New DNA markers with increased informativeness show diminished support for a chromosome 5q11-13 schizophrenia susceptibility locus and exclude linkage in two new cohorts of British and Icelandic families.
Genetic linkage of schizophrenia to markers at 5q11.2-13.3 had been reported previously in five Icelandic and two British families, but attempts at replication in independent samples have been unsuccessful. We report here an update on the diagnoses and results of linkage analyses using newer highly polymorphic microsatellite markers at or near the loci D5S76 and D5S39 in the original sample of pedigrees and in two new family samples from Iceland and from Britain. The new results show a reduction in evidence for linkage in the original sample and evidence against linkage in the two new family samples. Although it is possible that a rare locus is present, perhaps in the region 5p14.1-13.1 rather than 5q11.2-13.3, it appears most likely that the original positive lod scores represent an exaggeration of the 'true' lod scores due to random effects and that the small lod scores we now obtain could have arisen by chance.
Kalsi
G
G
Windeyer Institute for Medical Research, Department of Psychiatry and Behavioural Sciences, University College London Medical School.
Mankoo
B
B
Curtis
D
D
Sherrington
R
R
Melmer
G
G
Brynjolfsson
J
J
Sigmundsson
T
T
Read
T
T
Murphy
P
P
Petursson
H
H
Gurling
H
H
D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D004739:England; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007055:Iceland; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012559:Schizophrenia / Q000235:genetics*
D004247:DNA