Department of Biology and Medical Genetics, Medical University of Gdansk, Gdansk, Poland.
Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
J Appl Genet. 2022 Dec;63(4):691-701. doi: 10.1007/s13353-022-00713-z. Epub 2022 Aug 15.
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.
人群中遗传变异频率的差异是由隔离人群中的遗传漂变、历史迁移和人口统计学因素引起的。其中一些变异是由于同源重组而相同的，代表着起源突变，如果具有致病性，会导致原本罕见的疾病的频率增加。检测到致病性变异的区域性高发可能揭示了影响研究人群的历史进程，并有助于制定有效的筛查和诊断策略，作为个性化医学的一部分。在这里，我们讨论了生活在波兰北部的少数民族卡舒布人（Kashubs）的特定遗传多样性，这反映在一些重复出现的致病变异的偏倚分布上。这些变异包括：（1）LDLR 中的 c.662A>G（p.Asp221Gly），导致杂合子家族性高胆固醇血症；（2）BRCA1 中的 c.3700_3704del，与遗传性乳腺癌和卵巢癌综合征相关；（3）HADHA 中的 c.1528G>C（p.Glu510Gln），见于长链 3-羟基酰基辅酶 A 脱氢酶（LCHAD）缺乏症；（4）NPHS2 中的 c.1032delT，与类固醇耐药性肾病综合征相关。
