PMID- 10477733
OWN - NLM
STAT- MEDLINE
DCOM- 19991012
LR  - 20101118
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 94
IP  - 6
DP  - 1999 Sep 15
TI  - The human platelet alphaIIb gene is not closely linked to its integrin partner
      beta3.
PG  - 2039-47
AB  - alphaIIbb3 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 alphaIIb or beta3, we have developed a genetic 
      linkage map between the thyroid receptor hormone-1 gene (THRA1) and beta3 as
      follows: cen-THRA1-BRCA1-D17S579/alphaIIb-beta3-qte r, with a distance of 1.3
      centiMorgans (cM) between alphaIIb and beta3 and the two genes being oriented in 
      the same direction. PFGE genomic and YAC clone analysis showed that the beta3
      gene is distal and >/=365 kb upstream of alphaIIb. Additional restriction mapping
      shows alphaIIb is linked to the erythrocyte band 3 (EPB3) gene, and beta3 to the 
      homeobox HOX2b gene. Analysis of alphaIIb(+)-BAC and P1 clones confirm that the
      EPB3 gene is approximately 110 kb downstream of the alphaIIb gene. Sequencing the
      region surrounding the human alphaIIb locus showed the Granulin gene
      approximately 18 kb downstream to alphaIIb, and the KIAA0553 gene approximately
      5.7 kb upstream. This organization is conserved in the murine sequence. These
      studies show that alphaIIb and beta3 are not closely linked, with alphaIIb
      flanked by nonmegakaryocytic genes, and imply that they are unlikely to share
      common regulatory domains during megakaryopoiesis.
FAU - Thornton, M A
AU  - Thornton MA
AD  - Department of Pediatrics, University of Pennsylvania School of Medicine,
      Philadelphia, PA, USA.
FAU - Poncz, M
AU  - Poncz M
FAU - Korostishevsky, M
AU  - Korostishevsky M
FAU - Yakobson, E
AU  - Yakobson E
FAU - Usher, S
AU  - Usher S
FAU - Seligsohn, U
AU  - Seligsohn U
FAU - Peretz, H
AU  - Peretz H
LA  - eng
SI  - GENBANK/AF160252
GR  - HL40387/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Anion Exchange Protein 1, Erythrocyte)
RN  - 0 (Antigens, CD)
RN  - 0 (Genetic Markers)
RN  - 0 (Integrin beta3)
RN  - 0 (Platelet Glycoprotein GPIIb-IIIa Complex)
RN  - 0 (Platelet Membrane Glycoproteins)
SB  - AIM
SB  - IM
MH  - Anion Exchange Protein 1, Erythrocyte/genetics
MH  - Antigens, CD/*genetics
MH  - Arabs/*genetics
MH  - Chromosome Mapping
MH  - Chromosomes, Artificial, Yeast
MH  - *Chromosomes, Human, Pair 17
MH  - Exons
MH  - Female
MH  - Genetic Linkage
MH  - Genetic Markers
MH  - Humans
MH  - Integrin beta3
MH  - Introns
MH  - Iraq/ethnology
MH  - Israel
MH  - Jews/*genetics
MH  - Male
MH  - Pedigree
MH  - Platelet Glycoprotein GPIIb-IIIa Complex/*genetics
MH  - Platelet Membrane Glycoproteins/*genetics
MH  - Restriction Mapping
EDAT- 1999/09/09 00:00
MHDA- 1999/09/09 00:01
CRDT- 1999/09/09 00:00
PHST- 1999/09/09 00:00 [pubmed]
PHST- 1999/09/09 00:01 [medline]
PHST- 1999/09/09 00:00 [entrez]
PST - ppublish
SO  - Blood. 1999 Sep 15;94(6):2039-47.