Kalaydjieva L, Hallmayer J, Chandler D, Savov A, Nikolova A, Angelicheva D, King R H, Ishpekova B, Honeyman K, Calafell F, Shmarov A, Petrova J, Turnev I, Hristova A, Moskov M, Stancheva S, Petkova I, Bittles A H, Georgieva V, Middleton L, Thomas P K
Laboratory of Molecular Pathology, Medical University, Sofia, Bulgaria.
Nat Genet. 1996 Oct;14(2):214-7. doi: 10.1038/ng1096-214.
Founder effect and linkage disequilibrium have been successfully exploited to map single gene disorders, and the study of isolated populations is emerging as a major approach to the investigation of genetically complex diseases. In the search for genetic isolates ranging from Pacific islands to Middle East deserts, the 10 million Gypsies resident in Europe have largely escaped the attention of geneticists. Because of their geographical ubiquity, lack of written history and the presumed social and cultural nature of their isolation, Gypsies are construed as not meeting the criteria for a well defined founder population. Gypsy society has a complex structure with subdivisions and stratifications that are incomprehensible to the surrounding populations. Marginalization by the health care systems in most countries results in a lack of information on causes of morbidity and mortality and little is known about hereditary disorders or the population genetic characteristics of Gypsies. This study is the first example of mapping a disease gene in endogamous Gypsy groups. Using lod score analysis and linkage disequilibrium, we have located a novel demyelinating neuropathy to a narrow interval on chromosome 8q24. We show that the disease, occurring in Gypsy groups of different identity and history of migrations, is caused by a single mutation whose origin predates the divergence of these groups.
奠基者效应和连锁不平衡已成功用于定位单基因疾病，而对隔离人群的研究正成为调查遗传复杂性疾病的一种主要方法。在寻找从太平洋岛屿到中东沙漠的遗传隔离人群的过程中，居住在欧洲的1000万吉普赛人在很大程度上未受到遗传学家的关注。由于他们分布在各地、没有书面历史以及其隔离状态被认为具有社会和文化性质，吉普赛人被认为不符合明确界定的奠基人群的标准。吉普赛社会结构复杂，有一些周围人群难以理解的分支和阶层。大多数国家的医疗保健系统将其边缘化，导致缺乏有关发病和死亡原因的信息，对吉普赛人的遗传性疾病或群体遗传特征了解甚少。本研究是在族内通婚的吉普赛人群体中定位疾病基因的首个实例。通过对数优势计分分析和连锁不平衡，我们已将一种新型脱髓鞘性神经病变定位到8号染色体q24上的一个狭窄区间。我们表明，这种发生在具有不同身份和迁徙历史的吉普赛人群体中的疾病是由一个单一突变引起的，该突变的起源早于这些群体的分化。
