Human genome sequence and its implications – Past present, and future

2023, a very important year. Why? One of the reasons is because we have spent almost 7 decades since the structure of DNA was discovered by Watson and Crick for which the gentlemen received the noble prize, probably in the shortest time post any discovery. It was thought that identification of the exact base sequence of the human genome will usher in an era that will be beneficial to the human beings. However, even after 7 decades of a very exciting journey, we are still scratching our heads as to what really human genome sequence (HGS) has in store for us.

Since 1953, significant efforts have been made leading to development of technological prowess, the analytical tools to answer one and the most important question as to how HGS can be utilized to predict the future human health, and find ways that the risk of various diseases can be ameliorated. Needless to say, the advent of PCR by Kary Mullis added a big jump to the sequencing efforts, beginning from Sanger sequencing to large-scale next-generation sequencing (NGS). It was in 1990 that the major push for sequencing the human genome came up and the first draft was published in 2003, an event which was equated with the landing of man on the moon by the then US President, Bill Clinton. Clearly, this was a landmark achievement, which brought tremendous amount of excitement and I dare say, a lot of miscalculations, which are still being corrected, have provided opportunities to continue the quest for a few more decades.

Clearly, 2003 laid the foundation for today’s NGS-based approaches making a big difference in understanding the genetic basis of many complex diseases. So, sky seems to be the limit but the question remains – have we been able to make the best use of HGS to understand, to tame, and to treat the human genetic diseases? And friends, the answer is a surprising no! One of the biggest limitations is the fact it was not complete and had about 1.5 lakh gaps, largely due to technical limitations to sequence the repeat rich regions, which were considered as JUNK DNA at that time. A recent study on Icelandic population with advanced sequencing technology reported a 766 bp deletion (in one of the gap regions of HGS), to be associated with the risk of myocardial infarction. This mandates the need to a have a complete HGS, better known as the pan genome! The Pan Genome Project is a global effort in this direction covering 350 individuals from different parts of the world. The latest data on 47 trios published in Nature in May 2023 has many interesting observations, including better understanding of genetic variants in crucial regions associated with diseases, new variants in genes of medical importance like HLA and CYP have been identified. The importance of HLA in various autoimmune diseases including Type-1 diabetes and the CYP loci in pharmacogenetic implications hardly needs to be stressed. This furthers the fact that pan genome is the next level of understanding of HGS, and will have serious implications in identification of genetic basis of diseases.

So while the past was exciting and the present is no less, the future seems to be very fruitful and highly likely to achieve the objectives, which the discoverers of DNA structure would have envisaged. Best of luck to pan genome community and best of luck to everyone!