UNIVERSITY OF MALTA
LIFE SCIENCE RESEARCH SEMINARS
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Sequencing of genes in two Maltese families with severe osteoporosis
Adela Cachia
47, Pope Alexander Junction, Balzan
21487991/ 99855890
Nil
acac1@um.edu.mt
5th May 2008
Abstract
Osteoporosis is a polygenic disease involving multiple genes, each contributing to the
increased susceptibility of an individual to the disease. In a previous study, a genome-wide
scan in 2 Maltese families with a highly penetrant form of osteoporosis was performed
which identified chromosomal loci 5p14, 5q34 and 11p12 as areas of suggestive linkage
(Vidal et al., 2007).
In this study, the above chromosomal regions were investigated. Fine mapping at position
5q34 was performed on members of one of the families (Family 1). The marker D5S1960
gave the strongest linkage with a non- parametric LOD score (NPL) of 1.7137 (p= 0.0447)
and a parametric LOD score (pLOD) of 1.34 for the recessive mode of inheritance.
Searching the genome map revealed the MSX2 gene located at 5q34- q35. The 11p12 region
on chromosome 11 was also investigated in this family. Fine mapping of this region showed
evidence of linkage to a marker D11S4102 where an NPL score of 6.2606 (p= 0.0078) and a
pLOD score of 1.9173 for the dominant mode of inheritance were obtained. The EXT2 gene
was found to be located at 11p12- p11. Sequencing all exons and promoter region of both
MSX2 and EXT2 genes in affected family members and controls did not result in the
identification of any mutations.
Fine mapping of the 11p12 region on chromosome 11 in Family 2 showed strong evidence
of linkage to a marker D11S1392, with a NPL score of 5.8587 (p= 0.0156) and a pLOD
score of 1.7716 for the dominant mode of inheritance. The19 exons and promoter of the
CD44 gene found at position 11p13 were sequenced in both affected and control family
members. This identified a number of mutations which could be responsible for increased
susceptibility to osteoporosis in this family.