Complete sequence of chromosome 8 reveals new genes and disease risks

Earth about the structure, function and evolution of the complete composition of the chromosome. Credit: Kendra Hoekzema “width =” 800 “height =” 529 “/>

The complete composition of human chromosome 8 will be revealed this week in Earth. Although this chromosome on the outside looks typical, not short or long or characteristic, its DNA content and arrangement are important in primate and human evolution, in various immune and developmental disorders, and in the structure and function of the chromosome sequence.

This linear composition is the first for a human autosome – a chromosome that is not involved in sex determination. The entire range of chromosome 8 is 146,259,671 bases. The completed assembly fills the gap of more than 3 million bases missing in the current reference genome.

The Earth paper is entitled “The structure, function and evolution of a complete chromosome 8.”

One of several intriguing features of chromosome 8 is a rapidly evolving region, where the mutation rate appears to be very accelerated in humans and similar species, unlike the rest of the human genome.

While chromosome 8 provides insights into evolution and human biology, the researchers point out that the complete composition of all human chromosomes would be necessary to obtain a more complete picture.

An international team of scientists has collaborated on the compilation and analysis of chromosome 8. The lead author of the paper is Glennis Logsdon, a postdoctoral genome scientist at the University of Washington School of Medicine in Seattle.

The senior author is Evan Eichler, professor of genomics at the UW School of Medicine and a researcher at the Howard Hughes Medical Institute. His group is known for developing better methods for sequencing DNA and for analyzing mutation trends that may be important in research on primate evolution and neurological disorders.

In addition to the human chromosome 8 composition, the researchers of the project also created a high-quality traction composition of the linker at the center of the chromosome, the centromere, in the chimpanzee, orangutan, and macaque. The data enabled the scientists to begin mapping the evolutionary history of chromosome 8 centromere.

Almost like examining the depths of a geological terrain, the researchers observed on a molecular scale a layered, reflective symmetry in how this centromere structure of ancestors of great apes evolved. More antique parts were pushed to the periphery, similar to the place for new materials in the middle of a factory production line.

Other research institutes involved in the composition project for chromosome 8 include the Branch for Developmental Therapeutics of the National Cancer Institute, the Division of Genome Informatics of the National Human Genome Research Institute, University of Bari, Italy; the Center for Algorithmic Biology at the State University of St. Petersburg, Russia; University of California, San Diego, Washington University in St. Louis, University of Pittsburgh, and the University of California, Santa Cruz. Data were also generated with Oxford Nanopore Technologies and Pacific Biosciences long reading sequence to resolve gaps in the telomere-to-telomere, or end-to-end, chromosome composition.

Earlier research by a number of scientists pointed to regions of chromosome 8 that are important for the normal formation of the brain, as well as for some developmental variations, such as small head size or skull and facial differences. Mutations on this chromosome have also been implicated in some heart disorders, certain types of cancer, premature aging syndromes, immune responses and immune disorders such as psoriasis and Crohn’s disease.

However, the complete sequence of these and most other human chromosomes could only be attempted recently because the technology and methods of navigating through large parts of duplication and identical iterations were not available. To compile the puzzle accurately from short reading of DNA, for example, would have been extremely difficult.

The performance of the chromosome 8 composition has benefited from advances in long-reading technologies, as well as the availability of DNA material from hidatiforme moles. This is rare, abnormal growth in the placenta.

The complete sequence of chromosome 8 now provides information that could be improved, for example, understanding what specific parts of the chromosome’s DNA are susceptible to micro-eradications suspected in certain forms of developmental delays, brain and heart malformations, and autoimmune problems.

The researchers were also able to obtain more information about a portion of chromosome 8 that contains the largest variation between copy numbers among humans. The repeat unit can range from 53 to 326 copies.

With the compilation of chromosome 8, researchers look forward to the world scientific community that will complete other human chromosome assemblies, and to new challenges in applying the learning to further studies of human genome sequence.