Human genetics: methods and results

Human genetics: methods and results

book reviews TIG - - October1986 Human genetics:methods... Methodology in Medical We P g ~ p ~ and Pracli~ ol Genetics: an [nlIoduction to MedicalGr...

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book reviews

TIG - - October1986

Human genetics:methods... Methodology in Medical We P g ~ p ~ and Pracli~ ol Genetics: an [nlIoduction to MedicalGraVies), hut look~ through it I found methods for Statistical Methods me g r ~ nmiodty of me pmbby AlanE. H. Emery, Ckm~Mll ! I have faced or been asked Li~gsto~, 1986. t~4.00 (i + lems about over the last year. These 197Paws)ISBN 0 443 035091 include estimatinggene frequen. Thisis a short recipe beok cover. cies and checking for Hardying the main statistical methods Wdnbergequilibdum, twinstudneeded for research in human ies (but no mini-satellite probe) (not speci~a~ medical) gen- and hemam~ and ~ for etics. FuUof useful fommlae and heterogeneity, and parental age tables, it is aimed at a reader effects. There are good sections anned withoolya pocket calcula. on how to calculate coeMcients tor and some basic algebra. In of reJatiom~ in hinted fmni~a~du "~donedBM lies or populatimm, and how to n~rocom~m, perhapst~s is demmmtrate secular trends or an urmecesaarylimitatian. Link. cycles in the incidence of a conage ana~sis in pmicu~ is al- ditio~ The multifactodalsectian most wholly dependenton com. pedmps fails to stress how very puten - surely nobody really it is to prove multifaccalculates Io£ scores by hand todalinhedmnce, because multinowadays, and if they do they facto~ and shMe maior k m sbeu~ be d i s m m ~ . models can hoth be made to fit Thisis moantto be a short and most data sets. There is a thorhandy book. It does not daim to ongh exposil/on of Bayesianlogic cover everything (for that you for calculating genetic risks, inneed Emery and P,hnoin's mas. corporating much of Emery's

. . . and results Advances in Human Genetics VoL 15 e~ted by H. Harm and K. Hirschhom, P/mum Press, 1986. $45.00(=~//+ 2FJi0ages) ISBN 0 3O6421550 The Advances in Humam Gem. e~s seriesode~atedin 1970with the aim of providingdetailedreviewarticles on topics in human genetics. One vdume has appeared yearly since then, with five topics covered in each. The 1986 volume, number 15, claims to provide up-to-date coverage of five areas that are currently under intensive examination. Chapter 1, 'ChromosomalAb. normalities in Leukaemia and Lymphoma: Clinical and Bio-

logical Signilicance'by Michene Le Beat, and Janet Rowley, begins with the statement that'cytogenetic analysis of human tu. mours is one of the most rapidly progressing and excilmgareas of

cancer research'. However, the chapter itself fails to convey any sense of exdtement or rapid progress. It is basicallya detail. ed, historical description of the specific translocations found in each type of leukaemia and in Burkitt and non-Hodgkin lymphoma. The data used were mainly gathered between 1974 and 1983. Much clinicalinfonna. tion has also been included, reprognosis, re~ssion

induction and survival Tbe involvement of oncogenesis dealt with in a few pages and is manifestly out of date, which is not surpfish~ since no references after 1984 are quoted. TMs may not be the fault of these two

authors- poss~ they were the only ones to keep to a press deadline. However, if that were the case they should have been given the opportunity for a ~ cent developments' section, as were others in this volume. As it is, it is ~ to conceive to whom tHs chapter would be of use; possibly those intending to enter the fieM and gequh~ a

goods y n o p a l s o f t h e ~ cytogenetic dam up to 1984. Fullyathirdoftbevolumeisdevoted to Chapter 2, 'An AIgorithmfor Compm~ Two-Dimensienal EIectrophoretic Gels, with ParticslarR e f ~ totho Study of Mutation'by MichaelSkolnick andJamesNeeL Tbey beginwith the basic premise that there is widespread concern reganling the possHe mutagenic effects of exposure to chemicals and radiation. Nevertheless, compared withexperhnentalgenetics, most human exposures are low and mutationconsequently rare. The technique of tWo.dimensionul polyacrylamkle gel electrophoresis was chosen for detect~ mutations. Because of the need for extremely large numbers of observations and the enormous amount of labour involved, with

own work. This is excellent for readers with some ~ of the problem, but would frighten beginners. Segregation analysis is well covered, though I would question the prominence given to the a pm~ methods. AI.

timugh ~toricaUy hnpomnt, this method assumes the answer before it starts, and therefore tenda to come up with the ans. wer you first thought of, correct ornoL

As mentioned above, the main omissionwhich I regret is advice on computerized linkage analysis. Progtama like LIPED and LINKAGEare mainstream tools more or less standard throughout the world, and I see a lot of people who get into trivial but intractable problems because they don't undemtand how to set up the input files. The powerful mul~-locus location scores produced by LINKAGE look ltely to supplant two.locos 'led' scores, and some description would have beenvery welcome. I also missed the main methods consequent fiability to error in scor~ by the human eye, the authors have from the outset devoted a major effort toward development of computer algor"~ns for reading these gels. There follows what is described as a 'progress report on a very complex undertaking'. This confinu~ for about I00 pages. The topic appears to be a specialist interestintheextreme andrather out of place in a book of this natore.

The human argim'nosuccinate synthetase locus and citrulli. hernia are dealt with jointly by Arthur Beaudet, WiJlimn O'Brien, Hans-Georg Bock, Suend Fregtag and Tsung-Sharq~ Su in Chapter 3. This chapger describes almost nn that is known about this enzyme. Citthe syndrome which results fromgeneticdeficiencyof the enzyme in question, is discussed in considerable detail, indoding clinical aspects, patient management and prospects for therapy. The authors have concentrated on the more recent developments, particularlythose e.,r~rging since the gene was dened. Most of what has been learned about this enzyme and citrullinemiasince 19B0has been discovered by the authors and their collaborators. It is therefore disappointing that they present so little of the originaldata in graphic or tabular form. The chapter is comprehens;~e and

(de Vries or Green and Woodrow) that I use for l i e g e by sibship analysis. Fishers enct te~t is used without mentioning the need to include all the less probable distributions in the overall pmhability, or a wm'ning that the probabilityis one-tailed. As genetic material, humans have the great advantage that any distinctive visible abnormality with an incidencegreater than I in 10~ is likelyto be reported somewhere in the literature; but they nmte at random and then have small families, so human genetics needs more statistical sophistication than Drosophilaor mouse genetics. Despite the minor shortcomings noted, 1 reconunend this book without reservation to researchers in human genetics: they are unlikelyto find its combination of authority and accessanywhere else. ANDREWF; READ Department o/Me~;al G~,te~s, St Mmy's HosI~al, M~cd~s~ MI3 0]H, UK. ~he writing is at its best in the sections dealing with citrullinemia. It isless clearinthe earlier parts dealing with historical aspects and the biochemistry of arginine and urea synthesis. On the whole it is a chapter likelyto interest a general audience. The fourth ch~ter is on the molecular genetics of the human major ~tocompatib~ity complex, by CharlesAuffrayandJack Strominger. This is a successful attempt to make an intricate topic accessible to the general reader. After the introduction the authors concentrate on reviewing recent information on the HLA class I and II genes and their molecular probes. There is description of the techniques used in the isolationof the HLA genes: construction of cDNA libraries, screening by hybrid selection of mRNA, screening with synthetic oligonudeotides and hnmunopunli'cation of polysomes and subsequent mapping of these genes. The reader is then led gently through a descriptionofthe multiplicityofclass I and class !I genes. A particulady interesting section is that on structure, polymo~hism and evolution of the HLA genes. Here the writing is especially dear and succinct, conveying a sense of real interest and excitement at the implications of the information that has been gathered. The last section is on the use of HLAgenes as probes. 269