Hla typing using selective amplification and sequencing

A method of determining haplotypes in a sample comprising:

• (a) providing a nucleic acid molecule, said nucleic acid molecule comprising
• (i) at least a portion of a first exon of an HLA gene;
• (ii) at least a portion of a second exon of said HLA gene;
• and
• (iii) the intron between said first and second exons, thereby generating an exon pair;
• (b) carrying out a sequencing read of a first region of the exon pair, said first region comprising at least a portion of said first exon and a portion of the intron adjacent to said first exon;
• (c) carrying out a sequencing read of a second region of the exon pair, said second region comprising at least a portion of said second exon and a portion of the intron adjacent to said second exon;
• (d) performing steps (b) and (c) a plurality of times to generate a plurality of paired sequencing reads of said HLA gene, said plurality of paired sequencing reads comprising sequence information from at least two different haplotypes;
• (e) partitioning each sequencing read into one of two different haplotypes, wherein partitioning comprises computer implemented steps (f)-(i):
• (f) randomly selecting a first and second paired sequencing read and designating said reads as haplotype 1 and haplotype 2, respectively;
• (g) assigning each remaining paired sequencing read in said plurality of paired sequencing reads to said haplotype 1 or said haplotype 2 based on sequence similarity to either haplotype 1 or haplotype 2;
• (h) computing a consensus sequence for haplotype 1 and a consensus sequence for haplotype 2 using the paired sequence reads assigned to each haplotype;
• and
• (i) designating said consensus sequences as haplotypes 1 and 2 and repeating steps (g)-(h) until said consensus sequences no longer change;
• thereby determining haplotypes in said sample.