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301.
The determination of empirical confidence intervals for the location of quantitative trait loci (QTLs) was investigated using simulation. Empirical confidence intervals were calculated using a bootstrap resampling method for a backcross population derived from inbred lines. Sample sizes were either 200 or 500 individuals, and the QTL explained 1, 5, or 10% of the phenotypic variance. The method worked well in that the proportion of empirical confidence intervals that contained the simulated QTL was close to expectation. In general, the confidence intervals were slightly conservatively biased. Correlations between the test statistic and the width of the confidence interval were strongly negative, so that the stronger the evidence for a QTL segregating, the smaller the empirical confidence interval for its location. The size of the average confidence interval depended heavily on the population size and the effect of the QTL. Marker spacing had only a small effect on the average empirical confidence interval. The LOD drop-off method to calculate empirical support intervals gave confidence intervals that generally were too small, in particular if confidence intervals were calculated only for samples above a certain significance threshold. The bootstrap method is easy to implement and is useful in the analysis of experimental data. 相似文献
302.
Molecular evolution of mammalian aquaporin-2: further evidence that elephant shrew and aardvark join the paenungulate clade 总被引:1,自引:1,他引:0
Madsen O; Deen PM; Pesole G; Saccone C; de Jong WW 《Molecular biology and evolution》1997,14(4):363-371
A 328-bp sequence from exon 1 of the gene for aquaporin-2 (AQP2) was
compared in 12 mammalian species, representing as many eutherian orders.
This sequence encodes the N-terminal half of this kidney- specific water
channel protein. Most amino acid replacements, as well as an insertion,
have occurred in extracellular loops connecting the transmembrane helices,
in agreement with a lower functional importance of these loops.
Phylogenetic analyses were performed with parsimony, distance, and
maximum-likelihood methods. The AQP2 data set, alone as well as in
combination with previously published alpha A-crystallin protein sequences,
strongly supports a clade consisting of elephant, hyrax, aardvark, and
elephant shrew, reaching bootstrap values of 99%. This finding fully agrees
with the only other presently available sequence data sets that include
these taxa, those of von Willebrand factor and interphotoreceptor
retinoid-binding protein, and suggests that this extended paenungulate
clade is one of the most conspicuous superordinal groupings in eutherian
phylogeny. Some support was obtained for an artiodactyl/perissodactyl
clade, while the grouping of pholidotes with edentates was contradicted.
相似文献
303.
Summary The synthesis of pyrophosphate-linked oligomers from the bis-phosphoimidazolides of deoxyadenosine and deoxyguanosine, as well as from acyclic analogs of these nucleosides, is catalyzed much more effectively by Mn(II) than by Mg(II). The presence of Mn(II) reduces the extent of cyclization of the monomer-bis-phosphoimidazolide and thereby increases the yields of oligomeric products. The Mn(II)-catalyzed oligomerization is less sensitive to the presence of a complementary polynucleotide template than is the Mg(II)-catalyzed reaction.Nucleic Acid-Like Structures VII. For the previous paper in this series see Visscher et al. (1989) 相似文献
304.
De Graaf R. M. Visscher J. Schwartz Alan. W. 《Origins of life and evolution of the biosphere》1998,28(3):271-282
Phosphonoacetaldehyde (PAL), a phosphonic acid analogue of glycolaldehyde phosphate, reacts in the presence of formaldehyde under mildly basic conditions to produce several new products. The reaction proceeds in two stages: a fast aldol condensation of formaldehyde with PAL, and a slower reaction to produce products containing two phosphonic acid groups. We report on the derivatization, isolation by means of HPLC and characterization of these compounds. One of the products is of potential interest as a building block for a prebiotic informational polymer. 相似文献
305.
D W Visscher D S Gingrich C Leon-Armin P Tabaczka J D Crissman 《Analytical cellular pathology》1998,17(3):167-175
Two-color, multiparametric synthesis phase fraction (SPF) analysis of cytokeratin-labeled epithelial cells was flow cytometrically performed on both benign (SPFb) and malignant tissue samples (if available, SPFt) from 132 mastectomy/lumpectomy specimens. These data were then correlated with clinicopathologic features, including (1) tumor differentiation, (2) the proportion of tumor comprised of duct carcinoma-in situ (DCIS), and (3) the histology of accompanying benign breast tissue, classified by predominant microscopic pattern as intact, normal terminal duct lobular units (NTDLU, 34% of cases), atrophic (AT, 33% of cases), proliferative fibrocystic (PFC, 26% of cases), and non-proliferative fibrocystic (NPFC, 7% of cases). SPFt was inversely correlated with extent of DCIS (DCIS = 0-20% tumor volume - 12.7% mean SPFt, vs. DCIS >20% tumor volume - 6.4% mean SPFt, p = 0.001). SPFt also correlated with the histology of background benign breast tissue (NTDLU - 14.8% mean SPFt vs. AT - 6.9% mean SPFt vs. PFC - 12.7% mean SPFt, p = 0.05) but it did not correlate with patient age or SPFb (overall mean = 0.73%). SPFb was correlated with patient age (>56 yr - 0.59% mean SPFb vs. <56 yr - 0.84% mean SPFb, p = 0.02), with background histology (NTDLU - 1.1% mean SPFb vs. AT - 0.43% mean SPFb vs. PFC - 0.70% mean SPFb, p < 0.02) and with the grade of the neoplasm (well/moderate - 0.58% mean vs. poorly differentiated - 0.85% mean, p = 0.04). Patients having a background of PFC were significantly older than patients with a background of NTDLU (45.2 yr vs. 60.2 yr, p = 0.01). We conclude: (1) breast carcinomas arising from a background of more actively cycling pre-involutional or proliferative fibrocystic epithelium have a greater proliferative fraction than tumors arising from atrophic epithelium, implying that the differentiation status of target cells may impact the effect(s) of tumorigenic events; (2) PFC may represent delayed, abnormal or interrupted involution rather than a hyperproliferative state relative to NTDLU, suggesting that it facilitates neoplasia by extending the period of exposure to promoter agents such as endogenous hormones, and (3) lower SPFt in breast neoplasia with more abundant "residual" DCIS may reflect a lengthier pre-invasive disease interval due to intrinsically less aggressive phenotype. 相似文献
306.
Bias, precision and heritability of self-reported and clinically measured height in Australian twins
Many studies of quantitative and disease traits in human genetics rely upon self-reported measures. Such measures are based on questionnaires or interviews and are often cheaper and more readily available than alternatives. However, the precision and potential bias cannot usually be assessed. Here we report a detailed quantitative genetic analysis of stature. We characterise the degree of measurement error by utilising a large sample of Australian twin pairs (857 MZ, 815 DZ) with both clinical and self-reported measures of height. Self-report height measurements are shown to be more variable than clinical measures. This has led to lowered estimates of heritability in many previous studies of stature. In our twin sample the heritability estimate for clinical height exceeded 90%. Repeated measures analysis shows that 2–3 times as many self-report measures are required to recover heritability estimates similar to those obtained from clinical measures. Bivariate genetic repeated measures analysis of self-report and clinical height measures showed an additive genetic correlation >0.98. We show that the accuracy of self-report height is upwardly biased in older individuals and in individuals of short stature. By comparing clinical and self-report measures we also showed that there was a genetic component to females systematically reporting their height incorrectly; this phenomenon appeared to not be present in males. The results from the measurement error analysis were subsequently used to assess the effects of error on the power to detect linkage in a genome scan. Moderate reduction in error (through the use of accurate clinical or multiple self-report measures) increased the effective sample size by 22%; elimination of measurement error led to increases in effective sample size of 41%. 相似文献
307.
Lemmink KA Visscher SH 《Journal of strength and conditioning research / National Strength & Conditioning Association》2006,20(3):682-688
The energetics of 2 field tests that reflect physical performance in intermittent sports (i.e., the Interval Shuttle Sprint Test [ISST] and the Interval Shuttle Run Test [ISRT]) were examined in 21 women field hockey players. The ISST required the players to perform 10 shuttle sprints starting every 20 seconds. During the ISRT, players alternately ran 20-m shuttles for 30 seconds and walked for 15 seconds with increasing speed. Anaerobic and aerobic power tests included Wingate cycle sprints and a .V(O2)max cycle test, respectively. Based on correlation and regression analyses, it was concluded that for the ISST, anaerobic energetic pathways contribute mainly to energy supply for peak sprint time, while aerobic energetic pathways also contribute to energy supply for total sprint time. Energy during the ISRT is supplied mainly by the aerobic energy system. Depending on the aspect of physical performance a coach wants to determine, the ISST or ISRT can be used. 相似文献
308.
Analysis of pooled DNA samples on high density arrays without prior knowledge of differential hybridization rates 总被引:6,自引:2,他引:4
Array based DNA pooling techniques facilitate genome-wide scale genotyping of large samples. We describe a structured analysis method for pooled data using internal replication information in large scale genotyping sets. The method takes advantage of information from single nucleotide polymorphisms (SNPs) typed in parallel on a high density array to construct a test statistic with desirable statistical properties. We utilize a general linear model to appropriately account for the structured multiple measurements available with array data. The method does not require the use of additional arrays for the estimation of unequal hybridization rates and hence scales readily to accommodate arrays with several hundred thousand SNPs. Tests for differences between cases and controls can be conducted with very few arrays. We demonstrate the method on 384 endometriosis cases and controls, typed using Affymetrix Genechip© HindIII 50 K arrays. For a subset of this data there were accurate measures of hybridization rates available. Assuming equal hybridization rates is shown to have a negligible effect upon the results. With a total of only six arrays, the method extracted one-third of the information (in terms of equivalent sample size) available with individual genotyping (requiring 768 arrays). With 20 arrays (10 for cases, 10 for controls), over half of the information could be extracted from this sample. 相似文献
309.
Genome-wide association studies (GWAS) for quantitative traits and disease in humans and other species have shown that there are many loci that contribute to the observed resemblance between relatives. GWAS to date have mostly focussed on discovery of genes or regulatory regions habouring causative polymorphisms, using single SNP analyses and setting stringent type-I error rates. Genome-wide marker data can also be used to predict genetic values and therefore predict phenotypes. Here, we propose a Bayesian method that utilises all marker data simultaneously to predict phenotypes. We apply the method to three traits: coat colour, %CD8 cells, and mean cell haemoglobin, measured in a heterogeneous stock mouse population. We find that a model that contains both additive and dominance effects, estimated from genome-wide marker data, is successful in predicting unobserved phenotypes and is significantly better than a prediction based upon the phenotypes of close relatives. Correlations between predicted and actual phenotypes were in the range of 0.4 to 0.9 when half of the number of families was used to estimate effects and the other half for prediction. Posterior probabilities of SNPs being associated with coat colour were high for regions that are known to contain loci for this trait. The prediction of phenotypes using large samples, high-density SNP data, and appropriate statistical methodology is feasible and can be applied in human medicine, forensics, or artificial selection programs. 相似文献
310.
Quantitative trait loci variation for growth and obesity between and within lines of pigs (Sus scrofa) 总被引:2,自引:0,他引:2
The hypothesis that quantitative trait loci (QTL) that explain variation between divergent populations also account for genetic variation within populations was tested using pig populations. Two regions of the porcine genome that had previously been reported to harbor QTL with allelic effects that differed between the modern pig and its wild-type ancestor and between the modern pig and a more distantly related population of Asian pigs were studied. QTL for growth and obesity traits were mapped using selectively genotyped half-sib families from five domesticated modern populations. Strong support was found for at least one QTL segregating in each population. For all five populations there was evidence of a segregating QTL affecting fatness in a region on chromosome 7. These findings confirm that QTL can be detected in highly selected commercial populations and are consistent with the hypothesis that the same chromosome locations that account for variation between populations also explain genetic variation within populations. 相似文献