| CPC B01J 19/0046 (2013.01) [C12Q 1/6844 (2013.01); B01J 2219/00585 (2013.01); B01J 2219/00722 (2013.01)] | 20 Claims |
|
1. A method of preparing a nucleic acid library from a nucleic acid sample, the method comprising:
(a) providing a set of amplification primers comprising:
a plurality of random primers, wherein each random primer comprises a random 3′ portion, a constant 5′ priming portion and at least one nucleotide analogue comprising a non-natural base located between the random 3′ portion and the constant 5′ priming portion;
a plurality of locus specific primers configured to amplify a plurality of predetermined genomic regions; and
a plurality of blocked primers;
wherein each plurality of random primers and locus specific primers in the set of amplification primers is a mixture of different primers;
(b) hybridizing the set of amplification primers to the nucleic acid sample and extending the hybridized amplification primers to obtain extended polynucleotides, wherein the extending is performed in the absence of a nucleotide capable of hybridizing to the at least one nucleotide analogue;
(c) circularizing the extended polynucleotides to obtain circular polynucleotides; and
(d) amplifying the circular polynucleotides in the presence of the nucleotide capable of hybridizing to the at least one nucleotide analogue, thereby preparing the nucleic acid library.
|