RHD*DOL1 and RHD*DOL2 encode a partial D antigen and are in cis with the rare RHCE*ceBI allele in people of African descent

Abstract

BACKGROUND: Several studies showed in people of African descent the existence of a genetic linkage between RHD alleles encoding a variant D antigen and a given altered RHCE*ce allele. RHCE*ceBI is a rare allele encountered in people of African descent, that encodes a Hr– hrS– Rhce protein. Our study shows that RHCE*ceBI appears to be genetically linked to two very similar variant RHD alleles, RHD*DOL1 and RHD*DOL2, and demonstrates for the first time that DOL‐2 is a partial D antigen. STUDY DESIGN AND METHODS: After finding out an individual with both RHCE*ceBI and RHD*DOL presumed to be in cis, we hypothesized a genetic linkage between those two genes. All individuals (n = 7) known to carry RHCE*ceBI in our laboratory, including the index case, were fully investigated at the serologic and molecular level. RESULTS: One individual with alloanti‐D, being homozygous for RHCE*ceBI and RHD*DOL2, allowed us to confirm the genetic linkage between those two genes, as well as the partial D status of DOL‐2. In the six RHCE*ceBI remaining individuals, three were found with RHD*DOL2 and 3 with RHD*DOL1, likely in cis. Three of them made an alloanti‐D; one was DOL‐1 and two were DOL‐2. CONCLUSION: The rare RHCE*ceBI allele appears to be in cis either with RHD*DOL1 or with RHD*DOL2 in people of African descent. DOL‐1 and DOL‐2 must be considered as partial D antigens. We recommend a systematic search for RHD*DOL1 and RHD*DOL2 in people found to carry RHCE*ceBI and vice versa, especially in patients with sickle cell disease.

A comprehensive survey of both RHD and RHCE allele frequencies in sub‐Saharan Africa

“…While no prediction can be made about weak or partial phenotype of RHD*DAU(48C) , it can be assumed, based on the observed molecular background, that RHD*DIV (S103P) and DIV.DOL express a partial phenotype. We speculate that RHD*DIV.DOL evolved from recombination between alleles of the DIVa cluster and RHD*DOL or DOL3 , both of which segregate with RHCE*ceBI . Since this allele is predicted to encode RH54 (DAK) and RH49 (STEM) antigens, 1.8% of Africans were predicted to express RH49 (STEM).…”

Molecular tools for investigating immunohaematology problems

“…It is important to point out that no current routine molecular methods exist for haplotyping studies that involve two genes. For example, when a novel RHCE*Ce allele is found in a D/d individual (confirmed by RHD zygosity study), it is not possible to clearly know whether this variant RHCE*Ce allele is genetically linked (that is in cis) to D or d. Out of homozygous individuals for all the genes involved in a given haplotype, multigeneration family tree study and genetic segregation analysis represent an essential tool for haplotype investigation [68].…”

Molecular matching for patients with haematological diseases expressing altered RHD‐RHCE genotypes

“…Thus, patients with African descent can produce complex Rh alloantibody(ies), making to find compatible blood a challenge [11,12]. Furthermore, the variant RHCE can be inherited in cis with an altered RHD [13][14][15][16][17].…”