Alternative titles; symbols
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17q21.31 | [Blood group, Froese] | 601551 | 3 | SLC4A1 | 109270 |
A number sign (#) is used with this entry because of evidence that the low-incidence Froese blood group antigen polymorphism is based on a change in the SLC4A1 (109270) gene, which encodes erythrocyte protein band-3, on chromosome 17q21.
The low-incidence red cell antigen Fr(a) was described by Lewis et al. (1978) in Mennonite kindreds in Manitoba. It was shown to be inherited as an autosomal dominant trait, and although it was not very polymorphic in the general population, it was studied in sizable kindreds.
Genetic linkage excluded the FR locus from 17 of the 23 established blood group systems (Daniels et al., 1995). Another private blood group antigen, Wd(a), which defines the Waldner blood group locus (WD; 112010) was shown to map to 17q and to a point mutation in the SLC4A1 gene (109270). Zelinski et al. (1996) showed that the FR locus is tightly linked to SLC4A1 with a peak lod score of 5.72 in 5 nuclear families from 3 previously unpublished Mennonite kindreds. The Swann blood group locus (SW; 601550) and the WD and FR loci all mapped to the 17q12-q24 region, suggesting that they may represent separate alleles of the SLC4A1 gene.
In 2 unrelated Mennonite kindreds segregating for Fr(a), McManus et al. (2000) demonstrated an SLC4A1 exon 13 mobility shift in the SSCP analysis in the DNA from all Fr(a+) persons that was not seen in the DNA from Fr(a-) family members or control subjects. Linkage between the exon 13 SSCP and Fr(a) was established, with peak lods of 3.62 at theta = 0.00 for combined paternal and maternal meioses. DNA sequencing revealed a GAG-to-AAG mutation that underlies a glu480-to-lys substitution in erythrocyte protein band 3. McManus et al. (2000) defined Fr(a) as a Diego system (110500) member. On the basis of erythrocyte band-3 structural predictions, they concluded that the glu480-to-lys substitution is located in the second extracellular loop of the protein; thus, Fr(a) was the first antigen to be localized to this region of the molecule.
Daniels, G. L., Anstee, D. J., Cartron, J. P., Dahr, W., Issitt, P. D., Jorgensen, J., Kornstad, L., Levene, C., Lomas-Francis, C., Lubenko, A., Mallory, D., Moulds, J. J., and 9 others. Blood group terminology 1995: ISBT Working Party on terminology for red cell surface antigens. Vox Sang. 69: 265-279, 1995. [PubMed: 8578746] [Full Text: https://doi.org/10.1111/j.1423-0410.1995.tb02611.x]
Lewis, M., Kaita, H., McAlpine, P. J., Fletcher, J., Moulds, J. J. A 'new' blood group antigen Fr(a): incidence, inheritance and genetic linkage analysis. Vox Sang. 35: 251-254, 1978. [PubMed: 695442] [Full Text: https://doi.org/10.1111/j.1423-0410.1978.tb02930.x]
McManus, K., Lupe, K., Coghlan, G., Zelinski, T. An amino acid substitution in the putative second extracellular loop of RBC band 3 accounts for the Froese blood group polymorphism. Transfusion 40: 1246-1249, 2000. [PubMed: 11061863] [Full Text: https://doi.org/10.1046/j.1537-2995.2000.40101246.x]
Zelinski, T., McKeown, I., McAlpine, P. J., Philipps, S., Coghlan, G. Assignment of the gene(s) governing Froese and Swann blood group polymorphism to chromosome 17q. Transfusion 36: 419-420, 1996. [PubMed: 8693505] [Full Text: https://doi.org/10.1046/j.1537-2995.1996.36596282584.x]