The DNA sequence of the human X chromosome

Abstract

The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.

Expression of X‐linked genes in deceased neonates and surviving cloned female piglets

“…The mammalian X chromosome contains more than 1,000 genes and many are house-keeping genes (Ross et al 2005). X chromosome inactivation (XCI) is a biological process utilized by mammals to ensure equal expression of X-linked genes between males and females (Lyon 1961).…”

Is the Y chromosome disappearing?—Both sides of the argument

“…The present-day human X and Y chromosomes retain only traces of their shared ancestry as identical autosomes. The euchromatic portion of the male-specific region of the Y chromosome (MSY) is roughly 1/6th the size of the X chromosome and has onlỹ 1/12th of the number of genes Ross et al 2005). In other words, there is little doubt that, in essence, the Y chromosome is a degraded X (Ohno's hypothesis).…”

“…Fundamentally, the argument is that the Y chromosome has been degenerating for millions of years and it is only a matter of time before it disappears completely. Jenny explained that the human X is a decent-sized chromosome bearing~1,000 proteincoding genes (Ross et al 2005), over-endowed in "brains-and-balls" genes involved in reproduction and intelligence (often both). The tiny Y is a genetic wasteland, full of "junk" and bearing only 45 genes that code for different proteins, most of which are active only in the testis.…”

“…Jenn argued that there can be no doubt that the mammalian (including the human) Y chromosome can be thought of, at least in part, as a "rotting X." There are~1,000 genes on the 180-Mb X chromosome (Ross et al 2005), but only 78 genes on the 23 Mb Y . The degeneration on the Y is a consequence of its lack of a meiotic recombination partner over most of its length.…”

Promoter demethylation mediates the expression of ZNF645, a novel cancer/testis gene

“…Among them 83 genes are located on X chromosome (3). It is reported that, about 10% of the genes on the X chromosome are CT antigen genes (4), and these CT-X genes are notably more testis-restrictively than those on other chromosomes (5). However, CT proteins expression shows heterogeneous in many cancers including lung carcinoma, therefore more CT antigens need to be identified to develop the polyvalent vaccines to avoid immune escape of tumors (1,6).…”