Nair R P, Henseler T, Jenisch S, Stuart P, Bichakjian C K, Lenk W, Westphal E, Guo S W, Christophers E, Voorhees J J, Elder J T
Department of Dermatology, Medical School, University of Michigan, Ann Arbor 48109, USA.
Hum Mol Genet. 1997 Aug;6(8):1349-56. doi: 10.1093/hmg/6.8.1349.
In a 12.5 cM genome-wide scan for psoriasis susceptibility loci, recombination-based tests revealed linkage to the HLA region (Zmax = 3.52), as well as suggestive linkage to two novel regions: chromosome 16q (60-83.1 cM from pter, Zmax = 2.50), and chromosome 20p (7.5-25 cM from pter, Zmax = 2.62). All three regions yielded P values < or = 0.01 by non-parametric analysis. Recombination-based and allele sharing methods also confirmed a previous report of a dominant susceptibility locus on distal chromosome 17q (108.2 cM from pter, Zmax = 2.09, GENEHUNTER P = 0.0056). We could not confirm a previously reported locus on distal chromosome 4q; however, a broad region of unclear significance was identified proximal to this proposed locus (153.6-178.4 cM from pter, Zmax = 1.01). Taken together with our recent results demonstrating linkage to HLA-B and -C, this genome-wide scan identifies a psoriasis susceptibility locus at HLA, confirms linkage to 17q, and recommends two novel genomic regions for further scrutiny. One of these regions (16q) overlaps with a recently-identified susceptibility locus for Crohn's disease. Psoriasis is much more common in patients with Crohn's disease than in controls, suggesting that an immunomodulatory locus capable of influencing both diseases may reside in this region.
在一项针对银屑病易感基因座的全基因组扫描中，扫描范围为12.5厘摩，基于重组的检测显示与HLA区域存在连锁关系（Z最大值 = 3.52），同时还提示与两个新区域存在连锁关系：16号染色体q臂（距染色体短臂末端60 - 83.1厘摩，Z最大值 = 2.50）以及20号染色体p臂（距染色体短臂末端7.5 - 25厘摩，Z最大值 = 2.62）。通过非参数分析，所有这三个区域的P值均≤0.01。基于重组和等位基因共享的方法也证实了先前关于17号染色体远端显性易感基因座的报道（距染色体短臂末端108.2厘摩，Z最大值 = 2.09，GENEHUNTER软件计算的P值 = 0.0056）。我们未能证实先前报道的4号染色体远端的基因座；然而，在该假定基因座近端发现了一个意义不明确的宽泛区域（距染色体短臂末端153.6 - 178.4厘摩，Z最大值 = 1.01）。结合我们最近证明与HLA - B和 - C存在连锁关系的结果，这项全基因组扫描确定了HLA区域存在银屑病易感基因座，证实了与17号染色体q臂的连锁关系，并推荐了两个新的基因组区域以供进一步研究。其中一个区域（16号染色体q臂）与最近发现的克罗恩病易感基因座重叠。银屑病在克罗恩病患者中比在对照人群中更为常见，这表明一个能够影响这两种疾病的免疫调节基因座可能位于该区域。
