Arrayed biomolecules and their use in sequencing

1. A method for analysing genome wide variation in an individual comprising:

i) randomly fragmenting a genome of said individual;

ii) generating sequence reads of multiple bases on all fragments of said genome;

iii) aligning the sequence reads with a known genomic reference sequence; and

iv) analysing variations between the sequence reads derived from the genome of the individual and the known genomic reference sequence.

2. A method according to claim 1 further comprising identifying regions of variation across the whole of the genome of said individual with respect to said reference sequence to provide a genetic signature for said individual.

3. A method according to claim 1 , wherein said fragments of genomic DNA are immobilised onto the surface of a solid support to form an array of polynucleotide molecules capable of interrogation and which molecules can be individually resolved by optical microscopy.

4. A method according to claim 1 , wherein each molecule is immobilised by covalent attachment to the surface of said solid support other than at that part of each molecule that can be interrogated.

5. A method according to claim 4 , wherein the sequences of said fragments are established by contacting the array with each of the bases A, T G and C under conditions that permit the polymerase reaction to proceed and thereby form sequences complementary to those in the array, and determining the incorporation of a base at each of selected positions in the complementary sequences.

6. A method according to claim 5 , wherein the determination of the incorporation of said base is repeated between 10 and 20 times to generate a partial complementary sequence of between 10–20 nucleotides.

7. A method for analysing genome wide variation in an individual comprising:

i) randomly fragmenting a genome of said individual;

ii) arraying the fragments such that different fragments can be individually resolved by optical microscopy;

iii) generating sequence reads of multiple bases on all fragments of said genome;

iv) aligning said sequence reads with a known genomic reference sequence; and

v) analysing variations between the sequence reads derived from the individual sample and the known genomic reference sequence.

8. A method of generating a genetic signature for an individual, which method comprises:

i) immobilising fragments of the genome of said individual onto the surface of a solid support to form an array of polynucleotide molecules capable of interrogation, wherein the array allows the molecules to be individually resolved by optical microscopy, and wherein each molecule is immobilised by covalent bonding to the surface, other than at that part of each molecule that can be interrogated;

ii) contacting the fragments with a series of nucleotide primers comprising sequences capable of hybridising to regions on said fragments specific for each of the regions of variation identified according to claim 2 , in the presence of bases A, T, G and C under conditions that permit the polymerase reaction to proceed;

iii) determining the successive incorporation of a base at each of selected positions to produce sequences of a defined length complementary to the immobilised fragments;

iv) identifying the sequence of those fragments that have undergone the polymerase reaction to produce a genetic signature for said individual.

9. A method according to claim 7 or 8 , wherein in step iii) the incorporation of said base is repeated between 10 and 20 times to produce a complementary sequence of between 10 and 20 nucleotides.