title: Ultraspecific probes for high throughput HLA typing.
abstract: BACKGROUND
  The variations within an individual's HLA (Human Leukocyte Antigen) genes have been linked to many immunological events, e.g. susceptibility to disease, response to vaccines, and the success of blood, tissue, and organ transplants. Although the microarray format has the potential to achieve high-resolution typing, this has yet to be attained due to inefficiencies of current probe design strategies.
  
  
  RESULTS
  We present a novel three-step approach for the design of high-throughput microarray assays for HLA typing. This approach first selects sequences containing the SNPs present in all alleles of the locus of interest and next calculates the number of base changes necessary to convert a candidate probe sequences to the closest subsequence within the set of sequences that are likely to be present in the sample including the remainder of the human genome in order to identify those candidate probes which are "ultraspecific" for the allele of interest. Due to the high specificity of these sequences, it is possible that preliminary steps such as PCR amplification are no longer necessary. Lastly, the minimum number of these ultraspecific probes is selected such that the highest resolution typing can be achieved for the minimal cost of production. As an example, an array was designed and in silico results were obtained for typing of the HLA-B locus.
  
  
  CONCLUSIONS
  The assay presented here provides a higher resolution than has previously been developed and includes more alleles than previously considered. Based upon the in silico and preliminary experimental results, we believe that the proposed approach can be readily applied to any highly polymorphic gene system.
authors.affiliation: Department of Computer Science, University of Houston, Houston, TX, USA. cfeng@bioinfo.uh.edu
authors.forename: Chen
authors.initials: C
authors.lastname: Feng
authors.forename: Catherine
authors.initials: C
authors.lastname: Putonti
authors.forename: Meizhuo
authors.initials: M
authors.lastname: Zhang
authors.forename: Rick
authors.initials: R
authors.lastname: Eggers
authors.forename: Rahul
authors.initials: R
authors.lastname: Mitra
authors.forename: Mike
authors.initials: M
authors.lastname: Hogan
authors.forename: Krishna
authors.initials: K
authors.lastname: Jayaraman
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Fofanov
mesh_terms: D000483:Alleles; D015342:DNA Probes / Q000235:genetics*; D015894:Genome, Human; D015235:HLA-B Antigens / Q000235:genetics; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA
chemical_list: D015342:DNA Probes; D015235:HLA-B Antigens