A whole genome approach for discovering the genetic basis of blood group antigens: independent confirmation for P1 and Xga. Issue 3 (28th December 2018)

• Record Type: Journal Article
• Authors: Lane, William J.; Aguad, Maria; Smeland‐Wagman, Robin; Vege, Sunitha; Mah, Helen H.; Joseph, Abigail; Blout, Carrie L.; Nguyen, Tiffany T.; Lebo, Matthew S.; Sidhu, Manpreet; Lomas‐Francis, Christine; Kaufman, Richard M.; Green, Robert C.; Westhoff, Connie M.
• Other Names: Bates David W. investigator.; Blout Carrie investigator.; Christensen Kurt D. investigator.; Cirino Allison L. investigator.; Green Robert C. investigator.; Ho Carolyn Y. investigator.; Krier Joel B. investigator.; Lane William J. investigator.; Lehmann Lisa S. investigator.; MacRae Calum A. investigator.; Morton Cynthia C. investigator.; Perry Denise L. investigator.; Seidman Christine E. investigator.; Sunyaev Shamil R. investigator.; Vassy Jason L. investigator.; Schonman Erica investigator.; Nguyen Tiffany investigator.; Steffens Eleanor investigator.; Betting Wendi Nicole investigator.; Aronson Samuel J. investigator.; Ceyhan‐Birsoy Ozge investigator.; Lebo Matthew S. investigator.; Machini Kalotina investigator.; McLaughlin Heather M. investigator.; Azzariti Danielle R. investigator.; Rehm Heidi L. investigator.; Tsai Ellen A. investigator.; Blumenthal‐Barby Jennifer investigator.; Feuerman Lindsay Z. investigator.; McGuire Amy L. investigator.; Lee Kaitlyn investigator.; Robinson Jill O. investigator.; Slashinski Melody J. investigator.; Diamond Pamela M. investigator.; Davis Kelly investigator.; Ubel Peter A. investigator.; Kraft Peter investigator.; Scott Roberts J. investigator.; Garber Judy E. investigator.; Hambuch Tina investigator.; Murray Michael F. investigator.; Kohane Isaac investigator.; Kong Sek Won investigator.;
• Is Part Of: Transfusion. Volume 59:Issue 3(2019)
• Page Start: 908
• Page End: 915
• Publication Date: 2018-12-28
• Subjects: Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; Blood Group Antigens -- Periodicals; Blood Preservation -- Periodicals; Blood Transfusion -- Periodicals; 615
• DOI: 10.1111/trf.15089
• Languages: English
• ISSNs: 0041-1132

Abstract

Abstract : BACKGROUND: Although P1 and Xg a are known to be associated with the A4GALT and XG genes, respectively, the genetic basis of antigen expression has been elusive. Recent reports link both P1 and Xg a expression with nucleotide changes in the promotor regions and with antigen‐negative phenotypes due to disruption of transcription factor binding. STUDY DESIGN AND METHODS: Whole genome sequencing was performed on 113 individuals as part of the MedSeq Project with serologic RBC antigen typing for P1 (n = 77) and Xg a (n = 15). Genomic data were analyzed by two approaches, nucleotide frequency correlation and serologic correlation, to find A4GALT and XG changes associated with P1 and Xg a expression. RESULTS: For P1, the frequency approach identified 29 possible associated nucleotide changes, and the serologic approach revealed four among them correlating with the P1+/P1– phenotype: chr22:43, 115, 523_43, 115, 520AAAG/delAAAG (rs66781836); chr 22:43, 114, 551C/T (rs8138197); chr22:43, 114, 020 T/G (rs2143918); and chr22:43, 113, 793G/T (rs5751348). For Xg a, the frequency approach identified 82 possible associated nucleotide changes, and among these the serologic approach revealed one correlating with the Xg(a+)/Xg(a–) phenotype: chrX:2, 666, 384G/C (rs311103). CONCLUSION: A bioinformatics analysis pipeline was created to identify genetic changes responsible for RBC antigen expression. This study, in progress before the recently published reports, independently confirms the basis for P1 and Xg a . Although this enabled molecular typing of these antigens, the Y chromosome PAR1 region interfered with Xg a typing in males. This approach could be used to identify and confirm the genetic basis of antigens, potentially replacing the historical approach using family pedigrees as genomic sequencing becomes commonplace.