细胞遗传学Chapter 12遗传病的分子、生化和细胞基础
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Chapter 12
The Molecular, Biochemical and Cellular
Basis of Genetic Disease
遗传病的分子、生化和细胞基础
根据蛋白质的普遍性分类
Classes of Proteins according to their generalization
管家蛋白 Housekeeping proteins
present in virtually every cells and have fundamental roles in maintenance of cell structure and function
特异性蛋白 Specialty proteins
We will discuss
酶缺陷Enzyme Defects
Example: PKU, Methylmalonic acidemia，Lysosomal storage Disease
受体蛋白缺陷Defects in Receptor Proteins 转运蛋白缺陷Transport Defects 结构蛋白缺陷Disorders of Structural Proteins 药物遗传疾病 Pharmacogenetic Diseases
S’
phenylalanine
S’’
PAH
tyrosine
P’
PБайду номын сангаас’
• Mental retardation • “mousy” odor in urine • seizure disorder
• hypopigmentation of skin and hair
Therapy
1. Dietary reduction of phenylalanine 2. BH4
Human immunodeficiency virus
Toxoplasmosis
3-Methylcrotonyl-CoA carboxylase
Carnitine uptake defect (Carnitine transport defect)
注：我国部分地区开展
Comparison of Newborn Screening between China and
USA
Carbamoylphosphate synthetase
Hyperammonemia/ornithinemia/ citrullinemia Prolinemia
Ethylmalonic encephalopathy
临床表现Clinical features: Mental retardation 智力障碍 “mousy” odor in urine 鼠尿味 seizure disorder 癫痫 hypopigmentation浅染 of skin and hair
一家两个PKU，失查，但接受治疗
Phenylketonuria (PKU)
Newborn screening
Comparison of Newborn Screening between China and USA
Biotinidase Cystic fibrosis galactosemia (Classical) Sickle – C disease Hearing screening Congenital adrenal hyperplasia Congenital hypothyroidism Sickle cell disease β-thalassemia 5-oxoprolinuria (pyroglutamic aciduria) Glucose 6 phosphate dehydrogenase Nonketotic hyperglycinemia Benign hyperphenylalaninemia
酶 Enzymes 转运和储存 Transport and storage 细胞和器官的结构Structure of cells and organs 维持细胞外稳定Extracellular homeostasis 发育相关基因表达Development gene expression 控制生长和分化 Control of growth and differentiation 细胞内代谢和信息 Intercellular metabolism and communication
P’
S’’
P’’
Hyperphenylalaninemias
高苯丙氨酸血症
Hyperphenylalaninemias
Locus Heterogeneity
PAH 苯丙氨酸羟化酶 BH4 metabolism: BH4 recycling: PCD, DHPR
BH4 synthesis: GTP-CH, PTS
present in a limited number of cell types, have unique functions that contribute to the individuality of the cells
根据蛋白质的功能分类
Classes of Proteins according to their functions
Allelic Heterogeneity Different PAH mutation leads to different residual activity. 残留
活性多少决定症状轻重 Variant PKU
Phenylketonuria (PKU)
发病率Incidence: 1 /3500 - 16000 in population
遗传性酶病
Hereditary Enzymopathy
The inborn errors of metabolism is caused by gene mutation which lead to enzyme protein variants.
Mutant Enzyme
S’
Substrate
Product
The Molecular, Biochemical and Cellular
Basis of Genetic Disease
遗传病的分子、生化和细胞基础
根据蛋白质的普遍性分类
Classes of Proteins according to their generalization
管家蛋白 Housekeeping proteins
present in virtually every cells and have fundamental roles in maintenance of cell structure and function
特异性蛋白 Specialty proteins
We will discuss
酶缺陷Enzyme Defects
Example: PKU, Methylmalonic acidemia，Lysosomal storage Disease
受体蛋白缺陷Defects in Receptor Proteins 转运蛋白缺陷Transport Defects 结构蛋白缺陷Disorders of Structural Proteins 药物遗传疾病 Pharmacogenetic Diseases
S’
phenylalanine
S’’
PAH
tyrosine
P’
PБайду номын сангаас’
• Mental retardation • “mousy” odor in urine • seizure disorder
• hypopigmentation of skin and hair
Therapy
1. Dietary reduction of phenylalanine 2. BH4
Human immunodeficiency virus
Toxoplasmosis
3-Methylcrotonyl-CoA carboxylase
Carnitine uptake defect (Carnitine transport defect)
注：我国部分地区开展
Comparison of Newborn Screening between China and
USA
Carbamoylphosphate synthetase
Hyperammonemia/ornithinemia/ citrullinemia Prolinemia
Ethylmalonic encephalopathy
临床表现Clinical features: Mental retardation 智力障碍 “mousy” odor in urine 鼠尿味 seizure disorder 癫痫 hypopigmentation浅染 of skin and hair
一家两个PKU，失查，但接受治疗
Phenylketonuria (PKU)
Newborn screening
Comparison of Newborn Screening between China and USA
Biotinidase Cystic fibrosis galactosemia (Classical) Sickle – C disease Hearing screening Congenital adrenal hyperplasia Congenital hypothyroidism Sickle cell disease β-thalassemia 5-oxoprolinuria (pyroglutamic aciduria) Glucose 6 phosphate dehydrogenase Nonketotic hyperglycinemia Benign hyperphenylalaninemia
酶 Enzymes 转运和储存 Transport and storage 细胞和器官的结构Structure of cells and organs 维持细胞外稳定Extracellular homeostasis 发育相关基因表达Development gene expression 控制生长和分化 Control of growth and differentiation 细胞内代谢和信息 Intercellular metabolism and communication
P’
S’’
P’’
Hyperphenylalaninemias
高苯丙氨酸血症
Hyperphenylalaninemias
Locus Heterogeneity
PAH 苯丙氨酸羟化酶 BH4 metabolism: BH4 recycling: PCD, DHPR
BH4 synthesis: GTP-CH, PTS
present in a limited number of cell types, have unique functions that contribute to the individuality of the cells
根据蛋白质的功能分类
Classes of Proteins according to their functions
Allelic Heterogeneity Different PAH mutation leads to different residual activity. 残留
活性多少决定症状轻重 Variant PKU
Phenylketonuria (PKU)
发病率Incidence: 1 /3500 - 16000 in population
遗传性酶病
Hereditary Enzymopathy
The inborn errors of metabolism is caused by gene mutation which lead to enzyme protein variants.
Mutant Enzyme
S’
Substrate
Product