Proposed Nomenclature, Molecular Basis and Minimal Population Frequencies of RHD Alleles Coding for Weak D Phenotypes
| Trivial Name . | Molecular Basis (allele) . | Nucleotide Change . | Protein Sequence . | Exon . | Membrane Localization3-150 . | CpG3-151 . | Population Study . | |||
|---|---|---|---|---|---|---|---|---|---|---|
| No.3-152 . | % of Weak D . | Phenotype Frequency (%) . | Haplotype Frequency . | |||||||
| Weak D type 1 | RHD (V270G) | T → G at 809 | Val to Gly at 270 | 6 | TM | No | 95 | 70.29 | 0.2964 | 1:277 |
| Weak D type 2 | RHD (G385A) | G → C at 1154 | Gly to Ala at 385 | 9 | TM | No | 43 | 18.01 | 0.0759 | 1:1,082 |
| Weak D type 3 | RHD (S3C) | C → G at 8 | Ser to Cys at 3 | 1 | IC | No | 7 | 5.19 | 0.0219 | 1:3,759 |
| Weak D type 4 | RHD (T201R, F223V) | C → G at 602, T → G at 667, G → A at 819 | Thr to Arg at 201 Phe to Val at 223 no change | 4 5 6 | IC TM — | NA3-153 NA Yes | 6 | 1.30 | 0.0055 | 1:14,925 |
| Weak D type 5 | RHD (A149D) | C → A at 446 | Ala to Asp at 149 | 3 | TM | No | 2 | 0.84 | 0.0035 | 1:23,256 |
| Weak D type 6 | RHD (R10Q) | G → A at 29 | Arg to Gln at 10 | 1 | IC | Yes | 1 | 0.74 | 0.0031 | 1:26,316 |
| Weak D type 7 | RHD (G339E) | G → A at 1016 | Gly to Glu at 339 | 7 | TM | No | 1 | 0.74 | 0.0031 | 1:26,316 |
| Weak D type 8 | RHD (G307R) | G → A at 919 | Gly to Arg at 307 | 6 | IC | Yes | 1 | 0.74 | 0.0031 | 1:26,316 |
| Weak D type 9 | RHD (A294P) | G → C at 880 | Ala to Pro at 294 | 6 | TM | No | 1 | 0.42 | 0.0017 | 1:47,619 |
| Weak D type 10 | RHD (W393R) | T → C at 1177 | Trp to Arg at 393 | 9 | IC | No | 1 | 0.42 | 0.0017 | 1:47,619 |
| Weak D type 11 | RHD (M295I) | G → T at 885 | Met to Ile at 295 | 6 | TM | No | 1 | 0.22 | 0.0009 | 1:90,909 |
| Weak D type 12 | RHD(G277E) | G → A at 830 | Gly to Glu at 277 | 6 | TM | No | 0 | <2.223-155 | ||
| Weak D type 13 | RHD (A276P) | G → C at 826 | Ala to Pro at 276 | 6 | TM | No | 0 | <2.223-155 | ||
| Weak D type 14 | RHD (S182T, K198N, T201R) | T → A at 544, A → T at 594, C → G at 602 | Ser to Thr at 182 Lys to Asn at 198 Thr to Arg at 201 | 4 4 4 | TM IC IC | NA NA NA | 0 | <2.223-155 | ||
| Weak D type 15 | RHD (G282D) | G → A at 845 | Gly to Asp at 282 | 6 | TM | No | 0 | <1.263-155 | ||
| Weak D type 16 | RHD (W220R) | T → C at 658 | Trp to Arg at 220 | 5 | TM | No | 0 | <1.263-155 | ||
| DIV type III3-154 | RHD-CE(6-9)-D | multiple | multiple | 6 to 9 | EF/TM/IC | NA | 1 | 0.60 | 0.0025 | 1:32,448 |
| DHMi | RHD (T283I) | C → T at 848 | Thr to Ile at 283 | 6 | EF | No | 1 | 0.42 | 0.0017 | 1:47,619 |
| Trivial Name . | Molecular Basis (allele) . | Nucleotide Change . | Protein Sequence . | Exon . | Membrane Localization3-150 . | CpG3-151 . | Population Study . | |||
|---|---|---|---|---|---|---|---|---|---|---|
| No.3-152 . | % of Weak D . | Phenotype Frequency (%) . | Haplotype Frequency . | |||||||
| Weak D type 1 | RHD (V270G) | T → G at 809 | Val to Gly at 270 | 6 | TM | No | 95 | 70.29 | 0.2964 | 1:277 |
| Weak D type 2 | RHD (G385A) | G → C at 1154 | Gly to Ala at 385 | 9 | TM | No | 43 | 18.01 | 0.0759 | 1:1,082 |
| Weak D type 3 | RHD (S3C) | C → G at 8 | Ser to Cys at 3 | 1 | IC | No | 7 | 5.19 | 0.0219 | 1:3,759 |
| Weak D type 4 | RHD (T201R, F223V) | C → G at 602, T → G at 667, G → A at 819 | Thr to Arg at 201 Phe to Val at 223 no change | 4 5 6 | IC TM — | NA3-153 NA Yes | 6 | 1.30 | 0.0055 | 1:14,925 |
| Weak D type 5 | RHD (A149D) | C → A at 446 | Ala to Asp at 149 | 3 | TM | No | 2 | 0.84 | 0.0035 | 1:23,256 |
| Weak D type 6 | RHD (R10Q) | G → A at 29 | Arg to Gln at 10 | 1 | IC | Yes | 1 | 0.74 | 0.0031 | 1:26,316 |
| Weak D type 7 | RHD (G339E) | G → A at 1016 | Gly to Glu at 339 | 7 | TM | No | 1 | 0.74 | 0.0031 | 1:26,316 |
| Weak D type 8 | RHD (G307R) | G → A at 919 | Gly to Arg at 307 | 6 | IC | Yes | 1 | 0.74 | 0.0031 | 1:26,316 |
| Weak D type 9 | RHD (A294P) | G → C at 880 | Ala to Pro at 294 | 6 | TM | No | 1 | 0.42 | 0.0017 | 1:47,619 |
| Weak D type 10 | RHD (W393R) | T → C at 1177 | Trp to Arg at 393 | 9 | IC | No | 1 | 0.42 | 0.0017 | 1:47,619 |
| Weak D type 11 | RHD (M295I) | G → T at 885 | Met to Ile at 295 | 6 | TM | No | 1 | 0.22 | 0.0009 | 1:90,909 |
| Weak D type 12 | RHD(G277E) | G → A at 830 | Gly to Glu at 277 | 6 | TM | No | 0 | <2.223-155 | ||
| Weak D type 13 | RHD (A276P) | G → C at 826 | Ala to Pro at 276 | 6 | TM | No | 0 | <2.223-155 | ||
| Weak D type 14 | RHD (S182T, K198N, T201R) | T → A at 544, A → T at 594, C → G at 602 | Ser to Thr at 182 Lys to Asn at 198 Thr to Arg at 201 | 4 4 4 | TM IC IC | NA NA NA | 0 | <2.223-155 | ||
| Weak D type 15 | RHD (G282D) | G → A at 845 | Gly to Asp at 282 | 6 | TM | No | 0 | <1.263-155 | ||
| Weak D type 16 | RHD (W220R) | T → C at 658 | Trp to Arg at 220 | 5 | TM | No | 0 | <1.263-155 | ||
| DIV type III3-154 | RHD-CE(6-9)-D | multiple | multiple | 6 to 9 | EF/TM/IC | NA | 1 | 0.60 | 0.0025 | 1:32,448 |
| DHMi | RHD (T283I) | C → T at 848 | Thr to Ile at 283 | 6 | EF | No | 1 | 0.42 | 0.0017 | 1:47,619 |
IC, intracellular; TM, transmembraneous; EF, exofacial.
Mutation occurring in CpG doublet.
Number of samples (no.) observed among 161 random blood samples with weak antigen D expression. Types 12 to 16 were detected in additional weak D samples.
Not applicable, substitution(s) probably derived from gene conversion.
Upper limit of 95% confidence interval (Poisson distribution).
In the D IV type III allele, the presence of aRHCE-RHD hybrid was proven by RHD-specific sequencing of the 5′ breakpoint region. This breakpoint was located in intron 5 between −993 bp and −814 bp relative to the first nucleotide of exon 6 (range of 180 bp; Genbank accession numbers Z97333 andZ97364).