卡塔尔大学Younes Mokrab研究小组报道了接近完整的中东基因组改进了自合子性，增强了致病和人群特异性变异的发现。2025年5月5日出版的《自然—遗传学》发表了这项成果。

该课题组研究人员报告了来自6个具有神经发育疾病的中东（ME）家族三组（n = 18）的高度准确、接近完整和分阶段的基因组，代表了来自苏丹、约旦、叙利亚、卡塔尔和阿富汗的祖先。这些基因组揭示了42.2新序列的Mb（13.8%影响已知基因），75个新的HLA/KIR等位基因和强近交信号，ROH覆盖了一个个体的6号和12号染色体的三分之一。使用基于组合的变体调用，该课题组人员确定了23个新生和隐性变体作为先证中先前未解决的症状的强有力候选者。ME基因组显示出相对于现有参考文献的独特变异，显示出增强的可映射性和变异召唤。这些结果强调了从头组装在疾病变异发现中的价值，以及对ME特异性参考样本的需求，以更好地表征群体相关变异。

据介绍，长读测序技术的进步使人类基因组的常规完整组装成为可能，但要代表更广泛的人群并显示对疾病基因发现的影响，还有很多工作要做。

附：英文原文

Title: Near-complete Middle Eastern genomes refine autozygosity and enhance disease-causing and population-specific variant discovery

Author: Ghorbani, Mohammadmersad, Moosa, Shabir, Siddig, Zenab, Farhad, Radi, Naeem, Haroon, Harvey, William T., Mastrorosa, Francesco Kumara, Munson, Katherine M., Mohamad Razali, Rozaimi, Aliyev, Elbay, Diboun, Ilhame, Abouelhassan, Rawan, Tauro, Melissa, Hassan, Sondoss, Mathew, Rebecca, Al Hashmi, Muna, Mathew, Lisa S., Wang, Kun, Salhab, Abdul Rahman, Vempalli, Fazulur Rehaman, El Khouly, Ahmed, Alazwani, Iman, Tomei, Sara, Fakhro, Khalid A., Satti, Alia, Benini, Ruba, Rhie, Arang, Eichler, Evan E., Mokrab, Younes

Issue&Volume: 2025-05-05

Abstract: Advances in long-read sequencing have enabled routine complete assembly of human genomes, but much remains to be done to represent broader populations and show impact on disease-gene discovery. Here, we report highly accurate, near-complete and phased genomes from six Middle Eastern (ME) family trios (n=18) with neurodevelopmental conditions, representing ancestries from Sudan, Jordan, Syria, Qatar and Afghanistan. These genomes revealed 42.2Mb of new sequence (13.8% impacting known genes), 75 new HLA/KIR alleles and strong signals of inbreeding, with ROH covering up to one-third of chromosomes 6 and 12 in one individual. Using assembly-based variant calling, we identified 23 de novo and recessive variants as strong candidates for causing previously unresolved symptoms in the probands. The ME genomes revealed unique variation relative to existing references, showing enhanced mappability and variant calling. These results underscore the value of de novo assembly for disease variant discovery and the need for sampled ME-specific references to better characterize population-relevant variation.

DOI: 10.1038/s41588-025-02173-7

Source: https://www.nature.com/articles/s41588-025-02173-7