Mezzi Nessrine, Abassi Najla, Fatnassi Faten, Abdelhak Sonia, Romdhane Lilia
Biomedical Genomics and Oncogenetics Laboratory. Institut Pasteur de Tunis, University of Tunis El Manar, Tunisia.
Department of Life Sciences, Faculty of Sciences of Bizerte, University of Carthage, Tunisia.
Tunis Med. 2024 May 5;102(5):256-265. doi: 10.62438/tunismed.v102i5.4787.
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.
突尼斯的遗传疾病谱源于奠基者效应、遗传漂变、选择和近亲结婚。后者代表了对随机交配的偏离，其特征是婚姻选择非随机，可能受多种规则影响，如社会文化、经济或其他因素。这使遗传结构偏离哈迪-温伯格平衡，增加纯合基因型，减少杂合子，从而提高常染色体隐性疾病的发生率。与其他阿拉伯人群体类似，突尼斯的近亲结婚率较高且存在地域差异。突尼斯约60%的报告疾病为常染色体隐性疾病，特定疾病的家庭中约80%可能存在近亲结婚情况。在近亲繁殖的人群中，近亲结婚会增加常染色体隐性疾病风险，但不影响常染色体显性疾病的发生概率，而是影响其表型。近亲结婚也被认为是导致共病表达的有害变异纯合性的主要因素。在基因组水平上，近亲繁殖个体继承纯合突变以及称为纯合片段（ROH）的相邻基因组区域。短ROH表明远亲繁殖，而长ROH则表示近亲繁殖。ROH在基因组中的分布相当不规则，某些短区域存在过量的ROH，称为ROH岛。在本综述中，我们以突尼斯为模型，讨论近亲结婚对人群健康和基因组动态的影响。
