The Need for a Human Pangenome Reference Sequence.

The reference human genome sequence is inarguably the most important and widely used resource in the fields of human genetics and genomics. It has transformed the conduct of biomedical sciences and brought invaluable benefits to the understanding and improvement of human health. However, the commonly used reference sequence has profound limitations, because across much of its span, it represents the sequence of just one human haplotype. This single, monoploid reference structure presents a critical barrier to representing the broad genomic diversity in the human population. In this review, we discuss the modernization of the reference human genome sequence to a more complete reference of human genomic diversity, known as a human pangenome. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 22 is August 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.