Diagnosis
of the Hereditary Disease
Medical Genetics
Clinical Diagnosis
History taking
Physical examination
Other examination
Pedigree analysis
Family history
Marital history,marriageable age,times of
marriage,consanguineous Marriage
Childbearing history,Childbearing Age,
No of Children,abortion,fetal death,
pregnant history,exposure of teratogen,
age of onset
History Taking
Separately
Specialists
Physical Examination
Clinical chemistry
Radiology
Supersonics
Karyotype analysis
Molecular genetics
Other Examination
Pedigree Analysis
Mendelian inheritance
Non-Mendelian inheritance
Others
Cytogenetics
Fragile site
In situ hybridization
Cytogenetics
Growth retardation & Mental retardation
Balanced translocation & Mosaic
Affected in family
Multiple abortion woman and her husband
Infertility
Advanced maternal age
Internal/external genital malformation
Clinical Chemistry
Phenylketonuria,PKUⅠ
Enzyme activity PAH Liver
Blood sample Bacillus subtilis Guthrie test
FeCl3 Phenylpyruvic acid Green
Newborn Screening
Gene Diagnosis
Detection of genetic disorders by
DNA analysis
Gene Diagnosis
Pathway
Molecular hybridization
Polyperase chain reaction (PCR)
Mendelian Inheritance
Autosomal dominant diseases
Pedigree characteristics
Influencing factors
Penetrance
Expressivity
Sex
Pleotropy
Mendelian Inheritance
Autosomal dominant diseases
Pedigree characteristics
Influencing factors
Environmental factors
Somatic mutation
Dynamic mutation
Modifier gene
Mendelian Inheritance
Autosomal recessive diseases
Pedigree characteristics
Influencing factors
Genetic heterogeneity
o Genetic compound
o Double heterozygote
Uniparental disomy
Mendelian Inheritance
X-linked recessive diseases
Pedigree characteristics
Influencing factors
Lyonization
Recurrent mosaic
Mendelian Inheritance
X-linked dominant diseases
Pedigree characteristics
Influencing factors
Lyonization
Mendelian Inheritance
Y-linked diseases
Holandric inheritance
Back
Mendelian Inheritance
Partial sex-linked
Pseudoautosomal region
X-linked or Y-linked
Non-Mendelian Inheritance
Mitochondrial disorder
Replicative segregation
Matrilineal inheritance
Heteroplasmy & Homoplasmy
Degenerative diseases
Non-Mendelian Inheritance
Polygenic Disease
Heritability
Carter-effect
Back
Non-Mendelian Inheritance
Genetic Imprinting
Non-Mendelian Inheritance
Dynamic mutation
ATG TAA
CGG
Fra X
FraXE
11B
CAG
Gln
HD
SCA1
DRPLA
MJD
SBMA
GAA
FRDA
CGG
XF
16A
CTG
DM
Non-Mendelian Inheritance
Uniparental disomy
AR & Growth retardation,mental retardation
AR → dominant inheritance
X-linked → father to son
Balanced translocation & birth defect
Sex-influenced inheritance
Sex-limited inheritance
Non-Mendelian Inheritance
Sex
Non-Mendelian Inheritance
Modifier gene
Back
Molecular Hybridization
-
+
Southern
Blot
Pathologic Mutation
Sickle cell anemia (HbS),code 5~7
A?A?A?S?S?S
MstⅡ,CCTNAGG
1.2 Kb 0.2Kb
1.40 Kb
1.20 Kb
0.20 Kb
A,CCTGAGGAG
S,CCTGTGGAG
Neurofibroma,NF1
RFLP
Ⅰ
Ⅱ
Ⅲ
1 2
1 2 3 4 5 6 7 8
1 2 3 4 5 6 7 8
4.7 kb
3.0 kb
Linkage Analysis
Haplotype Analysis
A set of closely linked genetic markers
present on one chromosome which tend to
be inherited together (not easily separable
by recombination).
Haplotype Analysis
5.6 Kb
5.2 Kb
4.2 Kb
4.0 Kb
Hind Ⅲ
PKU,AR1 2Ⅰ
Ⅱ
1 2 3
SphⅠ
11.0 Kb
9.7 Kb
7.0 Kb
Back
ASO Hybridization
PKU,AR
Normal probe
Mutation probe
1.2 kb 0.2 kb
Sickle cell anemia (HbS),code 5~7
MstⅡ,CCTNAGG?A,CCTGAGGAG
S,CCTGTGGAG
PCR-RFLP
PCR-RFLP
PCR-ASO
PKU,AR
Normal probe
Mutation probe
1 2 3 4 5
a b
PCR-SSCP
single strand conformation polymorphism
PCR-SSCP
GAA→GA G TGT→T AT CTC→C AC
PCR-DGGE
Denaturing gradient gel electrophoresis
PCR-DGGE
1 2 3 4 5 6 7 8 9 10 11 19
24
28
33
37
42
Multi-PCR