Genetic Recombination at the Human RH Locus: a Family Study of the Red-cell Evans Phenotype Reveals a Transfer of Exons 2-6 from the RHD to the RHCE Gene

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 1996 Oct 1

PMID 8808597

Citations 3

Authors

C H Huang

Y Chen

M Reid

S Ghosh

Affiliations

Soon will be listed here.

Abstract

The human RH locus appears to consist of two structural genes, D and CE, which map on the short arm p34-36 of chromosome 1 and specify a most complex system of blood-group genetic polymorphisms. Here we describe a family study of the Evans (also known as "D..") phenotype, a codominant trait associated with both qualitative and quantitative changes in D-antigen expression. A cataract-causing mutation was also inherited in this family and was apparently cotransmitted with Evans, suggesting a chromosomal linkage of these two otherwise unrelated traits. Southern blot analysis and allele-specific PCR showed the linkage of Evans with a SphI RFLP marker and the presence of a hybrid gene in the RH locus. To delineate the pattern of gene expression, the composition and structure of Rh-polypeptide transcripts were characterized by reverse transcriptase-PCR and nucleotide sequencing. This resulted in the identification of a novel Rh transcript expressed only in the Evans-positive erythroid cells. Sequence analysis showed that the transcript maintained a normal open reading frame but occurred as a CE-D-CE composite in which exons 2-6 of the CE gene were replaced by the homologous counterpart of the D gene. This hybrid gene was predicted to encode a CE-D-CE fusion protein whose surface expression correlates with the Evans phenotype. The mode and consequence of such a recombination event suggest the occurrence, in the RH locus, of a segmental DNA transfer via the mechanism of gene conversion.

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References

Huang C, Blumenfeld O . Molecular genetics of human erythrocyte MiIII and MiVI glycophorins. Use of a pseudoexon in construction of two delta-alpha-delta hybrid genes resulting in antigenic diversification. J Biol Chem. 1991; 266(11):7248-55. View

Cherif-Zahar B, Mattei M, Le Van Kim C, Bailly P, Cartron J, Colin Y . Localization of the human Rh blood group gene structure to chromosome region 1p34.3-1p36.1 by in situ hybridization. Hum Genet. 1991; 86(4):398-400. DOI: 10.1007/BF00201843. View

MacGeoch C, Mitchell C, Carritt B, Avent N, Ridgwell K, Tanner M . Assignment of the chromosomal locus of the human 30-kDal Rh (rhesus) blood group-antigen-related protein (Rh30A) to chromosome region 1p36.13----p34. Cytogenet Cell Genet. 1992; 59(4):261-3. DOI: 10.1159/000133264. View

Le Van Kim C, Mouro I, Cherif-Zahar B, Raynal V, CHERRIER C, Cartron J . Molecular cloning and primary structure of the human blood group RhD polypeptide. Proc Natl Acad Sci U S A. 1992; 89(22):10925-9. PMC: 50455. DOI: 10.1073/pnas.89.22.10925. View

Arce M, Thompson E, Wagner S, Coyne K, Ferdman B, Lublin D . Molecular cloning of RhD cDNA derived from a gene present in RhD-positive, but not RhD-negative individuals. Blood. 1993; 82(2):651-5. View

Mouro I, Colin Y, Cherif-Zahar B, Cartron J, Le Van Kim C . Molecular genetic basis of the human Rhesus blood group system. Nat Genet. 1993; 5(1):62-5. DOI: 10.1038/ng0993-62. View

Mouro I, Le Van Kim C, ROUILLAC C, van Rhenen D, Le Pennec P, Bailly P . Rearrangements of the blood group RhD gene associated with the DVI category phenotype. Blood. 1994; 83(4):1129-35. View

Mathew S, Chaudhuri A, Murty V, Pogo A . Confirmation of Duffy blood group antigen locus (FY) at 1q22-->q23 by fluorescence in situ hybridization. Cytogenet Cell Genet. 1994; 67(1):68. DOI: 10.1159/000133801. View

Blunt T, Steers F, Daniels G, Carritt B . Lack of RH C/E expression in the Rhesus D--phenotype is the result of a gene deletion. Ann Hum Genet. 1994; 58(1):19-24. DOI: 10.1111/j.1469-1809.1994.tb00722.x. View

10.

Anstee D, Tanner M . Biochemical aspects of the blood group Rh (rhesus) antigens. Baillieres Clin Haematol. 1993; 6(2):401-22. DOI: 10.1016/s0950-3536(05)80152-0. View

11.

ROUILLAC C, Colin Y, Hughes-Jones N, Beolet M, DAmbrosio A, Cartron J . Transcript analysis of D category phenotypes predicts hybrid Rh D-CE-D proteins associated with alteration of D epitopes. Blood. 1995; 85(10):2937-44. View

12.

Huang C, Reid M, Chen Y . Identification of a partial internal deletion in the RH locus causing the human erythrocyte D--phenotype. Blood. 1995; 86(2):784-90. View

13.

Stambolian D, Ai Y, Sidjanin D, Nesburn K, Sathe G, Rosenberg M . Cloning of the galactokinase cDNA and identification of mutations in two families with cataracts. Nat Genet. 1995; 10(3):307-12. DOI: 10.1038/ng0795-307. View

14.

Huang C, Reid M, Chen Y, Coghlan G, Okubo Y . Molecular definition of red cell Rh haplotypes by tightly linked SphI RFLPs. Am J Hum Genet. 1996; 58(1):133-42. PMC: 1914946. View

15.

Smythe J, Avent N, Judson P, Parsons S, Martin P, Anstee D . Expression of RHD and RHCE gene products using retroviral transduction of K562 cells establishes the molecular basis of Rh blood group antigens. Blood. 1996; 87(7):2968-73. View

16.

Contreras M, Stebbing B, Blessing M, Gavin J . The Rh antigen Evans. Vox Sang. 1978; 34(4):208-11. DOI: 10.1111/j.1423-0410.1978.tb02469.x. View

17.

Goossens M, Kan Y . DNA analysis in the diagnosis of hemoglobin disorders. Methods Enzymol. 1981; 76:805-17. DOI: 10.1016/0076-6879(81)76159-7. View

18.

KYTE J, Doolittle R . A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982; 157(1):105-32. DOI: 10.1016/0022-2836(82)90515-0. View

19.

Feinberg A, Vogelstein B . "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984; 137(1):266-7. DOI: 10.1016/0003-2697(84)90381-6. View

20.

Lubsen N, Renwick J, Tsui L, Breitman M, Schoenmakers J . A locus for a human hereditary cataract is closely linked to the gamma-crystallin gene family. Proc Natl Acad Sci U S A. 1987; 84(2):489-92. PMC: 304234. DOI: 10.1073/pnas.84.2.489. View