Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/34219
Title: Sequencing of genes in two Maltese families with severe osteoporosis
Authors: Cachia, Adela
Keywords: Osteoporosis -- Malta
Genes
Genomes
Issue Date: 2008
Citation: Cachia, A. (2008). Sequencing of genes in two Maltese families with severe osteoporosis (Master's dissertation).
Abstract: Osteoporosis is a complex disease involving multiple genes, each contributing to the increased susceptibility of an individual to the disease. Following a genome-wide scan in two Maltese families with a high incidence of osteoporosis, chromosomal loci Sp 14, Sq34 and 11p12 were identified as areas of suggestive linkage (Vidal, 2007). Fine mapping at Sp14 was performed using 6 additional markers (D5S2054, D5S635, D5S1953, D5S208, D5S1486, D5S1954). Marker D5S1486 showed evidence of linkage with a non- parametric LOD (NPL) score of 4.41 (p= 0.0098) and a parametric LOD (pLOD) score of 1.98 for the dominant mode of inheritance. Searching the genome map at this region did not result in the identification of any plausible candidate genes which could be influencing bone physiology significantly. Fine mapping at 5q34 in one family (Family 1) showed evidence of linkage to marker D5S1960 with a NPL of 7.33 (p= 0.0005) and a pLOD score of 2.79 for the recessive mode of inheritance. Sequencing of the Msx2 gene located at 5q34- q35 did not reveal the presence of any causative variants. Fine mapping of chromosomal region 11p12 in the same family showed evidence of linkage to marker DllS4102 with a NPL score of 6.26 (p= 0.0078) and a pLOD score of 1.92 for the dominant mode of inheritance. Sequencing of exons and exon- intron boundaries of the EXT2 gene located at lip 12- P 11 did not result in the identification of any variants. The 11p12 region also showed evidence of linkage in Family 2 members to a marker D11S1392, with a NPL score of 5.86 (p= 0.0156) and a pLOD score of 1.77 for the dominant mode of inheritance. Sequencing of the CD44 gene found at position 11 p 13 identified three variants in intronic regions, one variant in exon 8, one in exon 9, two in exon 10 and one in exon 12. The most significant variant found was a synonymous G/A transition (rsll033026) in exon 9. This variant was found to be co-segregating with the marker haplotype in Family 2 members. It may be hypothesised that the G/ A synonymous transition in CD44 could result in altered binding of CD44 to its major ligand in bone OPN and thus to altered osteoclast activity. Functional studies may help shed light on the effect of the G/ A transition in CD44 on osteoporosis in this Maltese family.
Description: M.SC.PATHOLOGY
URI: https://www.um.edu.mt/library/oar//handle/123456789/34219
Appears in Collections:Dissertations - FacM&S - 2008
Dissertations - FacM&SPat - 2008

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