ARTICLE
Genomewide
Linkage Study in 1,176 Affected Sister Pair Families
Identifies a Significant Susceptibility Locus for
Endometriosis on Chromosome 10q26
After 10 years
of work and with a great deal of valued assistance
from gynaecologists and hospitals in confirming
diagnoses, the results of the first large-scale,
full genome scan genetic linkage study on endometriosis
were published in the September issue of the American
Journal of Human Genetics.
The results were
from 1,176 families with affected sister pairs included
genetic data from 931 Australian and New Zealand
families recruited by the Queensland Institute of
Medical Research (Brisbane, Australia) and 245 families
recruited by Dr. Stephen Kennedy, Department of
Obstetrics & Gynaecology, Oxford University
(Oxford, UK).
It is particularly
important because, being one of the largest studies
for any complex disease conducted worldwide, it
had the power to effectively narrow down the key
chromosomal regions for gene searching.
The study found
that sisters with endometriosis shared gene variants
at significantly more genetic loci than expected
in a region on the long arm of Chromosome 10. The
combined Australian and Oxford study also found
a region “suggestive” of linkage on
Chromosome 20, and several other chromosomal regions
with a hint of linkage (see summary below). This
means that the chromosome 10 region is harbouring
an important susceptibility gene for endometriosis,
with the chromosome 20 region also likely to harbour
a susceptibility gene, but a less important one.
The results were summarised as follows in the published
paper:
“We seek
to identify susceptibility loci [for endometriosis]
using a positional cloning approach, starting with
a linkage analysis to identify genomic regions likely
to harbour these genes. We conducted a linkage study
in 1,176 families (931 Australian, 245 UK), each
with at least two members - mainly affected sister
pairs (ASPs) - with surgically diagnosed disease.
We have identified a region of significant linkage
on chromosome 10q26 (MLS = 3.09, genome-wide P =
0.047) and another region of suggestive linkage
on chromosome 20p13 (MLS = 2.09). Minor peaks (MLS
> 1.0) were found on chromosomes 2, 6, 7, 8,
12, 14, 15, and 17. This is the first report of
linkage to a major locus for endometriosis. The
findings will facilitate discovery of novel, positional
genetic variants that influence the risk of developing
this debilitating disease. Greater understanding
of the aberrant cellular and molecular mechanisms
involved in the etiology and pathophysiology of
endometriosis should lead to better diagnostic methods
and targeted treatments.”
Authors and publication
details:
Susan
A. Treloar [1,2], Jacqueline Wicks [1,2], Dale R.
Nyholt [1,2], Grant W. Montgomery [1,2], Melanie
Bahlo [2,3], Vicki Smith [4], Gary Dawson [4], Ian
J. Mackay [4], Daniel E. Weeks [5], Simon T. Bennett
[4], Alisoun Carey [4], Kelly R. Ewen-White [6],
David L. Duffy [1,2], Daniel T. O'Connor [7], David
Barlow [8], Nicholas G. Martin [1,2], Stephen H.
Kennedy [8]
Genomewide Linkage Study in 1,176 Affected Sister
Pair Families Identifies a Significant Susceptibility
Locus for Endometriosis on Chromosome 10q26. American
Journal of Human Genetics 2005; 77: 365-376.
Authors’ affiliations:
[1] Queensland Institute of
Medical Research, Brisbane, Australia; [2] Cooperative
Research Centre for Discovery of Genes for Common
Human Diseases, Australia; [3] Walter and Eliza
Hall Institute, Melbourne, Australia; [4] Oxagen
Ltd., Abingdon, UK; [5] Department of Human Genetics,
Graduate School of Public Health, University of
Pittsburgh, Pittsburgh PA, USA; [6] Australian Genome
Research Facility, Melbourne, Australia; [7] Queensland
Endometriosis Research Institute, Brisbane, Australia;
[8] Nuffield Department of Obstetrics & Gynaecology,
University of Oxford, UK
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