The sex chromosomes or gonosomes, chromosome X (ChrX) and chromosome Y (ChrY) are unique and differ in several aspects from the other chromosomes, which are referred to as autosomes (AS). Both ChrX and ChrY are unique with regard to the major content of their genes and sequences. In the cells of normal human males not affected by chromosomal aberrations, sex chromosomes do not occur in pairs. Males carry one X and one Y chromosome. Hence, most ChrX and ChrY regions are hemizygous in males. However, blocks of sequence homology between X and Y chromosomes suggest a common origin. During male gametogenesis, recombination between X and Y chromosomes occurs in small sub-telomeric regions of the X and Y chromosomes called the pseudoautosomal regions. These segments are homologous. Genes and markers in the pseudoautosomal region are not sex-linked. Recombination frequencies in this region are 20 times higher than on autosomes.
There are two pseudoautosomal regions - the Xp and Xq telomeres - referred to as PARI and PAR2. Furthermore, ChrX and ChrY show several regions of homology in addition to the common pseudoautosomal regions. In females ChrX is present as a homologous pair and resembles autosomes in this respect. However, even individuals with more than one ChrX possess only one active ChrX per cell. According to the Lyon Hypothesis (Lyon, 1961) additional copies are inactivated, which explains why ChrX monosomies, trisomies and polyso-mies are compatible with life. Functional ChrX inactivation is connected with the formation of a morphologically visible heteropycnic chromatin that is also
Molecular Forensics. Edited by Ralph Rapley and David Whitehouse Copyright 2007 by John Wiley & Sons, Ltd.
called sex chromatin. Inactivated ChrXs are visible in many but not in all female cells as Barr bodies (Barr and Bertram, 1949; Barr and Carr, 1962) or 'drumsticks' (Davidson and Smith, 1954). The latter are structures in the nuclei of polymorphonuclear leucocytes. Chromosome X monosomies, trisomies and other polysomies occur in different forms of appearance and may be connected with serious handicaps and infertility. Triple X (trisomy X) females frequently have a nearly normal development.
For parental generations, such gonosomal irregularities can usually be excluded since they would be associated with infertility. Unexpected and undetected aberrant gonosomal karyotypes in an offspring may however occur and affect the accuracy of kinship testing using ChrX markers. Gonosomal genotype X0, for example, which is associated with Ullrich-Turner syndrome, occurs at an incidence of 1 in 2500 female live-births (Clement-Jones et al., 2000). Both complete and partial monosomies have been observed. Another unexpected situation is when an XY-karyotype occurs in phenotypic females (Wieacker et al., 1998). This happens in context with androgen insensitivity or XY gonadal dysgenesis. Such disturbances cause genetic males to present with an unobtrusive female phenotype, although the present of ChrY can easily be detected by an amelogenin test. The posterior probability of a full or partial ChrX monosomy, or an XY female, increases when several closely linked ChrX markers appear to be homozygous. In the way that they perturb kinship testing, karyotypes XO and female XY are formally equivalent to autosomal uniparental disomy (Bein et al., 1998; Wegener et al., 2006). As with AS markers, paternity exclusion that relies upon ChrX marker homozygosity thus requires independent experimental verification.
A gonosomal aberrant male karyotype with XXY (or XXXY, XXXXY, etc.) develops Klinefelter syndrome and shows a prevalence of about 1:500 males (Bojesen et al., 2003). Klinefelter syndrome may be detected in kinship testing when ChrX markers show heterozygosity. Ethical aspects are discussed below.
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