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1.
Evaluating pedigree data. II. Identifying the cause of error in families with inconsistencies 总被引:1,自引:0,他引:1
Pedigree data can be evaluated, and subsequently corrected, by analysis of the distribution of genetic markers, taking account of the possibility of mistyping . Using a model of pedigree error developed previously, we obtained the maximum likelihood estimates of error parameters in pedigree data from Tokelau. Posterior probabilities for the possible true relationships in each family are conditional on the putative relationships and the marker data are calculated using the parameter estimates. These probabilities are used as a basis for discriminating between pedigree error and genetic marker errors in families where inconsistencies have been observed. When applied to the Tokelau data and compared with the results of retyping inconsistent families, these statistical procedures are able to discriminate between pedigree and marker error, with approximately 90% accuracy, for families with two or more offspring. The large proportion of inconsistencies inferred to be due to marker error (61%) indicates the importance of discriminating between error sources when judging the reliability of putative relationship data. Application of our model of pedigree error has proved to be an efficient way of determining and subsequently correcting sources of error in extensive pedigree data collected in large surveys. 相似文献
2.
Calcium-independent activation of skeletal muscle fibers by a modified form of cardiac troponin C. 总被引:2,自引:1,他引:1 下载免费PDF全文
J D Hannon P B Chase D A Martyn L L Huntsman M J Kushmerick A M Gordon 《Biophysical journal》1993,64(5):1632-1637
A conformational change accompanying Ca2+ binding to troponin C (TnC) constitutes the initial event in contractile regulation of vertebrate striated muscle. We replaced endogenous TnC in single skinned fibers from rabbit psoas muscle with a modified form of cardiac TnC (cTnC) which, unlike native cTnC, probably contains an intramolecular disulfide bond. We found that such activating TnC (aTnC) enables force generation and shortening in the absence of calcium. With aTnC, both force and shortening velocity were the same at pCa 9.2 and pCa 4.0. aTnc could not be extracted under conditions which resulted in extraction of endogenous TnC. Thus, aTnC provides a stable model for structural studies of a calcium binding protein in the active conformation as well as a useful tool for physiological studies on the primary and secondary effects of Ca2+ on the molecular kinetics of muscle contraction. 相似文献
3.
Smith Walker O. Jr.; Barber Richard T.; Huntsman Susan A. 《Journal of plankton research》1982,4(3):651-663
Chelation bioassays were conducted off the coast of northwestAfrica during two seasons. The first (winter) was characterizedby strong shelf-break upwelling and the second (spring) wascharacterized by upwelling closer to shore. Phytoplankton insamples taken from surface waters during winter showed a markedstimulation in growth upon addition of the artificial chelatorEDTA. Optimal concentrations of the ligand were 106 M.No stimulation was observed during upwelling conditions encounteredin the spring. Primary productivity in the winter season wassignificantly lower than in the spring, averaging only 35% ofthe spring rates. Ionic copper additions reduced growth in phytoplanktonassayed in the spring and the growth reductions were eliminatedby addition of EDTA. It is hypothesized that the winter growthdepression resulted from either (1) a lack of organic compoundscapable of binding ionic copper as a result of either a lackof organic input from the sediments or surface waters becauseof direct advection to the surface, or by (2) the upwellingof water from a ligand-deficient water mass whose relative importanceas a source for newly upwelled water declined and disappearedas the season progressed. 相似文献
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Albert DG de Roos 《Biology direct》2007,2(1):7-17
Background
The timing of the origin of introns is of crucial importance for an understanding of early genome architecture. The Exon theory of genes proposed a role for introns in the formation of multi-exon proteins by exon shuffling and predicts the presence of conserved splice sites in ancient genes. In this study, large-scale analysis of potential conserved splice sites was performed using an intron-exon database (ExInt) derived from GenBank. 相似文献7.
8.
Brandon S. Sheffield Anna V. Tinker Yaoqing Shen Harry Hwang Hector H. Li-Chang Erin Pleasance Carolyn Ch’ng Amy Lum Julie Lorette Yarrow J. McConnell Sophie Sun Steven J. M. Jones Allen M. Gown David G. Huntsman David F. Schaeffer Andrew Churg Stephen Yip Janessa Laskin Marco A. Marra 《PloS one》2015,10(3)
Peritoneal mesothelioma is a rare and sometimes lethal malignancy that presents a clinical challenge for both diagnosis and management. Recent studies have led to a better understanding of the molecular biology of peritoneal mesothelioma. Translation of the emerging data into better treatments and outcome is needed. From two patients with peritoneal mesothelioma, we derived whole genome sequences, RNA expression profiles, and targeted deep sequencing data. Molecular data were made available for translation into a clinical treatment plan. Treatment responses and outcomes were later examined in the context of molecular findings. Molecular studies presented here provide the first reported whole genome sequences of peritoneal mesothelioma. Mutations in known mesothelioma-related genes NF2, CDKN2A, LATS2, amongst others, were identified. Activation of MET-related signaling pathways was demonstrated in both cases. A hypermutated phenotype was observed in one case (434 vs. 18 single nucleotide variants) and was associated with a favourable outcome despite sarcomatoid histology and multifocal disease. This study represents the first report of whole genome analyses of peritoneal mesothelioma, a key step in the understanding and treatment of this disease. 相似文献
9.
Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels 下载免费PDF全文
Reich D Patterson N Ramesh V De Jager PL McDonald GJ Tandon A Choy E Hu D Tamraz B Pawlikowska L Wassel-Fyr C Huntsman S Waliszewska A Rossin E Li R Garcia M Reiner A Ferrell R Cummings S Kwok PY Harris T Zmuda JM Ziv E;Health Aging Body Composition 《American journal of human genetics》2007,80(4):716-726
Circulating levels of inflammatory markers can predict cardiovascular disease risk. To identify genes influencing the levels of these markers, we genotyped 1,343 single-nucleotide polymorphisms (SNPs) in 1,184 African Americans from the Health, Aging and Body Composition (Health ABC) Study. Using admixture mapping, we found a significant association of interleukin 6 soluble receptor (IL-6 SR) with European ancestry on chromosome 1 (LOD 4.59), in a region that includes the gene for this receptor (IL-6R). Genotyping 19 SNPs showed that the effect is largely explained by an allele at 4% frequency in West Africans and at 35% frequency in European Americans, first described as associated with IL-6 SR in a Japanese cohort. We replicate this association (P<1.0x10-12) and also demonstrate a new association with circulating levels of a different molecule, IL-6 (P<3.4x10-5). After replication in 1,674 European Americans from Health ABC, the combined result is even more significant: P<1.0x10-12 for IL-6 SR, and P<2.0x10-9 for IL-6. These results also serve as an important proof of principle, showing that admixture mapping can not only coarsely localize but can also fine map a phenotypically important variant. 相似文献
10.
Gary Klečka Jack Zabik Kent Woodburn Carter Naylor Charles Staples Brent Huntsman 《人类与生态风险评估》2007,13(4):792-822
This study was conducted to develop a statistical understanding of exposures to C8- and C9-alkylphenol ethoxylates (APEO) and their metabolites (APEM) in U.S. surface waters. Concentrations of APEO/APEM (all analytes) in freshwater have been reported by 19 investigations over the past 15 years. Only limited data are available for sediments and marine ecosystems. Based on the frequency of detection in surface waters, 67% of all analytes were below their detection limits. Although maximum reported concentrations varied with time, the average and 90th centile concentrations have remained relatively constant. Examination of frequency distributions for nonylphenol (NP) concentrations indicated that 99% of the levels in fresh surface waters are below the U.S. Environmental Protection Agency's Aquatic Life Ambient Chronic Water Quality Criteria for NP (6.6 μg/L). A conservative evaluation of aggregated NPEO/NPEM concentrations suggested that 97% of the samples contained aggregate NP equivalent concentrations that are also below 6.6 μg/L. These results suggest that on a nationwide basis, the likelihood of surface water concentrations exceeding the chronic USEPA Water Quality Criterion for NP is low. 相似文献