Genetic diversity in Kashubs: the regional increase in the frequency of several disease-causing variants

Differential distribution of genetic variants' frequency among human populations is caused by the genetic drift in isolated populations, historical migrations, and demography. Some of these variants are identical by descent and represent founder mutations, which - if pathogenic in nature - lead to the increased frequency of otherwise rare diseases. The detection of the increased regional prevalence of pathogenic variants may shed light on the historical processes that affected studied populations and can help to develop effective screening and diagnostic strategies as a part of personalized medicine. Here, we discuss the specific genetic diversity in Kashubs, the minority group living in northern Poland, reflected in the biased distribution of some of the repetitively found disease-causing variants. These include the following: (1) c.662A > G (p.Asp221Gly) in LDLR, causing heterozygous familial hypercholesterolemia; (2) c.3700_3704del in BRCA1, associated with hereditary breast and ovarian cancer syndrome; (3) c.1528G> C (p.Glu510Gln) in HADHA, seen in long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) deficiency, and (4) c.1032delT in NPHS2, associated with steroid-resistant nephrotic syndrome.

Automated summary

The frequency distribution of genetic variants among human populations is influenced by genetic drift in isolated populations, historical migrations, and demography. Identical by descent variants can lead to the increased prevalence of pathogenic diseases if they are pathogenic in nature. Studying the increased regional prevalence of pathogenic variants can provide insights into historical processes and aid in personalized medicine. This article discusses the genetic diversity in the Kashub minority group in northern Poland, focusing on the biased distribution of disease-causing variants.