A two-stage, genome-wide screen for susceptibility loci in primary Raynaud's phenomenon

✍ Scribed by Elene Susol; Alexander J. MacGregor; Jennifer H. Barrett; Helen Wilson; Carol Black; Ken Welsh; Alan Silman; Bill Ollier; Jane Worthington

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 90 KB
• Volume: 43
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/1529-0131(200007)43:7<1641::aid-anr30>3.0.co;2-y

✦ Synopsis

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 < 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 ␤ 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.

PATIENTS AND METHODS

Family ascertainment. Families (n ϭ 39) with at least 3 individuals affected with primary RP were ascertained through a media campaign and patient societies in Great Britain. Six extended pedigrees that were British Caucasian in origin and comprised multiple affected individuals (n ϭ 37; median age at primary RP onset 12.7 years) were used to Supported by the Arthritis Research Campaign and the Raynaud's and Scleroderma Association.