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Blood, Vol. 94 No. 6 (September 15), 1999:
pp. 2039-2047
The Human Platelet  IIb Gene Is Not Closely Linked to Its Integrin
Partner  3
M.A. Thornton,
M. Poncz,
M. Korostishevsky,
E. Yakobson,
S. Usher,
U. Seligsohn, and
H. Peretz
From the Department of Pediatrics, University of Pennsylvania School
of Medicine, Philadelphia, PA; and the Department of Human Genetics,
Sackler School of Medicine and Clinical Biochemistry Laboratory,
Sourasky Medical Center, Institute of Thrombosis and Hemostasis, Sheba
Medical Center, Tel-Aviv University, Israel.
 IIbb3 integrin is a heterodimeric receptor facilitating platelet
aggregation. Both genes are on chromosome 17q21.32. Intergenic distance
between them has been reported to be 125 to 260 kilobasepairs (kb) by
pulsed-field gel electrophoresis (PFGE) genomic analysis, suggesting
that they may be regulated coordinately during megakaryopoiesis. In
contrast, other studies suggest these genes are greater than 2.0 megabasepairs (mb) apart. Because of the potential biological implications of having these two megakaryocytic-specific genes contiguous, we attempted to resolve this discrepancy. Taking advantage of large kindreds with mutations in either IIb or  3, we have developed a genetic linkage map between the thyroid receptor hormone-1 gene (THRA1) and 3 as follows:
cen-THRA1-BRCA1-D17S579/IIb-3-qter, with a distance of 1.3 centiMorgans (cM) between IIb and 3 and the two genes being
oriented in the same direction. PFGE genomic and YAC clone analysis
showed that the 3 gene is distal and  365 kb upstream of IIb.
Additional restriction mapping shows IIb is linked to the
erythrocyte band 3 (EPB3) gene, and 3 to the homeobox HOX2b gene.
Analysis of IIb+-BAC and P1 clones confirm that the
EPB3 gene is ~110 kb downstream of the IIb gene. Sequencing the
region surrounding the human IIb locus showed the Granulin gene
~18 kb downstream to IIb, and the KIAA0553 gene ~5.7 kb
upstream. This organization is conserved in the murine sequence. These
studies show that IIb and 3 are not closely linked, with IIb
flanked by nonmegakaryocytic genes, and imply that they are unlikely to
share common regulatory domains during megakaryopoiesis.
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