Methods and products related to genotyping and dna analysis

Abstract

The invention encompasses methods and products related to genotyping. The method of genotyping of the invention is based on the use of single nucleotide polymorphisms (SNPs) to perform high throughput genome scans. The high throughput method can be performed by hybridizing SNP allele-specific oligonucleotides and a reduced complexity genome (RCG). The invention also relates to methods of preparing the SNP specific oligonucleotides and RCGs, methods of fingerprinting, determining allele frequency for a SNP, characterizing tumors, generating a genomic classification code for a genome, identifying previously unknown SNPs, and related compositions and kits.

We claim: 
     
         1 - 148 . (canceled) 
     
     
         149 . A genotyping method for detecting the presence or absence of a single nucleotide polymorphism (SNP) allele in a human genomic DNA sample, the method comprising:
 preparing a reduced complexity genome (RCG) from the human genomic DNA sample by adapter-linker PCR amplification, wherein the RCG is prepared by restriction enzyme cleavage of the genomic DNA sample followed by ligation of at least one adapter sequence, and wherein amplification is primed by the adapter sequence;   labeling the RCG; and   analyzing the RCG for the presence or absence of a SNP allele by hybridizing the RCG to a solid support having bound to it at least one SNP allele specific oligonucleotide (SNP-ASO),   wherein the RCG is characterized by being a reproducible fraction of the genome and capable of being prepared to include at least 50% of the same SNP-ASO sequences if two or more RCG preparations are compared to one another.   
     
     
         150 . The method of  claim 149 , wherein a single restriction enzyme is used to prepare the RCG. 
     
     
         151 . The method of  claim 149 , wherein a single adapter sequence is used. 
     
     
         152 . The method of  claim 149 , wherein adapter sequences incorporate one or more random nucleotides. 
     
     
         153 . The method of  claim 149 , wherein the RCG represents less than 5% of the genome. 
     
     
         154 . The method of  claim 149 , wherein the RCG is characterized by being capable of including at least 90% of the same ASO-SNP sequences if two or more RCG preparations are compared to one another. 
     
     
         155 . The method of  claim 149 , wherein a genome-wide scan for the presence or absence of an ASO-SNP is performed in the analysis. 
     
     
         156 . A method comprising:
 preparing a randomly primed PCR-derived reduced complexity genome (RCG) using at least one polymerase chain reaction (PCR) primer, wherein the RCG contains less than 20% of genomic material present in a whole genome,   contacting single nucleotide polymorphisms-allele specific oligonucleotides (SNP-ASOs) immobilized on a surface with the RCG under hybridization conditions, wherein polymorphic loci corresponding to the SNP-ASOs are present with a frequency of at least 50% in a RCG made using the at least one PCR primer and   determining the presence or absence of a SNP allele in the RCG by hybridization of the RCG with a SNP-ASO to identify a genotype.   
     
     
         157 . The method of  claim 156 , wherein the RCG contains less than 5% of genomic material present in a whole genome. 
     
     
         158 . The method of  claim 156 , wherein the at least one PCR primer is a primer for degenerate oligonucleotide priming-PCR (DOP-PCR). 
     
     
         159 . The method of  claim 156 , wherein the at least one PCR primer is a primer for adapter-PCR. 
     
     
         160 . The method of  claim 156 , wherein the SNP-ASOs are composed of between 10 and 50 nucleotide residues. 
     
     
         161 . The method of  claim 156 , wherein the SNP-ASOs are composed of between 10 and 25 nucleotide residues. 
     
     
         162 . A method comprising:
 preparing a randomly primed PCR-derived reduced complexity genome (RCG) from a genome of a tumor cell using at least one polymerase chain reaction (PCR) primer, wherein the RCG contains less than 20% of genomic material present in a whole genome,   contacting single nucleotide polymorphisms-allele specific oligonucleotides (SNP-ASOs) immobilized on a surface with the RCG under hybridization conditions, wherein polymorphic loci associated with SNPs corresponding to the SNP-ASOs are present with a frequency of at least 50% in a RCG made using the at least one PCR primer, and   determining the presence or absence of a SNP allele in the RCG by hybridization of the RCG with a SNP-ASO to identify a loss of heterozygosity in the tumor.   
     
     
         163 . The method of  claim 162 , wherein the RCG contains less than 5% of genomic material present in a whole genome. 
     
     
         164 . The method of  claim 162 , wherein the at least one PCR primer is a primer for degenerate oligonucleotide priming-PCR (DOP-PCR. 
     
     
         165 . The method of  claim 162 , wherein the at least one PCR primer is a primer for adapter-PCR. 
     
     
         166 . A method for simultaneously detecting a plurality of single nucleotide polymorphism (SNP) alleles in a genomic DNA sample which comprises:
 preparing a randomly-primed PCR-derived reduced complexity genome (RCG) from the genomic DNA sample, wherein the RCG contains less than 30% of genomic material present in a whole genome;   hybridizing said RCG with an arrayed panel of oligonucleotides indicative of SNP alleles associated with said RCG; and   analyzing the hybridization pattern of said RCG with oligonucleotides to thereby determine the presence or absence of said SNP alleles.