《遗传学》遗传病的诊断和筛查.pptxVIP

遗传病的诊断和筛查 第一节 临床诊断 依据患者的表型，并结合家系分析，判定是否患有某种遗传病，并确定遗传方式和遗传规律 第二节 遗传学诊断 通过检测遗传物质、蛋白产物和代谢产物的异常类型，对遗传性疾病进行诊断。 依诊断方法分为：细胞遗传学和分子遗传学诊断 依据临床目的分为：诊断性检测，症状前检测，携带者检测和产前检测 依不同的遗传病分为：染色体病诊断、基因组病诊断和单基因病诊断 Types of genetic abnormality遗传异常类型 Three levels Genome mutation Chromosome mutation Gene mutation Genome Mutation基因组突变 Abnormalities of Chromosome number （染色体数量异常） Heteroploid: chromosome number other than 46 Euploidy （整倍体） – a chromosome number that is a multiple of the normal haploid set染色体数目是正常单倍体的多倍(2n, 3n, 4n): 92,XXXX or 92,XXYY Aneuploidy（非整倍体） Monosomy – having only one member of a homologous pair: Turner syndrome (45,X; 45,XY,-22) Trisomy– having three copies of a single chromosome: (47,XX,+21; 47,XY,+18 and 47,XY,+13) Chromosome mutation染色体突变 Abnormalities of Chromosome structure Unbalanced rearrangement Deletions/Duplications Marker/Ring Chromosome Isochromosome Balanced rearrangement Translocations Robertsonian translocation Insertions Inversions Gene Mutation 基因突变 Abnormalities of individual gene Approaches of Tests -Cytogenetics(细胞遗传学） Conventional Cytogenetics Karyotype（核型) Molecular Cytogenetics Fluorescence in situ Hybridization (FISH) Chromosomal microarray analysis (CMA) or Cytogenomic microarray -Molecular Genetics (分子遗传学） PCR Sequencing Banding 5-10 Mb FISH 150 kb aCGH5-10 Kb Sequencing 1 bp Chromosomes photographed during metaphase or prometaphase and arranged in a standard sequence G-banding (G显带） Standard 550 bands (5-10 Mb) High Resolution 850 bands (2-3 Mb) Whole genome level of Chromosome number and structure variations Karyotyping（核型分析） Karyotype Banding patterns are important for identification of chromosomes in karyotype analysis（显色带在核型分析的染色体鉴别中是非常重要的） Triploidy三倍体(69,XXX) 1/900 live births（出生率） Leading cause of mental retardation and heart defects（智力障碍和心脏缺陷） Wide flat skulls, 面宽平 40% congenital heart defects先天性心脏病 Trisomy 21:Down Syndrome (47,XX,+21) Trisomy 13: Patau Syndrome (47,XY,+13)  1/15,000 birt