New book improves understanding of rare disease genetics using genomic approaches

In 2018, Dr. Claudia Gonzaga-Jáuregui, who years before had completed her doctorate studies in Dr. James R. Lupski's lab at Baylor College of Medicine, received an email from an editor at Elsevier's Academic Press with a proposal that immediately caught her attention.

"The editor was considering adding a title on genomics of rare diseases to the Translational and Applied Genomics Series," Gonzaga-Jáuregui said. "Would such a title fill a current need in the field and with the general public?"

Gonzaga-Jáuregui, who is now an assistant professor in the International Laboratory for Human Genome Research at Universidad Nacional Autónoma de México, thought it was a great idea.

It is estimated that at least 350 million people worldwide are affected by a rare disorder, making these conditions a substantial healthcare challenge. Many patients can go undiagnosed for decades while receiving potentially misguided and often costly treatments for their condition, uninformed about the actual molecular defect and the underlying biology of the disease. In addition, counseling regarding recurrence risk, disease prognosis and clinical management are suboptimal due to the rarity of patients.

"At the time, there was no book that would present the lay of the land including information about genomics and its application to the study of rare diseases, from basic concepts to practical examples," Gonzaga-Jáuregui said. "There was no such a book that would appeal not only to students and professionals in the field of genomics but also would be accessible and useful to a broader public including patients and families with rare diseases to empower them in understanding current scientific approaches in genetics and genomics."

Long story short, the editor proposed that Gonzaga-Jáuregui developed this book project and she was delighted to accept. "But I did not realize in the beginning the tremendous amount of work that would be involved in this project. At the time, I also was starting a family and moving to a new academic position in Mexico, all in the middle of the COVID pandemic," Gonzaga-Jáuregui said.

It's no surprise that Gonzaga-Jáuregui took on the book project despite the personal and professional challenges. She is a dedicated genomics scientist who has led large-scale projects for genomic analyses of patients and families with rare and undiagnosed genetic disorders in academia and industry. Importantly, this book project fits perfectly with her interests in teaching both in a formal academic setting and through public science outreach where she talks about science, genetics and her career to middle and high school students.

"It was exciting putting together a proposal for a book that would be accessible to many people interested in the topic," she said. "Once the publisher gave a thumbs up to the project, I approached Jim [Lupski]. I said I was very excited about the book and that I would like him to be involved as co-editor. He accepted and we worked on this together."

"I have to admit that it was not so easy to convince me to work on this project. I have worked on three previous books and knew that there would be a lot of work involved. I finally gave in; it was about time to have a book like this," said Lupski, Cullen Professor of Genetics and Genomics and Professor of Pediatrics at Baylor and Texas Children's Hospital.

In addition to co-editing the book, Gonzaga-Jáuregui also co-authored some of the chapters. "Teaching while writing helped me see what concepts are hard for students to grasp and guided the writing to make those concepts clearer, presenting them in ways that are easy to understand," she said.

"As co-editor, I tried to keep the big picture and the writing consistent throughout the book, rather than putting my own perspective on specific chapters," Lupski said.

"Having Jim onboard definitely enhanced the book by offering a complete landscape of the field," Gonzaga-Jáuregui said. "It is easy for the younger generations of scientists to talk about the novel technological processes and advancements and their applications in the field, but it was important to put the current state of human genetics and genomics in perspective. Jim brings a historical view on how the field has moved forward through the years, weaving emerging new technologies and evolving knowledge."

"Genomics of Rare Diseases" offers readers a broad understanding of current knowledge on rare diseases from a genomics perspective. It clearly presents basic concepts and the latest molecular and genomic technologies used to elucidate the molecular causes of more than 5,000 genetic disorders, raising the possibility of uncovering many more that remain undefined and undiscovered. The challenges and opportunities associated with performing rare disease research are also discussed, and how the lessons learned from studying rare diseases also apply to other human diseases in general.

In addition, "Genomics of Rare Diseases" addresses the current need of the general public to better understand genetics and genomics.

"Genetics has become more mainstream in the last years through direct-to-consumer DNA testing. Genomic technologies are providing information to the general public about their genetic background and variation," Gonzaga-Jáuregui said. "But we feel that the public needs to have a better grasp of fundamental concepts in human genetics to appreciate the genetic and genomic information they are receiving and also to take it with a grain of salt when talking about risk and common diseases. "Genomics of Rare Diseases" helps readers understand what genetics and genomics findings mean, what to expect and how to use the information provided by genetic testing."