Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec, Canada H3A 2B4.
Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada H3T 1J4.
Proc Natl Acad Sci U S A. 2019 Aug 6;116(32):16012-16017. doi: 10.1073/pnas.1810388116. Epub 2019 Jul 22.
The Canadian Inuit have a distinct population background that may entail particular implications for the health of its individuals. However, the number of genetic studies examining this Inuit population is limited, and much remains to be discovered in regard to its genetic characteristics. In this study, we generated whole-exome sequences and genomewide genotypes for 170 Nunavik Inuit, a small and isolated founder population of Canadian Arctic indigenous people. Our study revealed the genetic background of Nunavik Inuit to be distinct from any known present-day population. The majority of Nunavik Inuit show little evidence of gene flow from European or present-day Native American peoples, and Inuit living around Hudson Bay are genetically distinct from those around Ungava Bay. We also inferred that Nunavik Inuit have a small effective population size of 3,000 and likely split from Greenlandic Inuit ∼10.5 kya. Nunavik Inuit went through a bottleneck at approximately the same time and might have admixed with a population related to the Paleo-Eskimos. Our study highlights population-specific genomic signatures in coding regions that show adaptations unique to Nunavik Inuit, particularly in pathways involving fatty acid metabolism and cellular adhesion (, , , and ). Subsequent analyses in selection footprints and the risk of intracranial aneurysms (IAs) in Nunavik Inuit revealed an exonic variant under weak negative selection to be significantly associated with IA (rs77470587; = 4.6 × 10).
加拿大因纽特人具有独特的人口背景，这可能对其个体健康产生特殊影响。然而，目前用于研究因纽特人群的遗传研究数量有限，其遗传特征仍有许多待发现。在这项研究中，我们对 170 名努纳武特因纽特人进行了全外显子组测序和全基因组基因型分析，这些人是加拿大北极地区的一个小型隔离的原住民群体。我们的研究揭示了努纳武特因纽特人的遗传背景与任何已知的现代人群都不同。大多数努纳武特因纽特人几乎没有证据表明与欧洲或现代美洲原住民发生基因流，居住在哈德逊湾的因纽特人与居住在昂加瓦湾的因纽特人在遗传上是不同的。我们还推断，努纳武特因纽特人的有效种群大小为 3000 人，可能与格陵兰因纽特人在约 10.5 千年前分离。努纳武特因纽特人经历了瓶颈期，大约在同一时间与与古爱斯基摩人有关的人群混合。我们的研究强调了编码区域中特定于人群的基因组特征，这些特征显示了努纳武特因纽特人独特的适应能力，特别是在涉及脂肪酸代谢和细胞黏附的途径中（、、、和）。在努纳武特因纽特人的选择足迹和颅内动脉瘤（IA）风险的后续分析中，发现一个处于弱负选择下的外显子变体与 IA 显著相关（rs77470587； = 4.6×10）。
