dna: extraction & purification by amr s. moustafa, m.d.; ph.d. assistant prof. & consultant,...

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Page 1: DNA: Extraction & Purification By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com
Page 2: DNA: Extraction & Purification By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com

DNA: Extraction & Purification

By

Amr S. Moustafa, M.D.; Ph.D.Assistant Prof. & Consultant, Medical

Biochemistry Dept.College of Medicine, KSU

[email protected]

Page 3: DNA: Extraction & Purification By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com

Objectives

The principle of standard method

The comparison of the standard Vs other methods

The evaluation of the purification procedure

The experimental protocol for DNA purification

Page 4: DNA: Extraction & Purification By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com

DNA Extraction & Purification: Key Steps

Removal of contaminantsProteinsRNAOther macromolecules

Lysis of the cells

Concentration of purified DNA (if required)

Page 5: DNA: Extraction & Purification By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com

DNA Extraction & Purification:

The Standard Method-1(1) Lysis of cells:

Lysis buffer: SDS and/or 8.0 M urea

(2) Removal of contaminants:Proteinase KPhenol:chloroform extraction

(3) Concentration of DNA:Ethanol precipitation

Page 6: DNA: Extraction & Purification By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com

DNA Extraction & Purification:

The Standard Method-2Phenol:chloroform:isoamyl alcohol mixture:

Denatures proteinsSolubilizes denatured proteins

Denatures proteinsStabilizes the aqueous/organic boundary

Isoamyl alcohol:Separation of aqueous/organic phasesPrevents foaming upon vortexing

Phenol:

Chloroform:

Page 7: DNA: Extraction & Purification By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com

DNA Extraction & Purification:

The Standard Method-3

Tris-buffered, redistilled phenol, pH 8.0: Oxidation products can damage DNA chains Addition of 8-hydroxyquinolone: antioxidant

yellow color of phenol

DNA is found in the upper aqueous layer

Exceptions: high salt content, the aqueous phase forms lower layer

If phenol is not equilibrated, DNA in the organic phase

Page 8: DNA: Extraction & Purification By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com

DNA Extraction & Purification:

The Standard Method-4Ethanol precipitation:

Concentration DNA solutionsRemoval of residual organic solventsDNA-free solutes

Ethanol induces a structural transition in DNA precipitation High monovalent cation conc. (0.1 – 0.5 M)

Most salts are soluble in 70% ethanol, precipitationand washing desalt DNA

Page 9: DNA: Extraction & Purification By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com

DNA Extraction & Purification:

The Standard Method-5

Time-consuming

Hazardous organic solvents

Residual amounts of organic solvents interfere with accurate measurement of DNA conc. with enzymatic manipulations of DNA

Disadvantages:

Page 10: DNA: Extraction & Purification By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com

DNA Extraction & Purification:

The Standard Vs other MethodsKey Differences:

Sample: Type Quantity/volume

Requirement:Time for extractionEquipments and reagentsCost/sample

DNA: Yield & conc.Purity

Page 11: DNA: Extraction & Purification By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com

DNA Extraction & Purification:

QIAamp DNA mini kits-1

(1) Lysis of cells

(2) Spin column: DNA adsorption to silica-gel membrane

(3) Two-different wash steps: Removal of contaminants

(4) Elution: Pure and concentrated DNA

Page 12: DNA: Extraction & Purification By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com

DNA Extraction & Purification:

QIAamp DNA mini kits-2Advantages

Sample: versatile

Simple and rapid

No use of organic solvents

Pure and concentrated DNA

Page 13: DNA: Extraction & Purification By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com

DNA Extraction & Purification:Evaluation

DNA purity: A260/A280 ratio1.7 – 1.9

DNA concentration (μg/ml):A260 X 50

DNA yield:DNA conc. X Total volume of DNA solution