Brown M A, Pile K D, Kennedy L G, Campbell D, Andrew L, March R, Shatford J L, Weeks D E, Calin A, Wordsworth B P
Wellcome Trust Centre for Human Genetics, Headington, UK.
Arthritis Rheum. 1998 Apr;41(4):588-95. doi: 10.1002/1529-0131(199804)41:4<588::AID-ART5>3.0.CO;2-0.
To localize the regions containing genes that determine susceptibility to ankylosing spondylitis (AS).
One hundred five white British families with 121 affected sibling pairs with AS were recruited, largely from the Royal National Hospital for Rheumatic Diseases AS database. A genome-wide linkage screen was undertaken using 254 highly polymorphic microsatellite markers from the Medical Research Council (UK) (MRC) set. The major histocompatibility complex (MHC) region was studied more intensively using 5 microsatellites lying within the HLA class III region and HLA-DRB1 typing. The Analyze package was used for 2-point analysis, and GeneHunter for multipoint analysis.
When only the MRC set was considered, 11 markers in 7 regions achieved a P value of < or =0.01. The maximum logarithm of odds score obtained was 3.8 (P = 1.4 x 10(-5)) using marker D6S273, which lies in the HLA class III region. A further marker used in mapping of the MHC class III region achieved a LOD score of 8.1 (P = 1 x 10(-9)). Nine of 118 affected sibling pairs (7.6%) did not share parental haplotypes identical by descent across the MHC, suggesting that only 31% of the susceptibility to AS is coded by genes linked to the MHC. The maximum non-MHC LOD score obtained was 2.6 (P = 0.0003) for marker D16S422.
The results of this study confirm the strong linkage of the MHC with AS, and provide suggestive evidence regarding the presence and location of non-MHC genes influencing susceptibility to the disease.
定位包含决定强直性脊柱炎（AS）易感性基因的区域。
招募了105个英国家庭，其中有121对患AS的同胞对，大部分来自皇家国立风湿病医院的AS数据库。使用医学研究理事会（英国）采集的254个高度多态性微卫星标记进行全基因组连锁筛查。利用位于HLAⅢ类区域内的5个微卫星和HLA-DRB1分型对主要组织相容性复合体（MHC）区域进行更深入的研究。使用Analyze软件包进行两点分析，使用GeneHunter软件进行多点分析。
仅考虑医学研究理事会采集的标记时，7个区域的11个标记获得的P值≤0.01。使用位于HLAⅢ类区域的标记D6S273获得的最大优势对数得分为3.8（P = 1.4×10⁻⁵）。用于MHCⅢ类区域定位的另一个标记获得的LOD评分为8.1（P = 1×10⁻⁹）。118对患AS的同胞对中有9对（7.6%）在MHC区域未共享相同的同源亲本单倍型，这表明AS易感性中只有31%由与MHC连锁的基因编码。标记D16S422获得的最大非MHC LOD评分为2.6（P = 0.0003）。
本研究结果证实了MHC与AS之间的强连锁关系，并为影响该病易感性的非MHC基因的存在和位置提供了提示性证据。
