Complexity management of Genomic DNA

A method for genotyping at least one individual comprising:

• reducing the complexity of a first nucleic acid sample, that is a genomic DNA sample from the individual, comprising a plurality of target sequences to produce a second nucleic acid sample by a method comprising amplifying a subset of the target sequences;
• generating a hybridization pattern by a method comprising hybridizing said second nucleic acid sample to an array of probes wherein said array of probes comprises at least one perfect match probe for each allele of each single nucleotide polymorphism in a collection of single nucleotide polymorphisms, said collection comprising between 10,000 and 1,500,000 single nucleotide polymorphisms, wherein a perfect match probe is exactly complementary to the polymorphic base of an allele and a region surrounding the polymorphic base;
• wherein greater than 80% of the single nucleotide polymorphisms in the collection are at least 10 kilo bases and less than 200 kilo bases from another single nucleotide polymorphism in the collection and the average minimum distance between single nucleotide polymorphisms in the collection is between 10 kilo bases and 400 kilo bases;
• and
• wherein each single nucleotide polymorphisms in the collection is located within a fragment that is within a selected size range when a genome is digested with a selected enzyme or enzyme combination;
• analyzing said hybridization pattern;
• and
• determining the genotype of the individual at a plurality of the single nucleotide polymorphisms in the collection of single nucleotide polymorphisms from the hybridization pattern.

An amplified sample containing a collection of target sequences selected by a method comprising:

• identifying a first collection of restriction fragments that are each less than 2000 base pairs in length when a genome is digested with a selected restriction enzyme;
• identifying a second collection of fragments that is a subset of said first collection, wherein each fragment in the second collection includes a single nucleotide polymorphism that has at least two alleles that occur in a selected population at a frequency of at least 10%;
• and
• selecting as target sequences fragments that are in the selected size range and comprise a sequence of interest.

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 a collection of target sequences, wherein said collection of target sequences comprises a collection of at least 10,000 single nucleotide polymorphisms, wherein greater than 80% of the single nucleotide polymorphisms in the collection are at least 10 kilo bases and less than 200 kilo bases from another single nucleotide polymorphism in the collection and the average minimum distance between single nucleotide polymorphisms in the collection is between 10 kilo bases and 400 kilo bases;
• 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.