Chromosome 11 rolls high number

By Nicole Davis, Communications, March 23rd, 2006

Of all the chromosomes that adorn the human genetic landscape, few have as full a past as chromosome 11. Now another chapter has been added to its crowded history with the completion and analysis of its DNA sequence, reported in the March 23 issue of Nature by an international scientific team. Among the findings are an unusually heavy burden of genes on the chromosome, which is already implicated in more than 150 human diseases, and a technique for predicting genes that may help researchers to more accurately inventory the contents of the human genome.

Chromosome 11 is among the last human chromosomes to be fully decoded, but its biography begins long before such efforts were even feasible. Two of its residents — the insulin and hemoglobin beta genes, and their respective proteins — have been particularly prominent characters. Insulin, a hormone that mediates the cellular uptake of glucose, was the first protein to have its amino acid sequence deciphered chemically. Hemoglobin beta, which encodes a subunit of the oxygen-ferrying protein hemoglobin, was among the first genes to be assigned, or "mapped" to a specific location in the human genome. Moreover, mutations in hemoglobin beta are the root cause of sickle cell anemia, the first human disease to be understood molecularly.

Time has done little to diminish the chromosome's importance. The scientists found that chromosome 11 contains more than 1,500 genes, placing it the fourth highest among all of the human chromosomes in gene content. Some of these genes were identified using DIGIT, a program that combines several existing gene-finding programs and does not rely on similarities in DNA sequence to predict the locations of protein-coding genes. About half of the genes detected in this manner show molecular evidence of gene expression, indicating that this gene-calling program may help to accurately annotate the human genome.

Many of the genes on chromosome 11 are grouped into related clusters known as gene families, the most notable of which is the olfactory receptor gene family. This family, whose corresponding proteins govern the sense of smell, is the largest known grouping of genes in vertebrate species. In humans, its members are sprinkled throughout the genome, with the exception of chromosomes 20 and Y. But chromosome 11, which constitutes just over 4% of the genome, contains more than 40% of the olfactory receptor genes, making it the largest chromosomal repository of such genes in the human genome.

In addition to being overly laden with genes, chromosome 11 is also plagued by human disease associations, with more than 150 at last count, but only half of these have been assigned a gene culprit so far. Clearly, there is much left to be unearthed in this chromosome. Having the complete DNA sequence and initial analysis in hand is a critical resource in this endeavor.

Paper(s) cited: