突尼斯的遗传病谱源于创始人的影响,遗传漂移,选择,和血缘关系.后者代表了与panmixia的偏离,其特征在于可能受几个规则约束的非随机婚姻选择,比如社会文化,经济,或其他因素。这使得遗传结构偏离了哈代-温伯格平衡,增加纯合基因型和减少杂合子,从而提高常染色体隐性遗传疾病的发生频率。与其他阿拉伯人口相似,突尼斯显示出很高的血缘关系率,在地理上有所不同。突尼斯大约60%的疾病是常染色体隐性遗传,与血缘关系可能发生在80%的家庭中的特定疾病。在近交种群中,血缘关系会增加常染色体隐性疾病的风险,然而,它不影响常染色体显性疾病的可能性,而是影响其表型。血缘关系也被认为是导致共病表达的有害变体纯合性的主要因素。在基因组水平,近交个体继承纯合突变和相邻基因组区域,称为纯合性序列(ROHs)。短ROHs表示远缘近亲繁殖,而长ROHs指的是最近的近亲繁殖。ROHs在整个基因组中分布相当不规则,某些短区域具有过量的ROH,被称为ROH群岛。在这次审查中,我们讨论血缘关系对人口健康和基因组动力学的影响,以突尼斯为榜样。
The genetic disease spectrum in Tunisia arises from the founder effect, genetic drift, selection, and consanguinity. The latter represents a deviation from panmixia, characterized by a non-random matrimonial choice that may be subject to several rules, such as socio-cultural, economic, or other factors. This shifts the genetic structure away from the Hardy-Weinberg equilibrium, increasing homozygous genotypes and decreasing heterozygotes, thus raising the frequency of autosomal recessive diseases. Similar to other Arab populations, Tunisia displays high consanguinity rates that vary geographically. Approximately 60% of reported diseases in Tunisia are autosomal recessive, with consanguinity possibly occurring in 80% of families for a specific disease. In inbred populations, consanguinity amplifies autosomal recessive disease risk, yet it does not influence autosomal dominant disease likelihood but rather impacts its phenotype. Consanguinity is also suggested to be a major factor in the homozygosity of deleterious variants leading to comorbid expression. At the genome level, inbred individuals inherit homozygous mutations and adjacent genomic regions known as runs of homozygosity (ROHs). Short ROHs indicate distant inbreeding, while long ROHs refer to recent inbreeding. ROHs are distributed rather irregularly across the genome, with certain short regions featuring an excess of ROH, known as ROH islands. In this review, we discuss consanguinity\'s impact on population health and genome dynamics, using Tunisia as a model.