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Colton Blood Group System

CO
Gene locus - AQP1
Alleles

Introduction

Colton antigens are produced by alleles of a single gene that encodes one member (AQP1) of the Aquaporin family of water channel proteins. So far 11 members of this family have been identified in mammals and more than 200 members in plants, microbes, and other members of the animal kingdom. Aquaporins are membrane proteins with six transmembrane spanning domains with conserved developmental patterns of tissue specific expression. AQP1 and AQP3 (see GIL blood group system) are the only Aquaporins expressed in erythrocyte membranes. The AQP1 protein assembles as a homotetramer with 1-2 of the 4 subunits N-glycosylated; each monomer is an independent water pore. The structure of AQP1 to 2.2 A resolution has been established (Sui et al).

The genes

Chromosomal location of AQP1 gene is 7p14.

Function of proteins

Facilitates water-selective movement across the lipid bilayer in response to an osmotic gradient

Tissue distribution

AQP1 is expressed in many tissues in addition to erythrocytes. In other tissues that express AQP1 (proximal tubules of nephron, capillaries, ciliary and lens epithelium, hepatic bile ducts and gall bladder, and the choroid plexus) the pattern of expression reflects epithelium known to have high constitutive water permeability. Many tissues with high basal or regulated water permeability that do not express AQP1 do express one of many aquaporin family members. For instance, the renal nephron collecting duct cells express at least 2 distinct aquaporins but do not express AQP1. In these cells AQP3 is constitutively expressed in the basal and lateral membranes, while AQP2 is transported to the apical membrane upon vasopressin stimulation.

Disease association

None apparent for AQP1, except impaired urinary concentration under conditions of fluid restriction. Subjects lacking or showing a deficiency of AQ1 (Co neg.) show no obvious clinical defect but their red cell lifespan is slightly decreased and their membrane surface area is slightly reduced (Mathai et al.).

Serological aspects

The designation of Colton antigens is as follows: Co(a) also named CO1 is the common antigen essenially detected universally; Co(b) or CO2 is the antithetical antigen of a prevalence of about 8%; CO3 and CO4 are high prevalence antigens, whose expression is not uniform in different Conull individuals.Their molecular basis is still unknown (Saison et al. Vox Sang 2012 102 online Feb.20). The Co(a-b-) phenotype and the expression of AQP1 at the cell surface may not be always directly linked; for example, this null phenotype is shown by a variant 140G allele encoding a fully expressed protein that is functionally active. (Arnaud et al.Transfusion 2010 50 2106-2116)

About the alleles

In the database sequence acc.no. M77829 is used as the reference sequence. It is the sequence of the Coa (CO!) allele, namely nucleotide 134 is a "C" corresponding to residue 45 being an "A"; the change in Cob(CO2) is 134C>T corresponding to A45V.
So far, individuals, bearing the rare alleles, were identified as lacking the Colton antigens. Subsequent molecular analyses revealed a variety of different homozygous mutations (deletions, insertions, and point mutations),which result in little or no detectable AQP1 protein in the erythrocyte membrane. It is not apparent, as yet, what clinical consequences may result from either homozygous or heterozygous mutaions in the AQP1 gene. None of the individuals had exhibited any clinical consequences; possibly, they may be sub-clinically compromised or other mechanisms may compensate for the absence of AQP1 in erythrocytes or other cells. Transgenic mice lacking AQP1 were grossly normal but became sensitive to water deprivation showing dehydration and increased serum and urine osmolality (Ma et al.).

Other database IDs and links

NCBI genes Uniprot ID Genbank proteins Gene nomenclature database ID Genbank nucleic acids
NM_198098 for variant 1 isoform
NCBI homologenes for homologs and orthologs NCBI dbSNP for single nucleotide polymorphisms OMIM ID - at Online Mendelian Inheritance in Man

Literature

Relevant literature is cited in relevant subsections. Also, see sections on common and rare alleles.

New PubMed entries with the terms Colton and blood from the last 30 days.
NCBI Book Sections with the terms Colton and blood.

Contributors

Gregory M . Preston, Ph.D, Department of Cardiovascular and Metabolic Diseases, Pfizer, Inc., Groton, CT 06340-8002 ;

Dr. Geoff Daniels (participated in the nomenclature of the alleles), Bristol Institute for Transfusion Sciences, Bristol, BS10 5ND, UK

Contributors for specific alleles are listed with the alleles.

Links


Updated 2014-09-26 07:06:16.000
 
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