Large-scale genomic studies have significantly increased our knowledge of genetic variability across populations. Regional genetic profiling is essential for distinguishing common benign variants from disease-causing ones. To this end, we conducted a comprehensive characterization of exonic variants in the population of Navarre (Spain), utilizing whole genome sequencing data from 358 unrelated individuals of Spanish origin. Our analysis revealed 61,410 biallelic single nucleotide variants (SNV) within the Navarrese cohort, with 35% classified as common (MAF > 1%). By comparing allele frequency data from 1000 Genome Project (excluding the Iberian cohort of Spain, IBS), Genome Aggregation Database, and a Spanish cohort (including IBS individuals and data from Medical Genome Project), we identified 1,069 SNVs common in Navarre but rare (MAF ≤ 1%) in all other populations. We further corroborated this observation with a second regional cohort of 239 unrelated exomes, which confirmed 676 of the 1,069 SNVs as common in Navarre. In conclusion, this study highlights the importance of population-specific characterization of genetic variation to improve allele frequency filtering in sequencing data analysis to identify disease-causing variants.

中文翻译：

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西班牙纳瓦拉人群常见遗传变异的特征

大规模基因组研究显着增加了我们对不同人群遗传变异性的了解。区域基因分析对于区分常见的良性变异和致病变异至关重要。为此，我们利用来自 358 个不相关的西班牙血统个体的全基因组测序数据，对纳瓦拉（西班牙）人群的外显子变异进行了全面表征。我们的分析显示 Navarrese 队列中有 61,410 个双等位基因单核苷酸变异 (SNV)，其中 35% 被归类为常见 (MAF > 1%)。通过比较 1000 基因组计划（不包括西班牙伊比利亚队列，IBS）、基因组聚合数据库和西班牙队列（包括 IBS 个体和来自医学基因组计划的数据）的等位基因频率数据，我们确定了 1,069 个在纳瓦拉常见但罕见的 SNV（所有其他人群中的 MAF ≤ 1%）。我们用包含 239 个不相关外显子组的第二个区域队列进一步证实了这一观察结果，该队列证实了 1,069 个 SNV 中的 676 个在纳瓦拉很常见。总之，本研究强调了遗传变异的人群特异性特征对于改善测序数据分析中的等位基因频率过滤以识别致病变异的重要性。