The human genome is said by some to be the “book of life,” and the X-chromosome a large part of the the plot. A team of genome researchers have described the nature of this mysterious “chapter” in the DNA story.
Dr. Steven Scherer, associate professor in the Baylor College of Medicine department of molecular and human genetics and director of mapping in the BCM Human Genome Sequencing Centre, says large numbers of medically related genes happen to fall on the X-chromosome, and for a chromosome that is bereft of genes compared to other chromosomes, it is well characterized with regard to disease genes.
Scherer and his colleagues in the BCM Sequencing Centre were the number two contributors to the sequencing effort directed at the X chromosome. It was led by the Wellcome Trust Sanger Institute in Britain.
Dr.Scherer says he has expectations that this chromosome is the all-star of the series and will make interesting reading for the general scientific population and the lay public; he says if a person was going to read a chromosome paper, this probably ought to be the one to read.
The role of the X and Y chromosomes has been evolutionary, and way before the split between birds and mammals, the X and Y chromosomes were just like any other pair of chromosomes – each was fairly similar and carried similar information.
While tracing the evolution of the X chromosome, the research showed that slowly, but surely, the Y chromosome “dropped off the face of the earth,” said Scherer, and became almost like the appendix of the human genome.
Each woman has two X chromosomes, each man has an X chromosome and a Y chromosome. In women, one of the X chromosomes is largely inactivated. Because there are actually few genes on the Y chromosome, inactivating most of one of the X chromosomes in women means that men and women each have one active X chromosome, where most of the coding information exists.
Among the most important functions of the Y chromosome is the determination of sex. In fact, the paper indicates that 10 percent of genes that cause production of proteins on the X produce genes most often expressed in the testis but that have increased activity in tumours of the testicles, melanoma and other cancers. The fact that men have just one copy of the X chromosome makes the mutated genes on that one piece of DNA much easier to find, said Scherer. The BCM sequencing centre and others around the world have previously concentrated on sequencing the genomes of organisms studied in the laboratory, in future researchers will look more closely at the human genome and its variations.
The National Human Genome Research Institute is developing a comprehensive program defining variations of all the genes in the genome, which means looking at both normal subjects and patients with diseases.
Scherer says such research is the starting point and now the research community is taking the next step. BCM is in a unique position being in the largest clinical concentration in the world with more samples and examples of human disease available than most other centres. They intend to take that information leverage and run with it and hope their community will be the first to benefit from these major advances in medical research.
Dr. Scherer believes the story of each chromosome will eventually be published with all the important features explained.