Biallelic markers for use in constructing a high density disequilibrium map of the human genome

Abstract

The present invention relates to genomic maps comprising biallelic markers, new biallelic markers, and methods of using biallelic markers. Primers hybridizing to regions flanking these biallelic markers are also provided. This invention provides polynucleotides and methods suitable for genotyping a nucleic acid containing sample for one or more biallelic markers of the invention. Further, the invention provides a number of methods utilizing the biallelic markers of the invention including methods to detect a statistical correlation between a biallelic marker allele and a phenotype and/or between a biallelic marker haplotype and a phenotype.

1 . An isolated or purified polynucleotide: 
 a) comprising a contiguous span of at least 12 nucleotides of a sequence selected from SEQ ID No. SEQ ID NOs: 3909 to 3934, and the complements thereof;    b) consisting essentially of a contiguous span of at least 8 to 43 nucleotides selected from SEQ ID No. SEQ ID NOs: 3909 to 3934, and the complements thereof; or    c) comprising a contiguous span of at least 12 nucleotides of a sequence selected from SEQ ID No. SEQ ID NOs: 3909 to 3934, and the complements thereof, wherein said span comprises a map-related biallelic marker and the 1 st  allele indicated in Table 1 is present at said map-related biallelic marker.    
     
     
         2 . The isolated or purified polynucleotide according to  claim 1 , wherein said span comprises a map-related biallelic marker.  
     
     
         3 . The isolated or purified polynucleotide according to  claim 1 , wherein said contiguous span is 19 nucleotides in length and said polynucleotide consists of said contiguous span.  
     
     
         4 . The isolated or purified polynucleotide according to  claim 1 , wherein said contiguous span comprises at least 21 contiguous nucleotides.  
     
     
         5 . The isolated or purified polynucleotide according to  claim 1 , wherein said contiguous span comprises at least 30 contiguous nucleotides.  
     
     
         6 . The isolated or purified polynucleotide according to  claim 1 , wherein said contiguous span comprises at least 43 contiguous nucleotides.  
     
     
         7 . The isolated or purified polynucleotide according to  claim 1 , wherein said polynucleotide is attached to a solid support.  
     
     
         8 . The isolated or purified polynucleotide according to  claim 7 , wherein the solid support provides an array of polynucleotides comprising at least one polynucleotide.  
     
     
         9 . The isolated or purified polynucleotide according to  claim 8 , wherein said array is addressable.  
     
     
         10 . The isolated or purified polynucleotide according to  claim 1 , wherein said polynucleotide further comprising a label.  
     
     
         11 . A method of genotyping comprising determining the identity of a nucleotide at a map-related biallelic marker selected from the biallelic markers of SEQ ID Nos. 3909 to 3934, and the complements thereto.  
     
     
         12 . The method according to  claim 11 , wherein said biological sample is derived from a single subject.  
     
     
         13 . The method according to  claim 12 , wherein the identity of the nucleotides at said biallelic marker is determined for both copies of said biallelic marker present in said subject's genome.  
     
     
         14 . The method according  claim 11 , wherein said biological sample is derived from multiple subjects.  
     
     
         15 . The method according to  claim 11 , further comprising amplifying a portion of said sequence comprising the biallelic marker prior to said determining step.  
     
     
         16 . The method according to  claim 15 , wherein said amplifying is performed by PCR.  
     
     
         17 . The method according to  claim 11 , wherein said determining is performed by a hybridization assay, a sequencing assay, a microsequencing assay, or an enzyme-based mismatch detection assay.  
     
     
         18 . The method according to  claim 11 , further comprising determining the proportional representation of said biallelic marker in said population to determine the frequency of an allele of a map-related biallelic marker in a population.  
     
     
         19 . The method according to  claim 18 , wherein said genotyping of step a) is performed on each individual of said population.  
     
     
         20 . The method according to  claim 18 , wherein said genotyping is performed on a single biological sample derived from said population.  
     
     
         21 . A method of detecting an association between an allele and a phenotype, comprising the steps of: 
 a) determining the frequency of at least one map-related biallelic marker allele in a trait positive population according to the method of  claim 18;     b) determining the frequency of said map-related biallelic marker allele in a control population according to the method of  claim 18;  and    c) determining whether a statistically significant association exists between said allele and said phenotype.