IthaID: 2561
Names and Sequences
| Functionality: | Disease modifying mutation | Pathogenicity: | N/A |
|---|---|---|---|
| Common Name: | ααα(anti-3.7) | HGVS Name: | NG_000006.1:g.34247_38050dup |
We follow the
HGVS sequence variant nomenclature
and
IUPAC standards.
Comments: Alpha-globin gene triplications are not associated with abnormal haematological parameters but may aggravate the phenotype of patients with beta-thalassaemia. The ααα(anti-3.7) allele is generated by unequal crossover between misaligned homologous sequences (Z boxes) on the α2 and α1 genes during recombination (rightward crossover). A second product generated is the hybrid -α3.7 gene [ithaID=300]. The PCR primers used by Wang et al [PMID: 14500599] place the triplicated allele between positions 173617-173635 (HBA2 3'UTR) and 175508-175528 (HBA1 upstream) (GRCh38.p12), producing an amplicon of around 1.9 kb. The α-triplication can be detected by the SALSA MLPA probemix P140 HBA C1. Two different types are reported with different breakpoints that can be detected by i) 18096-L22520 and 15857-L21812, and ii) 18092-L22516 and 14855-L23604 probe pairs.
External Links
No available links
Phenotype
| Allele Phenotype (Cis): | N/A |
|---|---|
| Allele Phenotype (Trans): | N/A |
| Associated Phenotypes: | Anaemia [HP:0001903] |
Location
| Chromosome: | 16 |
|---|---|
| Locus: | NG_000006.1 |
| Locus Location: | N/A |
| Size: | N/A |
| Located at: | α2, α1 |
Other details
| Type of Mutation: | Duplication |
|---|---|
| Ethnic Origin: | N/A |
| Molecular mechanism: | N/A |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Goossens M, Dozy AM, Embury SH, Zachariades Z, Hadjiminas MG, Stamatoyannopoulos G, Kan YW, Triplicated alpha-globin loci in humans., Proc. Natl. Acad. Sci. U.S.A. , 77(1), 518-21, 1980
- Kanavakis E, Metaxotou-Mavromati A, Kattamis C, Wainscoat JS, Wood WG, The triplicated alpha gene locus and beta thalassaemia., Br. J. Haematol. , 54(2), 201-7, 1983
- Traeger-Synodinos J, Kanavakis E, Vrettou C, Maragoudaki E, Michael T, Metaxotou-Mavromati A, Kattamis C, The triplicated alpha-globin gene locus in beta-thalassaemia heterozygotes: clinical, haematological, biosynthetic and molecular studies., Br. J. Haematol. , 95(3), 467-71, 1996
- Wang W, Ma ES, Chan AY, Prior J, Erber WN, Chan LC, Chui DH, Chong SS, Single-tube multiplex-PCR screen for anti-3.7 and anti-4.2 alpha-globin gene triplications., Clin. Chem., 49(10), 1679-82, 2003
- Moosavi SF, Amirian A, Zarbakhsh B, Kordafshari A, Mirzahoseini H, Zeinali S, Karimipoor M, The carrier frequency of α-globin gene triplication in an Iranian population with normal or borderline hematological parameters., Hemoglobin, 35(4), 323-30, 2011
- Farashi S, Bayat N, Faramarzi Garous N, Ashki M, Montajabi Niat M, Vakili S, Imanian H, Zeinali S, Najmabadi H, Azarkeivan A, Interaction of an α-Globin Gene Triplication with β-Globin Gene Mutations in Iranian Patients with β-Thalassemia Intermedia., Hemoglobin, 39(3), 201-6, 2015