Nocodazole-Resistant Mutants in Paramecium

The effect of the microtubule inhibitor nocodazole was studied on Paramecium and shown to arrest cell multiplication, depolymerize the internal microtubule network, and block the development of macro- and micronuclear spindles and of the cytospindle (a cortical microtubule array assembled during division). After ultraviolet mutagenesis, three mutants resistant to nocodazole, that is capable of continued growth in the presence of the drug, were isolated and shown to correspond to three nonallelic single-gene nuclear mutations. One ( noc ^r- 1 ) is semidominant while the other two ( noc ^r- 2 and noc ^r- 3 ) are recessive. Cytological and physiological studies of nocodazole's effects on the mutants demonstrate that their resistance is due neither to a lack of drug penetration nor to its degradation since, in each mutant in the presence of the drug, some microtubule networks are normal or subnormal while others remain affected as in wild-type cells. These are the first mutants resistant to microtubule depolymerizing drugs obtained in ciliates that provide a new tool for studying the assembly and dynamics of the diverse microtubule arrays in this type of organism.     

Zebrafish genetic models for arrhythmia

Over the last decade the zebrafish has emerged as a major genetic model organism. While stimulated originally by the utility of its transparent embryos for the study of vertebrate organogenesis, the success of the zebrafish was consolidated through multiple genetic screens, sequencing of the fish genome by the Sanger Center, and the advent of extensive genomic resources. In the last few years the potential of the zebrafish for in vivo cell biology, physiology, disease modeling and drug discovery has begun to be realized. This review will highlight work on cardiac electrophysiology, emphasizing the arenas in which the zebrafish complements other in vivo and in vitro models; developmental physiology, large-scale screens, high-throughput disease modeling and drug discovery. Much of this work is at an early stage, and so the focus will be on the general principles, the specific advantages of the zebrafish and on future potential.     

Developmental evolution: Going beyond the ‘just so’

Two new protocols for infecting non-mammalian embryos with viruses, together with RNA inhibition, have provided evolutionary developmental biologists with the tools to study the effects of manipulating gene activity in a wide range of species, allowing them to test hypotheses rather than rely on inference from similarity.     

Using <Emphasis Type="Italic">C. elegans</Emphasis> to screen for targets of ethanol and behavior-altering drugs

Caenorhabditis elegans is an attractive model system for determining the targets of neuroactive compounds. Genetic screens in C. elegans provide a relatively unbiased approach to the identification of genes that are essential for behavioral effects of drugs and neuroactive compounds such as alcohol. Much work in vertebrate systems has identified multiple potential targets of ethanol but which, if any, of those candidates are responsible for the behavioral effects of alcohol is uncertain. Here we provide detailed methodology for a genetic screen for mutants of C. elegans that are resistant to the depressive effects of ethanol on locomotion and for the subsequent behavioral analysis of those mutants. The methods we describe should also be applicable for use in screening for mutants that are resistant or hypersensitive to many neuroactive compounds and for identifying the molecular targets or biochemical pathways mediating drug responses. Published: June 8, 2004.     

Quantitative and qualitative trait loci affecting host-plant response to Exserohilum turcicum in maize (Zea mays L.)

Molecular markers at 103 loci were used to identify the location of quantitative sources of resistance to Exserohilum turcicum in 150 F₂₃ lines of a B52/Mo17 maize population. Host-plant response was measured in terms of the average number of lesions per leaf, the average percent leaf tissue diseased (severity), and the average size of lesions. The location of quantitative trait loci were compared with three loci having known qualitative effects, namely Ht1, Ht2 and bx1. Chromosomal regions containing the Ht1 and Ht2 loci showed a small contribution in determining lesion size, even though alleles with dominant, qualitative effects at these loci have never been reported in either inbred parent. Similar effects were not observed for the number of lesions or for disease severity. Likewise, some contribution was observed for chromosomal regions encompassing the bx1 locus in determining lesion size but not the number of lesions or disease severity. Overall the contribution of loci in the vicinity of Ht1, Ht2 and bx1 was small relative to variation attributable to loci with quantitative effects identified in this study. Molecular-marker-facilitated mapping concurred with previous reciprocal translocation mapping studies on the importance of chromosomes 3, 5 and 7, despite the fact that these studies utilized diverse sources of resistant germplasm.Journal Paper No. J-15177 of the Iowa Agriculture and Home Economics Experiment Station, Ames, Iowa. Project No. 3134     

The Inbred Mouse in Pigmentation Research:

Pigment mutations in inbred mice have been important to many new scientific developments over the past century. Inbred mice are essentially genetically alike because of 10–20 generations or more of sibling mating or the equivalent. Mice of the same inbred strain that differ at only one locus can be used to evaluate the phenotypic effects of that one locus without complication of variation at other loci. Similarly, genic interactions among the functions of two or more loci are evaluated by comparing them in all combinations against a uniform genetic background. The next logical step in describing the pigment system will occur when all pigment cell biologists who use mice (cells, tissues, DNA, RNA) make certain that their mice are congenic with C57BL/6J. As a result, the work of all investigators will be genetically comparable. Their work will also be comparable to those investigating other organ systems, because NIH has chosen C57BL/6J as one of its two standard strains. As a result of this standardization, interactions among the different gene loci that function in the pigment system will become more readily evident and the community of pigment cell biologists using congenic mice will be able to analyze the functional interplay of loci that regulate the entire pigment system in the same way that earlier researchers analyzed one mutant allele, or the interactions of two mutant loci.     

Sibling similarity in development of covariation among physical traits in early childhood

We studied the sibling similarity in development of covariation among body size characters (body weight (W), body length (S) and head circumference (HC) in Tel Aviv infants from birth up to 2 years of age. We investigated the effects of parental geographic origin, profession, age, current residence, and of family size. Multiple regression analysis with "dummy" procedure established that none of these variables had any significant effect on the aforementioned anthropometric traits. The matrices of phenotypic and genetic correlations, based on sibling similarity data, among age-specific W, S, and HC (measured for 12 different ages) were subjected to principal component analysis in order to elucidate patterns over the age groups. The patterns of both analyses, phenotypic and genetic, were quite similar: one factor in each (first genetic and second phenotypic) had a high positive correlation with early, first 2-3 months of life, W, S, and HC. Three other extracted factors correlated strongly, each with late W, S, and HC, respectively. The results of additional principal component analyses of age-specific W, S, and HC matrices separately, indicate the possibility of existence of two genetic subsystems, the first determining early postnatal stages of human ontogeny, and the second, later phases of child development.     

Closing remarks

Closing remarks to Human genetics - uncertainties and the financial implications ahead. A Discussion held at the Royal Society on 25 and 26 September 1996, and organized and edited by R. M. Anderson. <br>     

The Bacon Chow study: Genetic analysis of physical growth in assessment of energy–protein malnutrition

Estimates of the prevalence of energy–protein malnutrition almost universally employ physical growth measurements. In this study we focus on this disease and the role of body size of relatives as mediators of responses in individuals to one type of nutrition intervention: supplementation of pregnant and lactating women. In this study, initiated by Dr. Bacon Chow and others in 1967, during gestation of a first infant a mother was untreated, while during the lactation of the first infant and the gestation and lactation of a second infant she was treated with either a calorie supplement or a placebo. Supplement–placebo group differences were sought in sibling and mother–child correlations in growth from birth to 30 months, in order to assess the role of heredity as a mediator of supplement effects. There were 108 pairs of siblings whose mothers had received a high-calorie–high-protein supplement as described above and 105 pairs of siblings whose mothers had received a placebo. Among the latter, sibling correlations for most measurements are statistically significant at birth, and of the same magnitude seen in previous studies (～0.5), while among supplemented siblings, birth correlations are unusually low and often insignificant. The sibling correlations in Rohrer's index (wt/L³) differed the most between groups (p < 0.01). Group differences in the sibling correlation tended to disappear over the first 2.5 years of life. Correlations between mothers and their second children in subscapular skinfold tended to be higher in the supplemented than in the placebo group, birth to 30 months. In both supplement groups mother–second child correlations for body weight were higher than mother–first child correlations, suggesting the occurrence of secular changes in the environment unconnected with the treatment. The results suggest that: (1) genetic analysis of components of anthropometric variation may be a more sensitive method than the more conventional comparison of group means in detecting supplement effects; and (2) infant relative weight (Rohrer index), particularly the addition of subcutaneous fat, may be more affected by maternal supplementation than growth in weight or length alone.     

Conceptual and methodological issues in the genetics of mouse agonistic behavior

Currently, 36 genes have been reported to affect offensive behavior in male mice. Potentially, these genes could be used to analyze the mechanism of this behavior. But there are methodological flies in this conceptual ointment. The studies with these genes varied in the genetic background, the maternal environments, the postweaning housing, the strain or type of opponent, and the type of test. The effects of each of these on the genetics of offense are reviewed with examples. It is concluded that between-study variation in these environmental or experiential circumstances may make it difficult to impossible to relate the effect of one genetic variant to another and to use these to identify and relate the pathways for gene effects on offensive behaviors. For this reason, standardization of these conditions is recommended.     

Heifers sired by bulls with either high or low expected progeny differences (EPDs) for marbling do not differ in age at puberty

Selection for carcass traits such as deposition of intramuscular fat (marbling), which is a primary trait used as an indicator of meat quality, may incur additional effects such as younger age at puberty. Therefore, a trial was conducted for 2 years to determine age of puberty for two groups of crossbred heifers (n = 124) sired by purebred Angus bulls selected for either low (Low, n = 6) or high (High, n = 6) expected progeny differences (EPDs) for marbling. Our working hypothesis was that age at puberty would be reduced in heifers sired by bulls with high EPDs for marbling in comparison to those heifers sired by bulls with low EPDs for marbling. Puberty was determined by collecting weekly blood samples and assaying for concentrations of progesterone. Mean age at puberty for heifers during the study did not differ (392 ± 5 and 387 ± 5 days, Low and High respectively). Of the 124 heifers, 79% reached puberty within the 145 days allotted for the study. We conclude that use of sires that produce daughters with increased ability to marble does not result in decreased age at puberty.     

The genome of the malaria parasite

The genome of the human malaria parasite Plasmodium falciparum is being sequenced by an international consortium. Two of the parasite's 14 chromosomes have been completed and several other chromosomes are nearly finished. Even at this early stage of the project, analysis of the genome sequence has provided promising new leads for drug and vaccine development.     

Genetic analysis of tolerance for phosphorous deficiency in rice (Oryza sativa L.)

The inheritance of phosphorous (P) — deficiency tolerance in rice was investigated by a sevenparent diallel. The parent materials involved were four P-efficient (IR20, IR54, IR28, and Mahsuri), one moderately P-efficient (TN1), and two P-inefficient (IR31406333-1 and IR34686-179-1-2-1), genotypes. Relative tilering ability (RTA) under P-deficient and P-supplemented soil conditions was the parameter used in determining the tolerance level of the different genotypes. Diallel graph analysis revealed that tolerant parents have an excess of recessive genes, while moderate and susceptible parents possess more dominant genes. Genetic-component analysis suggested that both additive and dominance gene effects are involved in the inheritance of P-deficiency tolerance in rice. The trait exhibited over doiminance as confirmed by the graphical analysis. Narrow-sense heritability of the trait was moderate (0.50) and environmental effects were low. Both the general combining ability (GCA) and the specific combining ability (SCA) were significant, but GCA was more prevalent than SCA. Tolerant parents exhibited a high GCA whereas susceptibles have a very poor GCA, suggesting that tolerant parents were mostly enriched in additive genes and susceptible parents in non-additive genes. Crosses involving two high general combiners showed low SCA effects whereas crosses between poor general combiners manifested highly-significant SCA values.     

Evidence of genetic and maternal effects on secondary sex ratio in cattle

There is a paucity of estimates of genetic variation for secondary sex ratio (i.e., sex ratio at birth) in dairy cattle. The objective of this study was to estimate the direct and maternal genetic variance as well as maternal permanent environmental variance for offspring sex in dairy herds. The data consisted of 77,508 births from 61,963 dams and 2,859 sires in 1,369 Irish dairy herds across the years 2003 to 2008, inclusive. Mixed models were used to estimate all parameters. Significant genetic variation in sex ratio existed, with a heritability for secondary sex ratio estimated at 0.02; the genetic standard deviation was 0.07 percentage units. No maternal genetic effects on secondary sex ratio were identified but the proportion of phenotypic variance in secondary sex ratio attributable to maternal permanent environmental effects was similar to that attributable to the additive genetic variance (i.e., 0.02). These results, therefore, suggest that the paternal (genetic) influence on secondary sex ratio is just as large as the maternal (non-genetic) influence, both of which are biologically substantial. The results from this study will be useful in generating a sample population of divergent animals for inclusion in a controlled experiment to elucidate the physiological mechanism underpinning differences in secondary sex ratio.     

The effects of heterozygosity at the af,st and tl loci in peas

Summary Eight near-isogenic lines of pea representing all the homozygous combinations of three genes af, st and tl, which modify leaf shape and size, were crossed in all possible ways excepting reciprocals. An analysis of the resulting 36 families has shown that homozygous mutant alleles at the tl locus acting with homozygous mutant alleles at the af and st loci increase both seed weight and plant haulm weight. The mutant alleles at the af and st loci seem, when homozygous, to have little effect by themselves upon seed weight but they do increase or decrease haulm weight, respectively. There is clear evidence of heterotic effects resulting from heterozygosity at each one of the three loci which modify seed weight, haulm weight and basal branching. The implications of such heterotic effects in pea breeding programmes are discussed.     

The genetic basis of an adaptive radiation: warning colour in two Heliconius species

Mimetic colour pattern races of Heliconius butterflies provide a striking example of adaptive radiation and numerous crossing experiments have investigated the genetics of these racial differences. However, colour pattern differentiation between closely related Heliconius species has not been previously studied. Here we present data from crosses between H. erato cyrbia and its sister species, H. himera. The genetic architecture underlying colour pattern divergence between these species is identical to that observed between races of H. erato. As in inter-racial crosses, colour pattern differences resulted from segregation at a few major loci. Evidence from 1321 offspring in 4 F₁, 17 backcross, 7 F₂ and 21 further crosses showed that two major loci controlled most of the colour pattern differences between H. erato and H. himera. There were strong interactions between these loci in their patterns of expression and evidence for other loci with relatively minor phenotypic effects. More importantly, based on patterns of expression within broods and linkage with Aconitase, we conclude that these major loci were homologous with those known to be responsible for colour pattern differences within H. erato. Our crosses also permit a re-evaluation of the relationships between colour pattern races of H. erato. This suggests that H. e. hydara, which occurs across a major mtDNA break, is the ancestral phenotype from which other races have evolved. Based on this assumption, we find no evidence to support the recent suggestion that apparently homologous colour pattern alleles have arisen multiple times.     

利用文献精读教学新模式优化遗传学教学

《遗传学》是生命科学相关专业本科阶段最重要的课程之一。近年来,随着生命科学领域研究的不断深入,新知识与新技术也在不断更新。但遗传学的教学模式目前仍以理论讲授为主,这使得抽象的原理难以被学生理解接受,直接影响了教学效果。因此探索新的教学模式尤为必要。2010年以来我校在生物技术专业《微生物遗传学》教学中开展了新教学模式——文献精读,文章从文献精读的前期课程基础,如何选择专业文献,怎样组织教学过程,开展文献精读对学生和教师的意义等方面全面分析了实施情况和应用价值,指出该教学模式体现了“前沿”和“经典”的结合,使书本的知识在实践中具体化,既提高学生的学习效果,激发学习兴趣,又开拓了学生的思路,锻炼其能力。这种教学模式为《遗传学》教学授课不断探索新的模式、在“精准医疗”时代下如何培养兼具临床与科研能力的医疗人才提供新思路。     

AMONG-FAMILY VARIATION FOR ENVIRONMENTAL SEX DETERMINATION IN REPTILES

Unlike birds and mammals, in many reptiles the temperature experienced by a developing embryo determines its gonadal sex. To understand how temperature-dependent sex determination (TSD) evolves, we must first determine the nature of genetic variation for sex ratio. Here, we analyze among-family variation for sex ratio in three TSD species: the American alligator (Alligator mississipiensis), the common snapping turtle (Chelydra serpentina) and the painted turtle (Chrysemys picta). Significant family effects and significant temperature effects were detected in all three species. In addition, family-by-temperature interactions were evident in the alligator and the snapping turtle, but not in the painted turtle. Overall, the among-family variation detected in this study indicates potential for sex-ratio evolution in at least three reptiles with TSD. Consequently, climate change scenarios that are posited on the presumption that sex-ratio evolution in TSD reptiles is genetically constrained may require reevaluation.