Molecular Genetics Group

Group Leader: Dr Michael Buckley

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Research Projects

Investigators: Michael Buckley, Carol Cheung, Robert Lindeman
Co-Investigators: Jenny Donald, Christopher Moran

The aim of the first project is to identify genes that regulate the process of thrombopoiesis. We have shown that 85% of the normal variation in platelet count in humans is genetically determined. Therefore the approach we have chosen to use is genetic linkage in two inbred strains of laboratory mice and between people in the extreme deciles of the human population.

Our primary hypothesis is that the normal variation in platelet numbers is controlled by allelic variants of genes that control the process of platelet production. The expected outcome of the study is the identification of initially quantitative trait loci (qtls) and subsequently genes whose products may be able to be used in a therapeutic sense to manipulate platelet count or be involved in myeloproliferative diseases of the megakaryocytic lineage.

Results to date support the primary hypothesis. We have identified two qtls for platelet count in these strains of mice, and excluded TPO and TPO-receptor from having significant effects.

Investigators: Tony Roscioli, Robert Lindeman
Co-Investigators: Michael Buckley, Edwin Kirk, John Ziegler, Melanie Wong

We have recently identified four Australian families of Middle-Eastern origin with a novel disorder of Veno-occlussive disease of the liver with immunodeficiency. Homozygosity mapping studies have been undertaken which have identified a locus for gene controlling this disorder. Studies are in progress to further refine the critical region in which this gene must lie by testing other family members and a newly acquired family from Israel.

Group Members

Key Publications

Buckley MF, Loveland KA, McKinstry WJ, Garson OM, Goding JW (1990). Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human molecule, amino acid sequenceand chromosomal localisation. J. Biol. Chem., 265, 17 506-17 511.

Buckley MF, Goding JW (1992). Plasma cell membrane glycoprotein gene Pca-1 (alkaline phosphodiesterase I) is linked to the proto-oncogene Myb on mouse chromosome 10. Immunogenetics, 36, 199-201.

Ryan M, Taylor PJ, Donald JA, Ouvrier RA, Morgan G, Danta G, Buckley MF, North K (1999). A novel of episodic muscle weakness maps to Xp22.3. American Journal of Human Genetics, 65: 1104-1113

Buckley MF, James JW, Brown D, Whyte GS, Dean MG, Chesterman CN, Donald JA (2000). A novel approach to the assessment of variations in the human platelet count. Thrombosis and Haemostasis, 83, 480-484

Bahar AY, Taylor PJ, Andrews L, Proos A, Burnett L, Tucker K, Friedlander M. Buckley MF (2001). The frequency of founder mutations in the BRCA1, BRCA2 and APC genes in Australian Ashkenazi Jews: Implications for the generality of US population data.Cancer, 92, 440-445