医学遗传归纳课件.pptVIP

Summary of Chromosome disorders Involving the changes of a groups of genes: complicated symptom Syndrome: Featured by serious mental retardation精神发育迟滞, structural abnormality of face, body and multiple organs Summary of Chromosome disorders ? Duplication or deletion of the certain chromosomes or the certain chromosomal segments Number or structure abnormality 0.6 % in live birth and 50% in spontaneous abortions in first-trimester in microscopic observation AD ? requires mutation in only one allele to produce disease ? males and females equally affected ? family history usually positive, with affected members in each generation ? may show apparent generation skipping跳过due to variable penetrance, variable expressivity, or appearance of a new mutation in the family ? Examples: Huntington disease, Marfan syndrome (FBN1 gene), neurofibromatosis, familial breast/ovarian cancer, myotonic dystrophy Trinucleotide CAG repeat sizes in Huntington disease Normal ≤26 Mutable 27-35 Reduced penetrance 36-39 Fully penetrance ≥40 Fragile X Syndrome脆性X染色体综合征 Macrocephaly Large ear with soft cartilage Normal life span CGG trinucleotide repeat AD null or structural mutations in type I collagen a chain genes lead to different types of osteogenesis imperfecta (OI) dominant negative effect haploinsufficiency germline mosaicism镶嵌现象 Genetic Basis of Osteogenesis 骨生成Imperfecta不全 AR ? requires mutation of both alleles to produce disease ? males and females equally affected ? higher frequency in consanguineous血亲的matings ? higher frequency of mutation carriers in particular ethnic groups ? family history often negative ? often associated with enzymatic defects causing metabolic disorders ? Examples: sickle cell disease, phenylketonuria苯丙酮尿, cystic fibrosis囊性纤维化, spinal muscular atrophy, Wilson disease XR ? due to a recessive mutation located on the X-chromosome ? males predominantly or exclusively affected ? mothers are carriers ? no male-to-male transmission ? some cases due to