The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Institute of Oncology, Wolfson Medical Center, Holon, Israel.
Sci Rep. 2022 Sep 8;12(1):15206. doi: 10.1038/s41598-022-19538-1.
A growing number of familial Mediterranean fever (FMF) patients in Israel do not have a single country of origin for all four grandparents. We aimed to predict the Mediterranean fever gene (MEFV) variant most likely to be found for an individual FMF patient, by a machine learning approach. This study was conducted at the Sheba Medical Center, a referral center for FMF in Israel. All Jewish referrals included in this study carried an FMF associated variant in MEFV as shown by genetic testing performed between 2001 and 2017. We introduced the term 'origin score' to capture the dose and different combinations of the grandparents' origin. A machine learning approach was used to analyze the data. In a total of 1781 referrals included in this study, the p.Met694Val variant was the most common, and the variants p.Glu148Gln and p.Val726Ala second and third most common, respectively. Of 26 countries of origin analyzed, those that increased the likelihood of a referral to carry specific variants were identified in North Africa for p.Met694Val, Europe for p.Val726Ala, and west Asia for p.Glu148Gln. Fourteen of the studied countries did not show a highly probable variant. Based on our results, it is possible to describe an association between modern day origins of the three most common MEFV variant types and a geographical region. A strong geographic association could arise from positive selection of a specific MEFV variant conferring resistance to endemic infectious agents.
越来越多的以色列家族性地中海热（FMF）患者的四位祖父母并非来自同一国家。我们旨在通过机器学习方法预测个体 FMF 患者最有可能携带的地中海热基因（MEFV）变体。这项研究是在以色列的谢巴医疗中心进行的，该中心是 FMF 的转诊中心。本研究中所有被纳入的犹太转诊患者均携带 MEFV 中的 FMF 相关变体，这是通过 2001 年至 2017 年间进行的基因检测显示的。我们引入了“起源评分”这一术语，以捕捉祖父母的起源的剂量和不同组合。使用机器学习方法来分析数据。在本研究中总共纳入了 1781 名转诊患者，p.Met694Val 变体是最常见的，其次是 p.Glu148Gln 和 p.Val726Ala 变体，分别位列第二和第三。在分析的 26 个原籍国中，确定了增加携带特定变体转诊可能性的原籍国，在北非为 p.Met694Val，在欧洲为 p.Val726Ala，在西亚为 p.Glu148Gln。有 14 个研究国没有表现出高概率的变体。基于我们的研究结果，可以描述三种最常见的 MEFV 变体类型与地理区域之间的现代起源之间的关联。强烈的地理关联可能源于对赋予对地方性感染因子的抵抗力的特定 MEFV 变体的正向选择。
