How is a gene like a drug? The more there is of it, the bigger the effect. You have to be careful how you spoon it out. Of course, gene “doses” don’t come in teaspoons, they come in chromosomal copy numbers.
You typically have two copies of each gene – one on the chromosome dad gave you, and one on the chromosome you got from mom – although, it must be said, the “flavors” of these copies many not be identical (e.g., specifying blue versus brown eye color).
And sometimes – in fact, often – one copy of a gene is “turned off” altogether, its activation more or less blocked by biochemical stop-signs. That’s about the same as having only one copy, until and unless the light turns green at some point. A particularly pronounced case of single-dose-itis (my word) occurs on the sex chromosomes, designated either X (for female) or Y (for male) because if you view them under a microscope, that’s sort of what they look like. Unlike the other 22 pairs of paternally and maternally derived chromosomes contained in each human cell, X and Y chromosomes actually look noticeably different from one another even at the gross-inspection stage. “Viewed” closer up with the tools of molecular biology, the two versions of the sex chromosome turn out to have large numbers of lengthy stretches that really are different and indeed may be entirely absent on the Y chromosome. Those differences make every cell in a woman’s body different from every cell in a man’s, as UC-Berkeley biologist Art Arnold, PhD, once pointed out at a particularly lively Stanford symposium on gender differences last year.
Still, X and Y chromosomes share plenty of common regions. So a deviation from the usual double chromosome count, even when the extra or missing chromosome is an X or a Y, can make a big difference in the dosages for plenty of genes. One genetic defect called Klinefelter syndrome, characterized by the presence of a Y and two X chromosomes in each cell, leads to an excessive dose of many genes (three copies instead of two, to be specific). Another genetic defect, Turner syndrome, results in each cell containing only a solitary X chromosome – and only a single copy of numerous genes. Both Turner and Klinefelter syndromes are marked by characteristic cognitive deficits.
Allan Reiss, MD, PhD, director of Stanford’s Center for Interdisciplinary Brain Sciences Research, and his colleagues compared the brains of people with Klinefelter and Turner syndromes with those of individuals with normal sex-chromosome counts. They showed in this imaging study in the Journal of Neuroscience, that anatomical aberrations in particular brain regions among people with extra or absent copies of the sex chromosome closely track the neurological deviations associated with these syndromes – and, importantly, that these aberrations may be caused by the gene-dosage differences resulting from variant sex-chromosome counts.
Previously: Tomayto, tomahto: Separate genes exert control over differential male and female behaviors, Humor as a mate-selection strategy for women? and Brain imaging, and the image-management cells that make it possible
Photo by Naberacka