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.

It protects the red blood cells from being oxidized and destroyed.

About 5% of the HK population have G6PD deficiency (葡萄糖 -6-磷酸脫氫酶缺乏症／蠶豆症 ).

If they are exposed to substances with oxidizing properties, their red blood cells will break down rapidly.

How does a mutation in the gene forG6PD cause the enzyme deficiency

The chemical Basis of Inheritance

Chromatin / Chromosomes

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

Chromosome = Protein + DNA

Indirect Evidence of DNA as genetic material

Bacteria transforming factor- Griffiths 1928

27.2 Genes and heredity

What are genes?

gene (基因 )

• a segment of the DNA molecule of a chromosome

chromosome

protein

gene (基因 )

• basic unit of heredity

chromosome

protein

• position of a gene on a chromosome

chromosome

gene locus (基因位點 )

• different forms of a genealleles (等位基

• located at the same gene locus

homologous chromosomes

• the DNA of a gene carries genetic information for making a polypeptide

polypeptide

protein

structural proteins

enzymes

hormones

carrier proteins or

channel proteins

examples:Genes

polypeptide

protein

• each characteristic is controlled by one or more genes

genes determine the body characteristics or traits of an organism

What are nucleic acids?

chromosome

a kind of nucleic acids

Nucleic acids27.2 Genes and heredity

• consist of nucleotides (核苷酸 )

phosphate group

5-carbon sugar nitrogenous base

(含氮鹼基 )

Chemical structure

Nucleic acids

• many nucleotides are joined to form polynucleotide

bonding between sugar and phosphate

Chemical structureNucleic acids

Chemical structure• many nucleotides are joined to form

polynucleotide

Nucleic acids

sugar-phosphate backbone

Chemical structure• many nucleotides are joined to form

polynucleotide

Nucleic acids

DNA (脫氧核糖核酸 )

RNA (核糖核酸 )

• two common types:

Chemical structureNucleic acids

DNA – A Nucleotide unit

DNA – Sugar / pentose

double-stranded

single-stranded

DNA RNA

sugar:deoxy-

ribose (脫氧核糖 )

sugar:ribose (核糖 )

DNA RNA

base:base:adeninethyminecytosineguanine

adenineuracil

cytosineguanine

DNA RNA

base:base:A

thyminecytosineguanine

Auracil

cytosineguanine

DNA RNA

base:base:AT

cytosineguanine

DNA RNA

base:base:ATC

guanine

DNA RNA

base:base:ATCG

DNA vs

DNA vs RNA

What is the structure of DNA?

Watson-Crick model of DNA• proposed by James Watson

and Francis Crick in 1953

• 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

DNA – Base pairing

Complementary base pairing

Watson-Crick model of DNA• complementary base

pairing (互補鹼基配對 )

A pairs with TC pairs with G

hydrogen bond

Watson-Crick model of DNA27.2 Genes and heredity

3.4 nm

a complete turn contains 10 base pairs

DNA – Sugar phosphate backbone

DNA – 2 antiparallel chains

DNA - The molecule of life

Each cell:

•46 chromosomes

•2 meters of DNA

•3 billion DNA bases

•Approximately 30,000 genes

Why is DNA well suited to its function as a genetic material?

Genetic code

base sequence

amino acid sequence

determinesgenetic code

… four types of bases+

millions of bases in a chain

large amount of genetic information

Amount of genetic information

Stability

hydrogen bond• maintains the helical

structure

Replication

hydrogen bonds break

two strands separated

Replication

58template template

free nucleotides

Replication

59template template

Replication

under the action of DNA

polymerase…

60template template

Replication

new strands formed

Replication

identical

• pairing of specific bases allows accurate replication of DNA

Replication

same genetic information can be passed to offspring

Replication

DNA replication – overall process

DNA replication

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

4 bases

20 amino acids

The genetic code

• three bases code for one amino acid triplet code (三聯體密

碼 )DNA strand

amino acids

The genetic code

• 43 = 64 triplet codes

More than enough!

The genetic code

The triplet code I

• degenerate code (簡併密碼 )

Cys Cys

The genetic code

The triplet code IV- degenerate

• some are start signals and stop signals• no gaps, read in a non-overlapping

manner

The genetic code

The triplet code II- start

The triplet code III- termination

The triplet code IV- Non-overlapping

Breaking the code

• universal

The genetic code

• two stages:

transcription (轉錄 )

translation (轉譯 )

Protein synthesis28.1 From DNA to proteins

• DNA RNA

• RNA polypeptide

nucleus

cytoplasm

Animation

Central Dogma

1 Transcription28.1 From DNA to proteins

a The two DNA strands are held together by weak hydrogen bonds.

b The hydrogen bonds break and the two DNA strands separate.

1 Transcription

c Under the action of RNA polymerase, free nucleotides are added against a template.

1 Transcription

……

template strand

free nucleotides

1 Transcription

……

template strand

c A messenger RNA is synthesized.

triplet code

codon (密碼子 )

1 Transcription

……

template strand

d The messenger RNA leaves the nucleus.

to cytoplasm

Transcription

Transcription- animated

Transcription- coding strand

2 Translation28.1 From DNA to proteins

• occurs at ribosomes (核糖體 )

made up of ribosomal RNA

(rRNA) and proteins

attached to endoplasmic reticulum (ER)

free-floating

What happens during translation?

a The mRNA attached to a ribosome.

ribosome

codon 1 2 3 n(start) (stop)

b A specific amino acid is carried to the ribosome by a transfer RNA.

t-RNA binding sites

Aminoacyl-tRNA complex

Ribosome- P and A sites

Translation

Translation- animated

b A specific amino acid is carried to the ribosome by a transfer RNA.

amino acid

RNA strand

anticodon (反密碼子 )

c The anticodon on the tRNA molecule binds to the first codon on the mRNA.

… … …

… … … … … …

c The anticodon on the tRNA molecule binds to the first codon on the mRNA.

Complementary!

d Another tRNA molecule carrying an amino acid binds to the next codon.

… … … … … …

d The two amino acids link up by a peptide bond to form a dipeptide.

… … … … … …

Ribosome- P and A sites

… … … … … …

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

Translation- animated

f The polypeptide is then released.

f It coils and folds to form a protein. Some proteins are formed by two or more polypeptides binding together.

• 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

• proteins made at free-floating ribosomes will remain in the cytoplasm used by the cell

What happens to the proteins synthesized?

Replication - transcription -translation

GTCA song

•http://www.youtube.com/watch?v=ID6KY1QBR5s

Genetic code expressed in terms of mRNA codons:

1 Features:

a Each genetic codeis a that is made up of three bases.

triplet code

1 Features:

b The genetic codeis known as

as some amino acids have more than one code.

degenerate code

1 Features:

c The genetic codehas no gaps and isnon-overlapping .

1 Features:

d The genetic codeis asthe same triplet code codes for the same amino acid in all organisms.

universal

2 The process by which genetic information contained in a gene is decoded to make a protein is called .

gene expression

3 Protein synthesis:

DNA template strand

transcription

translation

polypeptide

coiling and folding

protein

4a Some of the proteins synthesized will be transported inside the

rough endoplasmic reticulum before being secreted out by the cell or embedded in the

.cell membrane

4b Some of the proteins synthesized will be used by the itself.

28.2 Mutations• sudden and permanent change of DNA• two types:

gene mutations (基因突變 )

chromosome mutations (染色體突變 )

Mutation

Mutation_altered genetic info

Mutation leads to changes in genotype

and phenotype

Types of mutation

Somatic vs Germinal mutation

Early vs Late somatic mutation

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

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

Amino acid sequence

Normal

ATG GCA TGT ATT G

Met–Ala–Cys–Ile

28.2 Mutations

ATG CAT GTA TTG

Insertion

1 Gene mutations

Amino acid sequence

Normal

ATG TAT GTA TTG

Met–Tyr–Val–Leu

28.2 Mutations

ATG CAT GTA TTG

Substitution

1 Gene mutations

Amino acid sequence

Normal

ATG ACT GTA TTG

Met–Thr–Val–Leu

28.2 Mutations

ATG CAT GTA TTG

Inversion

1 Gene mutations

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

ATG CAT GTA TTG

Altered!

1 Gene mutations

Frame-shift mutation

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

ATG CAT GTA TTG

Resulting protein is usually non-functional.

1 Gene mutations

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–Thr–Val–Leu

ATG CAT GTA TTG

It may affect the protein’s structure or function.

1 Gene mutations

28.2 Mutations

• sickle-cell anaemia (鐮狀細胞性貧血 ) is caused by the substitution of a base

1 Gene mutations

28.2 Mutations

normal DNA template

polypeptide

transcription

translation

Glu Val

sickle-cell anaemia

1 Gene mutations

28.2 Mutations

red blood cells

normal

sickle-shaped

can block blood vessels

1 Gene mutations

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

sickle cell anemia distribution in relation to malaria

28.2 Mutations

• a change in the structure or total number of chromosomes

2 Chromosome mutations

deletion

• different forms:

duplication (複製 ) inversion

translocation (易位 )

28.2 Mutations

i) Changes in chromosome structure2 Chromosome mutations

deletion

28.2 Mutations

i) Changes in chromosome structuregenes

loss of genes

duplication

28.2 Mutations

i) Changes in chromosome structure

gain of genes

inversion

28.2 Mutations

i) Changes in chromosome structure

order of genes reversed

translocation

28.2 Mutations

i) Changes in chromosome structure2 Chromosome mutations

28.2 Mutations

i) Changes in chromosome structure translocation

28.2 Mutations

exchange of genes

• homologous chromosomes or chromatids fail to separate during gamete formation

28.2 Mutations

ii) Changes in chromosome number2 Chromosome mutations

Karyotype – detect chromosome mutation

To obtain a karyotype

28.2 Mutations

ii) Changes in chromosome number

Downsyndrome

28.2 Mutations

mother’s age (years)appr

20 25 30 35 40 45

28.2 Mutations

abnormal ovum

two chromosome 21

28.2 Mutations

abnormal ovum

normal sperm

2n + 1

three chromosome 21

Downsyndrome

Kleinfelter syndrome

28.2 Mutations

parent cell (2n)

1st meiotic division

2nd meiotic division

chromatids fail to separate

n n n - 1 n + 1

Chromosome Mutation-non disjunction I

Chromosome Mutation-non disjunction II

polyploidy_of uneven chromosome no. --- seedless fruit

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.

Hybrid_sterililty

Unpaired chromosomes—results in abnormal gametes

• occur naturally and randomlySpontaneous mutations (自發突

變 )• occur at a very low rate

Causes of mutations28.2 Mutations

• 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

28.2 Mutations

mutagens (誘變劑 )

28.2 Mutations

change the chemical structure of DNA

28.2 Mutations

ionize water to form free radicals (自由基 )

highly reactive and can damage DNA

Mutagen Source

Chemical

Nitrous acid(亞硝酸 )

Food preservatives

Cigarette smoke

28.2 Mutations

Causes of mutations

Mutagen Source

Chemical

Asbestos(石棉 )

Mustard gas (芥子氣 )

Construction materials

Chemical warfare

28.2 Mutations

Causes of mutations

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

• usually harmful

Significance of mutations28.2 Mutations

diseases or death

Results of mutation

Extra compound eyes Variations in pigments

Both Wings on same side Sickled cell anaemia

Significance of mutation

• 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

1 A gene mutation is a change in the of the DNA in a gene.base sequence

28.2 Mutations

2 A chromosome mutation is a change in the or

of chromosomes.structure

total number

28.2 Mutations

3a mutations occur naturally and randomly.Spontaneous

28.2 Mutations

3b mutations are induced by exposure to mutagens.Induced

28.2 Mutations

Chemical

Radiation

Mutagen Examples

Nitrous acid, tar,asbestos, mustard gas

Ultraviolet light, X-ray, gamma ray

28.2 Mutations

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.

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.

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.

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.

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.

involves two stages

Protein synthesis

transcription

nucleus

translation

takes place in

produces

involves the following organelles

cytoplasm

translation

ribosomes

produces

polypeptide

located incoils and folds to form

protein

affected by

mutation

spontaneous mutation

induced mutation

mutagens

may be

induced by

Protein synthesis

occurs in

genes chromosomes

mutation

g6pd deficiency

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