Saturday, June 24, 2006

Female genetic study

This is one of the most intriguing bits of information yet, from current studies of the human genome.

In female mammals, most genes on one X chromosome are silenced as a result of X-chromosome inactivation. However, some genes escape X-inactivation and are expressed from both the active and inactive X chromosome. Such genes are potential contributors to sexually dimorphic traits, to phenotypic variability among females heterozygous for X-linked conditions, and to clinical abnormalities in patients with abnormal X chromosomes. Here, we present a comprehensive X-inactivation profile of the human X chromosome, representing an estimated 95% of assayable genes in fibroblast-based test systems. In total, about 15% of X-linked genes escape inactivation to some degree, and the proportion of genes escaping inactivation differs dramatically between different regions of the X chromosome, reflecting the evolutionary history of the sex chromosomes. An additional 10% of X-linked genes show variable patterns of inactivation and are expressed to different extents from some inactive X chromosomes. This suggests a remarkable and previously unsuspected degree of expression heterogeneity among females.

This does have some really fascinating implications.

Here's a fun article that discusses the function of X inactivation in producing tricolor female cats.

One thing that makes the new chromosome study so intriguing...

"Early in embryogenesis in mammals, all but one X chromosome are functionally inactivated through a process called X chromosome inactivation. Because this inactivation occurs randomly, all normal females have roughly equal populations of two genetically different cell types and are therefore a type of mosaic. In roughly half of their cells, the paternal X chromosome has been inactivated, and in the other half the maternal X chromosome is inactive. This has a number of important biological and medical implications, particularly with regard to X-linked genetic diseases."

This article reflects conventional thinking about X inactivation. But the latest study indicates that it isn't nearly this simple -- in human females, the X inactivation is incomplete and shows quite a range of variability. Apparently even in the cells within an individual.

Blascho's Lines revealed under UV

Part of the import is that alleles which are heterozygous may be pathogenic -- something like the possible adverse results from conditions like trisomy. It is pretty confusing to me when I try to think of exactly what happens when multiple different alleles in the same cell are actively transcribing to produce the same protein, but if they're very different, it seems obvious that the results will not be good.

At the very least this might explain why I have such a hard time understanding the female of the species.

Anyway, where this is taking me --

Imagine an organism with such fundamental characteristic capriciousness built in, from the level of chromosomes on up.

Little wonder that women should reserve the right to change their minds. Their very constituent cells are explicitly built, from the ground up, upon that very theme.

In more recent studies of genetic variation, it has been observed that males of the species exhibit a wider range of genetic variability than females, and this accounts for major gender differences in the relative level of intelligence.


a little music said...

You just think that men don't reserve the same right. It is a cliche, one that is well overdone. The same kind of cliche that claims that men won't stop and ask for directions. Stupid cliches. I don't believe in them. Do you, really?

Jim Cobabe said...

No, I guess I don't understand what you're unhappy about. I was trying to advance my own thinking about human genetics. These are some very fascinating glimpses into the makeup of humans, at the very cellular level. The references to capriciousness are not meant to insult anyone, just an attempt at humor about the way the genetics of human females works. It is so amazing that human females cells work the way they do. I marvel at the complexity an ingenious design that makes females so unique. None of the scientists prior to the last few years ever suspected anything so complicated at the cytogenetic level. Now that our understanding of the way the cells work has reached this level, it offers a more complete picture of the marvellous intricate machines that run our bodies, and our lives.

I find it fascinating that the process of x-inactivation functions imperfectly. If it didn't work as well as it does, the XX constituents would transcribe two copies of the proteins that make up the cells of your body. Some of them would clash and result in genetic disorders, resulting in something like trisomy, which causes serious disorders. But problems like this are very rare, almost to the point of never happening. If not so, you and I could never have been born.