PDF(Pubmed)
Abstract：
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 1069 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 1069 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.
摘要：
大规模的基因组研究大大增加了我们对种群遗传变异性的认识。区域遗传分析对于区分常见的良性变异与致病变异至关重要。为此,我们对纳瓦拉（西班牙）人口中的外显子变体进行了全面的表征，利用来自358名西班牙裔无关个体的全基因组测序数据。我们的分析揭示了Navarrese队列中的61,410个双等位基因单核苷酸变体（SNV），35%被归类为普通(MAF>1%)。通过比较来自1000基因组计划的等位基因频率数据（不包括西班牙的伊比利亚队列，IBS),基因组聚集数据库,和西班牙队列（包括IBS个体和来自医学基因组计划的数据），我们确定了纳瓦拉常见的1069个SNV，但在所有其他人群中罕见(MAF≤1%)。我们进一步证实了这一观察与239个不相关的外显子组的第二个区域队列，这证实了1069个SNV中有676个在纳瓦拉很常见。总之,这项研究强调了群体特异性遗传变异特征的重要性,以改善测序数据分析中的等位基因频率过滤,从而鉴定致病变异.
