1st ‘gapless’ human genome finally sequenced
Scientists have finally mapped a complete human genome, almost two decades after researchers first announced they had sequenced most of the roughly 3 billion letters that make up human DNA.
Although the Human Genome Project was celebrated around the world after its completion in 2003, many sections of the genome could not be localized at that time. The new work — conducted by a consortium of scientists led by the National Human Genome Research Institute, the University of California, Santa Cruz and the University of Washington in Seattle — finally fills in the final 8% of DNS Letters or base pairs that previously had no home in the sequence.
The new genome paves the way to a better understanding of how people’s DNA can differ and how genetic mutations can contribute to disease. The scientists published their findings March 31 in the journal science.
In 2003, scientists from the Human Genome Project and biotech company Celera Genomics solved most of the puzzle. But technological limitations meant they couldn’t fit 15% of the human DNA sequence into the picture. Most of the regions not mapped were concentrated around telomeres (the caps at the ends of chromosomes) and centromeres (the densely packed middle parts of the chromosomes). In 2013, researchers reduced that gap to just 8%, but they still couldn’t fit 200 million base pairs — the equivalent of an entire chromosome.
Related: New study provides first evidence of non-random mutations in DNA
“Ever since we had the first draft of the human genome sequence, determining the precise sequence of complex genomic regions has been a challenge,” said study co-author Evan Eichler, a researcher at the University of Washington School of Medicine. said in a statement. “I’m thrilled we got the job done. The full draft will revolutionize the way we think about human genome variation, disease and more evolution.”
DNA is made up of tiny molecules called nucleotides, each of which contains a phosphate group, a sugar molecule, and a nitrogenous base. The four types of nitrogenous bases (adenine, thymine, guanine, and cytosine) pair up to form the rungs on the DNA double helix that encodes our genetic identity. Two strands of these double helices make up a chromosome, and humans have a total of 23 pairs of chromosomes, one from each parent. DNA sequencing determines the order of the base pair building blocks in a stretch of DNA.
To complete the Human Genome Project, researchers relied on short-read technologies that scan several hundred base pairs at a time and separate them into snippets of DNA that are tiny compared to the much larger entire genome. This made the project akin to putting together a 10 million piece blue sky jigsaw puzzle, leaving many gaps. The task was also difficult because the two chromosomes in a chromosome pair came from a different person (one from each parent), making it more difficult to distinguish between DNA sequences from the same section of the genome that differed from person to person, and parts originating from different locations.
To circumvent these difficulties, the researchers in the new study turned to a strange type of human tissue called a complete hydatidiform mole, which forms when a sperm fertilizes an anucleate egg. The egg is non-viable and attaches to the uterus to grow as a “mole” with all of the father’s chromosomes but none of the mother’s.
From this mole, the scientists made a cell line (a group of cells that can be grown in the laboratory) that contained 23 pairs of chromosomes from just one individual. To sequence the mole’s DNA, the scientists used two new sequencing techniques that turned the sequencing project into a jigsaw puzzle with tens of thousands of pieces. The new long-read techniques use lasers to scan 20,000 to 1 million base pairs at a time, creating much larger puzzle pieces and therefore fewer gaps than before.
The long-read methods allowed the team to piece together some of the most difficult and repetitive sections of code. The result: They discovered 115 new genes that they think encode proteinsadding to a total genome of 19,969.
However, creating the first gapless sequence will not be the end of the researchers’ efforts. They estimate that around 0.3% of the genome could contain errors, and researchers will need better quality control methods to verify these difficult-to-sequence regions.
Additionally, the sperm cell that fertilized the sequenced mole contained only one X chromosome, requiring researchers to sequence a Y chromosome separately, resulting in an embryo developing as biologically male, as well as more ambitious sequencing of a genome of both parents.
The scientists believe that the more complete map of the human genome will enable future researchers to better understand how DNA differs between individuals and communities, and give them a better reference point for studying mutations in the genome that cause harmful diseases can cause.
The researchers have also partnered with the Human Pangenome Reference Consortium, a group that aims to sequence more than 300 human genomes from around the world. This initiative will not only give scientists better insight into which parts of the genome differ in individuals, but also help them better understand how different genetic diseases arise and how best to treat them.
“In the future, once someone has their genome sequenced, we will be able to identify all of the variants in their DNA and use that information to better guide their healthcare,” says Adam Phillippy, senior researcher at National Human Genome Research Institute said in the statement. “Truly completing the human genome sequence was like putting on new glasses. Now that we can see everything clearly, we’re one step closer to understanding what it all means.”
Originally published on Live Science.
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