# Pathogenic Variants in Mennonites From Southern Brazil: Implications for Preventive Measures in Public Health

## TL;DR

This study identifies harmful genetic variants in a Mennonite population in Brazil, highlighting the need for genetic screening and preventive health strategies.

## Contribution

The study reveals unique pathogenic variant frequencies in a genetically isolated Mennonite population, emphasizing their distinct genetic risks.

## Key findings

- 23 pathogenic and 27 likely pathogenic variants were identified, with notable frequencies in endocrine, metabolic, and nervous system diseases.
- Founder effects were observed for 96% of pathogenic variants, differing from non-Finnish Europeans, Amish, and Brazilian populations.
- Genomic and genealogical analysis confirmed European origin and random selection during migration from Russia to Brazil in 1930.

## Abstract

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.

In 325 exomes of South Brazilian Mennonites, we identified 23 pathogenic variants (P) and 27 likely P, with founder effects identified for 96% of P, whose frequencies differed from non‐Finnish Europeans, Amish, and Brazilian populations.