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91.
Lindsey J. Leach Lin Wang Michael J. Kearsey Zewei Luo 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(9):4270-4274
The availability of reliable genetic linkage maps is crucial for functional and evolutionary genomic analyses. Established theory and methods of genetic linkage analysis have made map construction a routine exercise in diploids. However, many evolutionarily, ecologically, and/or agronomically important species are autopolyploids, with autotetraploidy being a typical example. These species undergo much more complicated chromosomal segregation and recombination at meiosis than diploids. In addition, there is evidence of polyploidy-induced and highly dynamic changes in the structure of the genome. These polysomic characteristics indicate the inappropriateness of the theory and methods of linkage analysis in diploids for use in these species and a gap in the theory and methodology of tetraploid map construction. This paper presents a theoretical model and statistical framework for multilocus linkage analysis in autotetraploids for use with dominant and/or codominant DNA molecular markers. The theory and methods incorporate the essential features of allele segregation and recombination under tetrasomic inheritance and the major challenges in statistical modeling and marker data analysis. We validated the method and explored its statistical properties by intensive simulation study and demonstrated its utility by analysis of AFLP and SSR marker data from an outbred autotetraploid potato population. 相似文献
92.
Dipen J Parekh Donna Pauler Ankerst Jacques Baillargeon Betsy Higgins Elizabeth A Platz Dean Troyer Javier Hernandez Robin J Leach Anna Lokshin Ian M Thompson 《Cancer epidemiology, biomarkers & prevention》2007,16(10):1966-1972
OBJECTIVE: We analyzed the association of 54 biomarkers from seven classes including adipokines, immune response metalloproteinases, adhesion molecules, and growth factors with prostate cancer risk adjusting for the Prostate Cancer Prevention Trial (PCPT) risk score. METHODS: A total of 123 incident prostate cancer cases and 127 age-matched controls were selected from subjects in the San Antonio Center for Biomarkers of Risk of Prostate Cancer cohort study. Prediagnostic serum concentrations were measured in the sample collected at baseline using LabMAP technology. The odds ratios (OR) of prostate cancer risk associated with serum concentrations of 54 markers were estimated using univariate conditional logistic regression before and after adjustment for the PCPT risk score. Two-way hierarchical unsupervised clustering techniques were used to evaluate whether the 54-marker panel distinguished cases from controls. RESULTS: Vascular endothelial growth factor, resistin, interleukin 1Ra (IL-1Ra), granulocyte colony-stimulating factor, matrix metalloproteinase-3, plasminogen activator inhibitor, and kallikrein-8 were statistically significantly (P < 0.05) underexpressed in prostate cancer cases, and alpha-fetoprotein was statistically significantly overexpressed in prostate cancer cases, but all had area underneath the receiver-operating characteristic curve <60%; none were statistically significant adjusting for multiple comparisons (P < 0.0008) or after adjustment for the PCPT risk score. Statistical clustering of patients by the marker panel did not distinguish a separate group of cases from controls. CONCLUSIONS: This age-matched case-control study did not support findings of increased diagnostic potential from a 54-marker panel when compared with the conventional risk factors incorporated in the PCPT risk calculator. Future discovery of new biomarkers should always be tested and compared against conventional risk factors before applying them in clinical practice. 相似文献
93.
Michael Khazen Ruth M L Warren Caroline R M Boggis Emilie C Bryant Sadie Reed Iqbal Warsi Linda J Pointon Gek E Kwan-Lim Deborah Thompson Ros Eeles Doug Easton D Gareth Evans Martin O Leach 《Cancer epidemiology, biomarkers & prevention》2008,17(9):2268-2274
PURPOSE: A method and computer tool to estimate percentage magnetic resonance (MR) imaging (MRI) breast density using three-dimensional T(1)-weighted MRI is introduced, and compared with mammographic percentage density [X-ray mammography (XRM)]. MATERIALS AND METHODS: Ethical approval and informed consent were obtained. A method to assess MRI breast density as percentage volume occupied by water-containing tissue on three-dimensional T(1)-weighted MR images is described and applied in a pilot study to 138 subjects who were imaged by both MRI and XRM during the Magnetic Resonance Imaging in Breast Screening study. For comparison, percentage mammographic density was measured from matching XRMs as a ratio of dense to total projection areas scored visually using a 21-point score and measured by applying a two-dimensional interactive program (CUMULUS). The MRI and XRM percent methods were compared, including assessment of left-right and interreader consistency. RESULTS: Percent MRI density correlated strongly (r = 0.78; P < 0.0001) with percent mammographic density estimated using Cumulus. Comparison with visual assessment also showed a strong correlation. The mammographic methods overestimate density compared with MRI volumetric assessment by a factor approaching 2. DISCUSSION: MRI provides direct three-dimensional measurement of the proportion of water-based tissue in the breast. It correlates well with visual and computerized percent mammographic density measurements. This method may have direct application in women having breast cancer screening by breast MRI and may aid in determination of risk. 相似文献
94.
Genetic analysis, phenotypic diagnosis, and risk of venous thrombosis in families with inherited deficiencies of protein S 总被引:5,自引:1,他引:4
Makris M Leach M Beauchamp NJ Daly ME Cooper PC Hampton KK Bayliss P Peake IR Miller GJ Preston FE 《Blood》2000,95(6):1935-1941
Protein S deficiency is a recognized risk factor for venous thrombosis. Of all the inherited thrombophilic conditions, it remains the most difficult to diagnose because of phenotypic variability, which can lead to inconclusive results. We have overcome this problem by studying a cohort of patients from a single center where the diagnosis was confirmed at the genetic level. Twenty-eight index patients with protein S deficiency and a PROS1 gene defect were studied, together with 109 first-degree relatives. To avoid selection bias, we confined analysis of total and free protein S levels and thrombotic risk to the patients' relatives. In this group of relatives, a low free protein S level was the most reliable predictor of a PROS1 gene defect (sensitivity 97.7%, specificity 100%). First-degree relatives with a PROS1 gene defect had a 5.0-fold higher risk of thrombosis (95% confidence interval, 1. 5-16.8) than those with a normal PROS1 gene and no other recognized thrombophilic defect. Although pregnancy/puerperium and immobility/trauma were important precipitating factors for thrombosis, almost half of the events were spontaneous. Relatives with splice-site or major structural defects in the PROS1 gene were more likely to have had a thrombotic event and had significantly lower total and free protein S levels than those relatives having missense mutations. We conclude that persons with PROS1 gene defects and protein S deficiency are at increased risk of thrombosis and that free protein S estimation offers the most reliable way of diagnosing the deficiency. (Blood. 2000;95:1935-1941) 相似文献
95.
A case of combined interstitial and intrauterine pregnancy is described. The sonographic finding of a thick myometrial bridge separating a twin pregnancy may be unique to heterotopic cornual pregnancies and is illustrated. The method of selective embryo reduction with potassium chloride to terminate the interstitial pregnancy without damage to the intrauterine pregnancy is also described. The intrauterine pregnancy continued successfully to term. 相似文献
96.
J Haddad C W Senders C S Leach S E Stool 《International journal of pediatric otorhinolaryngology》1990,20(2):127-135
Congenital hairy polyp of the nasopharynx is an unusual but well-recognized entity. These benign lesions have not been reported in the modern literature in association with cleft palate. We report two cases of hairy polyp in association with cleft palate, and discuss the pathology of the tumor with emphasis on embryology and pathogenesis. 相似文献
97.
The effect of gestational age on the synthesis of prostaglandins (PG) by isolated preparations of uninucleate and binucleate cells of the ovine placentome has been investigated. PG synthesis by the cells was dependent upon cell number in a linear manner, and was significantly inhibited by indomethacin, but not affected by the addition of exogenous arachidonic acid. The net output of PG by the cells increased progressively with increasing gestational age of the ewe from 35 to 145 days, particularly after 100 days' gestation. The cells prepared from tissue obtained during the last trimester of pregnancy have the ability to produce PGE2 and PGF2 alpha in approximately equal amounts, and a lower synthetic capacity for 6-keto PGF2 alpha. The cells also have the capacity to metabolize PGF2 alpha to 13,14-dehydro, 15-keto PGF2 alpha. Thus the fetal trophoblast cells appear to be the major site of PG production by the placenta at parturition. 相似文献
98.
99.
Many have recommended changing the professional development of physicians. Concluding that further educational process specification was inadequate, the Accreditation Council for Graduate Medical Education (ACGME) decided to specify six general competencies of graduate medical education (GME): patient care; medical knowledge; practice-based learning and improvement; professionalism; interpersonal skills and communication; and systems-based practice. Coupling them with a developmental view of professional knowledge and skill acquisition, the ACGME invited further specification and development of desired learning from the extended medical specialty community, including the specialty boards. This collaborative process offers a model of the role accrediting agencies can play in fostering workforce developmental change. 相似文献
100.
As an attempt to improve accuracy in the grading of microcytes and macrocytes, a custom reticle was developed and evaluated. The evaluation looked at grading accuracy, reproducibility, speed, and opinion. In this study, the reticle improved the grading accuracy and reproducibility of graders who were "poorer performers." The reticle offered no advantage to the speed of the evaluation. The opinion survey indicated improved confidence with the reticle, and most of the participants found the device useful. The improvement to "poorer performers" is sufficient to warrant use in actual practice. 相似文献