Dark zones in your genome

Genome dark zones hide structural variants

Dark zones in your genome

There are dark zones in your genome, but nothing shadowy is going on. They’re “dark” because regions — long stretches of ATCG code — haven’t been entirely or correctly mapped. 

Scientists assumed the regions didn’t have important functions, such as genes coding for a protein. They thought the DNA in the dark zones was junk. That was just plain wrong. Now we know the zones have been hiding critical information about human genetic variation.

It’s taken a while to change the notion. The catalyst is new tech that can see into the dark zones. Older sequencing machines use older “short-read” technology. A fast and cheap method that sequences (reads) short stretches of DNA molecules. 

Adequate for most applications, but reassembling short pieces is tricky. The sequence order can get mixed up. More importantly, the machines can’t identify long, repetitive sequences and large duplications in the non-coding zones.

Newer, long-read technology from PacBio and Oxford Nanopore are Biotech companies specializing in lighting up complex areas of the genome. They sequence whole, individual molecules rather than breaking them into bits for reassembly.

Researchers are using long-read to drive the next advancements in medical genomics. They look at these structural alterations to:

  • Untangle long, repetitive elements to determine where a gene starts and ends
  • Reveal “camouflaged” areas to find new genes and de novo mutations that could be variants for disease
  • Identify and decipher copy number variants in long repetitive stretches
  • Find InDels — Insertions and deletions that alter the genomic sequence

In addition to medical applications, geneticists look in the dark zones for variants to add to the Pangenome reference library. New variants and other structural alterations also expand knowledge of human evolutionary history. For example, geneticist Dr. Evan Eichler uses long-read to identify species-specific structural variants that evolved over deep time and made us human. 

Dr. Eichler says, “Students! It’s a beautiful time to be alive and working in genomics. Long-read sequence and assembly are revolutionizing our ability to assemble new genomes and understand the full spectrum of genetic variation.”

No longer considered junk, the non-coding dark zones in your genome are the frontiers of exciting genomic discovery.

 

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