New maps and new challenges in the post-genomic era

Sometimes in science a discovery not only expands our knowledge but also changes how we approach and understand it. For much of modern biology, the human genome was a fragmented puzzle with individual parts studied separately. Researchers faced this complexity with limited tools and incomplete information, and often made progress through slow, meticulous effort. The publication of the human genome sequence by the International Human Genome Sequencing Consortium in Nature in 2001 heralded a fundamental shift. The genome became a reference — an accessible resource that could be systematically read, compared and analysed on a large scale. This change accelerated discoveries and reshaped scientific questions, which enabled new methodologies, and an integrated understanding of human biology.

The consortium’s research produced a detailed reference map of approximately 90% of the euchromatic genome and a comprehensive catalogue of human genes, including protein-coding sequences, regulatory regions and noncoding RNAs. One surprising finding was that the human genome contains far fewer protein-coding genes than expected, initially estimated at 100,000 but today believed to be just over 20,000. The project also revealed that nearly half of the genome comprises repetitive elements (such as transposable elements) and segmental duplications scattered throughout. These features provided early insights into genome structure, evolution and mechanisms of genetic regulation, including hotspots for chromosomal rearrangements linked to disease. Alongside this, the mapped genome spurred the development of new bioinformatics tools and methodologies, functional genomics, comparative genomics and large-scale genome-wide association studies. The openly available reference genome prompted data-driven, genome-wide approaches and established itself as the backbone of biomedical research. In endocrinology, it has facilitated the discovery of genetic variants involved in endocrine disorders and metabolic regulation, which has advanced our understanding of complex traits and supported the development of diagnostics and therapies.