Abstract: Introducing a new genetic model called the discrete allelic-state model, the evolutionary change of genetic variation of quantitative characters within and between populations is studied under the assumption of no selection. This model allows us to study the effects of mutation and random genetic drift in detail. It is shown that when the allelic effects on phenotype are additive, the rate of approach of the genetic variance within populations to the equilibrium value depends only on the effective population size. It is also shown that the distribution of genotypic value often deviates from normality particularly when the effective population size and the number of loci concerned are small. On the other hand, the interpopulational variance increases linearly with time, if the intrapopu-lational variance remains constant. Therefore, the ratio of interpopulational variance to intrapopulational variance can be used for testing the hypothesis of neutral evolution of quantitative characters.

Abstract: To investigate whether recurrent mutation has contributed to the high frequency of the beta E-globin gene in Southeast Asia, we used the haplotypes at three polymorphic restriction sites within and to the 3' side of the beta-globin gene to predict the framework of 23 beta E-globin genes. These haplotypes suggested that beta E-globin genes are present in two different beta-globin gene frameworks. DNA sequence determination of one gene representing each framework demonstrated that the same mutation (GAG leads to AAG at codon 26) was present in both frameworks. Moreover, the frameworks differed at three nucleotide positions known to be polymorphic in Mediterraneans. These polymorphic sites are located 70 nucleotides to the 5' side of the beta E mutation and 382 and 1032 nucleotides to the 3' side of it. The existence of the beta E mutation in these two beta-globin gene frameworks can be explained by (i) recurrent mutation giving rise to beta E-globin, (ii) a double crossing-over event, or (iii) two single crossing-over events. Mathematical analysis suggests that the first alternative, recurrent mutation of G leads to A at the first nucleotide of codon 26, is most likely.

Abstract: This represents the edited proceedings of the 11th Annual Symposium of the Birth Defects Institute of New York State. However, unlike many similar publications, the result is a thoroughly comprehensive text, which has been very well edited, and there is little repetition or irrelevant material. In fact it could well be recommended as the basis for a series of postgraduate lectures on mutation, as well as providing much useful information for the practising clinical geneticist. The book is divided into six main sections. The first is concerned with mutation, selection, and human evolution and naturally includes much on the neutralist-selectionist controversy. Recent findings in recombinant DNA technology are also detailed in regard to evolution. The second section is concerned with mutations at specific autosomal and X linked loci and includes discussions of the controversy as to whether the mutation rates for certain X linked loci are equal in males and females. On balance this now seems so for Duchenne muscular dystrophy but perhaps not for the Lesch-Nyhan syndrome. The third section is concerned with cytogenetic mutations, their frequency, their distribution in the genome, and the possibility of 'hot spots' for which there does seem to be some suggestive evidence. The fourth section is concerned with somatic cell mutation as studied in fibroblasts in vitro and in peripheral blood lymphocytes in vivo. The latter approach involves the identification in normal persons of rare erythrocytes that contain abnormal haemoglobins, an interesting but very laborious and tedious technology. The fifth section is concerned with radiation and mutation and includes a further assessment of the effects of the atomic explosions in Hiroshima and Nagasaki. The conclusion is that though radiation is certainly known to cause mutation ". . . there has yet to emerge compelling evidence ofgenetic change in the offspring of exposed parents". Current estimates of the 'doubling dose' in man may be somewhat higher than previously suggested, perhaps nearer 200 rem. The sixth section is concerned with fundamental problems ofmutation at the molecular level. Finally, there is an appendix, which includes details of the New York State Chromosome Registry, and there is an index. This book can be highly recommended to anyone who seeks a comprehensive and up-to-date summary of our present knowledge of mutation in man.

Abstract: INTRODUCTION 329 KINDS OF MUTATIONAL DAMAGE .. . ...... ....... 330 Mendelian Mutants 330 Chromosome Aberrations 330 Irregularly Inherited Disorders 331 THE RISK ESTIMATES 331 METHODS OF CALCULATION 332 The Doubling Dose Method 332 Mutation Component 335 The Direct Methods 336 First generation dominants 336 The problem of stating uncertainty 337 Translocations 338 Gene Number Methods 339 DATA 341 The Human Data 341 The human spontaneous genetic burden 341 The Japanese cohort 342 Radiation and Down's Syndrome 344 The Mouse Data 346 Opposing Viewpoints 347 CONCLUSION 352

Abstract: The problems of estimating the mutation rate to Huntington's chorea, or the proportion of new mutants among all sufferers, are discussed. The available survey data are reviewed. The prevalence of sporadic phenotypes, which include new mutations, is probably less than 2·5%. New mutants probably make up around 0·1% or less of all sufferers.

Abstract: The effects of α chain mutations cis and trans to the β6 mutation on the polymerization of sickle cell haemoglobin

Abstract: Exchange mapping locates the dominant mutation Scutoid to the right of Adh on chromosome arm 2L of D. melonogoster. However, deletion mapping indicates that Sco is to the left of Adh. The phenotype of Sco is sensitive to mutation, or deletion, of noc+ and of three genes, el, l(Z)br22, and l(2)br29 mapping immediately distal to noc. The four contiguous loci, el, 1(2)br22, l(2) br29 and noc, although separable by deletion end points, interact, because certain (or all) alleles of these four loci show partial failure of complementation, or even negative complementation. The simplest hypothesis is that Sco is a small reciprocal transposition, the genes noc, osp, and Adh exchanging places with three genes normally mapping proximal to them: 1(2)br34,1(2)br35 and rd. The Sco phenotype is thought to result from a position effect at the newly created noc/l(2)br28 junction. APPING close to the structural gene for alcohol dehydrogenase (Adh) on M chromosome arm 2L of Drosophila melanogaster is the dominant mutation Scutoid (Sco). This mutation was induced with X rays by KRIVSHENKO (1959) and, when heterozygous, results in a specific pattern of loss of bristles from the head and thorax of the adult fly. The map location of Sco made it an obvious marker to use for the genetic analysis of Adh and for the analysis of the genetic structure of the environs of Adh. It soon became apparent, however, that Sco is a rather exceptional mutation. For example, the map position of Sco determined by recombination and that determined by deletion analysis are contradictory. Moreover, Sco, although normally a stable mutation, can be reverted by X rays at a high frequency. Analysis of the revertants of Sco revealed an unexpected genetic complexity in the structure of the Sco chromosome. This and a following paper (M. ASHBURNER et al., unpublished results) are devoted to a genetic analysis of Sco and its revertants. It will probably help the reader if we begin by summarizing the structure of the Sco mutation that we consider the data warrant. MODEL

Abstract: The parallel induction of sister chromatid exchange (SCE) and single-gene mutation was quantified in Chinese hamster ovary cells following exposure to nine different physical or chemical agents representing a wide variety of inducing lesions. For each agent, the frequency of induced SCE was linearly related to the induction of mutation, but the efficiency of SCE formation relative to mutation induction differed for each. Studies in repair deficient cells suggested that unrepaired lesions enhanced the induction of both SCE and mutation but that the degree of enhancement was not necessarily the same for both endpoints.

Abstract: The T4 mutation ptg19-80 affects the mechanism of capsid-length determination It is located in gene 23, which encodes the major structural protein of the capsid The mutation results in the production of abnormal-length capsids in high frequencies This paper describes the isolation and partial characterization of second-site revertants of ptg19-80 In the course of their analysis, it was discovered that ptg19-80 is itself a double mutation consisting of a gene 23 mutation (ptg19-80c), which causes the morphogenetic defect, and a suppressor mutation located near the lysozyme gene Phenotypic characterization of nine pseudo-wild-type revertants of this double-mutation revealed that these revertants all produced lower frequencies of abnormal capsids than did ptg19-80 Seven of these revertants were shown to contain two suppressor mutations, one mapping in or near gene 22 and done mapping in or near gene 24 Both mutations were required for suppression These suppressors displayed no discernible phenotype in the absence of ptg19-80c

Abstract: The genetic properties of a pleiotropic mutant mapping at 1.4 +/- 0.1 in band 3B3 or its adjacent interbands on the X chromosome are described. The mutation is expressed autonomously in germ line cells, where it is recessive and has antimorphic properties. At 29 degrees, the mutation blocks oocyte differentiation, causing female sterility. At lower temperatures, it disturbs the maternal information in the egg; as a result, the progeny lack germ line cells (grandchildless phenotype) and exhibit defects of the cuticular pattern. The mutation is also expressed in somatic cells through zygotic interactions with neighboring regions, including 3A2, 3A3 (zeste), 3C1-2, 3C4 and 3C6-8 (Notch). We interpret the data by postulating that the expression of sets of dispersed genes might be controlled by the local topology of the chromosome, itself constrained by pairing of dispersed repeated elements. We call the mutation paralog.

Abstract: By in vitro mutagenesis of mastocytoma P815, it is possible to obtain tumor cell variants that are rejected by syngeneic mice (tum−). Most of these variants carry new individual antigens and stimulate a specific cytolytic T cell (CTL) response in mixed leukocyte tumor cell culture (MLTC). The H‐2 associativity of this response was examined for six different variants by measuring the inhibition of cell‐mediated cytolysis by antibodies directed against products of the K or the D end of the H−2d complex. The lysis was either not inhibited (variants P91 and PI 16) or inhibited selectively by anti‐Kd (variants P21, P32 and P198) or anti‐Dd antibodies (variant P35). All these tum− variants expressed Kd and Dd antigens as measured by absorption of H‐2 alloantisera.

Abstract: A single base pair change (AT to GC) is shown to be responsible for derepression of recA. The mutation (recAo281) alters the binding sequence for the LEXA repressor.