Dissertation > Excellent graduate degree dissertation topics show

Studies of the Deleterious SNPs in the ATP-binding Cassette (ABC) Transporter Superfamily

Author: LiYanHong
Tutor: YangLing
School: Dalian Institute of Chemical Physics
Course: Biochemical Engineering
Keywords: ABC transporters deleterious SNPs theoretic prediction MDR1 3435C>;T distribution
CLC: R341
Type: PhD thesis
Year: 2007
Downloads: 230
Quote: 0
Read: Download Dissertation

Abstract


It is generally said that the deleterious (or functional) SNPs always change the structure and functional activities of proteins or the expression of them, and cause various diseases. The deleterious SNPs in ABC (ATP-binding cassette) transporters may cause deleterious effects on them, and are close association with many serious diseases. According to the characteristics of ABC transporters, using building models in silico and experimental analysis, the deleterious SNPs in the ABC transporters have been explored in this work.In the theoretical study, the results are as follows: I. Applying the RPLS (ridge partial least square) and LDA (linear discriminant analysis) methods, we have developed the computational models to analyze the deleterious nsSNPs in the transporters and predict ones in ABCB (ATP-binding cassette B) transporters of interest. The prediction accuracy of two models for the training (762 nsSNPs) are more over 84%. Meanwhile, 28 nsSNPs in the ABCB proteins were always predicted to be deleterious. II. The silico models based on RPLS and cross-validation methods have been proposed to analyze the pathogenicity of missense mutations in the ABC transporters. The 5286 missense mutations, located on the quite different length of proteins, were selected to build the models. The accuracy were 82.2% (training: 4098 nsSNPs) and 81.4% (test: 752 nsSNPs), respectively. Moreover, 234 missense mutations were always analyzed to be of the pathogenicity among the ABC proteins.In the experimental analysis, the distribution of the functional MDR3435C>T (ABCB1) genotypes in 265 healthy subjects, which were selected from 2836 Chinesesamples of Han nationality, was studied. In this part, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay has been applied to assess 3435C>T genotypes. The genotype frequencies are: CC 32% (n = 85), CT 48% (n = 127) and TT 20% (n = 53), which is the first report in the Chinese samples.In conclusion, the evolutionary-conservation features and secondary structural features of the proteins were applied in this work. Moreover, it is always difficult to build the related models for the transmembrane and glycoproteins with the large molecular weight. Therefore, the models were built not only based on the deleterious nsSNPs in the transporters as datasets, but also based on ones of the non-transporters in the large proteins as datasets too. The high predicting accuracy was got for the deleterious nsSNPs model in the ABC transporters using different theoretic methods. On the other hand, we obtained the data about the distribution of the functional MDR1/ABCB1 3435C>T in the healthy Chinese Han samples because there has been a lack of data about them. The above studies are the exploratory attempts for validating the results of the theoretic models, exploring the pathogenesis of the diseases caused by ABC transporters and the therapy of them, and especially for improving the levels of individual treatments in our country.

Related Dissertations

  1. Research on Fault Detection and Network Reconfiguration Algorithms for Distribution Network,TM727
  2. Modeling of Sea Clutter and Effect of Sea Clutter on Isar Imaging,TN957.54
  3. Simulation and Experimental Study on the Scattering Properties of Two Dimensional Rough Surfaces,TP391.41
  4. Modeling Internet Link Delay Based on Measurement,TP393.4
  5. The Research on Space Layout of Characteristic Economy in Wenshan,F127
  6. Effects of the Exotic Invasive Plant Solidago Canadensis L. on the Community Structure of Soil Anmals,S451
  7. Chinese Sports Athletes Human Capital Development and Income Distribution Research,G812.0
  8. Studies on Leaf Epidermal and Pollen Micro-morphology and Geographical Distribution of the Genus Euonymus of Henan,Q944
  9. Study on the Distribution Pattern and Priority Areas of Endangered Terrestrial Animals in Jiangsu Province,Q948.2
  10. Sagitta Morephology, Distribution, Biology and Stock Assessment of Four Prlagic Species in the Mouth of Beibu Gulf,S932.4
  11. Community impact study of the distribution of benefits mechanism of development of ethnic village,D422.6
  12. Based on the Layout and Adjustment of Rural Primary and Secondary School Students to Go to School, the Traffic Problem Investigation and Strategy Research,G639.2
  13. The Influence of Long-term Regular Exercise to the Distribution and Change Regulation on Human Skin Temperature,G804.2
  14. Cadmium, Chromium and Lead Accumlation, Distribution in Aralia Elata Var. Inermia and Their Effect on Leaf Antioxidative System,S792
  15. The Studying of Temperature Distribution and Control Technique during Polymer Sheet Heat Process,TQ320.6
  16. The Selection of Leading Industry and Industry Distribution in Environmentally Vulnerable Area,X321
  17. Distribution and Bioavaiability of Polycyclic Aromatic Hydrocarbons in Soil Particle-size Separates,X131.3
  18. Research on the Revenue Distribution of PPP Mode about High-speed Railway Project,F283
  19. The Research on Influence of Line Losses in the Distrebution Network with Small Rural Hydropowers,TM727.1
  20. Mineralogical and Geochemical Evidence of the Presence of Ancient Paddy Soil Layer in Chuodun Ancient Agricultural Site, Kunshan,S-09
  21. Investigation of Cereal Cyst Nematode on Wheat in Jiangsu Province and the Sequence Analysis of rDNA-Its Region from Jiangsu Populations,S435.121

CLC: > Medicine, health > Basic Medical > Human biochemistry, molecular biology
© 2012 www.DissertationTopic.Net  Mobile