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TRENDS in Pharmacological Sciences Vol.22 No.3 March 2001
157
Book Review
A plethora of human genome sequences SNP and Microsatellite Genotyping: Markers for Genetic Analysis edited by Ali Hajeer et al., Eaton Publishing, 2000. (xii + 152) ISBN 1 88 1299 38 4
Why should pharmacologists be bothered reading a book about genotyping? The answer lies in the emerging picture that pharmacokinetic and pharmacodynamic processes depend on an individual’s genetic constititution. The individual variations in drug metabolism, response and toxicity observed within and across populations (phenotypic polymorphism, in genetic parlance) are in large part accounted for and predicted by variation at the DNA sequence level (genotypic polymorphisms). This book provides a timely introduction to the methods of detection and analysis of molecular genetic variations, focusing on the two currently most utilized types of variation: microsatellites, which are islands of very short repeating sequences (e.g. CACACACACACA), and single nucleotide polymorphisms (SNPs). One of the great successes of genetics during the latter half of the past century was the progressive development of laboratory-based methods for assaying polymorphisms. Variation is where the genetic information is; traits cannot be attributed to sequences when the sequences are all the same. Early on, the ABO blood group and other easily assayed blood groups were the primary biological markers of genetic variation, and electrophoretically assayed protein isoforms also played a role. The modern DNA-based laboratory world ushered in the RFLP [restriction fragment length polymorphisms (which are actually a small subset of SNPs in disguise)] revolution in the 1980s, which paved the way for the first truly comprehensive human genetic linkage maps. This was followed by the microsatellite revolution of the 1990s and the in-progress SNP revolution of the current decade. The editors of this book should be commended for including chapters that discuss polymorphism discovery; too http://tips.trends.com
often methodological reviews fail to mention processes for the derivation of tools underlying the methods. The genotyping methods discussed include those applicable to small laboratories, as well as methods for larger laboratories that can be adapted to high-throughput processes (e.g. sequencing and DNAbased microarrays). There is also a reasonable discussion of which methods are best applied to specific genotyping goals: high-throughput methods are best for whole-genome approaches, whereas less comprehensive but more laborintensive methods are best suited for smaller hypothesis-driven problems. Throughout the chapters, specific bench protocols and references are provided where appropriate; although these are not meant to be comprehensive, they do provide a jumping-off point for investigators eager to don gloves. For analytic protocols, software sources are also given. The chapter by Curtis (‘Data analysis for genetic studies’) is a true jewel, providing an excellent survey of the geneticist’s now-standard analytical armamentarium. This is an area that usually evokes the most confusion for newcomers to the field, and in these pages is handled with gentleness and aplomb. The mathematics used in illustrating the concepts is readily understood and not overly detailed. Additional discussion of analytical approaches is provided in the final chapter by Zhao and Zarbl. Although this book succeeds in achieving the editors’ overall goals, there are some specific weaknesses. The highthroughput chapter only mentions use of vertical PAGE (polyacrylamide gel electrophoresis) automation, which relies on a traditional labor-intensive gel approach, whereas state-of-the-art highthroughput electrophoretic analysis is better realized on capillary-based instruments; it is common to find capillary instruments in academic core facilities as well as in industry. Furthermore, the usefulness of sample pooling in SNP-based genotyping, where there is a phenomenal cost savings, was not mentioned. There are only two chapters that are truly centered on SNPs; one is well focused, whereas the other is rather broad. Hence, the title of the book
is somewhat overstated; the coverage was more microsatellite genotyping with SNPs on the side. The final chapter (‘SNPs & future applications’) includes a methodological survey that complements but also duplicates portions of the excellent chapter by Curtis. I recommend this as a reasonable book for introducing new investigators to a burgeoning field. I am not entirely convinced of the editors’ comment that it ‘will prove a useful source’ for scientists already experienced in this field. Although not targeted specifically at pharmacologists, the editors have scored a direct hit on the target audience of scientists with experience in other fields of biology who find themselves thrust into the arena of genotyping and polymorphisms. The chapters by Curtis and by Zhao et al. would also be good introductory material for advanced graduate coursework. John P. Alsobrook II Pharmacogenomics Discovery, CuraGen Corporation, 555 Long Wharf Drive, New Haven, CT 06511, USA. e-mail: [email protected]
What does the human genome sequence mean to you? For a thorough and independent analysis of the meaning and importance of the February publications of the draft human genome sequences, visit: http://news.bmn.com/hmsbeagle/ 96/notes/feature3 To mark the importance of the event, we are pre-publishing a selection of Trends articles on these publications in our free, online magazine, HMS Beagle. You cannot afford to miss these up-to-the-minute commentaries, opinions and updates, written by leading players from across the whole of biology. And they’re free!
TRENDS in Pharmacological Sciences Vol.22 No.3 March 2001
157
Book Review
A plethora of human genome sequences SNP and Microsatellite Genotyping: Markers for Genetic Analysis edited by Ali Hajeer et al., Eaton Publishing, 2000. (xii + 152) ISBN 1 88 1299 38 4
Why should pharmacologists be bothered reading a book about genotyping? The answer lies in the emerging picture that pharmacokinetic and pharmacodynamic processes depend on an individual’s genetic constititution. The individual variations in drug metabolism, response and toxicity observed within and across populations (phenotypic polymorphism, in genetic parlance) are in large part accounted for and predicted by variation at the DNA sequence level (genotypic polymorphisms). This book provides a timely introduction to the methods of detection and analysis of molecular genetic variations, focusing on the two currently most utilized types of variation: microsatellites, which are islands of very short repeating sequences (e.g. CACACACACACA), and single nucleotide polymorphisms (SNPs). One of the great successes of genetics during the latter half of the past century was the progressive development of laboratory-based methods for assaying polymorphisms. Variation is where the genetic information is; traits cannot be attributed to sequences when the sequences are all the same. Early on, the ABO blood group and other easily assayed blood groups were the primary biological markers of genetic variation, and electrophoretically assayed protein isoforms also played a role. The modern DNA-based laboratory world ushered in the RFLP [restriction fragment length polymorphisms (which are actually a small subset of SNPs in disguise)] revolution in the 1980s, which paved the way for the first truly comprehensive human genetic linkage maps. This was followed by the microsatellite revolution of the 1990s and the in-progress SNP revolution of the current decade. The editors of this book should be commended for including chapters that discuss polymorphism discovery; too http://tips.trends.com
often methodological reviews fail to mention processes for the derivation of tools underlying the methods. The genotyping methods discussed include those applicable to small laboratories, as well as methods for larger laboratories that can be adapted to high-throughput processes (e.g. sequencing and DNAbased microarrays). There is also a reasonable discussion of which methods are best applied to specific genotyping goals: high-throughput methods are best for whole-genome approaches, whereas less comprehensive but more laborintensive methods are best suited for smaller hypothesis-driven problems. Throughout the chapters, specific bench protocols and references are provided where appropriate; although these are not meant to be comprehensive, they do provide a jumping-off point for investigators eager to don gloves. For analytic protocols, software sources are also given. The chapter by Curtis (‘Data analysis for genetic studies’) is a true jewel, providing an excellent survey of the geneticist’s now-standard analytical armamentarium. This is an area that usually evokes the most confusion for newcomers to the field, and in these pages is handled with gentleness and aplomb. The mathematics used in illustrating the concepts is readily understood and not overly detailed. Additional discussion of analytical approaches is provided in the final chapter by Zhao and Zarbl. Although this book succeeds in achieving the editors’ overall goals, there are some specific weaknesses. The highthroughput chapter only mentions use of vertical PAGE (polyacrylamide gel electrophoresis) automation, which relies on a traditional labor-intensive gel approach, whereas state-of-the-art highthroughput electrophoretic analysis is better realized on capillary-based instruments; it is common to find capillary instruments in academic core facilities as well as in industry. Furthermore, the usefulness of sample pooling in SNP-based genotyping, where there is a phenomenal cost savings, was not mentioned. There are only two chapters that are truly centered on SNPs; one is well focused, whereas the other is rather broad. Hence, the title of the book
is somewhat overstated; the coverage was more microsatellite genotyping with SNPs on the side. The final chapter (‘SNPs & future applications’) includes a methodological survey that complements but also duplicates portions of the excellent chapter by Curtis. I recommend this as a reasonable book for introducing new investigators to a burgeoning field. I am not entirely convinced of the editors’ comment that it ‘will prove a useful source’ for scientists already experienced in this field. Although not targeted specifically at pharmacologists, the editors have scored a direct hit on the target audience of scientists with experience in other fields of biology who find themselves thrust into the arena of genotyping and polymorphisms. The chapters by Curtis and by Zhao et al. would also be good introductory material for advanced graduate coursework. John P. Alsobrook II Pharmacogenomics Discovery, CuraGen Corporation, 555 Long Wharf Drive, New Haven, CT 06511, USA. e-mail: [email protected]
What does the human genome sequence mean to you? For a thorough and independent analysis of the meaning and importance of the February publications of the draft human genome sequences, visit: http://news.bmn.com/hmsbeagle/ 96/notes/feature3 To mark the importance of the event, we are pre-publishing a selection of Trends articles on these publications in our free, online magazine, HMS Beagle. You cannot afford to miss these up-to-the-minute commentaries, opinions and updates, written by leading players from across the whole of biology. And they’re free!