Woolley Niina, Holopainen Päivi, Ollikainen Vesa, Mustalahti Kirsi, Mäki Markku, Kere Juha, Partanen Jukka
Department of Tissue Typing, Finnish Red Cross Blood Transfusion Service, Kivihaantie 7, 00310 Helsinki, Finland.
Hum Genet. 2002 Jul;111(1):40-5. doi: 10.1007/s00439-002-0745-z. Epub 2002 Jun 8.
Coeliac disease is a common multifactorial disease with a strong genetic component, which is not entirely explained by the HLA association. Four previous whole-genome screens have produced somewhat inconsistent results suggesting genetic heterogeneity. We attempted to overcome this problem by performing a genome-wide scan in a Finnish sub-population, expected to be more homogeneous than the general population of Finland. The families in our study originate from the northeastern part of Finland, the Koilliskaira region, which has been relatively isolated since its founding in the 16th century. Genealogical studies have confirmed that the families share a common ancestor in the 16th century. Nine families with altogether 23 patients were genotyped for 399 microsatellite markers and the data were analysed with parametric linkage analysis using two dominant and one recessive model. A region on chromosome 15q11-q13 was implicated with a LOD score of 3.14 using a highly penetrant dominant model. Addition of more markers and one more sib-pair increased the LOD score to 3.74. This result gives preliminary evidence for existence of a susceptibility factor in this chromosomal region.
乳糜泻是一种常见的多因素疾病，具有很强的遗传成分，而HLA关联并不能完全解释这种遗传成分。此前的四项全基因组筛查结果有些不一致，表明存在遗传异质性。我们试图通过在芬兰一个亚人群中进行全基因组扫描来克服这个问题，该亚人群预计比芬兰总人口更加同质。我们研究中的家庭来自芬兰东北部的科伊利斯凯拉地区，自16世纪建区以来该地区相对隔离。家谱研究证实这些家庭在16世纪有一个共同的祖先。对9个家庭共23名患者进行了399个微卫星标记的基因分型，并使用两个显性模型和一个隐性模型通过参数连锁分析对数据进行了分析。使用高度显性模型时，15号染色体q11 - q13区域的LOD评分为3.14。增加更多标记和一对同胞对后，LOD评分提高到3.74。这一结果为该染色体区域存在易感因素提供了初步证据。
