The human reference genome, maintained by Genome Reference Consortium, is conceivably the most complete genome assembly ever since its first construction. It has been improved continually by incorporating corrections made to the previous assemblies thanks to various technological advances. Based on this reference genome, many population sequencing projects are ongoing to better represent human diversity, increasing hope for medical usage of genomic information, with recent maturation of the high-throughput sequencing technologies. However, the one reference genome does not fit all the populations across the globe, because of large diversity in genomic structures and technical limitations inherent to short read sequencing methods. The recent success in de novo construction of highly contiguous Asian diploid genomeAK1, by combining single molecule technologies with routine sequencing data without resorting to traditional clone-by-clone sequencing and physical mapping, reveals the nature of genomic structure variation by detecting thousands of novel structural variations and by filling some of the persistently remained gaps in the current human reference genome. Now it is expected that the AK1genome, with more de novo assembled genomes comingup, will provide a chance to exploring what it is really like to use ancestry specific reference genomes instead of hg19/hg38 forpopulation genomics toward precision medicine.