HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huang, C.-H. Search for Related Content PubMed PubMed Citation Articles by Huang, C.-H. Social Bookmarking                      What's this?

Vol. 273, Issue 4, 2207-2213, January 23, 1998

The Human Rh50 Glycoprotein Gene
STRUCTURAL ORGANIZATION AND ASSOCIATED SPLICING DEFECT RESULTING IN Rh_null DISEASE

From the Laboratory of Biochemistry and Molecular Genetics, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10021

The Rh (Rhesus) protein family comprises Rh50 glycoprotein and Rh30 polypeptides, which form a complex essential for Rh antigen expression and erythrocyte membrane integrity. This article describes the structural organization of Rh50 gene and identification of its associated splicing defect causing Rh_null disease. The Rh50 gene, which maps at chromosome 6p11-21.1, has an exon/intron structure nearly identical to Rh30 genes, which map at 1p34-36. Of the 10 exons assigned, conservation of size and sequence is confined mainly to the region from exons 2 to 9, suggesting that RH50 and RH30 were formed as two separate genetic loci from a common ancestor via a transchromosomal insertion event. The available information on the structure of RH50 facilitated search for candidate mutations underlying the Rh deficiency syndrome, an autosomal recessive disorder characterized by mild to moderate chronic hemolytic anemia and spherostomatocytosis. In one patient with the Rh_null disease of regulator type, a shortened Rh50 transcript lacking the sequence of exon 7 was detected, while no abnormality was found in transcripts encoding Rh30 polypeptides and Rh-related CD47 glycoprotein. Amplification and sequencing of the genomic region spanning exon 7 revealed a G  A transition in the invariant GT motif of the donor splice site in both Rh50 alleles. This splicing mutation caused not only a total skipping of exon 7 but also a frameshift and premature chain termination. Thus, the deduced translation product contained 351 instead of 409 amino acids, with an entirely different C-terminal sequence following Thr³¹⁵. These results identify the donor splicing defect, for the first time, as a loss-of-function mutation at the RH50 locus and pinpoint the importance of the C-terminal region of Rh50 in Rh complex formation via protein-protein interactions.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. H. Braun, S. L. Steele, M. Ekker, and S. F. Perry Nitrogen excretion in developing zebrafish (Danio rerio): a role for Rh proteins and urea transporters Am J Physiol Renal Physiol, May 1, 2009; 296(5): F994 - F1005. [Abstract] [Full Text] [PDF]

				L. J. Bruce, H. Guizouarn, N. M. Burton, N. Gabillat, J. Poole, J. F. Flatt, R. L. Brady, F. Borgese, J. Delaunay, and G. W. Stewart The monovalent cation leak in overhydrated stomatocytic red blood cells results from amino acid substitutions in the Rh-associated glycoprotein Blood, February 5, 2009; 113(6): 1350 - 1357. [Abstract] [Full Text] [PDF]

				I. Mouro-Chanteloup, A. M. D'Ambrosio, P. Gane, C. Le Van Kim, V. Raynal, D. Dhermy, J.-P. Cartron, and Y. Colin Cell-surface expression of RhD blood group polypeptide is posttranscriptionally regulated by the RhAG glycoprotein Blood, July 18, 2002; 100(3): 1038 - 1047. [Abstract] [Full Text] [PDF]

				N. D. Avent and M. E. Reid The Rh blood group system: a review Blood, January 15, 2000; 95(2): 375 - 387. [Abstract] [Full Text] [PDF]

				K. Suyama, H. Li, and A. Zhu Surface expression of Rh-associated glycoprotein (RhAG) in nonerythroid COS-1 cells Blood, January 1, 2000; 95(1): 336 - 341. [Abstract] [Full Text] [PDF]

				F. F. Wagner, C. Gassner, T. H. Muller, D. Schonitzer, F. Schunter, and W. A. Flegel Molecular Basis of Weak D Phenotypes Blood, January 1, 1999; 93(1): 385 - 393. [Abstract] [Full Text] [PDF]

				C.-H. Huang, Z. Liu, G. Cheng, and Y. Chen Rh50 Glycoprotein Gene and Rhnull Disease: A Silent Splice Donor Is trans to a Gly279right-arrowGlu Missense Mutation in the Conserved Transmembrane Segment Blood, September 1, 1998; 92(5): 1776 - 1784. [Abstract] [Full Text] [PDF]

				B. Cherif-Zahar, G. Matassi, V. Raynal, P. Gane, W. Mempel, C. Perez, and J.-P. Cartron Molecular Defects of the RHCE Gene in Rh-Deficient Individuals of the Amorph Type Blood, July 15, 1998; 92(2): 639 - 646. [Abstract] [Full Text] [PDF]

				C.-H. Huang, Y. Chen, M. E. Reid, and C. Seidl Rhnull Disease: The Amorph Type Results From a Novel Double Mutation in RhCe Gene on D-Negative Background Blood, July 15, 1998; 92(2): 664 - 671. [Abstract] [Full Text] [PDF]

				S. Iwamoto, H. Suganuma, T. Kamesaki, T. Omi, H. Okuda, and E. Kajii Cloning and Characterization of Erythroid-specific DNase I-hypersensitive Site in Human Rhesus-associated Glycoprotein Gene J. Biol. Chem., August 25, 2000; 275(35): 27324 - 27331. [Abstract] [Full Text] [PDF]

				Z. Liu, Y. Chen, R. Mo, C.-c. Hui, J.-F. Cheng, N. Mohandas, and C.-H. Huang Characterization of Human RhCG and Mouse Rhcg as Novel Nonerythroid Rh Glycoprotein Homologues Predominantly Expressed in Kidney and Testis J. Biol. Chem., August 11, 2000; 275(33): 25641 - 25651. [Abstract] [Full Text] [PDF]

				Z. Liu, J. Peng, R. Mo, C.-c. Hui, and C.-H. Huang Rh Type B Glycoprotein Is a New Member of the Rh Superfamily and a Putative Ammonia Transporter in Mammals J. Biol. Chem., January 5, 2001; 276(2): 1424 - 1433. [Abstract] [Full Text] [PDF]