孟德尔方式遗传病演示文稿.ppt

Special features of mitochondrial genetics mtDNA is maternally inherited. Paternal inheritance of mtDNA disease has been documented in only 1 instance. Schwartz M, Vissing J. NEJM, 2002;347:576–580 Mitochondrial diseases Leber hereditary optical neuropathy, LHON（Leber视神经萎缩） 患者多在18～20岁发病，男性较多见，个体细胞中突变mtDNA超过96％时发病，少于80％时男性患者症状不明显。 临床表现为双侧视神经严重萎缩引起的急性或亚急性双侧中央视力丧失，可伴有神经、心血管、骨骼肌等系统异常，如头痛、癫痫及心律失常等。 Unusual Features of AD Reduced penetrance Variable expressivity High frequency of new mutations Factors affecting pedigree patterns Onset age Pleiotropy: multiple effects of a single gene (one gene, more than one effect ) Genetic heterogeneity Expressivity and penetrance Coefficient of relationship and consanguineous marriage Sex-limited phenotypes and sex-influenced phenotypes genomic imprinting Anticipation X inactivation, … Pleiotropy（多效性） multiple effects of a single gene (one gene, more than one effect ) E.g.: Marfan syndrome (FBN1 gene) Genetic Heterogeneity（遗传异质性） The phenomenon that a disorder can be caused by different allelic or non-allelic mutations. Locus heterogeneity Allelic heterogeneity Phenotypic (Clinical) heterogeneity Genetic Heterogeneity Allelic heterogeneity: In a population, there may be a number of different mutant alleles at a single locus. In an individual, the same or similar phenotypes may be caused by different mutant alleles rather than by identical alleles at the locus. E.g.: nearly 1400 different mutations have been found worldwide in the CFTR among patients with cystic fibrosis (CF). Genetic Heterogeneity Locus heterogeneity: The production of identical phenotypes by mutations at two or more different loci. Eg: Osteogenesis Imperfecta (OI) or Brittle bone disease: Cs 7 17. Genetic Heterogeneity Phenotypic (Clinical) heterogeneity: The term describing the occurrence of clinically different phenotypes from mutations in the same gene. Eg: RET gene mutation caused Hirschsprung disease or multiple endocrine neoplasi