Mutation tlx was induced in pea by gamma-irradiation in the homeotic gene Tl, responsible for transformation of the upper leaflets into tendrils. Heterozygotes tlx/Tl+ possess ‘flat tendrils’ having narrow rudimentary leaf blades. By 15 generations of selfing the line Delta was established, in which closely linked loci Tl and His1 were maintained heterozygous, His1 encoding the most abundant histone H1 subtype. The heterozygous chromosome region was flanked by several recessive markers. The genotype of line Delta with respect to loci His1 and Tl was: tlx His12/Tl+ His11. There were derived two sublines, Delta-s and Delta-f, homozygous for each of the His1 alleles but heterozygous for the Tl and flanking markers. The three lines were compared for a number of quantitative traits, including parameters of flat tendrils reflecting the expression of the gene Tl in heterozygote, and for recombination rate within the heterozygous segment. The line Delta-s exceeded Delta-f in terms of the level of the first inflorescence, length of the internode 8–9, number of pods on the main stem and mean seed mass, but was inferior regarding the mean number of seeds per pod. The flat tendrils were wider in the Delta-s as compared with the Delta-f line ; the difference was highly significant and exceeded 15% at node 17. Recombination rate between the flanking markers also showed significant differences, being highest in the Delta-f and lowest in the Delta line. We do not exclude the possibility that the observed differences in the quantitative traits are caused by the substitution of alleles of the histone H1 gene. The effects of such substitution appeared to be especially strong for expression of the homeotic gene Tl.

Characterizing deleterious genomic mutations is important. Most of the few current estimates come from the mutation–accumulation (M-A) approach, which has been extremely time- and labour-consuming. There is a resurgent interest in implementing this approach. However, its estimation properties under different experimental designs are poorly understood. By simulations we investigate these issues in detail. We found that many of the previous M-A experiments could have been more efficiently implemented with much less time and expense while still achieving the same estimation accuracy. If more than 100 lines are employed in M-A and if each line is replicated at least 10 times during each assay, an experiment of 10 M-A generations with two assays (at the beginning and at the end of M-A) may achieve at least the same estimation quality as a typical M-A experiment. The number of replicates per M-A line necessary for each assay largely depends on the magnitude of environmental variance. While 10 replicates are reasonable for assaying most fitness traits, many more are needed for viability, which has an exceptionally large environmental variance. The investigation is mainly carried out using Bateman–Mukai's method of moments for estimation. Estimation using Keightley's maximum likelihood is also investigated and discussed. These results should not only be useful for planning efficient M-A experiments, but also may help empiricists in deciding to adopt the M-A approach with manageable labour, time and resources.

A simple mathematical model of genic directional selection is developed to study frequency changes of genetic marker alleles that are partially linked to a quantitative trait locus (QTL) under artificial selection. The effects of population size, number of generations of artificial selection, recombination between marker locus and QTL, and the strength of selection on the change in allele frequency are analysed by the diffusion equation approach and by stimulation. Using these results, we investigate the power of statistical tests for the detection of QTLs based on the observation of significant marker allele frequency changes in selection experiments. The probability of inferring the correct location of a QTL is also obtained.

Theories on the evolution of recombination in regard to its ability to increase mean fitness require a consistent source of negative linkage disequilibrium among loci affecting fitness to show an advantage to recombination. Here we present evidence that, at least theoretically, genetic variation for recombination can spread in very large populations under a strictly multiplicative-fitness, deleterious-allele model. The model uses only Mendelian genetics in a multi-locus context to show that a dominant gene for recombination can spread when rare and resist invasion when common. In non-equilibrium populations driven by Muller's ratchet, the gene increases its probability of fixation by increasing the probability of being associated with the best individuals. This occurs at an optimal level of recombination. Its action results in both an immediate and a long-term advantage to recombination amongst the proto-meiotic organisms modelled. The genetic mechanism lends itself naturally to a model for the evolution of meiosis, where modern-day gametes are seen as derivative of ancient unicellular organisms.

Allozyme markers were used to estimate mating system parameters in nine fragmented populations of the grassland daisy Rutidosis leptorrhynchoides that differed in size and spatial isolation. Multilocus estimates of outcrossing rate did not differ significantly among populations, all indicating a high level of outcrossing (tm=0·84–1·0). Small populations showed greater divergence than large populations between the allele frequencies in the population and those in the pollen pool, indicating paternal bottlenecks. Isolated populations of fewer than 200 individuals also exhibited higher correlations of outcrossed paternity (rp) than larger populations, indicating the production of more full-sibs within families. The combination of paternal bottlenecks and correlated paternity increases the genetic identity of progeny across families and predisposes populations to biparental inbreeding in subsequent generations. As over half the remaining populations of R. leptorrhynchoides contain fewer than 200 plants, such second-order inbreeding may threaten the viability of the species if it is associated with significant inbreeding depression.

The effect of selection on the amounts of nucleotide variation within and between allelic classes was studied when two allelic classes exist in a population. Two selection models – the genic selection model and the overdominant selection model – were used. The average numbers of pairwise nucleotide differences within two allelic classes were investigated by computer simulation and the average number of pairwise differences between two allelic classes was obtained analytically. It was indicated that selection largely affects the amounts of variation within and between allelic classes. However, the sum of the average numbers of pairwise differences within two allelic classes is nearly constant and always close to θ(θ=4Nμ), even when selection is acting, where N is the effective population size and μ is the mutation rate per sequence per generation. This result suggests that the sum of the average numbers of pairwise differences within two allelic classes can be used to estimate θ. It may be useful for a region where selection may be acting. As examples, several gene regions of Drosophila melanogaster and a region of Mus domesticus were analysed. The effect of recombination on the sum of the average numbers of pairwise differences within two allelic classes was discussed.

A glutathione reductase (GR) mutant with approximately 50% residual enzyme activity in blood compared with wild-type was detected amongst offspring of isopropyl methanesulphonate-treated male mice. Homozygous mutants with only 2% residual enzyme activity were recovered in progeny of inter se matings of heterozygotes. Results of linkage studies indicate a mutation at the Gr1 structural locus on chromosome 8. The loss of GR activity was evident both in blood and in other tissue extracts. Erythrocyte and organo-somatic indices did not show differences between wild-types and homozygous mutants, indicating no association between the GR deficiency and haemolytic anaemia in this potential animal model.

The hAT family is a group of transposable elements of the terminal inverted repeat class, which includes Ac of maize, hobo of Drosophila and Tam3 of Antirrhinum (snapdragon). All the members of this family so far examined are known to comprise complete and defective copies, with a good correspondence to autonomous and non-autonomous elements, respectively. Internal deletion is the most common cause of defective copies. Tol2, a transposable element of the medaka fish Oryzias latipes, is a member of the hAT family. We examined, mainly by the genomic Southern blot analysis, variation in the structure of copies of this element, and revealed that there are few or no internally deleted copies. This situation is unusual in a member of the hAT family. Possible causes of this anomaly are discussed.

A mixture model approach is employed for the mapping of quantitative trait loci (QTL) for the situation where individuals, in an outbred population, are selectively genotyped. Maximum likelihood estimation of model parameters is obtained from an Expectation-Maximization (EM) algorithm facilitated by Monte Carlo sampling using a Gibbs sampler. All individuals with phenotypes, whether genotyped or not, are included in the analysis where both putative QTLs and missing marker genotypes are sampled conditional on known marker information and phenotype. A simulation of a half-sib family structure demonstrates that this mixture model approach will yield unbiased estimates of the allelic effects of a QTL affecting the trait on which selective genotyping is based. Unbiased estimates were also obtained for the QTL effect on a correlated trait provided both traits were analysed jointly in a bivariate model. The procedure is also compared with a standard linear model approach. The application of these methods is demonstrated for bovine chromosome six, the data arising from two Holstein–Friesian families selectively genotyped for protein yield in a daughter design.

The effect of population bottlenecks on the additive variance generated by two neutral independent epistatic loci has been studied theoretically. Three kinds of epistasis were considered: (1) additive×additive, (2) multiple dominant genotype favoured, and (3) Dobzhansky–Muller type. The additive variance in an infinitely large panmictic population (ancestral variance) was compared with its expected value at equilibrium, after t consecutive bottlenecks of equal size N (derived variance). Formulae were derived in terms of allele frequencies and effects at each locus and the corresponding epistatic effects. An increase in the additive variance after bottlenecks will occur only if its ancestral value is minimal or very small. This has been detected only for: (1) intermediate ancestral allele frequencies at both loci ; (2) extreme ancestral allele frequencies at one or both loci. The magnitude of the excess was inversely related to N and t. With dominance gene action, enhanced additive variance after bottlenecks implies a rise in the genotypic frequency of homozygous deleterious recessives, resulting in inbreeding depression. Considering multiple loci, simultaneous segregation of unfavourable alleles at intermediate frequencies, or of favourable recessives at low frequencies, cannot easily be conceived of unless there is strong genotype–environment interaction. With this possible exception, it is unlikely that the rate of evolution may be accelerated after population bottlenecks, in spite of occasional increments of the derived additive variance over its ancestral value.

The mouse lines were developed by long-term selection for fatness, after which the fat line (F) had about a 5-fold (23% vs 4%) higher fat percentage than the lean (L) line at 14 weeks; but the lines differed little in fat-free body weight. To assess the contribution of genetic changes in leptin hormone level to the selection response, plasma leptin levels were assayed in these lines in generation 60 and in an unselected control (C) from the same base population. With access to food prior to assay, the F, C and L lines had 16·5, 0·91 and 0·26 ng/ml leptin, respectively. In fasted animals these levels were much lower: 2·98, 0·171 and 0·0087 ng/ml, respectively. Thus the leptin levels differ greatly between the lines, with the fattest mice showing the highest level: almost 20 times higher than the control and 60–300 times higher than the L line. These correlated selection effects are an order of magnitude greater than the direct selection response, and believed to be much larger than seen for any hormonal or other trait. Correlations between leptin level and fat amount were high (over 0·86) in fed or fasted animals of the F line, indicative of leptin resistance.

A full-sib intercross line (FSIL) is constructed in an outcrossing species by mating two parents and intercrossing their progeny to form a large intercross line. For given statistical power, a FSIL design requires only slightly more individuals than an F2 design derived from inbred line cross, but 6- to 10-fold fewer than a half-sib or full-sib design. Due to population-wide linkage disequilibrium, a FSIL is amenable to analysis by selective DNA pooling. In addition, a FSIL is maintained by continued intercrossing so that DNA samples and phenotypic information are accumulated across generations. Continued intercrossing also leads to map expansion and thus to increased mapping accuracy in the later generations. A FSIL can thus provide a bridge to positional cloning of quantitative trait loci (QTL) and marker-assisted selection in outcrossers; and is particularly effective in exploiting the QTL mapping potential of crosses between selection lines or phenotypically differentiated populations that differ in frequency, but are not at fixation, for alternative QTL alleles. In the course of the power analyses, it is shown that for F2 and FSIL designs, power is a function of Nd2 alone, where N is the total size of the mapping population and d is the standardized gene effect; while for half-sib and full-sib populations, power is a function of Nd2 and of the number of families included in the mapping population. This provides a convenient means of estimating power for a wide variety of mapping designs.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type non-insulin-dependent diabetes mellitus (NIDDM) in humans. The OLETF rat exhibits sustained hyperglycaemia after partial pancreatectomy, while the normal control rat does not. This difference is thought to be genetically determined and to be caused by impairment of β-cell regrowth, a possible event involved in the pathogenesis of NIDDM. Our investigation was designed to identify quantitative trait loci (QTL) responsible for post-pancreatectomy hyperglycaemia by performing a genome-wide scan in an F2 intercross obtained by mating the OLETF and Fischer-344 (F344) rats. We have identified three possible QTL on rat chromosomes (Chrs) 3, 14 and 19 that account for a total of approximately 75% of the genetic variance in the F2. For the QTL on Chr 14, the OLETF allele corresponds with increased glucose levels, as expected. Surprisingly, for the QTL on Chr 19, the F344 allele corresponds with increased glucose levels. The Chr 3 QTL exhibits heterosis, heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. We also found evidence for interaction (epistasis) between the QTL on Chrs 14 and 19.

The patch (Ph) locus allele, patch-extended (Phe), has significantly less pigmentation than the original mutation and homozygotes have been known to survive to term. Analysing inter-subspecific F1 hybrids, we were able to demonstrate that Phe is a deletional mutation encompassing the platelet-derived growth factor receptor alpha subunit (Pdgfra). The deletion does not appear to extend into the coding sequence of the Kit gene (a related tyrosine kinase receptor). However, we were able to demonstrate that, while the Kit gene is transcribed, it does not encode a functionally active receptor.

Ifosfamide induced dominant lethal mutations in spermatozoa of mice at doses of 200 and 300 mg/kg and in spermatids and spermatocytes at 600 mg/kg. The highest dose also induced specific-locus mutations in post-spermatogonial germ-cell stages of mice but not in spermatogonial stem cells. The nature of the induced mutations suggests they are intergenic. The spermatogenic specificity of ifosfamide in mouse germ cells is similar to that of the structurally related cytostatic drugs cyclophosphamide and trofosfamide. Due to the post-spermatogonial germ cell specificity of ifosfamide, the genetic risk is limited to a few weeks after exposure.