The X Chromosome, Dosage Compensation, and X Inactivation

Abstract

The X chromosome is of medium size, making up 5.3% of the haploid karyotype. It is submetacentric, with a centromere index of 0.38 and a distinctive banding pattern (Fig. 17.1). In females, one X chromosome is condensed throughout interphase and is frequently visible in epithelial cells as a Barr body, or X heterochromatin. It is visible as a drumstick-shaped extrusion in 1–5% of polymorphonuclear white blood cells (Fig. 18.1a). The Barr body consists of a loop-shaped X chromosome in which the two telomeres lie close together at the nuclear membrane (Walker et al., 1991). Barr bodies can be scored in cells scraped from the mouth (buccal smears; Fig. 18.1b,c) or vagina, in cultured fibroblasts (Fig. 18.ld,e,f), or in follicle cells attached to a plucked hair. In normal females, a Barr body is visible in only 20–50% of buccal cells, in 30–80% of fibroblasts, and in over 90% of cells in amniotic membranes. In every individual (male or female) with two or more X chromosomes, the maximum number of Barr bodies is one less than the number of X chromosomes. That is, one X remains euchromatic and the additional ones are heterochromatic. The heterochromatic X chromosomes replicate later in S than the euchromatic X, as demonstrated over 35 years ago by autoradiography (Chapter 3). The allocyclic, or out-of-step, behavior of the inactive X chromosome expresses itself in other ways, some described in Chapter 3. In both prophase and metaphase, the inactive X is often more condensed, and thus shorter, than the active X.