Showing papers on "Mutation (genetic algorithm) published in 1995"

A measure of population subdivision based on microsatellite allele frequencies.

Abstract: A new measure of the extent of population subdivision as inferred from allele frequencies at microsatellite loci is proposed and tested with computer simulations. This measure, called R(ST), is analogous to Wright's F(ST) in representing the proportion of variation between populations. It differs in taking explicit account of the mutation process at microsatellite loci, for which a generalized stepwise mutation model appears appropriate. Simulations of subdivided populations were carried out to test the performance of R(ST) and F(ST). It was found that, under the generalized stepwise mutation model, R(ST) provides relatively unbiased estimates of migration rates and times of population divergence while F(ST) tends to show too much population similarity, particularly when migration rates are low or divergence times are long [corrected].

An introduction to genetic algorithms for electromagnetics

Abstract: This article is a tutorial on using genetic algorithms to optimize antenna and scattering patterns. Genetic algorithms are "global" numerical-optimization methods, patterned after the natural processes of genetic recombination and evolution. The algorithms encode each parameter into binary sequences, called a gene, and a set of genes is a chromosome. These chromosomes undergo natural selection, mating, and mutation, to arrive at the final optimal solution. After providing a detailed explanation of how a genetic algorithm works, and a listing of a MATLAB code, the article presents three examples. These examples demonstrate how to optimize antenna patterns and backscattering radar-cross-section patterns. Finally, additional details about algorithm design are given. >

Genetic absolute dating based on microsatellites and the origin of modern humans.

Abstract: We introduce a new genetic distance for microsatellite loci, incorporating features of the stepwise mutation model, and test its performance on microsatellite polymorphisms in humans, chimpanzees, and gorillas. We find that it performs well in determining the relations among the primates, but less well than other distance measures (not based on the stepwise mutation model) in determining the relations among closely related human populations. However, the deepest split in the human phylogeny seems to be accurately reconstructed by the new distance and separates African and non-African populations. The new distance is independent of population size and therefore allows direct estimation of divergence times if the mutation rate is known. Based on 30 microsatellite polymorphisms and a recently reported average mutation rate of 5.6 x 10(-4) at 15 dinucleotide microsatellites, we estimate that the deepest split in the human phylogeny occurred about 156,000 years ago. Unlike most previous estimates, ours requires no external calibration of the rate of molecular evolution. We can use such calibrations, however, to test our estimate.

Evolution and extinction in a changing environment: a quantitative-genetic analysis.

Abstract: Because of the ubiquity of genetic variation for quantitative traits, virtually all populations have some capacity to respond evolutionarily to selective challenges. However, natural selection imposes demographic costs on a population, and if these costs are sufficiently large, the likelihood of extinction will be high. We consider how the mean time to extinction depends on selective pressures (rate and stochasticity of environmental change, and strength of selection), population parameters (carrying capacity, and reproductive capacity), and genetics (rate of polygenic mutation). We assume that in a randomly mating, finite population subject to density-dependent population growth, individual fitness is determined by a single quantitative-genetic character under Gaussian stabilizing selection with the optimum phenotype exhibiting directional change, 'or random fluctuations, or both. The quantitative trait is de- termined by a finite number of freely recombining, mutationally equivalent, additive loci. The dynamics of evolution and extinction are investigated, assuming that the population is initially under mutation-selection-drift balance. Under this model, in a directionally changing environment, the mean phenotype lags behind the optimum, but on the average evolves parallel to it. The magnitude of the lag determines the vulnerability to extinction. In finite populations, stochastic variation in the genetic variance can be quite pronounced, and bottlenecks in the genetic variance temporarily can impair the population's adaptive capacity enough to cause extinction when it would otherwise be unlikely in an effectively infinite population. We find that maximum sustainable rates of evolution or, equivalently, critical rates of environmental change, may be considerably less than 10% of a phenotypic standard deviation per generation.

Coalescents and Genealogical Structure Under Neutrality

Abstract: Genealogical or coalescent methods have proved very useful in interpreting and understanding a wide range of population genetic data. Our aim is to illustrate some of the central ideas behind this approach. The primary focus is genealogy in neutral genetic models, for which the effects of demography can be separated from those of mutation. We describe the coalescent for panmictic populations of fixed size, and its extensions to incorporate various assumptions about variation in population size and nonrandom mating caused by geographical population subdivision. The effects of such genealogical structure on patterns and correlations in genetic data are discussed. An urn model is useful for simulating samples at loci with complex mutation mechanisms. We give two applications of the genealogical approach. The first concerns methods for estimating the mutation rate from infinitely-many-sites data, and the second relates to inference about recent common ancestors and population history.

Refined genetic algorithm-economic dispatch example

Abstract: A genetic-based algorithm is used to solve a power system economic dispatch (ED) problem. The algorithm utilizes payoff information of perspective solutions to evaluate optimality. Thus, the constraints of classical LaGrangian techniques on unit curves are eliminated. Using an economic dispatch problem as a basis for comparison, several different techniques which enhance program efficiency and accuracy, such as mutation prediction, elitism, interval approximation and penalty factors, are explored. Two unique genetic algorithms are also compared. The results are verified for a sample problem using a classical technique. >

Genetic Algorithms for Estimation Problems With Multiple Optima, Nondifferentiability, and Other Irregular Features

Abstract: The genetic algorithm is examined as a method for solving optimization problems in econometric estimation. It does not restrict either the form or regularity of the objective function, allows a reasonably large parameter space, and does not rely on a point-to-point search. The performance is evaluated through two sets of experiments on standard test problems as well as econometric problems from the literature. First, alternative genetic algorithms that vary over mutation and crossover rates, population sizes, and other features are contrasted. Second, the genetic algorithm is compared to Nelder–Mead simplex, simulated annealing, adaptive random search, and MSCORE.

Amplification‐Refractory Mutation System (ARMS) Analysis of Point Mutations

Abstract: The amplification-refractory mutation system (ARMS) is a simple method for detecting any mutation involving single base changes or small deletions. ARMS is based on the use of sequence-specific PCR primers that allow amplification of test DNA only when the target allele is contained within the sample. Following an ARMS reaction the presence or absence of a PCR product is diagnostic for the presence or absence of the target allele. The protocols detailed here outline methods that can be used to analyze human genomic DNA for one or more mutations. The Basic Protocol describes the development and application of an ARMS test for a single mutation; the Alternate Protocol extends this to multiplex ARMS for the analysis of two or more mutations. The Support Protocol describes a rapid DNA extraction method from blood or mouthwash samples that yields DNA compatible with the type of tests described. The amplification-refractory mutation system (ARMS) is a simple method for detecting any mutation involving single base change The amplification-refractory mutation system (ARMS) is a simple method for detecting any mutation involving single base change.

A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess

Abstract: A mutation in the HSD11B2 gene has been discovered in a consanguineous Iranian family with three sibs suffering from Apparent Mineralocorticoid Excess (AME). Sequence data demonstrate a C to T transition resulting in an R337C mutation.

On the Adaptation of Arbitrary Normal Mutation Distributions in Evolution Strategies: The Generating Set Adaptation

Abstract: A new adaptation scheme for adapting arbitrary normal mutation distributions in evolution strategies is introduced. It can adapt correct scaling and correlations between object parameters. Furthermore, it is independent of any rotation of the objective function and reliably adapts mutation distributions corresponding to hyperellipsoids with high axis ratio. In simulations, the generating set adaptation is compared to two other schemes which also can produce non axis-parallel mutation ellipsoids. It turns out to be the only adaptation scheme which is completely independent of the chosen coordinate system.

A mitochondrial DNA clone is associated with increased risk for Alzheimer disease

Abstract: Severe mitochondrial genetic mutations lead to early degeneration of specific human tissues; milder mitochondrial mutations may cause degeneration at a later point in life. A mutation at position 4336 was reported to occur at increased frequency in individuals with Alzheimer disease (AD) and Parkinson disease [Shoffner, J. M., Brown, M. D., Torroni, A., Lott, M. T., Cabell, M. F., Mirra, S. S., Beal, M. F., Yang, C.-C., Gearing, M., Salvo, R., Watts, R. L., Juncos, J. L., Hansen, L. A., Crain, B. J., Fayad, M., Reckord, C. L. & Wallace, D. C. (1993) Genomics 17, 171-184]. We have investigated the notion that this mutation leads to excess risk of AD by using a case-control study design of 72 AD autopsies and 296 race- and age-matched controls. The 4336G mutation occurred at higher frequency in AD autopsies than age-matched controls, a statistically significant difference. Evolutionary analysis of mtDNAs bearing the 4336G mutation indicated they were more closely related to each other than to other mtDNAs, consistent with the model of a single origin for this mutation. The tight evolutionary relatedness and homoplasmy of mtDNAs that confer elevated risk for a late-onset disease contrast strikingly with the distant relatedness and heteroplasmy of mitochondrial genomes that cause early-onset disease. The dichotomy can be explained by a lack of selection against mutations that confer a phenotype at advanced age during most of the evolution of humans. We estimate that approximately 1.5 million Caucasians in the United States bear the 4336G mutation and are at significantly increased risk of developing mitochondrial AD in their lifetime. A mechanism for 4336G-mediated cell death is proposed.

The molecular basis of homocystinuria due to cystathionine beta-synthase deficiency in Italian families, and report of four novel mutations.

Abstract: Four new mutations in the cystathionine beta-synthase (CBS) gene have been identified in Italian patients with homocystinuria. The first mutation is a G-to-A transition at base 374 in exon 3, causing an arginine-to-glutamic acid substitution at position 125 of the protein (R125Q). This mutation has been found in homozygosity in a patient partially responsive to pyridoxine treatment. The second mutation is a C-to-T transition at base 770 in exon 7, causing a threonine-to-methionine substitution at amino acid 257 of the protein (T257M). This mutation has been observed in homozygosity in a patient nonresponsive to the cofactor treatment. The third mutation, found in heterozygosity in a patient responsive to pyridoxine treatment, is an insertion of 68 bp in exon 8 at base 844, which introduces a premature termination codon. The fourth mutation is C-to-T transition in exon 2 at base 262, causing a proline-to-serine substitution at position 88 of the protein (P88S). This mutation is carried on a single allele in three affected sisters responsive to the cofactor treatment. In addition, six previously reported mutations (A114V, E131D, P145L, I278T, G307S, and A1224-2C) have been tested in 14 independent Italian families. Mutations A114V and I278T are carried by three and by seven independent alleles, respectively. The other four mutations--including G307S and A1224-2C, common among northern European patients--have not been detected.

A missense mutation in the glucagon receptor gene is associated with non-insulin-dependent diabetes mellitus.

Abstract: Non–insulin–dependent diabetes mellitus (NIDDM) affects about 5% of the world population. The disease presents a polygenic mode of inheritance, but mechanisms and genes involved in late–onset NIDDM are largely unknown. We report the association of a single heterozygous Gly to Ser missense mutation in the glucagon receptor gene with late–onset NIDDM. This mutation was highly associated with NIDDM in a pooled set of French and Sardinian patients (χ2= 14.4, P=0.0001) and showed some evidence for linkage to diabetes in 18 sibships from 9 French pedigrees (χ2=6.63, P<0.01). Receptor binding studies using cultured cells expressing the Gly40Ser mutation demonstrate that this mutation results in a receptor which binds glucagon with a three–fold lower affinity compared to the wild type receptor.

p53 gene mutations and photocarcinogenesis

Abstract: Nonmelanoma skin cancers (NMSC); are the most common type of human cancer./ It is estimated that 800000 new cases of skin cancer will be diagnosed this year alone.' Epidemiological, clinical and recent molecular studies have implicated UV radiation present in sunlight as the major etiological agent in human skin cancer.'\" Experimental studies in laboratory animals have demonstrated that wavelengths in the UV-B region (280-320 nm) are responsible for the carcinogenic effects of solar The incidence of skin cancer is reported to have increased and is predicted to increase further largely due to an increase in \"recreational\" exposure to sunlight as well as a result of the depletion of the stratospheric ozone layer./ Further depletion of the ozone layer can result in greater amounts of UVB radiation penetrating the earth's atmosphere. which in turn may result in a further increase in the incidence of skin cancer.2 Skin carcinogenesis is a complex process that involves aberration of various genes. including protooncogenes and tumor suppressor genes. The carcinogenic process is initiated when target cells are exposed to agents that damage the DNA, which then leads to a sequence of events. including induction or overexpression of various genes. cell cycle arrest, DNA repair, apoptosis or proliferation, mutation and finally neoplastic transformation. Research performed during the last few years has provided new insights into the role of oncogenes and tumor suppressor genes in the pathogenesis of human and mouse skin cancers. Although mutations in rus oncogenes have been implicated in UV carcinogenesis, they do not appear to be as prevalent as mutations in the p53 tumor suppressor gene. In human skin cancers and UVinduced mouse skin cancers, mutations in rus oncogenes occur at 1040% frequency,/'-'2 whereas mutations in the p53 gene occur at 60-1 00% f r e q ~ e n c y . ' , \" , ' ~ . ~ ~ ~ Additionally, Suarez et and Sato rt examined skin tumors from xeroderma pigmentosum (XP) patients and found a very low frequency of ru.T mutation. Because the risk of skin cancer

Rapid deoxyribonucleic acid analysis by allele-specific polymerase chain reaction for detection of mutations in the steroid 21-hydroxylase gene.

Abstract: Rapid DNA analysis based on allele-specific polymerase chain reaction (PCR) using mutation site-specific primers was developed to detect mutations in the CYP21 gene known to cause steroid 21-hydroxylase deficiency. In contrast to the previous method, in which PCR of genomic DNA was followed by dot blot analysis with radioactive probes and multiple rounds of stripping and reprobing for each of the 8 most common mutation sites, the results using this new method were immediately visualized after the PCR run by ethidium bromide-stained agarose gel electrophoresis. Using allele-specific PCR, mutation(s) were identified on 148 affected chromosomes out of 160 tested. Although mutation(s) were identified on only one chromosome of 11 of these patients, their parents showed a consistent pattern on DNA analysis. The only exception was that in one family, in which the parents each had a detectable mutation, a mutation was detected on only one allele of the patient. Most likely there is a mutation in the patient's other allele that could have arisen de novo or was inherited from the parent and was not evident in the transmitting parent's phenotype. When compared with the dot blot procedure, allele-specific PCR is more rapid, less labor-intensive, and avoids the use of radioactivity.

Mutation and Adaptation: The Directed Mutation Controversy in Evolutionary Perspective

Abstract: A central tenet of evolutionary theory is that mutation is random with respect to its adaptive consequences for individual organisms; that is, the production of variation precedes and does not cause adaptation. Several recent experimental reports have challenged this tenet by suggesting that bacteria (and yeast) "may have mechanisms for choosing which mutations will occur" (6, p. 142). The phenomenon of nonrandom mutation claimed in these experiments was initially called "directed mutation" but has undergone several name changes during its brief and controversial history. The directed mutation hypothesis has not fared well; many examples of apparently directed mutation have been rejected in favor of more conventional explanations, and several reviews questioning the validity of directed mutation have appeared (53, 54, 59-61, 79, 80). Nonetheless, directed mutation has recently been reincarnated under the confusing label "adaptive mutation" (5, 23, 24, 27, 35, 74). Here we discuss the many experimental and conceptual problems with directed/adaptive mutation, and we argue that the most plausible molecular models proposed to explain "adaptive mutation" are entirely consistent with the modem Darwinian concept of adaptation by natural selection on randomly occurring variation. In the concluding section of the paper, we discuss the importance of an informed evolutionary approach in the study of the potential adaptive significance of mutational phenomena. Knowledge of the molecular bases of muta

The ncl-1 gene and genetic mosaics of Caenorhabditis elegans.

Abstract: A ncl-1 mutation results in enlarged nucleoli, which can be detected in nearly all cells of living animals by Nomarski microscopy. Spontaneous mitotic loss of a ncl-1(+)-containing free duplication in an otherwise homozygous ncl-1 mutant animal results in mosaicism for ncl-1 expression, and the patterns of mosaicism lead us to conclude that ncl-1 acts cell autonomously. The probability of mitotic loss of the duplication sDp3 is approximately constant over many cell divisions. About 60% of the losses of sDp3 at the first embryonic cell division involve nondisjunction. Frequencies of mitotic loss of different ncl-1(+)-bearing free duplications varied over a 200-fold range. The frequencies of mitotic loss were enhanced by a chromosomal him-10 mutation. We have used ncl-1 as a cell autonomous marker in the mosaic analysis of dpy-1 and lin-37. The focus of action of dpy-1 is in hypodermis. A mutation in lin-37 combined with a mutation in another gene results in a synthetic multivulva phenotype. We show that lin-37 acts cell nonautonomously and propose that it plays a role, along with the previously studied gene lin-15, in the generation of an intercellular signal by hyp7 that represses vulval development.

Mechanisms of DNA expansion.

Abstract: Unstable transmission of repeating segments in genes is now recognized as a new class of mutations causing human disease Genetic instability observed in disease is termed an "expansion mutation" when the mutation is an increase in the copy number of a repeated unit, commonly a di- or trinucleotide While the expansion mutation is well characterized in disease, the mechanism by which expansion occurs is not clear This article focuses on physical properties of expansion at repeating nucleotides that may provide clues to the mechanism Both biochemical and genetic data indicate that DNA structure is part of the mechanism and the underlying cause for expansion

Insulin receptor substrate-1 gene mutations in NIDDM; implications for the study of polygenic disease

Abstract: Variations in the coding regions of the insulin receptor substrate-1 (IRS-1) gene have recently been suggested to contribute to the susceptibility of non-insulin-dependent diabetes mellitus (NIDDM). The purpose of this study was to examine the role of the IRS-1 missense mutations at codons 972 (glycine to arginine) and 513 (alanine to proline) in two diverse populations from South India and Finland at high risk for NIDDM. DNA was amplified and digested with restriction enzymes BstN1 to detect the codon 972 mutation and Dra III to detect the codon 513 mutation. The codon 513 mutation was not found in the study subjects. The codon 972 mutation was present in 10.3% of 126 middle-aged NIDDM subjects and 5.3% of 95 matched control subjects in the South Indians (p = 0.17). In elderly Finnish subjects the frequency of the mutation was 7.5% in 40 NIDDM subjects and 7% in 42 matched control subjects. The frequency of codon 972 mutation in the South Indian NIDDM subjects was very similar to the two previously published studies in Danish and French subjects although each study individually fails to reach conventional levels of significance. The data from all four ethnic groups were analysed together after ascertaining that significant heterogeneity did not exist between the studies. Overall, the frequency of the codon 972 mutation is found in 10.7% NIDDM subjects and 5.8% control subjects (p = 0.02). These studies suggest that the codon 972 mutation of the IRS-1 gene might act as a susceptibility gene predisposing to NIDDM in certain ethnic groups.

A common FGFR3 gene mutation in hypochondroplasia

Abstract: Hypochondroplasia is a genetic disorder of disproportionate short stature. Linkage analysis provisionally placed hypochondroplasia in the chromosome 4p 16.3 region, a location to which the FGFR3 gene has been mapped. The genotyping of a three-generation family showed no recombinants between the hypochondroplasia phenotype and three highly polymorphic markers flanking the FGFR3 gene. Mutation analysis was performed by RT-PCR and direct sequencing. Primers covering most of the coding sequence of the FGFR3 gene were used for RT-PCR of FGFR3 mRNA and PCR amplification of genomic DNA. A C-->A transversion was detected in nucleotide 1659 predicting an N540K substitution in exon 11 which encodes part of the TK1 domain. The same mutation was found in an individual suspected to be an achondroplasia/hypochondroplasia compound phenotype and affected individuals from three other unrelated families. A second mutation, a C-->G transversion, also in nucleotide 1659 was detected in all affected individuals of another family. The latter also predicts an N540K substitution. These findings establish that a common mutation in the FGFR3 gene underlies hypochondroplasia.