巴西南部门诺派教徒的致病变异:对公共卫生预防措施的影响。

IF 2.3 3区 医学 Q2 GENETICS & HEREDITY
Luiza Beatriz Mayer de Lima, Eduardo Delabio Auer, Isabela Dall'Oglio Bucco, Valéria Bumiller-Bini Hoch, Priscila Ianzen Dos Santos, Fabiana L Lopes, Alan Shuldiner, Emilton Lima Júnior, Angelica Beate Winter Boldt
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引用次数: 0

摘要

门诺派人口有一个独特的历史,500年的遗传隔离,形成了至少三个人口瓶颈,创始人效应,近亲繁殖,流行病和迁移。为了评估他们对单基因疾病(MD)的易感性,我们对来自两个南巴西门诺派定居点(一个城市,另一个农村)的325名志愿者进行了全外显子组测序。我们确定了23种致病变异(P)和27种可能的P,其中内分泌、营养和代谢性MDs占22.8%,发育异常占17.5%,神经系统MDs占10.5%。HFE rs1800562导致遗传性血色素沉着病的发生率最高(7.54%),其次是BTD rs13078881导致生物素酶缺乏症(7.08%),FLG rs61816761导致寻常性鱼鳞病和特应性皮炎(3.38%),FANCM rs147021911导致范可尼贫血(3.08%)。基因组和家谱分析证实了他们的欧洲血统,具有非常低的血缘关系和高杂合系数,证实了1930年从俄罗斯广泛定居点移民到巴西的随机选择的难民。对于自称是混合门诺派教徒的印第安人来说,也有轻微的偏差。即便如此,96%的P出现了创始人效应,其频率与非芬兰的欧洲人、阿米什人和巴西人不同。这些发现强调了这一人群的遗传风险,强调了遗传咨询、筛查计划以及个性化和预防医学策略的重要性,以减轻与遗传疾病相关的健康风险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pathogenic Variants in Mennonites From Southern Brazil: Implications for Preventive Measures in Public Health.

The Mennonite population has a unique history of 500 years of genetic isolation shaped by at least three demographic bottlenecks, founder effects, inbreeding, epidemics, and migrations. To evaluate their susceptibility for monogenic diseases (MD), we performed whole-exome sequencing on 325 volunteers from two South Brazilian Mennonite settlements (one urban and another rural). We identified 23 pathogenic variants (P) and 27 likely P, with 22.8% accounting for endocrine, nutritional, and metabolic MDs, 17.5% for developmental anomalies, and 10.5% for nervous system MDs. HFE rs1800562 causing hereditary hemochromatosis presented the highest frequency (7.54%), followed by BTD rs13078881 for biotinidase deficiency (7.08%), FLG rs61816761 for ichthyosis vulgaris and atopic dermatitis (3.38%), and FANCM rs147021911 for Fanconi anemia (3.08%). Genomic and genealogical analysis confirmed their European origin, with very low consanguinity and high heterozygosity coefficients, confirming a random selection of refugees that emigrated from widespread settlements in Russia to Brazil in 1930. There was also a slight deviation to Native Americans for self-reported admixed Mennonites. Even so, founder effects occurred for 96% of P, whose frequencies differed from non-Finnish Europeans, Amish, and Brazilian populations. These findings highlight the genetic risks in this population, reinforcing the importance of genetic counseling, screening programs, and Personalized and Preventive Medicine strategies to mitigate health risks associated with inherited conditions.

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来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
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