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Background: The Lu(b) antigen is expressed on red blood cells (RBCs) of the majority of individuals in all populations. Its absence in transfused patients may lead to alloantibody production and mild-to-moderate transfusion reactions, and in pregnancies to mild hemolytic disease of the fetus and newborn. This report describes the results of discrepancy resolution between apparent LU*A/LU*B or LU*B/LU*B genotypes and apparent Lu(b-) or Lu(b+ weak) phenotypes in one Asian and 10 Caucasian blood donors.Study Design and Methods: Whole blood samples were analyzed by molecular methods to resolve discrepancies between Lu(b-) phenotypes detected by serology and Lu(b+) phenotypes predicted by genotyping. RBC agglutination assays were performed with commercial and patient antisera by tube or gel column methods. Genotyping was performed on commercial arrays that target the LU*A/LU*B polymorphism at Position c.230. The discrepancies were resolved by sequencing of genomic DNA and in some cases by sequencing of cloned DNA fragments.Results: Eleven new alleles with coding sequence variants were identified, seven in the KLF1 gene, which are presumed to act dominantly to silence LU expression, and four in the LU gene itself. The alleles are KLF1*114delC, KLF1*298T, KLF1*304C,484insC, KLF1*304C,1000del2, KLF1*621G, KLF1*948delC, KLF1*1040A,1045delT, LU*B(559T,711T,714T), LU*B(611A,638T), LU*B(1049del2ins3), and LU*B(1306T,1340T,1671T,1742T).Conclusion: Besides confirming common phenotypes and detecting rare antigen-negative phenotypes, the use of molecular methods in blood donor typing can prompt the identification of new alleles through discrepancy resolution. [ABSTRACT FROM AUTHOR]

Background: The c.1-67C variant polymorphism in a GATA motif of the FY promoter is known to result in erythroid-specific FY silencing, that is, in Fy(a-) and Fy(b-) phenotypes. A Caucasian donor presented with the very rare Fy(a-b-) phenotype and was further investigated.Study Design and Methods: Genomic DNA was analyzed by sequencing to identify the cause of the Fy(a-b-) phenotype. Samples were collected from some of his relatives to establish a correlation between the serology and genotyping results. Red blood cells were analyzed by gel column agglutination and flow cytometry. Genomic DNA was analyzed on genotyping microarrays, by DNA sequencing and by allele-specific PCR.Results: In the donor, a single-nucleotide polymorphism T>C within the GATA motif was found at Position c.1-69 of the FY promoter and shown to occur in the FY*A allele. His genotype was found to be FY*A(-69C), FY*BW.01. In six FY*A/FY*B heterozygous members of the family, a perfect correlation was found between the presence vs. absence of the FY*A(-69C) variant allele and a Fy(a-) vs. Fy(a+) phenotype.Conclusion: The location of the c.1-69C polymorphism in a GATA motif whose disruption is known to result in a Fy null phenotype, together with the perfect correlation between the presence of the FY*A(-69C) allele and the Fy(a-) phenotype support a cause-effect relationship between the two. [ABSTRACT FROM AUTHOR]

Neuroblasts in Drosophila divide asymmetrically, sequentially expressing a series of intrinsic factors to generate a diversity of neuron types. These intrinsic factors known as temporal factors dictate timing of neuroblast transitions in response to steroid hormone signaling and specify early versus late temporal fates in neuroblast neuron progeny. After completing their temporal programs, neuroblasts differentiate or die, finalizing both neuron number and type within each neuroblast lineage. From a screen aimed at identifying genes required to terminate neuroblast divisions, we identified Notch and Notch pathway components. When Notch is knocked down, neuroblasts maintain early temporal factor expression longer, delay late temporal factor expression, and continue dividing into adulthood. We find that Delta, expressed in cortex glia, neuroblasts, and after division, their GMC progeny, regulates neuroblast Notch activity. We also find that Delta in neuroblasts is expressed high early, low late, and is controlled by the intrinsic temporal program: early factor Imp promotes Delta, late factors Syp/E93 reduce Delta. Thus, in addition to systemic steroid hormone cues, forward lineage progression is controlled by local cell-cell signaling between neuroblasts and their cortex glia/GMC neighbors: Delta transactivates Notch in neuroblasts bringing the early temporal program and early temporal factor expression to a close.