Complexity Management of Genomic DNA

Abstract

The presently claimed invention provides for novel methods and kits for analyzing a collection of target sequences in a nucleic acid sample. A sample is amplified under conditions that enrich for a subset of fragments that includes a collection of target sequences. The invention further provides for analysis of the above sample by hybridization to an array, which may be specifically designed to interrogate the collection of target sequences for particular characteristics, such as, for example, the presence or absence of one or more polymorphisms.

1 - 33 . (canceled) 
     
     
         34 . A method for selecting a collection of target sequences comprising:
 identifying fragments that are in a selected size range when a genome is digested with a selected enzyme or enzyme combination;   identifying sequences of interest present on the fragments in the selected size range; and selecting as target sequences: fragments that are in the selected size range and comprise a sequence of interest.   
     
     
         35 . A collection of target sequences selected according to the method of  claim 34 . 
     
     
         36 - 40 . (canceled) 
     
     
         41 . The method of  claim 34  wherein said sequences of interest comprise sequence variations. 
     
     
         42 - 68 . (canceled) 
     
     
         69 . A method for screening for DNA sequence variations in a population of individuals comprising:
 providing a first nucleic acid sample from each of said individuals;   providing a second nucleic acid sample by a method comprising:   fragmenting said first nucleic acid sample to produce fragments;   ligating at least one adaptor sequence to the population of fragments; and,   generating a second nucleic acid sample from said first nucleic acid sample wherein said second nucleic acid sample is enriched for a subset of fragments and said subset of fragments comprises sequences from said collection of target sequences;   providing a plurality of nucleic acid arrays wherein said arrays comprise probes designed to interrogate for DNA sequence variations;   hybridizing each of said second nucleic acid samples to one of said plurality of arrays;   generating a plurality of hybridization patterns resulting from said hybridizations;   and   analyzing the hybridization patterns to determine the presence or absence of sequence variation in the population of individuals.   
     
     
         70 . The method of  claim 69  wherein said sequence variation is one or more single nucleotide polymorphisms. 
     
     
         71 . The method of  claim 70  wherein at least one of the single nucleotide polymorphisms is associated with a phenotype. 
     
     
         72 . The method of  claim 70  wherein at least one of the single nucleotide polymorphisms is associated with a disease. 
     
     
         73 . The method of  claim 70  wherein at least one of the single nucleotide polymorphisms is associated with the efficacy of a drug. 
     
     
         74 . The method of  claim 70  wherein at least one of the single nucleotide polymorphisms is associated with a haplotype. 
     
     
         75 . The method of  claim 69  wherein the nucleic acid array is designed to interrogate sequence variations in said collection of target sequences. 
     
     
         76 - 77 . (canceled) 
     
     
         78 . A method for analyzing a first nucleic acid sample comprising:
 obtaining a second nucleic acid sample that is enriched for a subset of fragments said subset comprising selected target sequences by a method comprising:   selecting one or more target sequences that may be present in the first nucleic acid sample;   fragmenting the first nucleic acid sample so that the selected target sequences are present on fragments of a specific size range;   ligating at least one adaptor sequence to the fragments;   generating said second nucleic acid sample by amplifying the fragments so that the fragments containing the selected target sequences are enriched in the amplified product;   providing a nucleic acid array;   hybridizing said second nucleic acid sample to said array; and   analyzing a hybridization pattern resulting from said hybridization.   
     
     
         79 . The method of  claim 78  wherein said second nucleic acid sample comprises at least 0.01% of said first nucleic acid sample. 
     
     
         80 - 89 . (canceled) 
     
     
         90 . The method of  claim 78  wherein said method for analyzing a first nucleic acid sample comprises determining whether the first nucleic acid sample contains sequence variations. 
     
     
         91 . The method of  claim 90  wherein said sequence variations are single nucleotide polymorphisms. 
     
     
         92 . The method of  claim 91  wherein at least one of the single nucleotide polymorphisms is associated with a phenotype. 
     
     
         93 . The method of  claim 91  wherein at least one of the single nucleotide polymorphisms is associated with a disease. 
     
     
         94 . The method of  claim 91  wherein at least one of the single nucleotide polymorphisms is associated with the efficacy of a drug. 
     
     
         95 . The method of  claim 91  wherein at least one of the single nucleotide polymorphisms is associated with a haplotype. 
     
     
         96 . The method of  claim 78  wherein said target sequences are selected by a method comprising:
 identifying fragments that are in a selected size range when a genome is digested with a selected enzyme or enzyme combination; 
 identifying sequences of interest present on the fragments in the selected size range; and 
 selecting as target sequences fragments that are in the selected size range and comprise a sequence of interest. 
 
     
     
         97 - 98 . (canceled)