Why Sequence Homo Sapiens?

As a key sequencing center for the Human Genome project, JGI has decoded the sequence of human chromosomes 5, 16, and 19. The Human Genome Project was begun to determine the complete sequence of the 3 billion bases of the human genome, identify all the genes, and make them accessible for further biological study.

Human Chromosome 5

Chromosome 5 is one of the largest human chromosomes, yet it has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding and syntenic (on the same chromosome) conservation with non-mammalian vertebrates, suggesting they are functionally constrained. It also has many internal duplications. These duplications are very recent evolutionary events and play a likely mechanistic role, since deletions of these regions are the cause of debilitating disorders, including spinal muscular atrophy (SMA).

The US Department of Energy’s interest in chromosome 5 emerged from a series of pilot studies begun at the Lawrence Berkeley National Laboratory focusing on a cluster of interleukin genes located on the long arm of the chromosome (human 5q31). These studies of a million bases of chromosome 5 illustrated how finished human sequence could contribute to gene annotation and how multi-mammal sequence comparisons could lead to the sequence-based identification of noncoding elements that regulate genes. The finished sequence of chromosome 5, and its analysis alone and in comparison to orthologous regions in other vertebrate genomes now provides a chromosome-wide catalog of genes and evolutionarily conserved noncoding sequences. Many of these insights, as well as clues into disease-causing deletions arising from the segmented duplication landscape of chromosome 5, can only now be appreciated with the finished sequence of this chromosome in hand.

Genome Portal site: Homo sapiens chromosome 5

Human Chromosome 16

A focus of early studies at Los Alamos National Laboratory, chromosome 16 is highly enriched for segmental sequence duplications--regions that have been copied to other places within the chromosome, or copied to other chromosomes. Excluding the Y sex chromosome, chromosome 16 has the most segmental duplications in the human genome. At 88.7 Mb, it has 880 identified genes. It features genes implicated in the development of breast and prostate cancer, Crohn's disease, and adult polycystic kidney disease, which affects an estimated five million people worldwide. Half the affected people require dialysis or kidney transplant.

Genome Portal site: Homo sapiens chromosome 16

Human Chromosome 19

Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. Though one of the smallest human chromosomes, it has thus far been found to contain 1,461 protein-coding genes and 321 pseudogenes. They include genes that code for such diseases as insulin-dependent diabetes, myotonic dystrophy, migraines, and familial hypercholesterolemia (an inherited form of elevated blood cholesterol), which increases the risk of cardiovascular disease.

The DOE originally selected chromosome 19 as a sequencing target because of the agency's abiding mission of investigating the link between DNA damage from radiation exposure and human cancer. Embedded in the chromosome's sequence are critical regulatory networks of genes tasked with controlling such functions as repairing DNA damage caused by exposure to radiation and to other environmental pollutants. Studies of DNA-repair genes, initiated at the DOE national laboratories, are yielding insights into the development of certain cancers, many of which appear to be caused by defects in DNA-repair pathways. Also, new insights are being gleaned about other gene families implicated in detoxifying and excreting chemicals foreign to the body.

Genome Portal site: Homo sapiens chromosome 19