A HaemAtlas: characterizing gene expression in differentiated human blood cells
BLOOD
Authors: Watkins, Nicholas A.; Gusnanto, Arief; de Bono, Bernard; De, Subhajyoti; Miranda-Saavedra, Diego; Hardie, Debbie L.; Angenent, Will G. J.; Attwood, Antony P.; Ellis, Peter D.; Erber, Wendy; Foad, Nicola S.; Garner, Stephen F.; Isacke, Clare M.; Jolley, Jennifer; Koch, Kerstin; Macaulay, Iain C.; Morley, Sarah L.; Rendon, Augusto; Rice, Kate M.; Taylor, Niall; Thijssen-Timmer, Daphne C.; Tijssen, Marloes R.; van der Schoot, C. Ellen; Wernisch, Lorenz; Winzer, Thilo; Dudbridge, Frank; Buckley, Christopher D.; Langford, Cordelia F.; Teichmann, Sarah; Goettgens, Berthold; Ouwehand, Willem H.
Abstract
Hematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell-surface receptors. To further understand hematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B cells, cytotoxic and helper T cells, natural killer cells, granulocytes, and monocytes using whole genome microarrays. Abioinformatics analysis of these data was performed focusing ontranscription factors, immunoglobulin superfamily members, and lineage-specific transcripts. We observed that the numbers of lineage-specific genes varies by 2 orders of magnitude, ranging from 5 for cytotoxic T cells to 878 for granulocytes. In addition, we have identified novel coexpression patterns for key transcription factors involved in hematopoiesis (eg, GATA3-GFI1 and GATA2-KLF1). This study represents the most comprehensive analysis of gene expression in hematopoietic cells to date and has identified genes that play key roles in lineage commitment and cell function. The data, which are freely accessible, will be invaluable for future studies on hematopoiesis and the role of specific genes and will also aid the understanding of the recent genome-wide association studies. (Blood. 2009;113:e-e9)
Analysis of the Genotypes in a Chinese Population with Increased Hb A(2) and Low Hematological Indices
HEMOGLOBIN
Authors: Jiang, Fan; Chen, Gui-Lan; Li, Jian; Zhou, Jian-Ying; Liao, Can; Li, Dong-Zhi
Abstract
Increased Hb A(2) is considered the most reliable hematological finding for the identification of -thalassemia (-thal) carriers. The aim of this study was to determine the underlying genetic factors associated with a high Hb A(2) level in a Chinese population. Subjects were recruited from couples preparing for pregnancy who participated in the thalassemia screening program during a 2-year period. DNA analyses were used for diagnosis of -thal and other genetic factors. A total of 5985 adults who screened positive for -thal were recruited. Of these, 5933 (99.1%) were detected to have a -thal mutation. In the remaining 52 (0.9%) individuals without mutations involving the -globin gene cluster, 16 were found to have Kruppel-like factor 1 (KLF1) gene variants, and two had an -globin gene triplication. There were still 34 individuals with unknown genetic factors for their raised Hb A(2) values. The results of this study indicate that genetic factors other than -thal can rarely contribute to the elevation of Hb A(2). These subjects usually have borderline microcytic red cell indices and Hb A(2) values.