title: SARA: a "new" low-frequency MNS antigen (MNS47) provides further evidence of the extreme diversity of the MNS blood group system.
abstract: BACKGROUND
  Until recently, SARAH (SARA) was a low-frequency antigen within the 700 series (700.052). SARA was discovered in Australia and subsequently described in Canada where anti-SARA was implicated in severe hemolytic disease of the fetus and newborn (HDFN). This study investigated whether SARA could be recategorized into an existing, or novel, blood group system.
  
  
  METHODS
  Serologically typed Australian SARA family members (n = 9) were exome sequenced followed by bioinformatics analysis. Sanger sequencing of Exon 3 of GYPA of Australian (n = 9) and Canadian (n = 9) family members was then performed, as were peptide inhibition studies.
  
  
  RESULTS
  Exome sequencing identified 499,329 single-nucleotide variants (SNVs) within the nine individuals. Filtering excluded SNVs with an NCBI dbSNP ID (n = 482,177) and non-protein coding SNVs (n = 14,008); for the remaining 3144 SNVs, only one, c.240G>T of GYPA encoding p.Arg80Ser, was present in all six SARA-positive individuals. Sanger sequencing confirmed the presence of c.240G>T in the Australian SARA-positive individuals and demonstrated the same genetic basis in the Canadian SARA family. For a peptide representing the SARA sequence, inhibition of anti-SARA against SARA-positive cells was 84.6% at a concentration of 1.0 mg/mL.
  
  
  CONCLUSIONS
  We provide evidence that the SARA antigen is encoded by a SNV on GYPA and SARA has been reassigned to the MNS blood group system, now MNS47. This discovery provides a basis for application of genetic approaches in SARA typing when clinically indicated, for example, in HDFN.
authors.affiliation: Research and Development, Australian Red Cross Blood Service, Kelvin Grove, Queensland, Australia.
authors.forename: Rhiannon S
authors.initials: RS
authors.lastname: McBean
authors.affiliation: Research and Development, Australian Red Cross Blood Service, Kelvin Grove, Queensland, Australia.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Hyland
authors.affiliation: Transfusion Medicine, Calgary Laboratory Services, Calgary, Alberta, Canada.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Hendry
authors.affiliation: Transfusion Medicine, Calgary Laboratory Services, Calgary, Alberta, Canada.
authors.forename: Meer-Taher
authors.initials: MT
authors.lastname: Shabani-Rad
authors.affiliation: Research and Development, Australian Red Cross Blood Service, Kelvin Grove, Queensland, Australia.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Flower
mesh_terms: D001315:Australia; D002170:Canada; D004899:Erythroblastosis, Fetal / Q000235:genetics; D005190:Family; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D007231:Infant, Newborn; D007519:Isoantigens / Q000235:genetics*; D008951:MNSs Blood-Group System / Q000235:genetics*; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D017422:Sequence Analysis, DNA
chemical_list: D007519:Isoantigens; D008951:MNSs Blood-Group System; C090667:SARAH antigen