孟德尔遗传方式疾病.docVIP

Lecture Notes 孟德尔遗传方式疾病 张咸宁（细胞生物学与医学遗传学系） 2014/09 I. Mendelian疾病的主要分类和举例 A. Autosomal Dominant（常染色体显性遗传） ( 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 due to variable penetrance（可变的外显率）, variable expressivity（可变的表现度）, or appearance of a new mutation in the family ( Examples: Huntington disease, neurofibromatosis（神经纤维瘤）, familial breast/ovarian cancer B. Autosomal Recessive（常染色体隐性遗传） ( requires mutation of both alleles to produce disease ( males and females equally affected ( higher frequency in consanguineous matings（近亲婚配） ( 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（苯丙酮尿症）, cystic fibrosis（囊性纤维化） C. X-linked Dominant（X-连锁显性遗传） ( due to a dominant mutation located on the X-chromosome ( males and females usually equally affected ( no male-to-male transmission（传递）; all daughters of an affected father are affected ( Examples: hypophosphatemic rickets（低血磷性佝偻病）, incontinentia pigmenti（色素失调症） D. X-linked Recessive（X-连锁隐性遗传） ( due to a recessive mutation located on the X-chromosome ( males predominantly or exclusively affected ( mothers are carriers（携带者） ( no male-to-male transmission ( some cases due to appearance of a new mutation in the family ( Examples: Duchenne muscular dystrophy（DMD。假性肥大性肌营养不良）, color blindness（色盲）, hemophilia A（血友病A） E. Mitochondrial Inheritance（线粒体基因遗传） ( due to a mutant gene carried on the mitochondrial genome ( transmitted only through mothers because sperm contain very few mitochondria (maternal inheritance。母系遗传) ( inheritance and expression variable because of heteroplasmy (杂质性。differing proportions of normal and mutant DNA in oocytes and tissues) ( Examples: Leber hereditary op