Full assembly of human chromosome 8 reveals new genes, disease risks

The full set of human chromosome 8 is reported this week in Nature. While externally this chromosome looks typical, being neither short nor long or distinct, its DNA content and arrangement is of interest in primate and human evolution, in several immune and developmental disorders, and in structure and function of a consecutive chromosome.

This linear set is first for a human autosome – a chromosome not involved in sex decision making. The total sequence 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.

La Nature paper is titled “The structure, function, and evolution of a complete chromosome 8.”

One of several interesting features of chromosome 8 is a rapidly evolving region where the mutation rate appears to be highly accelerated in humans and human-like species, in contrast to the rest of the human genome.

While chromosome 8 offers some insights into evolution and human biology, the researchers point out that the complete set of all human chromosomes would be necessary to get a fuller picture.

An international team of scientists has collaborated on the assembly and analysis of chromosome 8. The lead author of the paper is Glennis Logsdon, a postdoctoral fellow in genomic science at the Washington School of Medicine in Seattle.

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

In addition to the assembly of human chromosome 8, the project researchers also created high-quality project assemblies from the link site at the waist of the chromosome, the centromere, in the chimpanzee, orangutan, and macaque. The data allowed scientists to begin mapping the evolutionary history of chromosome 8 centromere.

Almost as if inspecting the depths of a geological site, the researchers observed, on a molecular scale, a layered mirror symmetry as this centromeric structure evolved from large ape ancestors. Older parts were pushed to the periphery, similar to making room for new material in the middle of a factory chain saw.

Other research institutions involved in the chromosome 8 assembly project include the Therapeutic Development Branch of the National Cancer Institute, the Genome Information Section of the National Human Genome Research Institute, University of Bari, Italy; the Center for Algorithmic Biology at St. Petersburg State University, Russia; University of California, San Diego, University of Washington at St. Louis, University of Pittsburgh, and the University of California, Santa Cruz. Data were also generated using Oxford Nanoporous Technologies and Pacific Biosciences long read sequencing to resolve gaps in the telomere-to-telomere, or end-to-end, set of the chromosome.

Earlier research by some scientists showed regions of chromosome 8 as important and in the normal formation of the brain, as well as some evolutionary variations, such as small head size or skull and facial differences. Mutations on this chromosome have also been implicated in some heart defects, some forms of cancer, premature aging syndromes, immune responses, and immune disorders such as psoriasis and Crohn’s disease.

However, the full sequence of this and most other human chromosomes could not be tested until recently because the technology and methods for wading through large areas of multiplication and identical iterations were not made available. Composing the puzzle accurately from short readings of DNA, for example, would be extremely difficult.

The assembly of chromosome 8 has benefited from advances in long-read technologies, as well as from the availability of DNA material from hydatidiform skin patches. These are rare abnormal growths in the placenta.

The full sequence of chromosome 8 now provides information that could improve, for example, the understanding of what predisposes specific parts of chromosome DNA to suspected microdeletions in some forms of developmental delay, brain and heart malformations, and autoimmune problems.

The researchers were also able to obtain more information about part of chromosome 8, which contains some of the largest copy number variability among humans. The repeat unit can range from 53 to 326 specimens.

With the assembly of chromosome 8 completed, researchers look forward to the global scientific community complementing other human chromosome assemblies, and to new challenges in applying what has been learned to further studies of human genome succession.


University of Washington Medical School / UW Medicine

Reference journal reference:

Logsdon, GA, et al. (2021) The structure, function and evolution of a complete human chromosome 8. Nature. doi.org/10.1038/s41586-021-03420-7.