For females, the major consequence of the loss of genes from the Y chromosome is XCI, which equalizes the dosage of X-linked gene products between the sexes. The characteristic pattern of X-linked inheritance (affected males and no male-to-male transmission) was recognized by the eighteenth century for some cases of haemophilia, and gave impetus in the 1980s to the earliest successes in positional cloning-of the genes for chronic granulomatous disease 3 and Duchenne muscular dystrophy 4. The hemizygosity of males for almost all X chromosome genes exposes recessive phenotypes, thus accounting for the large number of diseases that have been associated with the X chromosome 2. In the process, the original, functional elements have been conserved on the X chromosome, but the Y chromosome has lost almost all traces of the ancestral autosome, including the genes that were once shared with the X chromosome. The sex chromosomes have evolved from a pair of autosomes within the last 300 million years (Myr) 1. The unique properties of the X chromosome are a consequence of the evolution of sex chromosomes in mammals. Genes outside these regions of the X chromosome are strictly X-linked, and the vast majority are present in a single copy in the male genome.

Genes inside these regions are shared between the sex chromosomes, and their behaviour is therefore described as ‘pseudoautosomal’. The male X chromosome fails to recombine along virtually its entire length during meiosis: instead, recombination is restricted to short regions at the tips of the X chromosome arms that recombine with equivalent segments on the Y chromosome. In the female germ line, the inactive chromosome is reactivated and undergoes meiotic recombination with the second X chromosome. Gene expression on one of the female X chromosomes is silenced early in development by the process of X-chromosome inactivation (XCI), and this chromosome remains inactive in somatic tissues thereafter. Females inherit an X chromosome from each parent, but males inherit a single, maternal X chromosome.

The X chromosome has many features that are unique in the human genome. Nature volume 434, pages 325–337 ( 2005) Cite this article The DNA sequence of the human X chromosome

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