UNIVERSITY OF MALTA
RESEARCH SEMINARS
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Gene Mapping in Complex Traits
Mr. Christopher Vidal B.Sc.(Hons) MLS
DNA Laboratory, Medical School, G’Mangia
25951882 / 99445926
cvidal02@onvol.net
Presentation date: 5th December 2005
(approximately 200-250 words)
Abstract
The identification of genes responsible for complex disorders is a great challenge since it is
complicated by several factors. Heterogeneity, incomplete penetrance, the involvement of
several genes as well as environmental factors is among the factors that complicates this
analysis. Linkage studies performed in large numbers of nuclear families rarely gave
significant association between genomic regions and disease such as osteoporosis. Whole
genome scanning performed in large pedigrees in homogeneous and/or consanguineous
populations might be a more promising approach.
A whole genome linkage scan using 400 microsatellite markers was performed in 27
members from two Maltese families with a highly penetrant form of osteoporosis. The
phenotype was defined by lumbar and femoral z-scores calculated after measurement of
bone mineral density (BMD) by DEXA. Both males and females were among the affected
individuals. Multipoint parametric and non-parametric linkage analyses were performed by
EasyLinkage v4.0 using GENEHUNTER v2.1, assuming dominant and recessive modes of
inheritance with variable penetrance.
Evidence of linkage was observed to a marker at 11p13 where a non-parametric LOD score
(NPL) of 4.99 was obtained. A maximum heterogeneity LOD (HLOD) score of 2.74
(p=0.0091) for this region was obtained for the dominant mode of inheritance with 90%
penetrance and a phenocopy rate of 1%. A higher resolution scan performed at this region
confirmed these findings and narrowed the critical interval to a 2cM region approximately
52cM from pTer. Suggestive linkage was observed at a number of other chromosomal loci
including 5q34, 6q22, 9q21, 13q33 and 17q21.
These results suggest that a major gene responsible for osteoporosis might be present in
region 11p13 while other contributing genes might be present on other chromosomes.
Identification of these genes is important for the early identification of individuals at risk and
for the development of effective treatments.