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 prim ary 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 p ossible linkage, with a nominal level of significance of P less than or equ al to 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-Xp11,2 3 (DXS8054; P = 0.006), Three potential candidate genes map to these region s: the beta subunit of the muscle acetylcholine receptor and the serotonin 1B and 1E receptors, Conclusion. These results provide evidence of the presence and location of genes that are involved in the genetic susceptibility to primary RP.