近亲繁殖、族内通婚、基因混合及远亲繁殖对人类健康的影响：一项（《101忠狗》）研究
Effects of inbreeding, endogamy, genetic admixture, and outbreeding on human health: a (1001 Dalmatians) study.
作者信息
Rudan Igor, Biloglav Zrinka, Vorko-Jović Ariana, Kujundzić-Tiljak Mirjana, Stevanović Ranko, Ropac Darko, Puntarić Dinko, Cucević Branka, Salzer Branka, Campbell Harry
机构信息
Department of Public Health Sciences, Faculty of Medicine, University of Edinburgh, Scotland, UK.
出版信息
Croat Med J. 2006 Aug;47(4):601-10.
AIM
(1001 Dalmatians) research program collects biomedical information from multiple small isolated populations ((metapopulation)) on Adriatic islands, Croatia, and investigates health effects of human population isolation, inbreeding, admixture, and outbreeding.
METHODS
We collected random samples of 100 individuals from 9 island settlements and an additional sample of 101 immigrants to the islands, pooled from all study populations. According to their personal genetic histories, the examinees were categorized as inbred, autochthonous, admixed, and outbred. A total of 76 inbred individuals from a total sample of 1001 examinees were matched to 76 autochthonous, 76 admixed, and 76 outbred controls by gender, age (+/-5 years), village of residence, education, and socio-economic status. We investigated the effects of presumed individual genome-wide heterozygosity predicted from personal genetic histories on the following 10 traits: systolic and diastolic blood pressure, body mass index, high and low density lipoproteins and total cholesterol, triglycerides, uric acid, creatinine, and blood glucose.
RESULTS
Personal genetic history significantly affected systolic blood pressure (Spearman rho=0.157, P=0.006), while the effect on cholesterol (rho=0.105, P=0.069), and high density lipoprotein cholesterol (rho=0.104, P=0.071) was suggestive. Admixed individuals and immigrants consistently showed values associated with lower health risk. When inbred and autochthonous samples were merged and compared with the admixed and outbred samples to increase the power of the study, the effects on the three traits above and also on body mass index and diastolic blood pressure became statistically significant. The medians for all 10 medically relevant traits in inbred and autochthonous group, with lower values of presumed individual genome-wide heterozygosity, were less favorable in terms of health.
CONCLUSION
The combined effects of founder effect, genetic drift, and inbreeding can increase the frequency of detrimental rare variants in human metapopulations, leading to overall worsening of population health, whereas admixture and outbreeding appear to have the opposite effect.
目的
“1001 只斑点狗”研究项目从克罗地亚亚得里亚海岛屿上的多个小型孤立种群（集合种群）收集生物医学信息，并调查人类种群隔离、近亲繁殖、混合繁殖和远系繁殖对健康的影响。
方法
我们从 9 个岛屿定居点随机抽取了 100 名个体样本，并从所有研究种群中汇总了另外 101 名岛屿移民样本。根据他们的个人遗传史，将受检者分为近亲繁殖、本地、混合和远系繁殖四类。在总共 1001 名受检者中，共有 76 名近亲繁殖个体按性别、年龄（±5 岁）、居住村庄、教育程度和社会经济地位与 76 名本地、76 名混合和 76 名远系繁殖对照个体进行匹配。我们研究了根据个人遗传史预测的假定个体全基因组杂合性对以下 10 个性状的影响：收缩压和舒张压、体重指数、高密度和低密度脂蛋白以及总胆固醇、甘油三酯、尿酸、肌酐和血糖。
结果
个人遗传史对收缩压有显著影响（斯皮尔曼相关系数 rho = 0.157，P = 0.006），而对胆固醇（rho = 0.105，P = 0.069）和高密度脂蛋白胆固醇（rho = 0.104，P = 0.071）的影响具有提示性。混合个体和移民始终表现出与较低健康风险相关的值。当将近亲繁殖和本地样本合并并与混合和远系繁殖样本进行比较以提高研究效能时，对上述三个性状以及体重指数和舒张压的影响变得具有统计学意义。在近亲繁殖和本地组中，所有 10 个医学相关性状的中位数，假定个体全基因组杂合性值较低，在健康方面不太有利。
结论
奠基者效应、遗传漂变和近亲繁殖的综合作用会增加人类集合种群中有害罕见变异的频率，导致种群健康总体恶化，而混合繁殖和远系繁殖似乎具有相反的效果。
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