Sequence diversity of the Rh blood group system in Basques

Abstract

Basques show specific cultural, demographic, and genetic characteristics that have placed them as an isolated and unique population within Europe, such as their non-Indo-European language, Euskara. They have historically lived along the Western Pyrenees, between Spain and France, in one of the most important European glacial refugia during the Last Glacial Maximum. The most striking genetic characteristic is their highest frequency of the RhD blood group negative allele, a variant related to the hemolytic disease of the newborn. Both demographic and adaptive processes have been suggested as possible causes of the high frequency of RhD negative in Basques, but neither hypothesis has been clearly demonstrated. While previous studies on the Rh system in Basques have been mostly focused on serological and genotyping diversity, in this work we analyze genotyping and next generation sequencing data in order to provide a general framework of the genetic scenario of the system in Basques. In particular, we genotyped the most relevant variants of the system (D/d, E/e, and C/c), and sequenced three ~6 kb flanking regions surrounding the Rh genes in Basques and also in other populations for comparison. Our results are in agreement with previous studies, with Basques presenting the highest frequency of the RHD deletion (47.2%). Haplotype analyses of D/d, E/e, and C/c variants confirmed an association between the RhC allele, previously suggested to be under positive selection, and the RhD positive variant in non-sub-Saharan populations, including Basques. We also found extreme differentiation for the C/c variant when comparing sub-Saharan to non-sub-Saharan populations.

Association Between ABO and Rh Blood Groups and SARS-CoV-2 Infection or Severe COVID-19 Illness

“…Given that Black and Asian persons may be at increased risk for SARS-CoV-2 infection and, possibly, worse clinical outcomes than White persons ( 15 ), future large-scale epidemiologic research should consider contrasting the risk for SARS-CoV-2 infection between different subpopulations on an international and regional level. For example, the Basque people of Spain are more likely to be O and Rh− ( 16 ) and thus would be expected to be at lower risk for SARS-CoV-2 infection. Other epidemiologic research could expand our current knowledge by measuring not only ABO and Rh status but also the presence of erythrocyte alloimmunization—namely, the formation of antibodies against non–self-antigens on erythrocytes ( 17 ).…”

Genetic origins, singularity, and heterogeneity of Basques

“…Such an interest in the genetics of Basques started with the remarkable observation of a high frequency of the Rh-negative blood group, 9 a genetic variant associated with the hemolytic disease of the newborn, which was confirmed in following studies. 10 Subsequent studies using more genetic markers revealed that Basques were particularly differentiated within the European genetic context. 11,12 These results, together with archaeological, cultural, and linguistic data, were interpreted as Basques descending from an ancient population that remained isolated in the region.…”

<p>Potential of next-generation sequencing to match blood group antigens for transfusion</p>

“…Patients from specific populations or those with unexplained complex serological results will particularly benefit from NGS analysis used as a first-line test instead of relying on extended phenotyping, multistep antibody identification and numerous single or screening genetic tests. [77][78][79] In 2014, Mazonson et al estimated the costs of pre-transfusion tests at about 195 USD per patient but for patients with autoimmune hemolytic anemia the cost increased to 1490 USD as compared to 65 USD for six blood genes when using the NGS approach. 80 3) The huge capacity of the NGS experiment makes this technology an ideal tool for mass screening of blood donors for all clinically important antigens and also to detect individuals with rare blood group antigens in various ethnic groups.…”

“…80 3) The huge capacity of the NGS experiment makes this technology an ideal tool for mass screening of blood donors for all clinically important antigens and also to detect individuals with rare blood group antigens in various ethnic groups. 78,79 This facilitates access to compatible donors for alloimmunised patients. 81 Patients with antibodies to high-frequency antigens and antibodies to numerous antigens will benefit when tested with the NGS approach which provides the recipient's profile of antigens in one step.…”