DNA amplification of a single cell

A method for the amplification of DNA comprising:

• (a) providing a sample comprising DNA;
• (b) digesting the DNA to be amplified with a restriction endonuclease under conditions suitable to obtain DNA fragments of similar length, wherein said restriction endonuclease is capable of providing 5′ overhangs wherein the terminal nucleotide of the overhang is phosphorylated or 3′ overhangs wherein the terminal nucleotide of the overhang is hydroxylated on said DNA fragments;
• (c) annealing at least one primer to said DNA fragments and further performing steps selected from the group consisting of
• (i) hybridizing, simultaneously or subsequently, oligonucleotides representing a first primer to said 5′ overhangs on said DNA fragments of step (b), and further hybridizing oligonucleotides representing a second primer to 3′ overhangs generated by said first primer, wherein said first and second primer are of different lengths;
• ligating said second primer to said 5′ overhangs;
• and removing said first primer from said DNA fragments;
• (ii) hybridizing, simultaneously or subsequently, oligonucleotides representing a first primer, wherein the nucleotide at the 5′ terminus is phosphorylated, to said 5′ overhangs on said DNA fragments of step (b), and further hybridizing oligonucleotides representing a second primer with said first primer;
• and ligating said first and second primer to said DNA fragments;
• and
• (iii) hybridizing oligonucleotides representing said primer to said 3′ overhangs so that 5′ overhangs are generated;
• and ligating said primer to recessed 5′ ends of said DNA fragments;
• (d) filling in generated 5′ overhangs;
• and
• (e) amplifying said DNA fragments with primers which are capable of hybridizing with the complementary strand of said primer(s) of step (c) to obtain said amplified DNA.