Markus B, Alshafee I, Birk O S
The Morris Kahn Laboratory of Human Genetics at the National Institute for Biotechnology in the Negev (NIBN) and Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel.
Soroka Medical Center, The Genetics Institute, Beer-sheva, Israel.
Heredity (Edinb). 2014 Feb;112(2):182-9. doi: 10.1038/hdy.2013.90. Epub 2013 Oct 2.
The Bedouin Israeli population is highly inbred and structured with a very high prevalence of recessive diseases. Many studies in the past two decades focused on linkage analysis in large, multiple consanguineous pedigrees of this population. The advent of high-throughput technologies motivated researchers to search for rare variants shared between smaller pedigrees, integrating data from clinically similar yet seemingly non-related sporadic cases. However, such analyses are challenging because, without pedigree data, there is no prior knowledge regarding possible relatedness between the sporadic cases. Here, we describe models and techniques for the study of relationships between pedigrees and use them for the inference of tribal co-ancestry, delineating the complex social interactions between different tribes in the Negev Bedouins of southern Israel. Through our analysis, we differentiate between tribes that share many yet small genomic segments because of co-ancestry versus tribes that share larger segments because of recent admixture. The emergent pattern is well correlated with the prevalence of rare mutations in the different tribes. Tribes that do not intermarry, mostly because of social restrictions, hold private mutations, whereas tribes that do intermarry demonstrate a genetic flow of mutations between them. Thus, social structure within an inbred community can be delineated through genomic data, with implications to genetic counseling and genetic mapping.
以色列贝都因人群高度近亲通婚且结构复杂,隐性疾病患病率极高。在过去二十年中,许多研究聚焦于该人群中大型多重近亲家系的连锁分析。高通量技术的出现促使研究人员在较小家系中寻找共享的罕见变异,整合来自临床相似但看似无亲缘关系的散发病例的数据。然而,此类分析具有挑战性,因为没有家系数据,就没有关于散发病例之间可能存在的亲缘关系的先验知识。在此,我们描述了用于研究家系之间关系的模型和技术,并将其用于推断部落共同祖先,描绘以色列南部内盖夫贝都因人不同部落之间复杂的社会互动。通过我们的分析,我们区分了因共同祖先而共享许多小基因组片段的部落与因近期混合而共享较大片段的部落。出现的模式与不同部落中罕见突变的患病率密切相关。主要由于社会限制而不与外族通婚的部落拥有私人突变,而相互通婚的部落则显示出突变在它们之间的基因流动。因此,可以通过基因组数据描绘近亲社区内的社会结构,这对遗传咨询和基因定位具有重要意义。