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A Gimelfarb

Publications and source records attributed to A Gimelfarb.

At least 19 recordsLinked to original sources
PubMed2000

Balance of fitnesses maintaining polymorphisms in two-locus genetic systems.

Maintenance of a stable two-locus polymorphism is analyzed statistically by fitting a logistic regression with a quadratic function of genotypic fitnesses to the probability for a fitness set to maintain a polymorphism. The regression is fitted using a data set containing information on stable equilibria maintained by 32,00 randomly generated fitness sets with three recombination values (0. 005, 0.05, 0.5). Fitted logistic regressions discriminate with 88 to 90% accuracy between fitness sets maintaining and not maintaining a stable internal equilibrium, which implies the existence of a fitness structure (balance of fitnesses) maintaining a two-locus polymorphism. Aspects of the balance of fitnesses revealed by logistic regressions are discussed. It is demonstrated that logistic regression also discriminates between types of a stable polymorphism: globally stable polymorphism, several simultaneously stable polymorphisms, and stable equilibria in addition to a polymorphic one, which implies that different balances of fitnesses are responsible for the maintenance of different types of polymorphism.

Alleles↗
PubMed1999

Haptoglobin genotype and natural fertility in humans.

OBJECTIVE: To study the possible relation between human natural fertility and haptoglobin (Hp) genotype. DESIGN: Prospective study. SETTING: Maternity departments of local hospitals in two Italian localities. PATIENT(S): Healthy women who had just given birth in the maternity departments of two local hospitals (n = 679). INTERVENTION(S): Venous blood collection for determination of Hp genotype with the use of starch gel electrophoresis of hemoglobin-supplemented serum. MAIN OUTCOME MEASURE(S): Distribution of Hp genotypes in relation to age of puerperae. RESULT(S): In both populations, the proportion of young mothers was much higher among women who were homozygous for the Hp*1 allele (the Hp*1/*1 genotype) than among women who had other Hp genotypes. In addition, the proportion of multiparous women among the older mothers was higher among those with the Hp*1/*1 genotype than among those with other Hp genotypes. CONCLUSION(S): The data suggest that women with the Hp*1/*1 genotype reproduce at an earlier age and have higher natural fertility potential than women with other Hp genotypes.

Adult↗
PubMed1999

Genetic variation maintained in multilocus models of additive quantitative traits under stabilizing selection.

Stabilizing selection for an intermediate optimum is generally considered to deplete genetic variation in quantitative traits. However, conflicting results from various types of models have been obtained. While classical analyses assuming a large number of independent additive loci with individually small effects indicated that no genetic variation is preserved under stabilizing selection, several analyses of two-locus models showed the contrary. We perform a complete analysis of a generalization of Wright's two-locus quadratic-optimum model and investigate numerically the ability of quadratic stabilizing selection to maintain genetic variation in additive quantitative traits controlled by up to five loci. A statistical approach is employed by choosing randomly 4000 parameter sets (allelic effects, recombination rates, and strength of selection) for a given number of loci. For each parameter set we iterate the recursion equations that describe the dynamics of gamete frequencies starting from 20 randomly chosen initial conditions until an equilibrium is reached, record the quantities of interest, and calculate their corresponding mean values. As the number of loci increases from two to five, the fraction of the genome expected to be polymorphic declines surprisingly rapidly, and the loci that are polymorphic increasingly are those with small effects on the trait. As a result, the genetic variance expected to be maintained under stabilizing selection decreases very rapidly with increased number of loci. The equilibrium structure expected under stabilizing selection on an additive trait differs markedly from that expected under selection with no constraints on genotypic fitness values. The expected genetic variance, the expected polymorphic fraction of the genome, as well as other quantities of interest, are only weakly dependent on the selection intensity and the level of recombination.

Alleles↗
PubMed1998

Stable equilibria in multilocus genetic systems: a statistical investigation.

A data base of gametic distributions at a stable equilibrium for genetic systems with up to five diallelic loci was created by numerically iterating equations for the dynamics of gametic frequencies in multilocus systems under selection. For a given number of loci, iterations were conducted for 4000 random sets of genotypic fitnesses, 6 values of recombination, and 10 different initial distributions. The data base was used to investigate the following properties of stable equilibria maintaining a polymorphism in a given number of loci that are expected a priori, i.e., without any constraints on fitnesses of genotypes: probability for a fitness set to yield a such equilibrium; probability for a random trajectory to converge to a such equilibrium; genetic load at a such equilibrium. The expected number of simultaneously stable equilibria, and the fraction of genome maintained polymorphic were also investigated as well as some parameters expected at an equilibrium maintaining all loci polymorphic. One of the most important findings is that multilocus genetic systems have a potential for maintaining a polymorphism in a large number of loci under selection without an input of new genetic variation.

Genetic Linkage↗
PubMed1998

Adenosine deaminase and human reproduction: a comparative study of fertile women and women with recurrent spontaneous abortion.

PROBLEM: We have investigated the possible role of adenosine deaminase (ADA) genetic polymorphism in human fertility through a comparative study of couples with recurrent spontaneous abortion (RSA) and healthy puerperae. METHOD OF STUDY: Adenosine deaminase phenotype has been determined in 209 women with repeated episodes of unexplained spontaneous abortion (RSA) and their husbands, as well as in 115 healthy pregnant women from the population of Rome. An independent sample of 286 puerperae along with their newborn infants in the population of Penne was also studied. RESULTS: The proportion of carriers of ADA*2 allele, which is associated with the lowest enzymatic activity, is lower among women with RSA than among healthy pregnant women from the same population of Rome. Preliminary observations suggest a protective effect of ADA*2 against the development of autoantibodies in RSA. Such an effect seems to be mediated by an interaction with AB0 blood groups. In the population of Penne the proportion of women carrying ADA*2 allele is higher among those who have had two or more previously born children than among women with only one or no children. CONCLUSIONS: The data suggest that women carrying the ADA*2 allele are better protected against the spontaneous loss of embryos and have a higher fertility rate.

ABO Blood-Group System↗
PubMed1996

Interethnic variability in birth weight and genetic background: a study of placental alkaline phosphatase.

The relationship between human placental alkaline phosphatase (PLAP) genotype and birth weight is investigated in a sample of white, black and Puerto-Rican new-born infants from New Haven, Connecticut (total 710 subjects). Black and Puerto-Rican infants show a higher incidence of growth retardation and a higher frequency of ALPp*1/*1 genotype as compared to whites. The proportion of newborns with a low birth weight (below the 10th percentile) is lower in infants with ALPp*1/*1 genotype than in those with other PLAP genotypes, especially among non-whites. It is argued that the higher frequency of ALPp*1 allele among non-whites might be, at least in part, a consequence of their adaptation in the past to environmental conditions adverse to optimal intrauterine development.

Black or African American↗
PubMed1996

Some additional results about polymorphisms in models of an additive quantitative trait under stabilizing selection.

The existence of two stable, symmetric (allelic frequency 0.5 in each locus) polymorphic states is demonstrated for a two-locus model of an additive quantitative trait under strong Gaussian selection. Linkage disequilibrium at one of the states is negative whereas it is positive at the other state. For a three-locus model, it is shown that in order to maintain a stable polymorphism in all three loci, selection must be sufficiently but not excessively strong relative to recombination. Also, positive linkage disequilibrium can be maintained in a three-locus model under stabilizing selection that is not very strong.

Alleles↗
PubMed1996

Phosphotyrosine-protein-phosphatases and human reproduction: an association between low molecular weight acid phosphatase (ACP1) and spontaneous abortion.

ACP1 (low molecular weight acid phosphatase) genetic polymorphism has been studied in 173 women with a history of two or more consecutive spontaneous abortions and in 1508 control subjects, including 482 normal pregnant women. The proportion of carriers of ACP1*C allele (*A/ *C, *B/*C) in women with a history of repeated spontaneous abortion is lower than in normal pregnant women and other control groups. Women with repeated spontaneous abortion show a specific decrease of ACP1 S isoform concentration as compared to normal pregnant women. The other component of ACP1 activity, the F isoform, does not show a significant difference between the two groups. The data suggest that women with ACP1 genotypes showing a high concentration of S isoform are relatively 'protected' against spontaneous abortion. Preliminary analysis of a sample of 352 normal puerperae along with their newborn babies supports this hypothesis.

Abortion, Habitual↗
PubMed1994

Simulation of marker assisted selection in hybrid populations.

A computer model is developed that simulates Marker Assisted Selection (MAS) in a population produced by a cross between two inbred lines. Selection is based on an index that incorporates both phenotypic and molecular information. Molecular markers contributing to the index and their relative weights are determined by multiple regression of individual phenotype on the markers. The model is applied to investigate the efficiency of MAS as affected by several factors including total number of markers in the genome, number of markers contributing to the index, population size and heritability of the character. It is demonstrated that selection based on genetic markers can effectively utilize the linkage disequilibrium between genetic markers and QTLs created by crossing inbred lines. Selection is more efficient if markers contributing to the index are re-evaluated each generation than if they are evaluated only once. Increasing the total number of markers in the genome as well as the number of markers contributing to the index does not necessarily result in a higher efficiency of selection. Moreover, too many markers may result in a weaker response to selection. Population size is shown to be the most important factor affecting the efficiency of MAS.

Animals↗
PubMed1994

Simulation of marker assisted selection for non-additive traits.

Marker Assisted Selection (MAS) based on additive effects associated with alleles at marker loci, estimated by linear regression of individual phenotype on the markers, was applied to characters with non-additive gene action and non-additive environment. The base population was the F2 generation of a cross between two inbred lines. Computer simulations of MAS were conducted for characters with dominance, epistasis and genotype-environment interaction approximated by the 'additive-multiplicative' model. MAS was more effective than purely phenotypic selection in all cases. The efficiency of MAS for characters with non-additive gene action is comparable to (and for negative dominance even higher than) the efficiency of MAS for strictly additive characters. Environmental non-additivity, however, lowers the efficiency of MAS. Almost all results concerning the efficiency of MAS in our previous simulations of purely additive traits are applicable to non-additive traits.

Animals↗
PubMed1994

Linearity Versus nonlinearity of offspring-parent regression: an experimental study of Drosophila melanogaster.

An experiment was conducted to investigate the offspring-parent regression for three quantitative traits (weight, abdominal bristles and wing length) in Drosophila melanogaster. Linear and polynomial models were fitted for the regressions of a character in offspring on both parents. It is demonstrated that responses by the characters to selection predicted by the nonlinear regressions may differ substantially from those predicted by the linear regressions. This is true even, and especially, if selection is weak. The realized heritability for a character under selection is shown to be determined not only by the offspring-parent regression but also by the distribution of the character and by the form and strength of selection.

Analysis of Variance↗
PubMed1994

Additive-multiplicative approximation of genotype-environment interaction.

A model of genotype-environment interaction in quantitative traits is considered. The model represents an expansion of the traditional additive (first degree polynomial) approximation of genotypic and environmental effects to a second degree polynomial incorporating a multiplicative term besides the additive terms. An experimental evaluation of the model is suggested and applied to a trait in Drosophila melanogaster. The environmental variance of a genotype in the model is shown to be a function of the genotypic value: it is a convex parabola. The broad sense heritability in a population depends not only on the genotypic and environmental variances, but also on the position of the genotypic mean in the population relative to the minimum of the parabola. It is demonstrated, using the model, that G x E interaction may cause a substantial non-linearity in offspring-parent regression and a reversed response to directional selection. It is also shown that directional selection may be accompanied by an increase in the heritability.

Animals↗
PubMed1992

Pleiotropy and multilocus polymorphisms.

It is demonstrated that systems of two pleiotropically related characters controlled by additive diallelic loci can maintain under Gaussian stabilizing selection a stable polymorphism in more than two loci. It is also shown that such systems may have multiple stable polymorphic equilibria. Stabilizing selection generates negative linkage disequilibrium, as a result of which the equilibrium phenotypic variances are quite low, even though the level of allelic polymorphisms can be very high. Consequently, large amounts of additive genetic variation can be hidden in populations at equilibrium under stabilizing selection on pleiotropically related characters.

Genetic Linkage↗
PubMed1989

Age differences between distributions of genotypes among pregnant women: evidence of fertility selection.

The number of children produced by a modern woman is usually below her total reproductive capacity and is determined by circumstances other than natural selection. It is, therefore, practically impossible to detect differences in natural fertilities associated with different types (e.g. phenotypes, genotypes) of women. This does not mean, however, that natural selection at the reproductive level cannot at all be detected today. If women of a particular type have high natural fertility, this usually means that they reproduce (become pregnant) at a higher rate than women of a type with lower natural fertility. Hence, when there is a limit on the number of children, women of the first type will reach the limit at an earlier age than women of the second type. As a result, types that have a higher natural fertility should be overrepresented among pregnant women of younger ages and, consequently, underrepresented among older ones, as compared to types with a lower natural fertility. Based on this notion, a model of age-related differences between distributions of types among pregnant women is suggested. The model is applied to data on MNSs-blood group and PGM1 (phosphoglucomutase) types in a sample of pregnant women and an evidence of natural selection at the reproduction level associated with these genetic markers is obtained.

Adolescent↗
PubMed1989

Genotypic variation for a quantitative character maintained under stabilizing selection without mutations: epistasis.

A model of the gene action on a quantitative character is suggested. The model takes into account epistasis by combining multiplicative with the traditional additive approximation of the action of loci. It is demonstrated on the basis of this model that a high level of genotypic variation can be maintained in a population for a quantitative character under stabilizing selection in the absence of mutations, if there is epistasis. It is also shown that a large amount of additive variation as well as high heritability can be "hidden" in such a population and "released" if stabilizing selection is relaxed.

Computer Simulation↗
PubMed1988

Processes of pair formation leading to assortative mating in biological populations: dynamic interaction model.

A model of pair formation that treats mating between two individuals as a dynamic process rather than an instant event is suggested. A number of cases corresponding to polygamous and monogamous matings of individuals are considered. The individual mating preferences are represented in the model by a set of "compatibility probabilities." It is shown that the mating pattern (the distribution of characters among mating pairs) established in a population as a result of the process of pair formation does not uniquely reflect the pattern of mating preferences. Quite different mating patterns may occur in populations with very similar mating preferences, as well as similar mating patterns may occur in populations with different individual mating preferences. The model demonstrates that not only mating preferences of individuals but also specific mechanisms of pair formation play an important role in determining the mating pattern of a population.

Animals↗