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. 2018 Nov;58(11):2693-2704.
doi: 10.1111/trf.14953. Epub 2018 Oct 12.

Genomic coordinates and continental distribution of 120 blood group variants reported by the 1000 Genomes Project

Celina Montemayor-Garcia  1 , Panagiota Karagianni  2 , David A Stiles  1 , Erika M Reese  1 , Danielle A Smellie  1 , Debrean A Loy  1 , Kimberly Y Levy  1 , Magdalene Nwokocha  1 , Marina U Bueno  1 , Jeffery L Miller  3 , Harvey G Klein  1
Affiliations

Genomic coordinates and continental distribution of 120 blood group variants reported by the 1000 Genomes Project

Celina Montemayor-Garcia et al. Transfusion. 2018 Nov.

Abstract

Background: The 1000 Genomes Project provides a database of genomic variants from whole genome sequencing of 2504 individuals across five continental superpopulations. This database can enrich our background knowledge of worldwide blood group variant geographic distribution and identify novel variants of potential clinical significance.

Study design and methods: The 1000 Genomes database was analyzed to 1) expand knowledge about continental distributions of known blood group variants, 2) identify novel variants with antigenic potential and their geographic association, and 3) establish a baseline scaffold of chromosomal coordinates to translate next-generation sequencing output files into a predicted red blood cell (RBC) phenotype.

Results: Forty-two genes were investigated. A total of 604 known variants were mapped to the GRCh37 assembly; 120 of these were reported by 1000 Genomes in at least one superpopulation. All queried variants, including the ACKR1 promoter silencing mutation, are located within exon pull-down boundaries. The analysis yielded 41 novel population distributions for 34 known variants, as well as 12 novel blood group variants that warrant further validation and study. Four prediction algorithms collectively flagged 79 of 109 (72%) known antigenic or enzymatically detrimental blood group variants, while 4 of 12 variants that do not result in an altered RBC phenotype were flagged as deleterious.

Conclusion: Next-generation sequencing has known potential for high-throughput and extended RBC phenotype prediction; a database of GRCh37 and GRCh38 chromosomal coordinates for 120 worldwide blood group variants is provided as a basis for this clinical application.

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Conflict of interest statement

Conflict of Interest: The authors declare that they have no conflicts of interest relevant to the manuscript submitted to TRANSFUSION.

Disclosure of Conflicts of Interest

The authors declare having no competing financial interest relevant to this article.

Figures

Figure 1.
Figure 1.
Schematic flowchart of methods, data acquisition, and analysis.
Figure 2.
Figure 2.
Alleles/phenotypes associated with group variants that demonstrate novel superpopulation distributions in the 1000 Genomes Database. Colored stars represent populations of European (blue) or African (yellow) descent sampled within the USA. See 1000 Genomes Project reference manuscript for population sample details. Table S1 provides the full dataset and specifies gene and nucleotide variant queried.
See this image and copyright information in PMC

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