Autoantibodies against thyroid hormones can lead to an erroneous diagnosis and potentially harmful treatment.
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Aged↗
Biomedical subjects
A Caballero
Publications and source records attributed to A Caballero.
Plasma lipoprotein(a) levels are not influenced by glycemic control in type 1 diabetes.
OBJECTIVE: To determine the influence of glycemic control improvement with intensive therapy on lipoprotein(a) [Lp(a)] concentrations in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 105 poorly controlled type 1 diabetic patients (60 men, 45 women) without diabetic complications participated in a longitudinal study performed in a tertiary referral center, to compare lipid, lipoprotein, and Lp(a) levels before and after 3 months of intensive therapy with multiple insulin doses. Lp(a) levels were measured by the Terumo method. Differences between the two periods were assessed by the paired t test and Wilcoxon's test. RESULTS: After 3 months of intensive therapy, all patients exhibited improved glycemic control. HbA1c decreased from 8.9 +/- 2.4 to 6.5 +/- 1.6% (P < 0.0001), being < or =6% in 47% of patients. However, although a more favorable lipoprotein profile was obtained, no changes in Lp(a) concentrations were observed in the whole group of patients (16.7 +/- 17.3 vs. 17.2 +/- 17.7 mg/dl) or in patients with baseline Lp(a) levels above 30 mg/dl (47.1 +/- 14.8 vs. 47.4 +/- 18.9 mg/dl) or below 30 mg/dl (9.6 +/- 7.3 vs. 10.2 +/- 6.7 mg/dl). In addition, patients reaching HbA1c < or =6 or >6% presented similar Lp(a) levels (19.7 +/- 18.0 vs. 15.0 +/- 17.4 mg/dl), and changes in Lp(a) did not correlate with those observed in HbA1c. CONCLUSIONS: These data demonstrate that the improvement of glycemic control does not influence plasma Lp(a) concentrations in type 1 diabetic patients independently of baseline Lp(a) levels and the degree of glycemic control.
Adult↗
Inferences on genome-wide deleterious mutation rates in inbred populations of Drosophila and mice.
A theoretical analysis was carried out on the mutation load observed in long-maintained inbred lines from two experiments with Drosophila and mice. The rate of decline in fitness and its sampling distribution were predicted for both experiments using Monte Carlo simulation with a range of mutational parameters and models. The predicted rates of change in fitness were compared to the empirical observed rates, which were close to zero. The classical hypothesis of many deleterious mutations (about one event per genome per generation) of small effect (1-2%) resulting in a mutation pressure for fitness of about 1% per generation is incompatible with the data. Recent estimates suggesting an overall mutation pressure for fitness traits of about 0.1% are, however, compatible with the observed load.
Animals↗
Genomic mutation rates for lifetime reproductive output and lifespan in Caenorhabditis elegans.
Theory concerning the evolution of sex and recombination and mutation load relies on information on rates and distributions of effects of deleterious mutations. Direct information on the genomic mutation rate in Drosophila implies that an accumulation of mildly deleterious mutations reduces viability of populations by at least 1% per generation. We carried out an experiment to measure the deleterious mutation rate in Caenorhabditis elegans, in which independent sublines were maintained with one hermaphrodite parent per generation, conditions that minimize the opportunity for natural selection and lead to random fixation of deleterious mutations. After 60 generations of mutation accumulation, negligible changes in mean reproductive output and lifespan occurred, but the genetic variance increased at rates typical for life history traits in other species. The estimated deleterious mutation rate per haploid genome for fitness, U, was 0.0026, a figure two orders of magnitude smaller than previously measured for viability in Drosophila.
Animals↗
Spontaneous disappearance of Elschnig pearls after neodymium:YAG laser posterior capsulotomy.
Posterior capsule opacification (PCO) from Elschnig pearl formation is a common complication of extracapsular cataract extraction. After PCO treatment by neodymium:YAG (Nd:YAG) laser posterior capsulotomy, Elschnig pearls may undergo hyperproliferation at the edge of the capsulotomy, which may close it. We have seen six eyes in five patients who presented with spontaneous disappearance of Elschnig pearls, resulting in a perfectly clear posterior capsule several years after an Nd:YAG posterior capsulotomy. Possible causes include (1) falling of pearls into the vitreous through the capsulotomy; (2) phagocytosis of pearls by macrophages; (3) cell death by apoptosis.
Aged↗
Average dominance for polygenes: drawbacks of regression estimates.
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Animals↗
Does preconceptional counselling in diabetic women influence perinatal outcome?
We aimed to assess the impact of a preconceptional clinic (PC) on the perinatal outcome (PO) of diabetic pregnancies attended in our centre. We studied 185 pregnancies attended in the 1986-1996 period (152 in women with insulin dependent diabetes mellitus (IDDM) and 33 with non insulin-dependent diabetes mellitus (NIDDM)) and we analysed the perinatal outcome for both mother and fetus. Sixty-six women (36.1%) had enrolled in the PC, 41.4% for IDDM and 9.1% for NIDDM pregnancies, p < 0.01. First pregnancy HbA1c (in SD around the mean) was 3.98 +/- 3.00 in non-attenders (NA) vs 2.57 +/- 2.41 in attenders (A), p < 0.01. The final HbA1c was in the normal range in both groups. D-R class according to White classification was 33.0% for NA vs 54.5% for A, p < 0.01. There were no differences in the rates of abortion and major malformations (8.8% NA vs 3.6% A, ns). Both groups differed in the rate of cesarean sections (54.9% NA vs 71.0% A, p < 0.05) and in the rate of small for gestational age infants (SGA) (8.7% NA vs 1.8% A, p < 0.05). There were no differences between groups in maternal or neonatal outcomes. In this group of diabetic women with a moderate although less than optimal metabolic control at the beginning of pregnancy, the impact of PC on PO is less evident than described.
Adult↗
A note on the change in gene frequency of a selected allele in partial full-sib mating populations.
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Alleles↗
Selection response in finite populations.
Formulae were derived to predict genetic response under various selection schemes assuming an infinitesimal model. Account was taken of genetic drift, gametic (linkage) disequilibrium (Bulmer effect), inbreeding depression, common environmental variance, and both initial segregating variance within families (sigma AW02) and mutational (sigma M2) variance. The cumulative response to selection until generation t(CRt) can be approximated as [equation: see text] where Ne is the effective population size, sigma AW infinity 2 = Ne sigma M2 is the genetic variance within families at the steady state (or one-half the genic variance, which is unaffected by selection), and D is the inbreeding depression per unit of inbreeding. R0 is the selection response at generation 0 assuming preselection so that the linkage disequilibrium effect has stabilized. beta is the derivative of the logarithm of the asymptotic response with respect to the logarithm of the within-family genetic variance, i.e., their relative rate of change. R0 is the major determinant of the short term selection response, but sigma Me2 Ne and beta are also important for the long term. A selection method of high accuracy using family information gives a small Ne and will lead to a larger response in the short term and a smaller response in the long term, utilizing mutation less efficiently.
Animals↗
Long-term decentration of intraocular lenses implanted with envelope capsulotomy and continuous curvilinear capsulotomy: a comparative study.
Intraocular lens (IOL) decentration was studied in a series of 569 consecutive eyes that had extracapsular cataract extraction (ECCE) and posterior chamber IOL implantation. In 383 of the eyes, an envelope capsulotomy (EC) was performed; in 186, a continuous curvilinear capsulotomy (CCC). In 33 eyes, the anterior capsule had one radial tear that reached the lens equator. In all eyes, IOL decentration was determined more than six months after surgery. Mean IOL decentration was 0.42 +/- 0.02 mm in the EC eyes and 0.27 +/- 0.01 mm in the CCC eyes (P < .001). In the CCC eyes, mean IOL decentration was 0.23 +/- 0.02 mm when the anterior capsule had no tears and 0.42 +/- 0.06 mm when it had one radial tear (P < .01). In the EC eyes, mean decentration was less with lenses with a total diameter of 11.0 mm or less and 360 degree circular loops (compressible disc and circular open-loop lenses) than with C- and J-loop lenses with a total length of 13.5 mm to 14.0 mm. With the C- and J-loop lenses in all three capsulotomy groups, mean decentration was related to the presence and number of tears in the anterior capsule: 0.58 mm in the EC eyes, 0.41 mm in the CCC with tear eyes, and 0.23 mm in the CCC without tear eyes. A similar relationship was seen with the bag-implanted lenses: 0.48 mm in the EC eyes, 0.28 mm in the CCC with tear eyes; 0.22 mm in the CCC without tear eyes.
Cataract Extraction↗
Accumulation of mutations affecting body weight in inbred mouse lines.
The variation from spontaneous mutations for 6-week body weight in the mouse was estimated by selection from a cross of two inbred sublines, C57BL/6 and C57BL/10, separated about 50 years previously from the same inbred line. Selection was practised high and low for 12 generations from the F2, followed by one generation of relaxation. The lines diverged by approximately 1.7 g or 0.7 sd. The additive genetic variance was estimated in the F2 by restricted maximum likelihood and from the selection response, and from this variance the mutational heritability hM2 was estimated using the number of generations since divergence. Estimates of hM2 range from 0.08 to 0.10% depending on the method of analysis. These estimates are similar to those found for other species, but lower than other estimates for the mouse. It is concluded that substantial natural and, perhaps, artificial selection operated during the maintenance of the sublines.
Animals↗
Response to selection from new mutation and effective size of partially inbred populations. II. Experiments with Drosophila melanogaster.
Divergent artificial selection for abdominal bristle number in Drosophila melanogaster has been carried out starting from a genetically homogeneous base population. Lines with two different systems of mating, random (P lines) or between full sibs whenever possible (about 50%), random otherwise (I lines) were compared. Responses after 40 generations of selection were mostly due to one or two mutations of large effect (0.2 to 2 phenotypic standard deviations) per line. Ten mutations affecting the selected trait were individually studied (five lethal and five non-lethal, these being predominantly additive). These mutations satisfactorily explain the response attained, although some minor mutations may also be involved. No evidence of epistasis for bristle number was found. The average final divergence was 57% larger in the P lines, but it was mostly due to lethals or highly deleterious mutations. Thus, after relaxation of selection, the ranking reversed and the mean divergence became significantly larger in the I lines (14%). Analysis of inbreeding showed that the very small amount of variation created by spontaneous mutations (a heritability for the selected trait of about 3%) was responsible for a reduction in the effective size of about 50% in the I lines (relative to the case with random selection), but only about 10% in the P lines. Mutational heritabilities estimated from the response to selection (0.05-0.18%) were within the range usually found for this trait in previous experiments. REML estimates account for correlations between relatives, and were much larger in those lines where the response was due to lethal mutations, as these do not contribute to response after reaching maximum frequency.
Animals↗
On the effective size of populations with separate sexes, with particular reference to sex-linked genes.
Inconsistencies between equations for the effective population size of populations with separate sexes obtained by two different approaches are explained. One approach, which is the most common in the literature, is based on the assumption that the sex of the progeny cannot be identified. The second approach incorporates identification of the sexes of both parents and offspring. The approaches lead to identical expressions for effective size under some situations, such as Poisson distributions of offspring numbers. In general, however, the first approach gives incorrect answers, which become particularly severe for sex-linked genes, because then only numbers of daughters of males are relevant. Predictions of the effective size for sex-linked genes are illustrated for different systems of mating.
Animals↗
Effective size of populations under selection.
Equations to approximate the effective size (Ne) of populations under continued selection are obtained that include the possibility of partial full-sib mating and other systems such as assortative mating. The general equation for the case of equal number of sexes and constant number of breeding individuals (N) is Ne = 4N/[2(1 - alpha I) + (Sk2 + 4Q2C2) (1 + alpha I + 2 alpha O)], where Sk2 is the variance of family size due to sampling without selection, C2 is the variance of selective advantages among families (the squared coefficient of variation of the expected number of offspring per family), alpha I is the deviation from Hardy-Weinberg proportions, alpha O is the correlation between genes of male and female parents, and Q2 is the term accounting for the cumulative effect of selection on an inherited trait. This is obtained as Q = 2/[2 - G(1 + r)], where G is the remaining proportion of genetic variance in selected individuals and r is the correlation of the expected selective values of male and female parents. The method is also extended to the general case of different numbers of male and female parents. The predictive value of the formulae is tested under a model of truncation selection with the infinitesimal model of gene effects, where C2 and G are a function of the selection intensity, the heritability and the intraclass correlation of sibs. Under random mating r = alpha I = -1/(N - 1) and alpha O = 0. Under partial full-sib mating with an average proportion beta of full-sib matings per generation, r approximately beta and alpha O approximately alpha I approximately beta/(4 - 3 beta). The prediction equation is compared to other approximations based on the long-term contributions of ancestors to descendants. Finally, based on the approach followed, a system of mating (compensatory mating) is proposed to reduce rates of inbreeding without loss of response in selection programs in which selected individuals from the largest families are mated to those from the smallest families.
Animals↗
Developments in the prediction of effective population size.
Effective population size is a key parameter in evolutionary and quantitative genetics because it measures the rate of genetic drift and inbreeding. Predictive equations of effective size under a range of circumstances and some of their implications are reviewed in this paper. Derivations are made for the simplest cases, and inter-relations between different formulae and methods are discussed.
Animals↗
A pleiotropic nonadditive model of variation in quantitative traits.
A model of mutation-selection-drift balance incorporating pleiotropic and dominance effects of new mutations on quantitative traits and fitness is investigated and used to predict the amount and nature of genetic variation maintained in segregating populations. The model is based on recent information on the joint distribution of mutant effects on bristle traits and fitness in Drosophila melanogaster from experiments on the accumulation of spontaneous and P element-induced mutations. These experiments suggest a leptokurtic distribution of effects with an intermediate correlation between effects on the trait and fitness. Mutants of large effect tend to be partially recessive while those with smaller effect are on average additive, but apparently with very variable gene action. The model is parameterized with two different sets of information derived from P element insertion and spontaneous mutation data, though the latter are not fully known. They differ in the number of mutations per generation which is assumed to affect the trait. Predictions of the variance maintained for bristle number assuming parameters derived from effects of P element insertions, in which the proportion of mutations with an effect on the trait is small, fit reasonably well with experimental observations. The equilibrium genetic variance is nearly independent of the degree of dominance of new mutations. Heritabilities of between 0.4 and 0.6 are predicted with population sizes from 10(4) to 10(6), and most of the variance for the metric trait in segregating population is due to a small proportion of mutations (about 1% of the total number) with neutral or nearly neutral effects on fitness and intermediate effects on the trait (0.1-0.5 sigma P).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Accounting for bias in estimates of the rate of polygenic mutation.
Experimental data on the rate of response to artificial selection in initially inbred lines or the rate of divergence among inbred sublines can be used to estimate the rate of increase in variance of quantitative traits from new mutations. So far estimates have been based on the infinitesimal model of many genes with small additive effects which imply a rate of increase in heritability for Drosophila melanogaster bristle number traits of about 0.1% per generation. Such estimates are biased because mutants tend to have large effects, to have non-additive gene action, and to be deleterious. Here, recent information on the distribution of effects of new mutations on Drosophila melanogaster bristle number and viability is used to infer the direction and magnitude of this bias. The infinitesimal model tends to underestimate the mutational variance, typically by a factor of about 3, but this factor depends on the experimental design. Averages of revised estimates, accounting for this bias, of the per generation increment in heritability from mutation are 0.36% and 0.21% for abdominal and sternopleural bristle number, respectively, in experiments involving M strains, and 1.4% and 0.7% for abdominals and sternopleurals, respectively, in P strains.
Animals↗
The time of detection of recessive visible genes with non-random mating.
Expressions for the probability and average time of detection of a recessive visible gene in populations where there is partial selfing or partial full-sib mating are presented. A small increase in the proportion of inbred matings greatly reduces the average time until detection and increases the proportion detected. Unless the proportion of inbred matings or the population size is very small, the time and proportion detected are approximately independent of the population size.
Crosses, Genetic↗