J Med Genet 2000;37:186-191
( March )
Age and sex based genetic locus heterogeneity in type 1 diabetes
Andrew D Paterson, Arturas Petronis
Neurogenetics
Section, Clarke Division, Centre for Addiction and Mental Health,
Department of Psychiatry, University of Toronto, 250 College Street,
Toronto, Ontario M5T 1R8, Canada
Correspondence to: Dr Paterson
Revised version received 25 October 1999;
Accepted for publication 27 October
1999
BACKGROUND
Two genome scans for
susceptibility loci for type 1 diabetes using large collections of
families have recently been reported. Apart from strong linkage in both
studies of the HLA region on chromosome 6p, clear consistent evidence
for linkage was not observed at any other loci. One possible
explanation for this is a high degree of locus heterogeneity in type 1 diabetes, and we hypothesised that the sex of affected offspring, age
of diagnosis, and parental origin of shared alleles may be the bases of
heterogeneity at some loci.
METHODSUsing data from a genome
wide linkage study of 356 affected sib pairs with type 1 diabetes, we
performed linkage analyses using parental origin of shared alleles in
subgroups based on (1) sex of affected sibs and (2) age of diagnosis.
RESULTSAmong the results obtained,
we observed that evidence for linkage to
IDDM4 on chromosome 11q13 occurred
predominantly from opposite sex, rather than same sex sib pairs. At a
locus on chromosome 4q, evidence for linkage was observed in sibs where
one was diagnosed above the age of 10 years and the other diagnosed
below 10 years of age.
CONCLUSIONSWe show that
heterogeneity tests based on age of diagnosis, sex of affected subject,
and parental origin of shared alleles may be helpful in reducing locus
heterogeneity in type 1 diabetes. If repeated in other samples, these
findings may assist in the mapping of susceptibility loci for type 1 diabetes. Similar analyses can be recommended in other complex diseases.
Keywords:
type 1 diabetes;
age of diagnosis;
sex;
parental
origin of alleles
© 2000 by J Med Genet
