g6pd deficiency
DESCRIPTION
G6PD deficiency. Glucose-6-phosphate dehydrogenase ( G6PD ) ( 葡萄糖 -6- 磷酸脫氫酶 ) is an enzyme produced in immature red blood cells. G6PD deficiency. It protects the red blood cells from being oxidized and destroyed. G6PD deficiency. - PowerPoint PPT PresentationTRANSCRIPT
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Glucose-6-phosphate dehydrogenase (G6PD) (葡萄糖 -6-磷酸脫氫酶 ) is an enzyme produced in immature red blood cells.
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It protects the red blood cells from being oxidized and destroyed.
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About 5% of the HK population have G6PD deficiency (葡萄糖 -6-磷酸脫氫酶缺乏症/蠶豆症 ).
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If they are exposed to substances with oxidizing properties, their red blood cells will break down rapidly.
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How does a mutation in the gene forG6PD cause the enzyme deficiency
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The chemical Basis of Inheritance
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Chromatin / Chromosomes
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Organism estimated size estimated gene number average gene density chromosome # Homo sapiens (human) 2900 million bases ~30,000 1 gene per 100,000 bases 46
Rattus norvegicus (rat) 2,750 million bases ~30,000 1 gene per 100,000 bases 42
Mus musculus (mouse) 2500 million bases ~30,000 1 gene per 100,000 bases 40
Drosophila melanogaster 180 million bases 13,600 1 gene per 9,000 bases 8 (fruit fly)
Arabidopsis thaliana 125 million bases 25,500 1 gene per 4000 bases 5(plant)
Zea mays (corn) 5000 million bases ~25,000 1 gene per 200,000 bases 10
Oryza sativa (rice) 565 ~25,000 1 gene per 23000 bases 12
Caenorhabditis elegans 97 million bases 19,100 1 gene per 5000 bases 6(roundworm)
Saccharomyces cerevisiae 12 million bases 6300 1 gene per 2000 bases 16(yeast)
Escherichia coli 4.7 million bases 3200 1 gene per 1400 bases 1(bacteria)
H. influenzae (bacteria) 1.8 million bases 1700 1 gene per 1000 bases 1
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Chromosome = Protein + DNA
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Indirect Evidence of DNA as genetic material
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Bacteria transforming factor- Griffiths 1928
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27.2 Genes and heredity
What are genes?
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gene (基因 )
• a segment of the DNA molecule of a chromosome
chromosome
Genes
DNA
27.2 Genes and heredity
protein
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gene (基因 )
• basic unit of heredity
chromosome
DNA
27.2 Genes and heredity
protein
Genes
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• position of a gene on a chromosome
chromosome
gene locus (基因位點 )
27.2 Genes and heredity
Genes
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• different forms of a genealleles (等位基
因 )
• located at the same gene locus
27.2 Genes and heredity
homologous chromosomes
Genes
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• the DNA of a gene carries genetic information for making a polypeptide
gene
polypeptide
protein
27.2 Genes and heredity
Genes
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structural proteins
enzymes
hormones
carrier proteins or
channel proteins
27.2 Genes and heredity
examples:Genes
gene
polypeptide
protein
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• each characteristic is controlled by one or more genes
27.2 Genes and heredity
genes determine the body characteristics or traits of an organism
Genes
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What are nucleic acids?
27.2 Genes and heredity
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chromosome
a kind of nucleic acids
Nucleic acids27.2 Genes and heredity
DNA
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• consist of nucleotides (核苷酸 )
phosphate group
5-carbon sugar nitrogenous base
(含氮鹼基 )
Chemical structure
27.2 Genes and heredity
Nucleic acids
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• many nucleotides are joined to form polynucleotide
bonding between sugar and phosphate
group
27.2 Genes and heredity
Chemical structureNucleic acids
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27.2 Genes and heredity
Chemical structure• many nucleotides are joined to form
polynucleotide
Nucleic acids
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sugar-phosphate backbone
27.2 Genes and heredity
Chemical structure• many nucleotides are joined to form
polynucleotide
Nucleic acids
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DNA (脫氧核糖核酸 )
RNA (核糖核酸 )
• two common types:
27.2 Genes and heredity
Chemical structureNucleic acids
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DNA – A Nucleotide unit
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DNA – Sugar / pentose
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double-stranded
single-stranded
DNA RNA
27.2 Genes and heredity
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DNA RNA
27.2 Genes and heredity
sugar:deoxy-
ribose (脫氧核糖 )
sugar:ribose (核糖 )
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DNA RNA
27.2 Genes and heredity
base:base:adeninethyminecytosineguanine
adenineuracil
cytosineguanine
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DNA RNA
27.2 Genes and heredity
base:base:A
thyminecytosineguanine
Auracil
cytosineguanine
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DNA RNA
27.2 Genes and heredity
base:base:AT
cytosineguanine
AU
cytosineguanine
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DNA RNA
27.2 Genes and heredity
base:base:ATC
guanine
AUC
guanine
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DNA RNA
27.2 Genes and heredity
base:base:ATCG
AUCG
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DNA vs
RNA
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DNA vs RNA
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What is the structure of DNA?
27.2 Genes and heredity
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Watson-Crick model of DNA• proposed by James Watson
and Francis Crick in 1953
27.2 Genes and heredity
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• two chains twist around each other to form a double
helix (雙螺旋 )
Watson-Crick model of DNA• two polynucleotide chains
run in opposite directions
27.2 Genes and heredity
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DNA – Base pairing
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Complementary base pairing
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Watson-Crick model of DNA• complementary base
pairing (互補鹼基配對 )
A pairs with TC pairs with G
hydrogen bond
27.2 Genes and heredity
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Watson-Crick model of DNA27.2 Genes and heredity
2 nm
3.4 nm
a complete turn contains 10 base pairs
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DNA – Sugar phosphate backbone
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DNA – 2 antiparallel chains
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DNA - The molecule of life
Each cell:
•46 chromosomes
•2 meters of DNA
•3 billion DNA bases
•Approximately 30,000 genes
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Why is DNA well suited to its function as a genetic material?
27.2 Genes and heredity
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Genetic code
base sequence
amino acid sequence
27.2 Genes and heredity
…
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determinesgenetic code
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27.2 Genes and heredity
…
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… four types of bases+
millions of bases in a chain
large amount of genetic information
Amount of genetic information
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27.2 Genes and heredity
Stability
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hydrogen bond• maintains the helical
structure
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Replication
27.2 Genes and heredity
hydrogen bonds break
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two strands separated
27.2 Genes and heredity
Replication
58template template
free nucleotides
27.2 Genes and heredity
Replication
59template template
27.2 Genes and heredity
Replication
under the action of DNA
polymerase…
60template template
27.2 Genes and heredity
Replication
new strands formed
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27.2 Genes and heredity
Replication
identical
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• pairing of specific bases allows accurate replication of DNA
27.2 Genes and heredity
Replication
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27.2 Genes and heredity
Replication
• pairing of specific bases allows accurate replication of DNA
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same genetic information can be passed to offspring
27.2 Genes and heredity
Replication
• pairing of specific bases allows accurate replication of DNA
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DNA replication – overall process
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DNA replication
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28.1 From DNA to proteins
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28.1 From DNA to proteins
• the way in which the base sequence in a DNA strand determines the amino acid sequence in a polypeptide
The genetic code
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28.1 From DNA to proteins
4 bases
Glu
Gln
His
Gly
Ile
Lys
Leu
Phe
Met
Pro
Thr
Ser
Tyr
Trp
Val
Arg
Ala
Asp
Asn
Cys
20 amino acids
The genetic code
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28.1 From DNA to proteins
• three bases code for one amino acid triplet code (三聯體密
碼 )DNA strand
amino acids
The genetic code
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28.1 From DNA to proteins
• 43 = 64 triplet codes
More than enough!
The genetic code
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The triplet code I
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28.1 From DNA to proteins
• degenerate code (簡併密碼 )
Cys Cys
The genetic code
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The triplet code IV- degenerate
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28.1 From DNA to proteins
• some are start signals and stop signals• no gaps, read in a non-overlapping
manner
The genetic code
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The triplet code II- start
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The triplet code III- termination
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The triplet code IV- Non-overlapping
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Breaking the code
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Breaking the code
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28.1 From DNA to proteins
• universal
Cys
The genetic code
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• two stages:
transcription (轉錄 )
translation (轉譯 )
Protein synthesis28.1 From DNA to proteins
• DNA RNA
• RNA polypeptide
nucleus
cytoplasm
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2
Animation
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Central Dogma
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1 Transcription28.1 From DNA to proteins
a The two DNA strands are held together by weak hydrogen bonds.
…
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28.1 From DNA to proteins
b The hydrogen bonds break and the two DNA strands separate.
…
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1 Transcription
…
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28.1 From DNA to proteins
c Under the action of RNA polymerase, free nucleotides are added against a template.
1 Transcription
…
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…
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…
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template strand
free nucleotides
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28.1 From DNA to proteins
1 Transcription
…
…
……
…
……
…
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template strand
mRNA
c A messenger RNA is synthesized.
triplet code
codon (密碼子 )
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28.1 From DNA to proteins
1 Transcription
…
…
……
…
……
…
……
template strand
mRNA
d The messenger RNA leaves the nucleus.
to cytoplasm
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Transcription
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Transcription- animated
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Transcription- coding strand
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2 Translation28.1 From DNA to proteins
• occurs at ribosomes (核糖體 )
made up of ribosomal RNA
(rRNA) and proteins
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2 Translation28.1 From DNA to proteins
• occurs at ribosomes (核糖體 )
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2 Translation28.1 From DNA to proteins
• occurs at ribosomes (核糖體 )
attached to endoplasmic reticulum (ER)
free-floating
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2 Translation28.1 From DNA to proteins
• occurs at ribosomes (核糖體 )
What happens during translation?
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2 Translation28.1 From DNA to proteins
a The mRNA attached to a ribosome.
mRNA
ribosome
codon 1 2 3 n(start) (stop)
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2 Translation28.1 From DNA to proteins
b A specific amino acid is carried to the ribosome by a transfer RNA.
tRNA
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t-RNA
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t-RNA binding sites
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Aminoacyl-tRNA complex
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Ribosome- P and A sites
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Ribosome- P and A sites
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Translation
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Translation- animated
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2 Translation28.1 From DNA to proteins
b A specific amino acid is carried to the ribosome by a transfer RNA.
amino acid
RNA strand
anticodon (反密碼子 )
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2 Translation28.1 From DNA to proteins
c The anticodon on the tRNA molecule binds to the first codon on the mRNA.
… … …
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2 Translation28.1 From DNA to proteins
… … … … … …
c The anticodon on the tRNA molecule binds to the first codon on the mRNA.
Complementary!
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2 Translation28.1 From DNA to proteins
d Another tRNA molecule carrying an amino acid binds to the next codon.
… … … … … …
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2 Translation28.1 From DNA to proteins
d The two amino acids link up by a peptide bond to form a dipeptide.
… … … … … …
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Ribosome- P and A sites
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… … … … … …
2 Translation28.1 From DNA to proteins
e The ribosome moves along the mRNA until a stop codon is met.
direction of translation
stop codon
one amino acid added at a time
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Translation- animated
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2 Translation28.1 From DNA to proteins
f The polypeptide is then released.
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2 Translation28.1 From DNA to proteins
f It coils and folds to form a protein. Some proteins are formed by two or more polypeptides binding together.
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28.1 From DNA to proteins
• proteins made at ribosomes on rough ER will be transported inside the ER
What happens to the proteins synthesized?
secreted by the cell
embedded in cell membrane
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28.1 From DNA to proteins
• proteins made at free-floating ribosomes will remain in the cytoplasm used by the cell
What happens to the proteins synthesized?
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Replication - transcription -translation
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GTCA song
•http://www.youtube.com/watch?v=ID6KY1QBR5s
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Genetic code expressed in terms of mRNA codons:
28.1 From DNA to proteins
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1 Features:
28.1 From DNA to proteins
a Each genetic codeis a that is made up of three bases.
triplet code
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1 Features:
28.1 From DNA to proteins
b The genetic codeis known as
as some amino acids have more than one code.
degenerate code
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1 Features:
28.1 From DNA to proteins
c The genetic codehas no gaps and isnon-overlapping .
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1 Features:
28.1 From DNA to proteins
d The genetic codeis asthe same triplet code codes for the same amino acid in all organisms.
universal
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2 The process by which genetic information contained in a gene is decoded to make a protein is called .
28.1 From DNA to proteins
gene expression
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3 Protein synthesis:
28.1 From DNA to proteins
DNA template strand
mRNA
transcription
translation
polypeptide
coiling and folding
protein
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4a Some of the proteins synthesized will be transported inside the
28.1 From DNA to proteins
rough endoplasmic reticulum before being secreted out by the cell or embedded in the
.cell membrane
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4b Some of the proteins synthesized will be used by the itself.
28.1 From DNA to proteins
cell
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28.2 Mutations• sudden and permanent change of DNA• two types:
gene mutations (基因突變 )
chromosome mutations (染色體突變 )
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Mutation
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Mutation_altered genetic info
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Mutation leads to changes in genotype
and phenotype
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Types of mutation
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Somatic vs Germinal mutation
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Early vs Late somatic mutation
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deletion (缺失 )
• different forms:
insertion (插入 ) substitution (取代 ) inversion (倒位 )
28.2 Mutations
• a change in the base sequence of the DNA in a gene
1 Gene mutationsAnimation
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Base sequence in coding strand
Amino acid sequence
Normal
Deletion
ATG CAT GTA TTG
ATG ATG TAT TG
Met–His–Val–Leu
Met–Met–Tyr
28.2 Mutations
1 Gene mutations
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Base sequence in coding strand
Amino acid sequence
Normal
ATG GCA TGT ATT G
Met–His–Val–Leu
Met–Ala–Cys–Ile
28.2 Mutations
ATG CAT GTA TTG
Insertion
1 Gene mutations
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Base sequence in coding strand
Amino acid sequence
Normal
ATG TAT GTA TTG
Met–His–Val–Leu
Met–Tyr–Val–Leu
28.2 Mutations
ATG CAT GTA TTG
Substitution
1 Gene mutations
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Base sequence in coding strand
Amino acid sequence
Normal
ATG ACT GTA TTG
Met–His–Val–Leu
Met–Thr–Val–Leu
28.2 Mutations
ATG CAT GTA TTG
Inversion
1 Gene mutations
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28.2 Mutations
• deleting or inserting a number of bases that is not a multiple of three will shift the reading frame (讀框 )
Normal
Insertion ATG GCA TGT ATT G
Met–His–Val–Leu
Met–Ala–Cys–Ile
ATG CAT GTA TTG
Altered!
1 Gene mutations
Frame-shift mutation
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28.2 Mutations
• deleting or inserting a number of bases that is not a multiple of three will shift the reading frame (讀框 )
Normal
Insertion ATG GCA TGT ATT G
Met–His–Val–Leu
Met–Ala–Cys–Ile
ATG CAT GTA TTG
Resulting protein is usually non-functional.
1 Gene mutations
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28.2 Mutations
• a substitution or an inversion of base(s) may result in a different amino acid
Normal
Inversion ATG ACT GTA TTG
Met–His–Val–Leu
Met–Thr–Val–Leu
ATG CAT GTA TTG
It may affect the protein’s structure or function.
1 Gene mutations
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28.2 Mutations
• sickle-cell anaemia (鐮狀細胞性貧血 ) is caused by the substitution of a base
1 Gene mutations
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28.2 Mutations
normal DNA template
mRNA
polypeptide
transcription
translation
Glu Val
sickle-cell anaemia
1 Gene mutations
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28.2 Mutations
red blood cells
normal
sickle-shaped
can block blood vessels
1 Gene mutations
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Gene-mutation:Sickled-cell
anaemiaThe amino acid sequences for the normal and abnormal P chains differ in the substitution of valine for glutamic acid at one point in the abnormal polypeptide chains of haemoglobin S
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sickle cell anemia distribution in relation to malaria
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28.2 Mutations
• a change in the structure or total number of chromosomes
2 Chromosome mutations
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deletion
• different forms:
duplication (複製 ) inversion
translocation (易位 )
28.2 Mutations
i) Changes in chromosome structure2 Chromosome mutations
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deletion
28.2 Mutations
i) Changes in chromosome structuregenes
loss of genes
2 Chromosome mutations
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duplication
28.2 Mutations
i) Changes in chromosome structure
gain of genes
2 Chromosome mutations
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inversion
28.2 Mutations
i) Changes in chromosome structure
order of genes reversed
2 Chromosome mutations
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translocation
28.2 Mutations
i) Changes in chromosome structure2 Chromosome mutations
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28.2 Mutations
i) Changes in chromosome structure translocation
2 Chromosome mutations
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28.2 Mutations
i) Changes in chromosome structure translocation
2 Chromosome mutations
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28.2 Mutations
i) Changes in chromosome structure translocation
exchange of genes
2 Chromosome mutations
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• homologous chromosomes or chromatids fail to separate during gamete formation
28.2 Mutations
ii) Changes in chromosome number2 Chromosome mutations
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Karyotype – detect chromosome mutation
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To obtain a karyotype
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28.2 Mutations
ii) Changes in chromosome number2 Chromosome mutations
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28.2 Mutations
ii) Changes in chromosome number
Downsyndrome
2 Chromosome mutations
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28.2 Mutations
ii) Changes in chromosome number
mother’s age (years)appr
oxim
ate
risk
of
havi
ng c
hild
ren
with
D
own
synd
rom
e
0
1/35
20 25 30 35 40 45
2 Chromosome mutations
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28.2 Mutations
abnormal ovum
n + 1
ii) Changes in chromosome number
two chromosome 21
2 Chromosome mutations
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28.2 Mutations
abnormal ovum
n + 1
ii) Changes in chromosome number
n
normal sperm
2n + 1
three chromosome 21
Downsyndrome
2 Chromosome mutations
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Kleinfelter syndrome
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28.2 Mutations
parent cell (2n)
1st meiotic division
2nd meiotic division
chromatids fail to separate
n n n - 1 n + 1
ii) Changes in chromosome number2 Chromosome mutations
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Chromosome Mutation-non disjunction I
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Chromosome Mutation-non disjunction II
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polyploidy_of uneven chromosome no. --- seedless fruit
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How to make seedless fruits?
Triploid plants have three sets of chromosomes, and three sets cannot be divided evenly when they go into two daughter cells during meiosis. Since the triploid hybrid is female sterile, the fruit are seedless. Because the triploid is also male sterile, it is necessary to plant a diploid cultivar in the production field to provide the pollen that stimulates fruit to form.
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Hybrid_sterililty
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Unpaired chromosomes—results in abnormal gametes
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• occur naturally and randomlySpontaneous mutations (自發突
變 )• occur at a very low rate
Causes of mutations28.2 Mutations
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• induced by exposure to certain chemicals and radiation
Induced mutations (誘發突變 )Causes of mutations
28.2 Mutations
increase the rate of mutation
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• induced by exposure to certain chemicals and radiation
Induced mutations (誘發突變 )Causes of mutations
28.2 Mutations
mutagens (誘變劑 )
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• induced by exposure to certain chemicals and radiation
Induced mutations (誘發突變 )Causes of mutations
28.2 Mutations
change the chemical structure of DNA
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• induced by exposure to certain chemicals and radiation
Induced mutations (誘發突變 )Causes of mutations
28.2 Mutations
ionize water to form free radicals (自由基 )
highly reactive and can damage DNA
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Mutagen Source
Chemical
Nitrous acid(亞硝酸 )
Tar
Food preservatives
Cigarette smoke
28.2 Mutations
Causes of mutations
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Mutagen Source
Chemical
Asbestos(石棉 )
Mustard gas (芥子氣 )
Construction materials
Chemical warfare
28.2 Mutations
Causes of mutations
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Mutagen Source
Radiation
Ultraviolet light (紫外光 )X-ray
Sunlight
Medical examination
28.2 Mutations
Causes of mutations
Gamma ray (伽瑪射線 )
Radiotherapy, nuclear bombs
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• usually harmful
Significance of mutations28.2 Mutations
diseases or death
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Results of mutation
Extra compound eyes Variations in pigments
Both Wings on same side Sickled cell anaemia
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Significance of mutation
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• sometimes beneficial
28.2 Mutations
• mutations occurring in gametes or gamete-producing cells are inheritable source of variations essential for natural selection
(自然選擇 ) to bring about evolution
Significance of mutations
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1 A gene mutation is a change in the of the DNA in a gene.base sequence
28.2 Mutations
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2 A chromosome mutation is a change in the or
of chromosomes.structure
total number
28.2 Mutations
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3a mutations occur naturally and randomly.Spontaneous
28.2 Mutations
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3b mutations are induced by exposure to mutagens.Induced
28.2 Mutations
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4
Chemical
Radiation
Mutagen Examples
Nitrous acid, tar,asbestos, mustard gas
Ultraviolet light, X-ray, gamma ray
28.2 Mutations
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How can G6PD be produced only inred blood cells?1
Although each cell has a copy of all the genes in an organism, some genes are expressed in certain types of cells only.
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How can G6PD be produced only inred blood cells?1
In this case, the G6PD gene is ‘switched on’ in immature red blood cells, but ‘switched off’ in all other cells.
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How is G6PD made in the cells?2In the synthesis of G6PD, information in the genes is first copied to mRNA in transcription. Then translation takes place to produce a polypeptide. The polypeptide coils, folds and binds with other polypeptides to form G6PD.
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How does a mutation in the gene forG6PD cause the enzyme deficiency?3In G6PD deficiency, the mutation in the G6PD gene results in a change of the triplet codes.
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How does a mutation in the gene forG6PD cause the enzyme deficiency?3That in turns results in a polypeptide with a wrong sequence of amino acids and normal G6PD cannot be produced.
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involves two stages
Protein synthesis
transcription
nucleus
translation
takes place in
mRNA
produces
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involves the following organelles
cytoplasm
translation
ribosomes
produces
polypeptide
located incoils and folds to form
protein
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affected by
mutation
spontaneous mutation
induced mutation
mutagens
may be
induced by
Protein synthesis
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occurs in
genes chromosomes
mutation