From the human genome to its pangenome through the ENCODE and T2T consortia

Abstract

We have been exploiting a chimeric human genome full of gaps for 21 years. Fortunately,  we know that the genome has more than coding genes because the ENCODE Consortium scrutinised it in depth. Among the most unexpected findings are that more than 75 % of the genome is transcribed, that each gene undergoes 6.3 types of alternative splicing and makes 4 different transcripts, that there are many, many regulatory regions scattered throughout the genome and, the most surprising of all, that there are only five transcriptionally different cell types. In these 21 years, the initial sequence has been improved and a better understanding of what genomic sequences are for was achieved. But research has also moved from indiscriminate pre-amplified sequencing of short reads (75 to 600 nt) to single molecule sequencing that provides thousands of contiguous bases. Consequently, the first complete, non-chimeric, human genome (except for the Y chromosome) without gaps has just been published, opening new doors to genomics and medicine, including obtaining the human pangenome to gather the whole genetic diversity of our species.