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News from the human genome

The 1 April edition of Science announced the publication of the human genome with the previously-missing 8% now added to it. Comments from the Genopole Director of Research.
Read the special edition of Science « Completing the human genome » >
Human Genome - Genoscope Human Genome - Genoscope

The first—mostly complete—sequence of the human genome, of which chromosome 14 was decoded in France by Genoscope, was published eleven years ago, and the adventure continues today. Indeed, in an article dated 31 March 2022 and earning the cover of the 1 April edition of Science, the international Telomere-to-Telomere Consortium reported sequencing the 8% of the human genome that had remained unaddressed. Genopole Research & Platforms Director Christophe Lanneau discusses this important advancement.

Under the codename GRCh38, the most recent human genome reference sequence represented a consensus of several different genomes that had progressively enriched the very first sequence established in 2001. Despite that headway, 8% of the human genome had remained inaccessible because it was composed of highly-repetitive sequences that eluded discrimination and ordering by sequencing techniques*.

Today however, using novel sequencing technologies able to read very long sequences, the Telomere-to-Telomere consortium has filled in those holes. That consortium was created in 2019 with the objective of gaplessly reading each chromosome from one end (the “telomere”) to the other.

Genopole Research & Platforms Director CitationChristophe Lanneau, analyzes this major scientific breakthrough:
« This new human genome reference assembly, called CHM13, provides a very precise map of the highly-repetitive DNA sequences. It determined more than 225 million additional base pairs in a genome counting 3.1 billion. These highly-repetitive regions had remained inaccessible and received insufficient attention for many years. However, we’ve now come to realize their importance in cellular function and some of their roles in disease. This work is a major step forward for science.

These repetitive sequences are found mainly in two key regions of the chromosome: the centromere, a central region that plays a role in cell division and the correct transmission of the chromosome to the daughter cell, and the telomeres, the ends of the chromosome, that shorten as cells age and thus regulate their lifespans.

Being able to explore these sequences will yield new discoveries as to the genetic diversity they contain. These previously hidden sequences are also involved in epigenetic modifications. Epigenetics describes reversible and potentially inheritable mechanisms able to modify gene expression without modifying the underlying code. Epigenetics adapts gene expression to the environment or cell function. An increasing amount of evidence supports its role in organism function and adaptation.

Thus, with the rapidity of Illumina’s next-generation sequencing technology, researchers will be able to generate genomes in a matter of hours while benefiting in parallel from the quality and exhaustivity of this new reference sequence to better understand and interpret DNA sequences. »

In an interview with the newspaper Le Figaro, Citationthe director of the National Center of Human Genomics Research Jean-François Deleuze, underlines the importance of this work for «understanding key biological mechanisms.» He adds:«With current sequencing methods, we understand only about 50% of genetic diseases. Now, we may finally be able to better explain certain orphan diseases.»

In conclusion

Having a nearly-totally complete sequence of the human genome will contribute immeasurably to a better understanding not only of human evolution and cellular multiplication & differentiation but also of a range of diseases including cancers, cardiovascular diseases and many more.
Progress remains necessary in the determination of individual genetic diversity in human populations and the exploration of the y chromosome (resulting in male sex), which, for technical reasons, remains out of the reach of the technology deployed in the study.

  • * Genome sequencing technologies

    Genome sequencing describes the determination of the specific order of the “bases” (adenine (A), cytosine (C), guanine (G), and thymine (T)) that constitute the DNA sequence. Next-generation sequencing (NGS), developed notably by Illumina, involves cutting the genome into small fragments of about 100 base pairs then reading them individually. Because the cuts do not occur in the same place across different cells, the identification of identical sequence ends enables the reassembly and reconstitution of the DNA sequence via computerized analysis.

    More recently, the Oxford Nanopore technology has made it possible to read sequences with several tens of thousands of base pairs and even more. This technology involves forcing the passage of a DNA fragment through a nanometer-wide pore carrying an electrical current, which is modified in a specific manner by the passage of each base (A, C, G or T). Those current modifications progressively reveal the DNA sequence.

    Pacific Biosciences’ technology is also able to read sequences of at least 20,000 base pairs with 99.9% precision.


Special edition of Science « Completing the human genome »

Article posted on 4 April 2022


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