Met
Tyr
Glu
Aia
Asn
Ser
Tyr
Val
Gly
His
STO P
Same sense
mutation 同义突变
ATG TAT GAG GCG AAT TCT TAC GTG GGT CAC TAA GTG ……
Met
Tyr
Glu
Aia
Asn
天门
Ser
Tyr
Val Gly
His
STO P
Missense
Control the gene expression in correct location, time and amount
Gene Mutation
Base substitution: Transition（转换） and transversion（颠换）
Wild type 正常
ATG TAT GAG GCG AAC TCT TAC GTG GGT CAC TAA GTG ……
heterogeneous nuclear RNA
Gene: regulatory regions
Start point
CAAT Box TATA box
Coding region
Gene Structure
Terminate point
Flanking sequence: Regulatory regions on both sides, Promoter, Enhancer, Terminator
Met
Tyr
Glu
Aia
Asn
Ser
STO P
Termination
ATG TAT GAG GCG AAC TCT TAC GTG GGT CAC TAC GTG ……
codon mutation 终止密码子突变
Met Tyr Glu
Aia Asn Ser Tyr来自Val Gly His
Tyr Val
Clinical Genetics 临床遗传学
绪论
一、临床遗传学定义和特点 遗传学和临床医学的交叉课程, 应用遗传学原理和方法开
展人类遗传性疾病（inherited disease, genetic disorder） 诊断、治疗和预防的科学。 医学遗传学（medical genetics）的分支, 1950s 末人类染 色体病发现和医学遗传学建立以后逐渐发展起来 预修: 医学遗传学和诊断学
mutation 错义突变
ATG TAT GAG GCG AAC TTT TAC GTG GGT CAC TAA GTG ……
Met
Tyr
Glu
Aia
Asn
Pha
苯丙
Tyr
Val Gly
His
STO P
Nonsense
mutation 无义突变
ATG TAT GAG GCG AAC TCT TAA GTG GGT CAC TAA GTG ……
Carrier
ATG CGG CGG CGG CGG …… CGG CGG CAC
50-200 triplet repeat
Tendency to expansion of triplet repeat
Fragile X
ATG CGG CGG CGG CGG …… CGG CGG CAC
>200 triplet repeat
Met
Tyr
Aia
Asn
Ser
Tyr
Val
Met 蛋
Gly 甘
His 组
STOP
Dynamic mutation （动态突变）
Normal
ATG CGG CGG CGG CGG …… CGG CGG CAC
6-50 triplet repeat
in the non-coding region of 5’ FMR-1 gene, normal expression
containing the code for the amino acid sequence of a polypeptide chain
controlling the expression of specific characteristics of a living organism.
Gene: exon(外显子) and intron(内含子)
Deletion 缺失
ATG TAT GCG AAC TCT TAC TGG GTC ACT AAG TGT ……
Met
Tyr
Aia
Asn
Ser
Tyr
Trp 色
Val 缬
Thr 苏
Gin Cys 谷 半胱 ……
Insertion
ATG TAT GCG AAC TCT TAC GTG ATG GGT CAC TAA GTG T……
About 1% of genome directing the synthesizing proteins, coding for about 20,000 proteins Structural Gene Region
Other: non-encoding regions
基因: A specific DNA segment
临床遗传学特点
1．遗传病起因于遗传物质的突变 基因和染色体诊断（genetic diagnosis)是最重要的 诊断手段
“—”SRY 48 44 19 17 M
2．遗传病具有家系成员反复发生的风险
家谱分析 pedigree analysis
遗传咨询 genetic counseling
临床遗传学的重要内容
……
蛋 酪 谷 丙 天门 丝 酪 缬 甘 组 酪 缬
Gene Mutation
蛋 酪 丙 天门 丝 酪 缬 甘 组
Frame shift mutation
Wild type 正常
ATG TAT GCG AAC TCT TAC GTG GGT CAC TAA GTG T…… Met Tyr Aia Asn Ser Tyr Val Gly His STOP
3．遗传病多症重而无有效治疗方法
产前遗传学诊断（prenatal genetic diagnosis）预 防遗传病患儿出生是临床遗传学最为有效的技术 手段。
二、遗传学基本概念、原理复习
1.遗传的物质基础： DNA，基因组Genome, 基因 Gene
Human genome: a haploidy set of chromosomes with the mitochondrial DNA, 3.1×109 bp, enough for encoding: 1.5×106 proteins