核受体与临床疾病发病与治疗 ◼ 神经系统疾病 ◼ 神经退行性变,慢性炎症(PPARΥ),疼痛,抑郁症、阿尔茨海默病(ER) ◼ 代谢性疾病 ◼ II型糖尿病、高脂血症、肥胖、高血压、脂肪肝、肿瘤、炎症（免疫）性疾病、水盐电解质代谢紊乱等 ◼ 血液系统疾病 ◼ 白血病(RXR,ER) ◼ Nuclear Receptor Pathway ◼ Hotspot in NRs research ◼ Basic Medicine (case I) ◼ Translational Medicine (case II) ◼ Applied Basic Research (case III) Hotspot in Gene Expression Regulation of Nuclear Receptors ➢乳腺癌治疗抵抗新机制的研究 ➢寻找乳腺癌治疗抵抗新策略

Gene clusters are formed by duplication and divergence Sequence divergence is the basis for the evolutionary clock Pseudogenes are dead ends of evolution Unequal crossing-over rearranges gene clusters Genes for rRNA form tandem repeats ( The repeated genes for rRNA maintain constant sequence) Crossover fixation could maintain identical repeats Satellite DNAs often lie in heterochromatin Arthropod satellites have very short identical repeats Mammalian satellites consist of hierarchical repeats Minisatellites are useful for genetic mapping

29.1 Introduction 29.2 Fly development uses a cascade of transcription factors 29.3 A gradient must be converted into discrete compartments 29.4 Maternal gene products establish gradients in early embryogenesis 29.5 Anterior development uses localized gene regulators

第一节 癌基因 Oncogenes 第二节 肿瘤抑制基因 tumor suppressor gene 第三节 生长因子 Growth factors

1.Genes can be mutated in many ways The most common gene change involves a single base mismatch--a misspelling--placing the wrong base in the DNA. At other times, a single base may be dropped or added. And sometimes large pieces of DNA are mistakenly repeated or deleted

Chapter 1: Plasmids and Their Usefulness in Molecular Cloning Chapter 2: Bacteriophage and Its Vectors Chapter 3: Working with Bacteriophage M13 Vectors Chapter 4: Working with High-Capacity Vectors Chapter 5: Gel Electrophoresis of DNA and Pulsed-Field Agarose Chapter 6: Preparation and Analysis of Eukaryotic Genomic DNA Chapter 7: Extraction, Purification, and Analysis of mRNA from Eukaryotic Cells Chapter 8: In Vitro Amplification of DNA by the Polymerase Chain Reaction Chapter 9: Preparation of Radiolabeled DNA and RNA Probes Chapter 10: Working with Synthetic Oligonucleotide Probes Chapter 11: Preparation of cDNA Libraries and Gene Identification Chapter 12: DNA Sequencing Chapter 13: Mutagenesis Chapter 14: Screening Expression Libraries Chapter 15: Expression of Cloned Genes in Escherichia coli Chapter 16: Introducing Cloned Genes into Cultured Mammalian Cells Chapter 17: Analysis of Gene Expression in Cultured Mammalian Cells Chapter 18: Protein Interaction Technologies

1. Variability and Gene (or Allelic) Frequencies 2. The Hardy-Weinberg Law 3. Factors that Affect Stability of Gene Frequencies

Medical Genetics Gene Mutation Change in genes caused by change in structure of the DNA

1. What are the gene expression stages that can be regulated? (10 points) Regulated stages in gene expression: (1) transcription initiation (the most important stage): RNAP binding of the promoter, transition from the closed complex to the open complex; promoter escape 4’ (2) stages after initiation (elongation and termination) 2’ (3) RNA processing (alternative splicing) in eukaryotes 2’ (4) translation 2’

Similarity of regulation between eukaryotes and prokaryote 1.Principles are the same: • signals (信号), • activators and repressors (激活蛋白和阻 遏蛋白) • recruitment and allostery, cooperative binding (招募，异构和协同结合) 2. The gene expression steps subjected to regulation are similar, and the initiation of transcription is the most pervasively regulated step