Sequencing of the ART4 gene in sub‐Saharan cohorts reveals ethnic differences and two new DO alleles: DO*B‐Ile5Thr and DO*B‐Trp266Arg. Issue 10 (18th May 2015)

• Record Type: Journal Article
• Authors: Durousseau de Coulgeans, Cécile; Chiaroni, Jacques; Bailly, Pascal; Chapel‐Fernandes, Sylvie
• Is Part Of: Transfusion. Volume 55:Issue 10(2015)
• Page Start: 2376
• Page End: 2383
• Publication Date: 2015-05-18
• Subjects: Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; Blood Group Antigens -- Periodicals; Blood Preservation -- Periodicals; Blood Transfusion -- Periodicals; 615
• DOI: 10.1111/trf.13153
• Languages: English
• ISSNs: 0041-1132

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="trf13153-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Given the high heterogeneity of sub‐Saharan populations especially between nonpygmoids and pygmoids, differences are expected during investigation of the <italic>DO/ART4</italic> gene.</p> </sec> <sec id="trf13153-sec-0002" sec-type="section"> <title>STUDY DESIGN AND METHODS</title> <p>Using genomic DNA extracted from blood samples collected from 77 Tswa pygmoids and 39 Teke and seven San nonpygmoids, <italic>DO</italic> coding regions were amplified and sequenced. A tetra‐primer amplification refractory mutation system‐polymerase chain reaction method was developed to specifically detect the <italic>DO*B‐SH‐Gln149Lys</italic> variant. Membrane expression of newly identified variant alleles in K562‐transduced cells was studied by flow cytometry.</p> </sec> <sec id="trf13153-sec-0003" sec-type="section"> <title>RESULTS</title> <p>Extensive polymorphism was confirmed in Teke or San nonpygmoids and Tswa pygmoids with, respectively, 12, zero, and 24 <italic>DO*A</italic>; 54, 10, and 115 <italic>DO*B</italic> or <italic>DO*B‐WL</italic>; five, zero, and 14 <italic>DO*HY</italic>; and six <italic>DO*JO</italic> alleles in Teke only. The <italic>DO*B‐SH‐Gln149Lys</italic> variant was observed as the third most frequent after the <italic>DO*HY</italic> and <italic>DO*JO</italic> alleles. Two novel <italic>DO*B</italic> alleles were identified in the San samples, that is, <italic>DO*B‐Ile5Thr</italic> and <italic>DO*B‐Trp266Arg</italic>. Study of K562‐transduced cells showed that compared to the <italic>DO*B</italic> allele, <italic>DO*B‐Ile5Thr</italic> was expressed more strongly while <italic>DO*B‐Trp266Arg</italic> variant was expressed to a lesser extent and was not recognized by MIMA‐123 monoclonal antibodies.</p> </sec> <sec id="trf13153-sec-0004" sec-type="section"> <title>CONCLUSION</title> <p>Sequencing analysis showed more allelic combinations in nonpygmoids than in pygmoids with high frequencies of <italic>DO*HY</italic>, <italic>DO*JO, </italic> and <italic>DO*B‐SH‐Gln149Lys</italic> variant alleles. This finding underlines the importance of including <italic>DO*HY</italic> and <italic>DO*JO</italic> single‐nucleotide polymorphisms in genotyping tests to improve transfusion safety. Characterization of two novel <italic>DO*B</italic> alleles highlights the value of testing selected ethnic groups in understanding <italic>DO</italic> allele diversity.</p> </sec> </abstract>