the Basis of Genetics
Medical Genetics
Cellular Basis of Genetics
Structure of Eukaryote
1,Strongly condensed
Euchromatin & heterochromatin
Euchromatin
Heterochromatin
Chromotin & Chromosome
2,Genetic inertia
3,Be late to replicate
a,Constitutive heterochromatin
b,Facultative heterochromatin
Sex chromotin
X chromatin
X body
Barr body
Chromotin & Chromosome
Sex chromotin
Lyon hypothesis (1961)
1,Inactivation of all but one X chromosome
2,Happened at an early stage of embryogenesis
3,Happened on a random basis and maintained
in all descendant cells
Dosage compensation
Chromotin & Chromosome
Sex chromotin
Y-chromatin
Chromotin & Chromosome
Sex Determining Mechanism
Chromosomal mechanisms (XY)
Y chromosome
Two sex chromosomes of different sizes,X is larger
TDF,testis-determining factor
SRY,sex-determining region of Y chromosome
Females are XX,males are XY
Males determine the sex of the offspring
Molecular Basis of Genetics
bp
P
A T G
C
Structure of DNA
Deoxyribose
Adenine(A)
N
N
N H
N
N H 2
Guanine(G)
N
NH
N H
N
NH 2
O
Cytosine(C)
N
NH
NH2
O
Thymine(T)
N H
NH
O
O
C H 3
Structure of DNA
Structure of DNA
Genome
Unique sequence
Repetitive sequence
Highly repetitive sequence
Intermediate repetitive sequence
Multigene family & Pseudogene
Structure of DNA
Molecule Structure of
Eukaryotic Gene
Gene,a structural unit of inheritance,A
sequence of chromosome DNA
that is required for production of
a functional product.
Molecule Structure of
Eukaryotic Gene
Split gene,genes containing coding regions
(exons) that are interrupted by
noncoding regions (introns).
Molecule Structure of
Eukaryotic Gene
Molecule Structure of
Eukaryotic Gene
Molecule Structure of
Eukaryotic Gene
Exon
Intron
GT - AG law
Molecule Structure of
Eukaryotic Gene
Molecule Structure of
Eukaryotic Gene
Flanking Sequence
TATA
box Exon
Intron
T A T A AHogness box AT AT
Hogness Box
Molecule Structure of
Eukaryotic Gene
CAAT
box
TATA
box Exon
Intron
CAAT box G G C A A T C TCT
Molecule Structure of
Eukaryotic Gene
GC box G G C G G G
CAAT
box
GC box
TATA
box Exon
Intron
Molecule Structure of
Eukaryotic Gene
CAAT
box
GC box
Enhancer
TATA
box Exon
Intron
Core sequence GGTGTGG GAAATTT
Molecule Structure of
Eukaryotic Gene
Regulator Sequence
CAAT
box
GC box AATAAA
Enhancer
TATA
box Exon
Intron
1,Semi – conservative replication
DNA Replication
2,Semi – discontinuous replication
1,Semi – conservative replication
DNA Replication
Expression
Gene Expression
Transcription
Coding strand (sense strand)
Anticoding strand (antisense strand)
hnRNA (heterogenious RNA)
Expression
Gene Expression
Transcription
1,Methylated cap (m7?G)
O
CH
C H
O
C H
C H
CH
2
O H O H
O
O
-
O
O
P
C
C
C
N
NH
C
N
C H
N
+
NH
2
O C H
3
R
Methylated cap (m7?G)
Expression
Gene Expression
Transcription
1,Methylated cap (m7?G)
2,Splicing
Expression
Gene Expression
Expression
Gene Expression
Transcription
1,Methylated cap (m7?G)
2,Splicing
3,Ploy A
Expression
Gene Expression
Expression
Gene Expression
Transcription
1,Methylated cap (m7?G)
2,Splicing
3,Ploy A
4,mRNA editing
Expression
Gene Expression
Translation
Codon,the nucleotide triplet in the mRNA
that specifying a single amino acid
during translation.
Degeneracy,more than one codons for the
same amino acid.
DNA
RT
Central dagma of eukaryote
Gene Expression
RNAtranscription Proteintranslation
replicationreplication
Information flow
Genetic Imprinting
The phenomenon whereby the degree
to which a gene expresses itself depends
upon the parent transmitting it.
Genomic imprinting
Parental imprinting
Uniparental disomy
Genetic Imprinting
Prader-Willi syndrome(PWS) & Angleman syndrome(AS)
Paternal deletions in PWS
Maternal deletions in AS
del(15)(q11-q13)
Genetic Imprinting
Huntington chorea (MIM 143100)
1 2 3 4 5
Ⅰ
Ⅱ
Ⅲ
1 2
1 2 3 4 5
44
45
42
31
41
30 46
Structure of Lac operon
DNAR P O LacZ LacY LacA
Operon：
Structural genes or Regulatory region
Gene Regulation
Gene Regulation
Mutation
Gene mutation
Point mutation
Wild-type & Mutant gene
Base-pair substitution
Same sense mutation
Missense mutation
Nonsense mutation
Termination codon mutation
Mutation
Transition & Transversion
Tyr Lys Ser Tyr Arg Lys Gly
Frame shift mutation
Tyr Ser Pro Thr Glu Arg Glu
UAC AGU CCU ACA GAA AGG GAG
Tyr Val Leu Gln Lys Gly
UAC AAG UCC UAC AGA AAG GGA GInsertion
UAC GUC CUA CAG AAA GGG AGDeletion
Mutation
Fra X syndrome (CGG)n
n = 6 ～ 46； normal
n = 60 ～ 200； pre - mutation
n = 200 ～ 230； patient
Dynamic mutation
Mutation
Huntington chorea (MIM 143100)
Photo - repair
DNA Repair
Excision repair
Postreplication repair
Recombination repair
Photo - repair
DNA Repair
Highly Repetitive Sequence
1,Satellite DNA
2,Minisatellite DNA
Microsatellite DNA or STR
3,Inverted repeat sequence
Highly Repetitive Sequence
1,Satellite DNA
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G T C C T G A C C G T G T C A G G A T
C A G G A C T G G C A C A G T C C T A
G T C C T G A C G T C A G G A T
C A G G A C T G C A G T C C T A
Palindrome
Highly Repetitive Sequence
Alu family
Intermediate Repetitive Sequence
1,SINE(short interspersing element)
2,LINE(long interspersing element)
KpnⅠ family
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Multigene Family
A set of genes descended by duplication
and variation from some ancestral gene.
Such genes may be clustered together on the
same chromosome or dispersed on different
chromosomes.
crystallin gene
Globin gene
Pseudogene
An inactive gene within a gene family,
derived by mutation of an ancestral active
gene and frequently located within the
same region of the chromosome as its
functional counterpart.
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