” postions 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, Dr. 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 examples from their application to the hemoglobinopathies. The addition of familial hypercholesterolemia as an example of “dominance” caused by a receptor protein defect, a detailed explanation of methylmalonicacidemia heterogeneity, and a discussion of Wernicke-Korsakoff syndrome in chronic al- coholism complete the changes in the final chapter.

Both appendixes are longer. Appendix 1, listing disorders due to specific enzyme deficiencies, has 19 new entries, while Appendix 2, listing enzyme and protein polymorphisms, has nearly 4 times the former number of entries. The reference list has also been brought up-to-date.

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

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

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

Sally Kelly, PhD, MD Division of Laboratories and Research New York State Department of Health Birth Defects Institute Albany, New York