The present invention provides a novel method for specifically isolating
and separating large segments of genomic DNA that can subsequently be
used to determine a genomic haplotype. The invention relies on using a
solid phase having a flat surface arrayed with oligonucleotides designed
to specifically hybridize to each particular haplotype of an individual
sample, e.g., oligonucleotides designed to specifically hybridize with
each of the two HLA-B haplotypes, HLA-A, HLA-C, HLA-DR, HLA-DQ, and the
like. The genomic DNA is contacted and hybridized to the arrayed
oligonucleotides to form a genomic DNA/oligonucleotide complex. The
excess genomic DNA is washed away and the haplotype separated genomic DNA
is denatured from the oligonucleotide probe and collected. The method of
the present invention allows for the separation of genomic DNA fragments
of between approximately 2 to about 4 megabases (Mb). Separation of the
haplotypes of large genomic DNA fragments allows for linkage analysis of
other HLA alleles and polymorphisms, microsatellite, SNPs, and the like
across a large span of the HLA region, including HLA-A, -B, -C, and
HLA-DRB1 regions. This linkage analysis is particularly useful when HLA
typing for an individual with limited family HLA typing available.