Polymorphism
Kidd Blood Group System JK Gene locus - SLC14A1 Alleles
See Also
Introduction
The protein carrying the antigen for the Kidd blood group is a product of a single gene, JK or SLC14A1 (Solute carrier family 14, member 1; previously known as HUT11) of the urea-transporter gene family. It is an integral membrane glycoprotein with 10 membrane-spanning domains. As a urea transporter it may play a role in preserving the osmotic stability and deformability of the erythrocyte. The erythroid transporter gene bears 61% sequence identity to the human kidney urea transporter.
The genes
The gene is organized in 11 exons distributed over 30 kb. The mature 45-kd protein is encoded by exons 4-11. Chromosomal location of the SLC14A1 gene is 18q12-q21.
Linkage analysis in dominant optic atrophy
Am J Hum Genet. 1983 Nov;35(6):1190-5. Kivlin JD, Lovrien EW, Bishop DT, Maumenee IH.
- A kindred of German descent was studied for dominant optic atrophy, type Kjer (McKusick catalog no. 16540). One hundred twenty-three family members were examined clinically, and 36 affected, 81 normal, and six uncertain members were ascertained. Twenty-seven markers were analyzed for 121 members. The maximum lod score obtained was 2.0 at theta = .18 for linkage between the Kidd locus and dominant optic atrophy. Twenty-eight offspring were informative with 2-generation data. There was insufficient information for the acid phosphatase locus to aid gene localization. These data suggest that the locus for dominant optic atrophy is on chromosome 2.
Function of proteins
Urea transporter.
Urea transporters
Nephrologie. 1996;17(7):383-8. Ripoche P, Rousselet G.
- Water and urea use different pathways to cross biological membranes: channels and carriers. Numerous water channels were cloned (aquaporins); only two urea transporters are characterized in mammalians (UT2 and UT11) with sequence homologies suggesting two different carriers. This was confirmed by different localizations: UT2 was only found in renal medulla and probably was the AVP-sensitive urea carrier while UT11 was found in testis, spleen, brain and kidney and represents the constitutive urea carrier described in red blood cell. UT2 hybridized two transcripts, 4.1 kb and 2.9 kb. The large transcript expression was regulated by low protein diet whereas the short transcript was regulated by hydratation conditions. The heterologous expression into Xenopus oocytes showed a large increase of the urea uptake (UT2 > UT11), inhibitable by phloretin for UT11 and UT2 and by pCMBS only for UT11. A saturable transport of thiourea was only observed into oocytes expressing UT11. Moreover, hUT11 is encoded by the kidd locus, but, Jk (a-b-) individuals, in the absence of this urea transporter did not present related pathology. Other carriers still have to be identified and characterized in different renal segments and other tissues.
Tissue distribution
Erythocytes, white blood cells, kidney medulla (information still incomplete due to the existence of homologs)
About the alleles
So far, the molecular basis has been documented for only a few alleles; all specify the JK null phenotype and fail to express the protein on the red cells. This phenotype is rare, and has been observed in Asia, Polynesia and Finland.
Novel alleles at the JK blood group locus explain the absence of the erythrocyte urea transporter in European families
Br J Haematol. 2002 Feb;116(2):445-53.
Irshaid NM, Eicher NI, Hustinx H, Poole J, Olsson ML.
- The Kidd (JK) blood group system is of importance in transfusion medicine. The Jk(null) phenotype is associated with absence of the urea transporter in erythrocytes and moderately reduced ability to concentrate urine. We and others recently reported different molecular alterations in the silenced Jkb-like alleles of Polynesians and Finns, populations with higher Jk(null) frequencies. Here we report novel molecular bases of this phenotype in Caucasians. Blood samples from a Swiss and an English family were investigated by serological methods, urea haemolysis test and JK genotyping. Genomic DNA and JK mRNA were sequenced. Genotyping showed homozygosity for Jka-like alleles. The Swiss Jk(null) alleles deviated from wild-type Jka sequence by a nonsense mutation in exon 7 causing an immediate stop codon (Tyr194stop). The English Jk(null) alleles revealed a genomic 1.6 kilobase pair deletion including exons 4 and 5, the former of which includes the translation start codon. Multiple mRNA splicing variants were detected in reticulocytes but exons 3-5 were absent in all transcripts analysed. Screening for these alleles was negative in random donors. Two novel molecular alterations at the JK locus were defined and a multiplex polymerase chain reaction method for detection of the five known silent Jk alleles was developed to complement JK genotyping in clinical transfusion medicine.
Abstracts
References
Blood groups and affective disorders
Jpn J Psychiatry Neurol. 1988 Dec;42(4):753-8. Takazawa N, Kimura T, Nanko S.
- Distributions of seven blood groups (ABO, MNSs, P, Rh, Duffy, Kidd and Xg) were studied in a total of 118 Japanese patients with affective disorders. The patients were diagnosed according to the DSM-III: (1) Major Depression (= Unipolar Disorder, UP) (2) Bipolar Disorder (BP) and (3) Other Affective Disorders. The following results were found: (1) a high frequency of the B blood group in all patients with affective disorders compared with controls; (2) a high frequency of the Fy(a+b+) and a low frequency of the Fy(a+b-) in all patients with affective disorders, UP and BP compared with controls; (3) a low frequency of the Jk(a+b+) and a high frequency of the Jk(a+b-) in BP compared with controls and with UP.
References
MN and Jk systems influence environmental variability in serum lipid levels
Clin Genet. 1983 Jul;24(1):1-14. Martin NG, Rowell DM, Whitfield JB.
- Significant heterogeneity in the distribution of within pair variances of serum total cholesterol, HDL cholesterol, non HDL cholesterol and triglyceride levels has been found in one or both of two samples of MZ twins. We have found some support for the observation of Magnus et al. (1981) that M- pairs have greater environmental variability in cholesterol levels than M+ pairs and weaker evidence that Jka+ pairs are more variable than Jka- pairs. However, these effects appear to be more striking on triglyceride levels. The low power of the variance ratio test is advanced as a possible reason for the inconsistencies in these findings.
Links
Attribution
- This article is licensed under the GNU Free Documentation License. Sections excerpted from Blood Group Antigen Gene Mutation Database. See: Blumenfeld OO, Patnaik SK. Allelic genes of blood group antigens: a source of human mutations and cSNPs documented in the Blood Group Antigen Gene Mutation Database. Human Mutation. 2004 Jan; 23(1):8-16. PubMed ID: 14695527
