Identification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis.
Psoriasis is a common chronic inflammatory disorder of the skin. To further understand the pathogenesis of psoriasis we have chosen to investigate the molecular genetic basis of the disorder. We have used a two-stage approach to search the human genome for the location of genes conferring susceptibility to psoriasis, using a total of 106 affected sibling pairs identified from 68 independent families. As over a third of the extended kindreds included affected relatives besides siblings, in addition to an analysis of allele sharing between affected sibling pairs, a novel linkage strategy was applied that extracts full non-parametric information. Four principal regions of possible linkage were identified on chromosomes 2, 8, 20 (p <0.005) and markers from the MHC region at 6p21 (p <0.0000006) for which significant evidence of linkage disequilibrium was also observed (p <0.00002). Whilst data from limited case control associations exist to implicate the MHC, the results of this genome wide analysis demonstrate that, at least in the population studied, a gene or genes located within the MHC and close to the class 1 HLA loci, represent the major determinant of the genetic basis of psoriasis.
Trembath
R C
RC
Department of Genetics, University of Leicester, UK. rtrembat@hgmp.mrc.ac.uk
Clough
R L
RL
Rosbotham
J L
JL
Jones
A B
AB
Camp
R D
RD
Frodsham
A
A
Browne
J
J
Barber
R
R
Terwilliger
J
J
Lathrop
G M
GM
Barker
J N
JN
D002896:Chromosomes, Human, Pair 6; D008040:Genetic Linkage; D005819:Genetic Markers; D015894:Genome, Human; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D010375:Pedigree; D011565:Psoriasis / Q000235:genetics*
D005819:Genetic Markers