Charles Lee continues to sequence the 'hard-to-reach' areas of the human genome

The logo to the Human Genome Structural Variation Consortium (HGSVC)

Charles Lee is uncovering structural variations in the human genome. He co-leads The Human Genome Structural Variation Consortium, a select group of 130 scientists from around the world that provide better computational methods for genomic discovery, creating a more accurate picture of the complete human genome and linking relevant findings to the clinic.

Uncovering new evolutionary insights

Certain areas of the genome, such as the tightly coiled center of chromosomes as well as highly repetitive DNA regions, remain extremely difficult to sequence accurately. However, improvements to sequencing technologies combined with the development of better computational methods are allowing researchers to finally unravel these hard-to-sequence areas of the human genome.

The National Human Genome Research Institute has now awarded an $8.9 million grant over four years to Scientific Director and Professor of The Jackson Laboratory for Genomic Medicine Charles Lee, Ph.D., DSc, FACMG, to build new visualization and analysis tools that can accurately and comprehensively decipher these “hard-to-reach” areas. Lee and colleagues, as well as The Human Genome Structural Variation Consortium that he co-leads, will also leverage these tools with the scientific and medical community to assess how structural variations within these hard-to-reach areas are distributed in the human population and how they contribute to human disease. Assistant Professor Christine Beck, Ph.D., from The Jackson Laboratory for Genomic Medicine and UConn Health is also one of the investigators on this grant, specializing on transposable elements (“jumping genes”) that move from one location of the genome to another.

“The hard-to-reach areas of the human genome are often dismissed as ‘junk DNA’ but continue to be shown as anything but,” said Lee. “As we study these regions more, we uncover new evolutionary insights and novel mechanisms of transcriptional regulation and achieve a better understanding of the genetic etiologies of human diseases.” 

With this renewed support, Lee will continue to investigate the differences between human genomes to understand how they contribute to individual traits such as how people metabolize drugs differently and why people have differential susceptibilities to disease. In a recent study published in Nature, the Lee lab fully sequenced 43 diverse human Y chromosomes, uncovering significant variations in size and structure across 180,000 years of human evolution. Over the last two decades, Lee’s team has investigated structural variants across diverse genomes to reveal human genomic complexity and provide a more comprehensive reference for future disease and trait association studies.