Blood group terminology 2004: from the International Society of Blood Transfusion committee on terminology for red cell surface antigens

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73460/1/j.1423-0410.2004.00564.x.pd

The Tetraspanins CD9 and CD81 Regulate CD9P1-Induced Effects on Cell Migration

CD9P-1 is a cell surface protein with immunoglobulin domains and an unknown function that specifically associates with tetraspanins CD9 and CD81. Overexpression of CD9P-1 in HEK-293 cells induces dramatic changes in cell spreading and migration on various matrices. Experiments using time-lapse videomicroscopy revealed that CD9P-1 expression has led to higher cell motility on collagen I but lower motility on fibronectin through a β1-integrins dependent mechanism. On collagen I, the increase in cell motility induced by CD9P-1 expression was found to involve integrin α2β1 and CD9P-1 was observed to associate with this collagen receptor. The generation of CD9P-1 mutants demonstrated that the transmembrane and the cytoplasmic domains are necessary for inducing effects on cell motility. On the other hand, expression of tetraspanins CD9 or CD81 was shown to reverse the effects of CD9P-1 on cell motility on collagen I or fibronectin with a concomitant association with CD9P-1. Thus, the ratio of expression levels between CD9P-1 and its tetraspanin partners can regulate cell motility

Molecular genetic analysis of podocyte genes in focal segmental glomerulosclerosis—a review

This review deals with podocyte proteins that play a significant role in the structure and function of the glomerular filter. Genetic linkage studies has identified several genes involved in the development of nephrotic syndrome and contributed to the understanding of the pathophysiology of glomerular proteinuria and/or focal segmental glomerulosclerosis. Here, we describe already well-characterized genetic diseases due to mutations in nephrin, podocin, CD2AP, alpha-actinin-4, WT1, and laminin β2 chain, as well as more recently identified genetic abnormalities in TRPC6, phospholipase C epsilon, and the proteins encoded by the mitochondrial genome. In addition, the role of the proteins which have shown to be important for the structure and functions by gene knockout studies in mice, are also discussed. Furthermore, some rare syndromes with glomerular involvement, in which molecular defects have been recently identified, are briefly described. In summary, this review updates the current knowledge of genetic causes of congenital and childhood nephrotic syndrome and provides new insights into mechanisms of glomerular dysfunction

Finding New Genes for Non-Syndromic Hearing Loss through an In Silico Prioritization Study

At present, 51 genes are already known to be responsible for Non-Syndromic hereditary Hearing Loss (NSHL), but the knowledge of 121 NSHL-linked chromosomal regions brings to the hypothesis that a number of disease genes have still to be uncovered. To help scientists to find new NSHL genes, we built a gene-scoring system, integrating Gene Ontology, NCBI Gene and Map Viewer databases, which prioritizes the candidate genes according to their probability to cause NSHL. We defined a set of candidates and measured their functional similarity with respect to the disease gene set, computing a score () that relies on the assumption that functionally related genes might contribute to the same (disease) phenotype. A Kolmogorov-Smirnov test, comparing the pair-wise distribution on the disease gene set with the distribution on the remaining human genes, provided a statistical assessment of this assumption. We found at a p-value that the former pair-wise is greater than the latter, justifying a prioritization strategy based on the functional similarity of candidate genes respect to the disease gene set. A cross-validation test measured to what extent the ranking for NSHL is different from a random ordering: adding 15% of the disease genes to the candidate gene set, the ranking of the disease genes in the first eight positions resulted statistically different from a hypergeometric distribution with a p-value and a power. The twenty top-scored genes were finally examined to evaluate their possible involvement in NSHL. We found that half of them are known to be expressed in human inner ear or cochlea and are mainly involved in remodeling and organization of actin formation and maintenance of the cilia and the endocochlear potential. These findings strongly indicate that our metric was able to suggest excellent NSHL candidates to be screened in patients and controls for causative mutations

DO/ART4 gene sequencing in sub‐Saharan cohorts and African migrants: useful data describing the diversity and spreading of rare variants

International audienceDue to the unavailability of immunological reagents, the Dombrock blood group is insufficiently explored in African populations and can be a source of alloimmunization. A large study including pygmoid and nonpygmoid ethnic groups from East, Central, and West continental Africa, together with African migrants like Comorians, Afro-Caribbean from Martinique, and Maroons from French Guiana would be helpful to increase transfusion safety

The Second Example of LU:-4: a Serological and Molecular Study

Introduction The Lutheran (LU) blood group system consists of 19 antigens numbered 1–21 (LU10, LU15 designated obsolete). There are four pairs of allelic and polymorphic antigens; Lua/Lub(LU1/LU2), LU6/LU9, LU8/LU14 and Aua/Aub(LU18/LU19). The remaining 11 are all antigens of high frequency. For the majority of Lutheran antigens the molecular bases have been determined and their expression is nearly always associated with a single amino acid change in the Lu-glycoprotein. Lutheran antigens are carried on two red cell membrane glycoproteins, Lu-glycoprotein and epithelial cancer antigen. The two isoforms are encoded by a single gene LU located on chromosome 19q13.2 and organised into 15 exons. Case Study and Methods We investigated a case of a prenatal patient with no known history of transfusion or previous pregnancies, whose serum contained an antibody giving positive reactions with all donor cells tested. Serological tests were performed by standard agglutination techniques. Genomic DNA was isolated from whole blood of the patient, all the exons of the LU gene were amplified by PCR and directly sequenced. Results Serological tests confirmed the presence of a Lutheran antibody in the patient's serum. All tested cells were incompatible with the patient's serum, except several examples of Lu(a-b-) cells of both the dominant and recessive phenotype. Her red cells were tested with antibodies to high frequency Lutheran antigens and failed to react with anti-Lu4. Sequencing of the LU gene revealed a novel homozygous mutation in exon 5 524G>T, causing an amino acid change Arg175Leu in the protein. This novel mutation was found in the same codon (523CGG) in LU exon 5 as the only other known example of LU:-4, where the change at the same nucleotide was 524G>A, leading to Arg175Gln substitution. Conclusion We report the second individual with the rare LU:-4 phenotype. We have confirmed the patient's serum contained an anti-Lu4 antibody. This phenotype results from a single point mutation in LU leading to an Arg175Leu amino acid change in the protein. This new point mutation occurred at the same nucleotide as the mutation in the only other known example of LU:-4. However, it caused a different amino acid substitution than in the original example, indicating a potential hot spot for mutations in LU