Biomedical subjects

F Hospital

Publications and source records attributed to F Hospital.

10 recordsLinked to original sources

PubMed2001

Genetic and nongenetic bases for the L-shaped distribution of quantitative trait loci effects.

The L-shaped distribution of estimated QTL effects (R(2)) has long been reported. We recently showed that a metabolic mechanism could account for this phenomenon. But other nonexclusive genetic or nongenetic causes may contribute to generate such a distribution. Using analysis and simulations of an additive genetic model, we show that linkage disequilibrium between QTL, low heritability, and small population size may also be involved, regardless of the gene effect distribution. In addition, a comparison of the additive and metabolic genetic models revealed that estimates of the QTL effects for traits proportional to metabolic flux are far less robust than for additive traits. However, in both models the highest R(2)'s repeatedly correspond to the same set of QTL.

Linkage Disequilibrium↗

PubMed2001

Size of donor chromosome segments around introgressed loci and reduction of linkage drag in marker-assisted backcross programs.

This article investigates the efficiency of marker-assisted selection in reducing the length of the donor chromosome segment retained around a locus held heterozygous by backcrossing. First, the efficiency of marker-assisted selection is evaluated from the length of the donor segment in backcrossed individuals that are (double) recombinants for two markers flanking the introgressed gene on each side. Analytical expressions for the probability density function, the mean, and the variance of this length are given for any number of backcross generations, as well as numerical applications. For a given marker distance, the number of backcross generations performed has little impact on the reduction of donor segment length, except for distant markers. In practical situations, the most important parameter is the distance between the introgressed gene and the flanking markers, which should be chosen to be as closely linked as possible to the introgressed gene. Second, the minimal population sizes required to obtain double recombinants for such closely linked markers are computed and optimized in the context of a multigeneration backcross program. The results indicate that it is generally more profitable to allow for three or more successive backcross generations rather than to favor recombinations in early generations.

Chromosomes↗

PubMed2000

Efficient marker-based recurrent selection for multiple quantitative trait loci.

We studied the efficiency of recurrent selection based solely on marker genotypes (marker-based selection), in order to increase favourable allele frequency at 50 previously detected quantitative trait loci (QTLs). Two selection procedures were investigated, using computer simulations: (1) Truncation Selection (MTS), in which individuals are ranked based on marker score, and best individuals are selected for recombination; and (2) QTL Complementation Selection (QCS), in which individuals are selected such that their QTL composition complements those individuals already selected. Provided QTL locations are accurate, marker-based selection with a population size of 200 was very effective in rapidly increasing frequencies of favourable QTL alleles. QCS methods were more effective than MTS for improving the mean frequency and fixation of favourable QTL alleles. Marker-based selection was not very sensitive to a reduction in population size, and appears valuable to optimize the use of molecular markers in recurrent selection programmes.

Alleles↗

PubMed1998

Marker-assisted selection efficiency in populations of finite size.

The efficiency of marker-assisted selection (MAS) based on an index incorporating both phenotypic and molecular information is evaluated with an analytical approach that takes into account the size of the experiment. We consider the case of a population derived from a cross between two homozygous lines, which is commonly used in plant breeding, and we study the relative efficiency of MAS compared with selection based only on phenotype in the first cycle of selection. It is shown that the selection of the markers included in the index leads to an overestimation of the effects associated with these markers. Taking this bias into account, we study the influence of several parameters, including experiment size and heritability, on MAS efficiency. Even if MAS appears to be most interesting for low heritabilities, we point out the existence of an optimal heritability (approximately 0.2) below which the low power of quantitative trait loci detection and the bias caused by the selection of markers reduce the efficiency. In this situation, increasing the power of detection by using a higher probability of type I error can improve MAS efficiency. This approach, validated by simulations, gives results that are generally consistent with those previously obtained by simulations using a more sophisticated biological model than ours. Thus, though developed from a simple genetic model, our approach may be a useful tool to optimize the experimental means for more complex genetic situations.

Genetic Markers↗

PubMed1997

Marker-assisted introgression of quantitative trait loci.

The use of molecular markers for the introgression of one or several superior QTL alleles into a recipient line is investigated using analytic and simulation results. The positions of the markers devoted to the control of the genotype at the QTLs in a "foreground selection" step are optimized given the confidence interval of the QTL position. Results demonstrate that using at least three markers per QTL allows a good control over several generations. Population sizes that should be recommended for various numbers of QTLs are calculated and are used to determine the limit in the number of QTLs that can be monitored simultaneously. If "background selection" devoted to accelerate the return to the recipient parent genotype outside the QTL regions is applied, the positions of the markers devoted to the control of the QTLs have to be reconsidered. When several QTLs are monitored simultaneously, background selection among the limited number of individuals resulting from the foreground selection step accelerates the increase in genomic similarity with the recipient parent, with only limited costs. Background selection is even more efficient in a pyramidal backcross program where QTLs are first monitored one by one.

Alleles↗

PubMed1996

Interactions of selection, linkage and drift in the dynamics of polygenic characters.

We study the dynamics under directional truncation selection of the genetic variability of a quantitative character controlled by a finite number of possibly linked loci with additive effects. After the first generation of selection, the build-up of linkage disequilibria (Bulmer effect) is analytically demonstrated from a genetical point of view in an infinite population. In the following generations, the dynamics of the system in a finite population are predicted using analytic recurrences under a multi-normal approximation, and computer simulations. The effects of recombination on the dynamics of linkage disequilibria induced by selection and drift, and the consequences for the additive genetic variance are then analysed and discussed from the simulation results. Compared to the rapid exploitation of genetic variability promoted by high recombination rates, low recombination rates promote an early storage of genetic variability in repulsion associations of alleles and a possible late release of genetic variance in the population, so that the variability of the character may be maintained over a longer period of time. In some cases, favourable recombination events in tightly linked systems induce an increase of the additive variance of the character, which may explain some results observed in long-term selection experiments. Our results emphasize that the joint effects of selection, linkage and drift must not be neglected in theoretical quantitative genetics, and require further investigation.

Computer Simulation↗

PubMed1996

A general algorithm to compute multilocus genotype frequencies under various mating systems.

This paper provides a general method to derive algebraic expressions of genotype frequencies for multiple loci under various mating systems, including random mating, back-crossing, selfing, and full-sib mating. For each mating system, general equations are presented. In the case of three loci, comprehensive tables provide recurrence equations for genotype frequencies under random or self mating, and expected genotype frequencies after two generations of full-sib mating. Our results should prove useful in genetic linkage analysis.

Algorithms↗

PubMed1995

A FORTRAN program to simulate the evolution of genetic variability in a small population.

This paper presents a FORTRAN-77 program that performs Monte Carlo simulation of the evolution of genetic structure in a small population under selection. The aim is to study the possibility of foreseeing a response plateau in a theoretical population, depending on population size and management, and to apply this to small populations actually selected, to predict a possible exhaustion of genetic variability. A set of subroutines describing the different steps in a selection cycle (birth, expression of phenotypic value, genetic evaluation, selection, reproduction, death) is available and the user can choose the sequence of subroutines, the characteristics of individuals submitted to each step, and also build more personal subroutines if necessary. The program is based on the generation of exact genotypes and their transmission from parents to offspring, through simulation of meiosis and pairing of gametes. Parameters concerning the genome, the initial structure of the population and its management are required. The genetic mean and variance of the population for each new cycle of selection are given as outputs. Examples of applications are given and discussed.

Algorithms↗

PubMed1992

Using markers in gene introgression breeding programs.

We investigate the use of markers to hasten the recovery of the recipient genome during an introgression breeding program. The effects of time and intensity of selection, population size, number and position of selected markers are studied for chromosomes either carrying or not carrying the introgressed gene. We show that marker assisted selection may lead to a gain in time of about two generations, an efficiency below previous theoretical predictions. Markers are most useful when their map position is known. In the early generations, it is shown that increasing the number of markers over three per non-carrier chromosome is not efficient, that the segment surrounding the introgressed gene is better controlled by rather distant markers unless high selection intensity can be applied, and that selection on this segment first can reduce the selection intensity available for selection on non-carrier chromosomes. These results are used to propose an optimal strategy for selection on the whole genome, making the most of available material and conditions (e.g., population size and fertility, genetic map).

Alleles↗

PubMed1992

Genetic analysis of fingerprints in Mérinos d'Arles x Booroola Merino crossbred sheep.

The M13.13 minisatellite probe, consisting of a polymer of the M13 VNTR consensus sequence, cross-hybridized to ovine DNA and allowed detection of several polymorphic loci. Individual specific patterns were obtained in sheep using this probe. Pedigree analysis showed that individuals were heterozygous for most of the DNA fragments detected (88%). By studying the segregation of male's variable DNA fragments, a minimum of 10 loci were defined. The ovine DNA 'fingerprint' obtained with M13.13 is polymorphic enough to be used efficiently in animal identification, paternity testing, and possibly as a source of genetic markers for linkage analysis.

Animals↗