A two-stage, genome-wide screen for susceptibility loci in primary Raynaud's phenomenon.
OBJECTIVE
To identify chromosomal regions containing genes involved in the susceptibility to primary Raynaud's phenomenon (RP).


METHODS
Six extended families with multiple individuals affected with primary RP (n = 37) were examined for linkage in a 2-stage, whole-genome screen, using a total of 298 microsatellite markers.


RESULTS
Multipoint, nonparametric linkage analysis identified 5 areas of possible linkage, with a nominal level of significance of P < or = 0.05. Analysis of a finer map of markers in these regions defined the regions of linkage as 21.4 cM on 6q13-6q23.3 (D6S261; P = 0.0004), 10.2 cM on 7p22-7p15 (D7S664; P = 0.014), 1.6 cM on 9p23-9p22 (D9S156; P = 0.0075), 5.1 cM on 17p13.1-17p12 (D17S1791; P = 0.036), and 11.8 cM on Xp11.4-Xp11.23 (DXS8054; P = 0.006). Three potential candidate genes map to these regions: the beta subunit of the muscle acetylcholine receptor and the serotonin 1B and 1E receptors.


CONCLUSIONS
These results provide evidence of the presence and location of genes that are involved in the genetic susceptibility to primary RP.
Susol
E
E
ARC Epidemiology Research Unit, University of Manchester, UK.
MacGregor
A J
AJ
Barrett
J H
JH
Wilson
H
H
Black
C
C
Welsh
K
K
Silman
A
A
Ollier
B
B
Worthington
J
J
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D004247:DNA / Q000032:analysis; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D015894:Genome, Human; D006801:Humans; D007223:Infant; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D011928:Raynaud Disease / Q000145:classification / Q000235:genetics*; D044302:Receptor, Serotonin, 5-HT1B; D011950:Receptors, Cholinergic / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics
C470302:HTR1B protein, human; D044302:Receptor, Serotonin, 5-HT1B; D011950:Receptors, Cholinergic; D011985:Receptors, Serotonin; C076396:serotonin 1E receptor; D004247:DNA