7 results on '"William J. Lane"'
Search Results
2. Multiple GYPB gene deletions associated with the U− phenotype in those of African ancestry
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Nicholas Gleadall, Prathik K. Vijay Kumar, Jonathan Stephens, Alba Sanchis-Juan, Judith Aeschlimann, Helen Mah, Richard M. Kaufman, Willem H. Ouwehand, William J. Lane, Robin Smeland-Wagman, Robert C. Green, Connie M. Westhoff, Matthew S. Lebo, Maria Aguad, Sunitha Vege, and Jensyn Cone Sullivan more...
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Genetics ,Whole genome sequencing ,Sanger sequencing ,GYPA ,GYPB ,Immunology ,Exons ,Hematology ,030204 cardiovascular system & hematology ,Biology ,MNS antigen system ,Black or African American ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,symbols ,Humans ,MNSs Blood-Group System ,Immunology and Allergy ,Glycophorins ,Allele ,1000 Genomes Project ,Allele frequency ,Gene Deletion ,030215 immunology - Abstract
Background The MNS blood group system is defined by three homologous genes: GYPA, GYPB, and GYPE. GYPB encodes for glycophorin B (GPB) carrying S/s and the "universal" antigen U. RBCs of approximately 1% of individuals of African ancestry are U- due to absence of GPB. The U- phenotype has long been attributed to a deletion encompassing GYPB exons 2 to 5 and GYPE exon 1 (GYPB*01N). Study design and methods Samples from two U-individuals underwent Illumina short read whole genome sequencing (WGS) and Nanopore long read WGS. In addition, two existing WGS datasets, MedSeq (n = 110) and 1000 Genomes (1000G, n = 2535), were analyzed for GYPB deletions. Deletions were confirmed by Sanger sequencing. Twenty known U- donor samples were tested by a PCR assay to determine the specific deletion alleles present in African Americans. Results Two large GYPB deletions in U- samples of African ancestry were identified: a 110 kb deletion extending left of GYPB (DEL_B_LEFT) and a 103 kb deletion extending right (DEL_B_RIGHT). DEL_B_LEFT and DEL_B_RIGHT were the most common GYPB deletions in the 1000 Genomes Project 669 African genomes (allele frequencies 0.04 and 0.02). Seven additional deletions involving GYPB were seen in African, Admixed American, and South Asian samples. No samples analyzed had GYPB*01N. Conclusions The U- phenotype in those of African ancestry is primarily associated with two different complete deletions of GYPB (with intact GYPE). Seven additional less common GYPB deletion backgrounds were found. GYPB*01N, long assumed to be the allele commonly encoding U- phenotypes, appears to be rare. more...
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- 2020
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3. A whole genome approach for discovering the genetic basis of blood group antigens: independent confirmation for P1 and Xg a
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Abigail Joseph, Manpreet Sidhu, William J. Lane, Robin Smeland-Wagman, Helen Mah, Connie M. Westhoff, Carrie L. Blout, Richard M. Kaufman, Maria Aguad, Christine Lomas-Francis, Tiffany T. Nguyen, Robert C. Green, Sunitha Vege, and Matthew S. Lebo more...
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Genotype ,Immunology ,030204 cardiovascular system & hematology ,Biology ,Y chromosome ,Polymorphism, Single Nucleotide ,Genome ,Article ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Humans ,Immunology and Allergy ,Typing ,Allele ,Gene ,Alleles ,Whole genome sequencing ,Genetics ,Whole Genome Sequencing ,Computational Biology ,Hematology ,Galactosyltransferases ,Phenotype ,Blood Group Antigens ,030215 immunology - Abstract
BACKGROUND: Although P1 and Xg(a) are known to be associated with the A4GALT and XG genes respectively, the genetic basis of antigen expression has been elusive. Recent reports link both P1 and Xg(a) expression with nucleotide changes in the promotor regions and with antigen negative phenotypes due to disruption of transcription factor binding. STUDY DESIGN AND METHODS: Whole genome sequencing was performed on 113 individuals as part of the MedSeq Project with serologic RBC antigen typing for P1 (n=77) and Xg(a) (n=15). Genomic data were analyzed by two approaches, nucleotide frequency correlation or serologic correlation, to find A4GALT and XG changes associated with P1 and Xg(a) expression. RESULTS: For P1, the frequency approach identified 29 possible associated nucleotide changes, and the serologic approach revealed four among them correlating with the P1+/P1− phenotype: chr22:43,115,523_43,115,520AAAG/delAAAG (rs66781836); chr 22:43,114,551C/T (rs8138197); chr22:43,114,020T/G (rs2143918); and chr22:43,113,793G/T (rs5751348). For Xg(a), the frequency approach identified 82 possible associated nucleotide changes, and among these the serologic approach revealed one correlating with the Xg(a+)/Xg(a–) phenotype: chrX:2,666,384G/C (rs311103). CONCLUSION: A bioinformatics analysis pipeline was created to identify genetic changes responsible for RBC antigen expression. This study, in progress prior to the recently published reports, independently confirms the basis for P1 and Xg(a). Although, this enabled molecular typing of these antigens, the Y chromosome PAR1 region interfered with Xg(a) typing in males. This approach could be used to identify and confirm the genetic basis of antigens, potentially replacing the historical approach using family pedigrees as genomic sequencing becomes common place. more...
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- 2018
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4. Using direct antiglobulin test results to reduce unnecessary cold agglutinin testing
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Garrett S. Booth, William J. Lane, Penny C. Szklarski, Craig B. Wilen, Ronald Jackups, and Brenda J. Grossman
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Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,Cold agglutinin disease ,Anemia ,business.industry ,Immunology ,Autoantibody ,Hematology ,030204 cardiovascular system & hematology ,medicine.disease ,Cold Agglutinin ,03 medical and health sciences ,0302 clinical medicine ,Coombs test ,medicine ,Immunology and Allergy ,In patient ,Autoimmune hemolytic anemia ,Direct antiglobulin test ,business ,030215 immunology - Abstract
BACKGROUND:Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia mediated by autoantibodies that preferentially react at 4°C. Laboratory testing for cold-reactive autoantibodies is laborious and may not be ordered judiciously, particularly in patients with a negative direct antiglobuli more...
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- 2017
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5. Comprehensive red blood cell and platelet antigen prediction from whole genome sequencing: proof of principle
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Richard M. Kaufman, Leslie E. Silberstein, Robert C. Green, Heidi L. Rehm, Maria Aguad, William J. Lane, Robin Smeland-Wagman, Connie M. Westhoff, and Jon Michael Uy
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0301 basic medicine ,Whole genome sequencing ,Genetics ,Immunology ,Genomics ,Hematology ,030204 cardiovascular system & hematology ,Biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Antigen ,ABO blood group system ,Complementary DNA ,Immunology and Allergy ,Typing ,Gene ,Reference genome - Abstract
BACKGROUND There are 346 serologically defined red blood cell (RBC) antigens and 33 serologically defined platelet (PLT) antigens, most of which have known genetic changes in 45 RBC or six PLT genes that correlate with antigen expression. Polymorphic sites associated with antigen expression in the primary literature and reference databases are annotated according to nucleotide positions in cDNA. This makes antigen prediction from next-generation sequencing data challenging, since it uses genomic coordinates. STUDY DESIGN AND METHODS The conventional cDNA reference sequences for all known RBC and PLT genes that correlate with antigen expression were aligned to the human reference genome. The alignments allowed conversion of conventional cDNA nucleotide positions to the corresponding genomic coordinates. RBC and PLT antigen prediction was then performed using the human reference genome and whole genome sequencing (WGS) data with serologic confirmation. RESULTS Some major differences and alignment issues were found when attempting to convert the conventional cDNA to human reference genome sequences for the following genes: ABO, A4GALT, RHD, RHCE, FUT3, ACKR1 (previously DARC), ACHE, FUT2, CR1, GCNT2, and RHAG. However, it was possible to create usable alignments, which facilitated the prediction of all RBC and PLT antigens with a known molecular basis from WGS data. Traditional serologic typing for 18 RBC antigens were in agreement with the WGS-based antigen predictions, providing proof of principle for this approach. CONCLUSION Detailed mapping of conventional cDNA annotated RBC and PLT alleles can enable accurate prediction of RBC and PLT antigens from whole genomic sequencing data. more...
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- 2015
- Full Text
- View/download PDF
6. Using direct antiglobulin test results to reduce unnecessary cold agglutinin testing
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Craig B, Wilen, Garrett S, Booth, Brenda J, Grossman, William J, Lane, Penny C, Szklarski, and Ronald, Jackups
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Coombs Test ,Humans ,Anemia, Hemolytic, Autoimmune ,Cryoglobulins ,Autoantibodies ,Retrospective Studies - Abstract
Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia mediated by autoantibodies that preferentially react at 4°C. Laboratory testing for cold-reactive autoantibodies is laborious and may not be ordered judiciously, particularly in patients with a negative direct antiglobulin test (DAT). We sought to determine whether a negative DAT using anti-human complement (anti-C3) rules out elevated cold agglutinin (CA) titers and the diagnosis of CAD.We performed a retrospective study of patients with a CA test performed at three major academic medical centers: Barnes-Jewish Hospital (2003-2014), Vanderbilt University Medical Center (2007-2009), and Massachusetts General Hospital (2009-2014).This study included 801 patients, of whom 51% (n = 410) had a DAT within the 7 days before CA testing. A total of 98% of patients with a negative DAT using anti-C3 had a negative CA titer (64). Only five subjects had a negative DAT using anti-C3 and an elevated CA titer.Overutilization of CA testing could be reduced by establishing laboratory acceptance criteria based on a positive DAT using anti-C3. Such acceptance criteria would have reduced CA testing by 68% for those with an available DAT result. more...
- Published
- 2016
7. Comprehensive red blood cell and platelet antigen prediction from whole genome sequencing: proof of principle
- Author
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William J, Lane, Connie M, Westhoff, Jon Michael, Uy, Maria, Aguad, Robin, Smeland-Wagman, Richard M, Kaufman, Heidi L, Rehm, Robert C, Green, Leslie E, Silberstein, and Sek Won, Kong
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Blood Group Genomics ,Erythrocytes ,Blood Group Antigens ,Humans ,Antigens, Human Platelet ,Genomics - Abstract
BACKGROUND There are 346 serologically defined red blood cell (RBC) antigens and 33 serologically defined platelet (PLT) antigens, most of which have known genetic changes in 45 RBC or six PLT genes that correlate with antigen expression. Polymorphic sites associated with antigen expression in the primary literature and reference databases are annotated according to nucleotide positions in cDNA. This makes antigen prediction from next‐generation sequencing data challenging, since it uses genomic coordinates. STUDY DESIGN AND METHODS The conventional cDNA reference sequences for all known RBC and PLT genes that correlate with antigen expression were aligned to the human reference genome. The alignments allowed conversion of conventional cDNA nucleotide positions to the corresponding genomic coordinates. RBC and PLT antigen prediction was then performed using the human reference genome and whole genome sequencing (WGS) data with serologic confirmation. RESULTS Some major differences and alignment issues were found when attempting to convert the conventional cDNA to human reference genome sequences for the following genes: ABO, A4GALT, RHD, RHCE, FUT3, ACKR1 (previously DARC), ACHE, FUT2, CR1, GCNT2, and RHAG. However, it was possible to create usable alignments, which facilitated the prediction of all RBC and PLT antigens with a known molecular basis from WGS data. Traditional serologic typing for 18 RBC antigens were in agreement with the WGS‐based antigen predictions, providing proof of principle for this approach. CONCLUSION Detailed mapping of conventional cDNA annotated RBC and PLT alleles can enable accurate prediction of RBC and PLT antigens from whole genomic sequencing data. more...
- Published
- 2015
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