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Genetic control of quantitative variation in self-incompatibility proteins detected by immunodiffusion.

Single radial immunodiffusion was used to study the self-incompatibility (S) proteins present in stigmas of two inbred lines of Brassica oleracea: a self-incompatible line and a self-compatible mutant derived from it. The genetic basis of observed quantitative differences in S proteins between the two inbreds was shown to be determined by a single gene with dosage effects. Self-pollination of individual plants with high, intermediate and low levels of S protein in the stigmas, respectively, resulted in low, intermediate and high seed set.

Animals↗

Validation of an immunoassay for detection and quantitation of a genetically modified soybean in food and food fractions using reference materials: interlaboratory study.

An immunoassay for detection of a specific genetically modified soybean (Roundup-Ready) was validated on dried soybean powder in an interlaboratory study. Different percentages of genetically modified soybeans in nonmodified soybean matrix were evaluated in a blind study. Thirty-eight laboratories from 13 countries participated. The immunoassay was evaluated for 2 endpoints: (1) To give a semiquantitative result, i.e., determination of a given sample above or below a given threshold, or (2) to compute a quantitative result, i.e., percentage of genetically modified soybeans in the sample. Semiquantitative results showed that a given sample which contained <2% genetically modified soybeans was identified as below 2% with a 99% confidence level. Quantitative use of the assay resulted in a repeatability (r) and reproducibility (R) that were computed to be RSDr = 7% and RSDR = 10%, respectively, for a sample containing 2% genetically modified soybeans. Application of this method depends on availability of appropriate reference materials for a specific food matrix. Only matrix-matched reference materials can be used for analysis of food or food fractions.

Antibodies, Monoclonal↗

A genetic method to quantitate induced chromosome breaks using a mouse/human monochromosomal hybrid cell line: identification of potential clastogenic agents.

A genetic assay to detect the clastogenic potential of environmental agents is described. This assay is based on the cloning efficiency of cells in a medium that permits the growth of cells following loss of a specific chromosome segment resulting from a chromosome break. For this purpose a mouse/human hybrid cell line R12-2 containing a dominantly marked chromosome 5 as the only human component has been constructed. This chromosome 5 carries two dominant selectable markers, Ecogpt and the gene for sensitivity to diphtheria toxin (DTs). Ecogpt codes for the enzyme xanthine-guanine phosphoribosyltransferase which allows selection for cells containing chromosome 5 or the segment carrying Ecogpt as judged by growth in medium supplemented with mycophenolic acid and xanthine (MX medium). Human cells are sensitive to 10(-13) M DT, whereas mouse cells are resistant to 10(-7) M DT and DTs is expressed as a dominant phenotype. Cultivation of R12-2 cells in the medium containing 10(-13) M DT permit the selection of cells that have lost chromosome 5 or the segment carrying DTs. The presence of two selectable markers on the same chromosome permits the identification and quantitation of cells for the selective loss of a specific chromosome segment. Growth of R12-2 cells in MX medium containing 10(-13) M DT therefore, provides a convenient method to determine the frequency of clastogen induced breaks in chromosome 5. The utility of the proposed genetic assay is assessed using X-irradiation as a model clastogen. Our results clearly show a dose related response that is consistent with cytogenetic observations.

Animals↗

Genetic isolation of quantitative trait loci for blood pressure development and renal mass on chromosome 5 in the spontaneously hypertensive rat.

Total genome scans of genetically segregating populations derived from spontaneously hypertensive rats (SHR) and other rat models of essential hypertension suggested a presence of quantitative trait loci (QTL) regulating blood pressure on multiple chromosomes, including chromosome 5. The objective of the current study was to test directly a hypothesis that chromosome 5 of the SHR carries a blood pressure regulatory QTL. A new congenic strain was derived by replacing a segment of chromosome 5 in the SHR/Ola between the D5Wox20 and D5Rat63 markers with the corresponding chromosome segment from the normotensive Brown Norway (BN/Crl) rat. Arterial pressures were directly monitored in conscious, unrestrained rats by radiotelemetry. The transfer of a segment of chromosome 5 from the BN strain onto the SHR genetic background was associated with a significant decrease of systolic blood pressure, that was accompanied by amelioration of renal hypertrophy. The heart rates were not significantly different in the SHR compared to SHR chromosome 5 congenic strain. The findings of the current study demonstrate that gene(s) with major effects on blood pressure and renal mass exist in the differential segment of chromosome 5 trapped within the new SHR.BN congenic strain.

Analysis of Variance↗

Genetic analyses and quantitative trait loci detection, using a partial genome scan, for intramuscular fatty acid composition in Scottish Blackface sheep.

Genetic parameters for LM fatty acid composition were estimated in Scottish Blackface sheep, previously divergently selected for carcass lean content (LEAN and FAT lines). Furthermore, QTL were identified for the same fatty acids. Fatty acid phenotypic measurements were made on 350 male lambs, at approximately 8 mo of age, and 300 of these lambs were genotyped across candidate regions on chromosomes 1, 2, 3, 5, 14, 18, 20, and 21. Fatty acid composition measurements included in total 17 fatty acids of 3 categories: saturated, monounsaturated, and polyunsaturated. Total i.m. fat content was estimated as the sum of the fatty acids. The FAT line had a greater i.m. fat content and more oleic acid, but less linoleic acid (18:2 n-6) and docosapentaenoic acid (22:5 n-3) than did the LEAN line. Saturated fatty acids were moderately heritable, ranging from 0.19 to 0.29, and total SFA were highly heritable (0.90). Monounsaturated fatty acids were moderately to highly heritable, with cis-vaccenic acid (18:1 n-7) being the most heritable (0.67), and total MUFA were highly heritable (0.73). Polyunsaturated fatty acids were also moderately to highly heritable; arachidonic acid (20:4 n-6) and CLA were the most heritable, with values of 0.60 and 0.48, respectively. The total PUFA were moderately heritable (0.40). The QTL analyses were performed using regression interval mapping techniques. In total, 21 chromosome-wide QTL were detected in 6 out of 8 chromosomal regions. The chromosome-wide, significant QTL affected 3 SFA, 5 MUFA, and 13 PUFA. The most significant result was a QTL affecting linolenic acid (18:3 n-3) on chromosome 2. This QTL segregated in 2 of the 9 families and explained 37.6% of the phenotypic variance. Also, 10 significant QTL were identified on chromosome 21, where 8 out of 10 QTL were segregating in the same families and detected at the same position. The results of this study demonstrate that altering carcass fatness will simultaneously change i.m. fat content and oleic, linoleic, and docosapentaenoic acid content. The heritabilities of the fatty acids indicate opportunities for genetically altering most fatty acids. Moreover, this is the first report of detection of QTL directly affecting fatty acid composition in sheep.

Animals↗

[Quantitative study of the genetics of haptoglobin levels].

A quantitative study, based on several African and Pyrenean populations led to the estimate of the effect of some factors on haptoglobin rate: it shows an influence of age and electrophoretic phenotype, but no apparent effect of sex. Moreover, this study led to the conclusion that there is heritability of haptoglobin rate.

Age Factors↗

Risk assessment in genetics: a semi-quantitative approach.

Public awareness of genetic predisposition to diseases such as breast cancer threatens to put severe strain on genetics services. Computer-based decision support for general practitioners (GPs) has the potential to reduce unnecessary referrals, but issues of communicating about levels of risk and uncertainty must be addressed. An argumentation logic formalism can subsume both traditional probability theory and more qualitative, reason-based approaches to communicating uncertainty, and we propose that qualitative, argument-based presentation will make uncertainty information more accessible and comprehensible to both patient and GP. We describe software that uses an argumentation approach to assess genetic risk during a GP consultation and provide referral advice along with detailed qualitative explanations for its advice. The software was evaluated in real-life GP consultations in which actors played patients concerned about genetic risk, and in use by GPs evaluating simulated cases. Significant improvement in accuracy of assessment and appropriateness of referrals was found. GPs viewed the software and the qualitative reporting approach highly favourably.

Breast Neoplasms↗

[How long the way from QTL to QTGS?].

Most of the important economic traits in higher plants are quantitative traits. Genetic basic researches for quantitative traits were strongly promoted. This article fully elaborated the complicated relationship between quantitative phenotype and its genotype, introduced the recently developed strategy of fine mapping. discussed the current difficulty and hardness among the process of dissect the genetic basis of target traits, then brought forward several research direction that remained to be improved , and finally gave a view of such prospect. Generally speaking,, however, a QTL is still a considerable DNA fragment frequently containing multiplex genes. We also provided some ways and means from QTL coarse locus research to the variation at quantitative trait gene (QTG) level and from QTG to quantitative trait nucleotides (QTN) corresponding to alleles resulted from the intragenetic polymorphism. This is a major challenge for quantitative genetics in the post-genome era.

Animals↗

Genetic markers for quantitative mutagenesis studies in Chinese hamster ovary cells: characteristics of some recently developed selective systems.

Selection conditions have been optimized in the Chinese hamster ovary (CHO) cell system for a number of genetic markers. The genetic systems studied include resistance to the protein-synthesis inhibitors emetine (Emtr) and diphtheria toxin (Dipr), resistance to methylglyoxalbisguanylhydrazone (Mbgr) which affects polyamine transport, resistance to the nucleoside analogs toyocamycin and tubercidin (Toyr), and resistance to thioguanine (Thgr) and ouabain (OuaR). The optimal expression time following mutagenesis for various markers was between 2 and 6 days. A linear dose--response relationship between the concentration of mutagen (ethyl methanesulfonate) and mutation frequency has been observed over the range of 10--700 micrograms/ml, for all of the above markers except Toyr. The response of these markers to other mutagens such as tritium (3H) decay and ICR-191 show some specificity. Since the response of a number of genetic markers can be studied simultaneously in the CHO system, it should prove very useful for studies of quantitative mutagenesis and in assay systems for mutagen detection.

Animals↗

Multipoint genetic mapping of quantitative trait loci using a variable number of sibs per family.

We present a multipoint algorithm to map quantitative trait loci (QTLs) using families from outbred populations with a variable number of sibs. The algorithm uses information from all markers on a chromosome simultaneously to extract information of QTL segregation. A previous multipoint method (Kruglyak & Lander (1995) American Journal of Human Genetics 57, 439-454) extracts information using a hidden Markov model. However, this method is restricted to small families (< 10 sibs). We present an approximate hidden Markov model approach that can handle large sibships while retaining similar efficiency to the previous method. Computer simulations support the notion that data sampled from a small number of large families provide more power than data obtained from a large number of small families, under the constraint that the total number of individuals for the two schemes is the same. This is further reflected in simulations with variable family sizes, where variance in family size improves the statistical power of QTL detection relative to a constant size control.

Chromosome Mapping↗

Comparative genetic analysis of quantitative traits in sunflower (Helianthus annuus L.). 2. Characterisation of QTL involved in developmental and agronomic traits.

Seed weight and oil content are important properties of cultivated sunflower under complex genetic and environmental control, and associated with morphological and developmental characteristics such as plant height or flowering dates. Using a genetic map with 290 markers for a cross between two inbred sunflower lines and 2 years of observations on F3 families, QTL controlling seed weight, oil content, plant height, plant lodging, flowering dates, maturity dates and delay from flowering to maturity were detected. QTL detected were compared between the F2 and F3 generations and between the 2 years of testing for the F3 families in 1997 and 1999. Some of the QTL controlling seed weight overlapped with those controlling oil content. Several other co-localisations of QTL controlling developmental or morphological characteristics were observed and the relationships between the traits were also shown by correlation analyses. The relationships between all these traits and with resistance to Sclerotinia sclerotiorum and Diaporthe helianthi are discussed.

Chromosome Mapping↗

[Using genetic algorithm for quantitative analysis of overlapped spectra in FTIR].

Technique for the quantitative analysis of FTIR spectra, which are serious overlapped in the spectral bands, is studied by genetic algorithm. The multicomponent in the mixture, which contains ten air toxic organic components, such as benzene, phenixin, chlorobenzene, nitrobenzene, phenol, toluene, methanol, o-cresol, m-cresol and p-cresol, is simultaneously determined. The effect of the probability of crossover and the establishment of objective function are discussed. The method of adaptive mutation is used. The results indicate that genetic algorithm has excellent non-linear ability of solution. Mean relative error of each results is really small, generally not bigger than 1%, when the conditions are properly controlled.

Algorithms↗

Multifactorial genetic models for quantitative traits in humans.

Quantitative traits measured in human families can be analyzed to partition the total population variance into genetic and environmental components, or to elucidate the genetic mechanism involved. We review the estimation of variance components directly from human pedigree data, or in the form of path coefficients from correlations between pairs of relatives. To elucidate genetic mechanisms, a mixed model that allows for segregation at a major locus, a polygenic effect and a sibling environmental correlation is described for nuclear families. In each case appropriate likelihoods are derived as a basis, using numerical maximum likelihood methods, for parameter estimation and hypothesis testing. A general model is then described that allows for several familial sources of environmental variation, assortative mating, and both major gene and polygenic effects; and an algorithm for calculating the likelihood of a pedigree under this model is indicated. Finally, some of the remaining problems in this area of biometric analysis are pointed out.

Genetic Variation↗

Bone density in sheep: genetic variation and quantitative trait loci localisation.

Bone density (BD) is an important factor in osteoporotic fracture risk in humans. However, BD is a complex trait confounded by environmental influences and polygenic inheritance. Sheep provide a potentially useful model for studying differences in BD, as they provide a means of circumventing complex environmental factors and are a similar weight to humans. The aims of this study were to establish whether there is genetic variation in BD in sheep and then to localise quantitative trait loci (QTLs) associated with this variation. We also aimed to evaluate the relationship between fat and muscle body components and BD in sheep. Results showed that there was significant (P < 0.01) genetic variation among Coopworth sheep sires for BD. This genetic difference was correlated (P < 0.01) with body weight and muscle mass. A number of QTLs exceeding the suggestive threshold were identified (nine in total). Of these, two (chromosomes 1, P < 0.05; chromosome 24, P < 0.01) were significant using genome-wide permutation significance thresholds (2000 iterations). The position of the QTL on chromosome 24 coincided with a number of other body composition QTLs, indicating possible pleiotropic effects or the presence of multiple genes affecting body composition at that site. This study shows that sheep are potentially a useful model for studying the genetics of BD.

Animals↗

Genetics of the quantitative Lp(a) lipoprotein trait. II. Inheritance of Lp(a) glycoprotein phenotypes.

Lp(a) glycoprotein exhibits an apparent size polymorphism that is associated with genetically controlled Lp(a) lipoprotein concentrations in plasma (Utermann et al. 1988). We have tested the hypothesis that this polymorphism is genetically controlled by studying 15 matings with a total of 44 offspring. This confirmed our conclusion that Lp(a) types are controlled by a series of codominant alleles LpF, LpB, LpS1, LpS2, LpS3 and LpS4 and by a null allele LpO. Together with the data from the accompanying paper this indicates that the structural gene for the Lp(a) protein is the major gene locus determining Lp(a) lipoprotein concentrations in plasma.

Electrophoresis, Polyacrylamide Gel↗

Comparative genetic analysis of quantitative traits in sunflower (Helianthus annuus L.) 3. Characterisation of QTL involved in resistance to Sclerotinia sclerotiorum and Phoma macdonaldi.

One hundred and fifty F(2)-F(3) families from a cross between two inbred sunflower lines FU and PAZ2 were used to map quantitative trait loci (QTL) for resistance to white rot (Sclerotinia sclerotiorum) attacks of terminal buds and capitula, and black stem ( Phoma macdonaldii). A genetic linkage map of 18 linkage groups with 216 molecular markers spanning 1,937 cM was constructed. Disease resistances were measured in field experiments for S. sclerotiorum and under controlled conditions for P. macdonaldii. For resistance to S. sclerotiorum terminal bud attack, seven QTL were identified, each explaining less than 10% of phenotypic variance. For capitulum attack by this parasite, there were four QTL (each explaining up to 20% of variation) and for P. macdonaldii resistance, four QTL were identified, each having effects of up to 16%. The S. sclerotiorum capitulum resistance QTL were compared with those reported previously and it was concluded that resistance to this disease is governed by a considerable number of QTL, located on almost all the sunflower linkage groups.

Ascomycota↗

Phenotypic plasticity of body pigmentation in Drosophila melanogaster: genetic repeatability of quantitative parameters in two successive generations.

In Drosophila melanogaster, body pigmentation is a quantitative trait that depends on developmental temperature. When investigated over the whole thermal range of the species, pigmentation exhibits nonlinear reaction norms that differ among segments. The isofemale line method was used to analyse the genetic variability in two natural populations that affected the shape of reaction norms. Each line was considered as an experimental repeat, and polynomial reaction norms fitted to calculate the characteristic values (eg the coordinates of a maximum). In total, 20 lines from two geographically distant populations (France and India) were investigated at seven developmental temperatures (12-31 degrees C) in two successive generations (G2 and G3). We analysed the genetic repeatability (ie the correlation between generations) of three kinds of parameters: intraclass correlation coefficients (isofemale heritability), family means at different temperatures and the characteristic values of the reaction norms. For intraclass correlation, a low genetic repeatability was found. For family mean values grown at various temperatures, an overall positive and highly significant repeatability was found (r=0.55+/-0.024). Finally, a positive significant G2-G3 correlation was also the rule for the characteristic values of the reaction norms. Significant differences could be found between values describing either the trait or its plasticity, but with no general trend. A slightly higher repeatability was observed in the Indian population. These results show that, with a family selection design, the shape of the reaction norms might be modified in various ways.

Abdomen↗