Fróðskaparrit - 31.12.2000, Page 52

56
SEARCH FOR SUSCEPTIBILITY LOCI ON SELECTED CHROMOSOMES
IN PATIENTS WITH PANIC DISORDER FROM THE FAROEISLANDS
Introduction
Although genetic factors have considerable
influence in mental disorders, so far no can-
didate genes associated with a specific dis-
order have been located. Many of the genes
that cause Mendelian diseases have been
identified by traditional genetic methods.
These traditional methods, although effec-
tive, have not been as successful when
complex diseases, such as mental disor-
ders, have been investigated.
The search is complicated by the fact that
the aetiology of most complex diseases is
unknown. In addition, a complex disease is
likely the result of perhaps more than one
gene, each exerting its effect of unknown
strength to contribute to the manifestation
of the disease. With the emergence of
strong, genetic and statistical methods, new
strategies are evolving. In recent years,
much interest has turned towards isolated
populations, which, with their presumed
genetic and environmental homogeneity,
might fulfil the requirements for Linkage
Disequilibrium (LD) mapping. Shared,
haplotype-based analyses have been used
in several studies in recent years (de la
Chapelle, 1993; Te Meerman and van der
Meulen, 1997; van Houwen et al., 1994).
The method has also been tried in the Faroe
Islands in the North Atlantic, which has a
bottleneck population (Wang, 1996; Wang
et al., 1998; Ewald et al., 1999b; Tygstrup
etal., 1999; á Steig et al., 1999). The pop-
ulation in the Faroe Islands remained
around 4,000 for several hundred years,
with periods with population bottlenecks,
and has recently undergone a ten-fold in-
crease, mainly due to reproduction. These
conditions may give rise to the so-called
“founder effect”, where a disease-bearing
chromosome is introduced at some point in
time into this homogeneous genetic pool,
and the disease locus is subsequently
passed down though the generations to a
number of present-day relatives. These rel-
atives will share a relatively large chromo-
somal segment around the disease locus.
Material and Methods
Method
A population-based method is used in a
search for Linkage Disequilibrium (LD)
within a “founder population”. Under con-
ditions ofLD, the location of the disease lo-
cus is inferred from association between
marker and disease loci, inherited identical-
ly by descent (IBD) from a founding ances-
tor. By selecting cases that are related 5-12
generations ago, a low rate of recombina-
tive fragmentation of the genome is ob-
tained. As the flanking region around an
IBD inherited disease locus is relatively
large following 10 generations, it is possi-
ble to perform a genome-wide scan with a
moderate number of polymorphic markers.
In the present study, the distance between
the markers is approximately 7-10 cM, re-
sulting in a total coverage of the genome
with approximately 500 markers.
Clinical Material
Well-documented cases of patients with
psychiatric disorders (autism, bipolar af-
fective disorder, schizophrenia, panic dis-
order, and alcoholism) from the Faroe Is-
lands, where local psychiatry was estab-
lished in 1968 (Joensen and Wang, 1983),