SMIM1 underlies the Vel blood group and influences red blood cell traits

Abstract

+ Correspondence should be addressed to CAA (c.albers@gen.umcn.nl), WHO (who1000@cam.ac.uk) or AC (as889@cam.ac.uk) . Author Contributions: AC performed zebrafish knock down, analysis of zebrafish gene sequence; LHW, collected clinical cases with anti-Vel, performed confirmatory Sanger sequencing and phenotyping by flow cytometry and haem-agglutination; JCS performed confirmatory Sanger sequencing and analyzed the genotyping data; MK and PB analyzed the RNA-Sequencing data; PAS performed SMIM1 transfection experiments, MF and SF performed isolation of precursor cells; BS, GJ, AT and NG performed the analysis of the evolutionary conservation of the SMIM genes; AAS performed genotyping; EA, erythroblast culture and transfection; EB performed zebrafish knock down experiment with input from DS; HS, HHWS, VGH, NV performed cell culture experiments and performed EMSA's and transfection experiments and Q-PCR for SMIM1; RSNF, JK, HJW and LF performed eQTL and gene ontology analysis; AG, MN, JP, JGS, HLJ, KR, MdH were responsible for identification of Vel-negative and Vel-weak individuals by typing >360,000 samples; HHDK performed RNA-Seq with supervisory input from HGS who leads and coordinates the BluePrint epigenome project; GK supervised exome-sequencing; AR analysed expression data from whole genome expression arrays and RNAseq; HS expression data and vectors; DS iron homeostasis and other relevant laboratory measurements; D.St. oversaw zebrafish experiments. NS provided pre-publication access to red blood cell GWAS meta-analysis; PH eQTL analysis, expression data, SMIM1 vectors, pre-publication access to red blood cell GWAS meta-analysis; EvdS and WHO designed the study, CAA performed exome sequence analysis, Sanger sequence analysis, genetic analysis and statistical analysis; AC, LHW, EvdS, WHO and CAA wrote the paper.

Molecular Screening for Vel- Blood Donors in Southwestern Germany

“…The frequency of the SMIM1 64-80del allele of 1.81% in our study cohort corresponds to the observations of approximately 1.6% in other European populations [6,7]. The highest allele frequencies were reported for Scandinavian countries, e.g.…”

“…In the more sensitive ScanGel cards all heterozygotes showed at least a very weak agglutination. The DNA marker rs1175550 is a SNP (A>G) in the non-coding region of the SMIM1 gene and is significantly associated with weak expression of the Vel antigen [6]. We genotyped rs1175550 in the 45 Vel-phenotyped samples and could confirm a significantly higher expression of the Vel antigen in carriers (n = 5) of the minor G allele of rs1175550 (fig.…”

“…In addition, a PCR-SSP method was developed for genotyping the rs1175550 SNP in SMIM1 that was reported to be associated with expression levels of the Vel antigen [6]. The sequences of primers and probes are listed in table 1.…”

“…In 2013 different groups reported the genetic basis of the Vel- blood type [4,5,6]. A 17 bp frame-shift deletion (64-80del) in the coding region of the SMIM1 gene was homozygous in all Vel- samples.…”

Erythrogene: a database for in-depth analysis of the extensive variation in 36 blood group systems in the 1000 Genomes Project

“…Nine of the 53 non-Alu SVs were found in the GYPA and GYPB genes, known to have a high rate of recombination and gene conversions. However, we noted that neither the 37-bp insertion characteristic of the RHD pseudogene 31 nor the 17-bp deletion in SMIM1 underlying the Vel-negative phenotype [32][33][34] were called in 1000G. While the former allele was still detected because of a downstream stop codon (p.Tyr269Ter), the latter remained invisible.…”