MUTASI
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Transcript of MUTASI
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Agustina Setiawati, M.Sc., Apt
MUTASI
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Mutasi, mutan & mutagenMutasi• Perubahan basa dalam sekuen DNA (Pd umumnya di dalam suatu gene). • Perubahan ini termasuk : substitusi basa, adisi, penyusunan ulang dan delesiMutan• Organisme yang mengalami mutasi. • Mutasi tersebut tentunya terjadi dalam gena yang menyebabkan terjadinya perbedaan yang nyata dengan bentuk normal (Wild-Type).
Mutagen• pengaruh fisika atau senyawa kimia yang menyebabkan
mutasi.
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Mutagens
A spontaneous mutation occurs once in 108 cells.
The mutation rate can be increased by exposing cells to mutagens, which are either chemicals or physical agents such as UV-irradiation.
Both chemicals and physical agents act by causing genetic damage that results in base changes in DNA
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Mutagenesis
- Proses terjadinya suatu mutasi- Bisa terjadi secara:
(a) Spontan (natural process) terjadi <1 in 108
E. coli misalnya saat kesalahan replikasi DNA(b)Diinduksi (mis. dengan mutagen(EMS atau sinar
UV).
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Mismatches saat DNA replikasi
5’-ATTGG-3’3’-TAACC-5’
5’-ATGGG-3’3’-TAACC-5’
5’-ATGGG-3’3’-TACCC-5’
5’-ATTGG-3’3’-TAACC-5’
Normal
Mutan
Replikasi
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Perubahan struktur Mutasi DNA
5’-ATXGG-3’3’-TAGCC-5’
5’-ATXGG-3’3’-TAGCC-5’
Normal
5’-ATXGG-3’3’-TAACC-5’
5’-ATTGG-3’3’-TAACC-5’
5’-ATCGG-3’3’-TAGCC-5’
Kerusakan
nukleotida
Mutan
Mutan
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Tipe mutasiA. Point mutation/Mutasi Titik a. Substitusi satu basa dengan nukleotida yang lain
2 tipe:Transisi – perubahan purine ke purine (A to G, G to A)
atau pirimidin ke pirimidin (C to T, T to C)
Transversi – perubahan purine ke pirimidin atau sebaliknya, e.g. A to C/T, C to A/G
b. Insersi atau delesi Penambahan atau pengurangan satu base-pairs.
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MUTASI TITIK1. Silent mutation
Perubahan basa tidak meyebabkan perubahan pada kodon
5’ ATG GGA GCT CTA TTA ACC TAA 3’ met glyala leu leu thr stop
5’ ATG GGA GCT CTA TTG ACC TAA 3’ met glyala leu leu thr stop
Silent mutationtransisi
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2. Missense mutation Perubahan basa Perubahan kodon
5’ ATG GGA GCT CTA TTA ACC TAA 3’ met glyala leu leu thr stop
5’ ATG GGA GCT CTA TTT ACC TAA 3’ met glyala leu phe thr stop
Mutasi pada aras gena
Missense mutation( transversi)
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3. Nonsense mutation Perubahan basa menjadi stop kodon
5’ ATG GGA GCT CTA TTA ACC TAA 3’ met glyala leu leu thr stop
5’ ATG GGA GCT CTA TGA ACC TAA 3’ met glyala leu stop
Mutasi pada aras gena
Nonsense mutation( & transversion)
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4. Frameshift mutation Hilangnya satu basa perubahan pada pembacaan
5’ ATG GGA GCT CTA TTA ACC TAA 3’ met glyala leu leu thr stop
5’ ATG GGG AGC TCT ATT AAC CTA A 3’ met glyser ser ile asn leu
Mutasi pada aras gena
Frameshift mutation
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KODON DAN ASAM AMINO YG DISANDI
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Base-pair and Frameshift Mutations
THE NUS AWO URC ATE ATT HER AT
THE NUN SAW OUR CAT EAT THE RAT
Mutation type
THE NSN SAW OUR CAT EAT THE RAT
THE SUN SAW OUR CAT EAT THE FAT
Nonsense
Missense
Frameshift
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Tipe mutasiB. Inversi Pemotongan sebagian DNA dan kemudian disisipkan
pada tempat yg sama tetapi pada orientasi yg berbeda
5’-ATTGG-3’
3’-TAACC-5’
5’-ATCAG-3’
3’-TAGTC-5’
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ReversionThis is the reverse process of mutation and involves a mutant regaining a wild-type phenotype, either through:
1. A back mutation (direct reverse of the mutation)2. A reverse or suppressor mutation (not a direct reverse, but a mutation at a second site generally within the same gene which
suppresses the effect of the first mutation). The mutant is described as a revertant.
A practical example of reversion is the Ames test which is used to test for carcinogens.
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What is reversion?
+-
WT, active
+
+
Mutate - to + Mutant, inactive
+-
WT, activeSame site revertant
+-
Mutate + to -
WT ?, activedifferent site revertant
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C.M
uta
si p
ada
Kro
mos
om
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Depurinasi spontan
Kehilangan 300 purin perhari pada pH 7, 37CPada sel mamalia 10.000 purin/hariKecepatan meningkat jika suhu naik atau pH turunAdanya senyawa alkikasi (etil etena sulfonat, nitrogen
mustrat) menaikkan kecepatan depurinasi
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MUTAGEN FISIKA
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Fotoliase
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MUTAGEN KIMIAWI
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MUTAGEN KIMIAWI
BASA ANALOG◦5-Bromourasil dan 2-aminopurin bergabung pada DNA seperti
asam nukleat lainnya◦BU = analog timin, yang berpasangan dengan A tetapi juga dapat
berpasangan dengan G◦Terjadi mutasi dari A:T menjadi G:C
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BROMURASIL DALAM BENTUK ENOL BU:G
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AFLATOKSIN B1
AFLATOKSIN B1 OLEH SITOKROM P450 DIUBAH MENJADI SENYAWA EPOKSID YG BEREAKSI DENGAN G
G:C MENJADI T:A
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SENYAWA INI BEREAKSI DENGAN 7-N GUANOSINmenghasilkan radikal
G:C MENJADI T:A
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endo-8,9-epoxide
H O
O
O O
OH
O
OCH 3
GST
H O
O
O O
HO
OCH 3
HO
SG
H O
O
O O
O H O
OCH 3
OCH 3NH2
H
H O
O
HO O
O O
HN
N
DNAdR
DNA
N
O
N+
exo-8,9-epoxide DNA-Adduct (N7-dGuo)H O
O
O O
OCH 3
H O
Aflatoxin B1
P450
P450
Aflatoxin B1 exo-8,9-Epoxide forms DNA-Adducts
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ASAM NITRIT
MENGOKSIDASI ADENIN (A) MENJADI HIPOSANTIN◦HIPOSANTIN INI AKAN BERPASANGAN DENGAN C◦A:T MENJADI G:C
A:T G:C
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Etil Metil Sulfoksida (EMS)
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AKRIDIN ORANYE
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PENYAKIT AKIBAT MUTASI Xerodermal pigmentosum
Huntington Disease Leukimia
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Xeroderma Pigmentosum (XP)
Autosomal resesiveMutasi pada beberapa gene yang terlibat dalam repair –
pemotongan dimer pirimidinPeka terhadap sinar UV –kanker kulit
CC 4.7
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HUNTINGTON DISEASE
CAG : GLUTAMINNORMAL PENDERITA 36 -82 KOPI
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HUNTINGTON DISEASECAG : GLUTAMINPENDERITA 36 -82 KOPI
Fagile X syndrome: berpengaruh pada sistem regulasinya
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AAAAAAA
Gene A
Gene B
Fusion Gene
Primary transcript
Fusion mRNA
Chimaericprotein
Unique Properties Altered Pattern of gene expression
Differentiation Blocked
Continued self-renewal
65% of leukaemias are characterisedby particular somatically acquired chromosome translocations
Chromosome 1
Chromosome 2
Acts as an oncogene
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Chronic myeloid leukaemia (CML) is characterised bythe t(9;22)(q34;q11) reciprocal translocation
(The protein product from this fusion gene only found in ~70% of patients)
Bcr-abl = constitutivelyactive tyrosine kinase
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TERIMA KASIH