The Y chromosome

19 Apr

The Y chromosome
In humans the Y chromosome is approximately 60 Mb long (million base pairs) long and contains just 78 genes [39]. The SRY gene (sex-determining region Y) located on the Y chromosome encodes a protein that triggers the development of the testes and through an extended hormonal pathway causes a developing foetus to become male [40]. With the exception of two regions, PAR 1 and 2 (PAR = pseudoautosomal region), located at the tips of the chromosome, no recombination occurs during meiosis. The remaining 95% of the Y chromosome is non-recombining, male specific, and is passed from father to son unchanged, except when mutations occur. The lack of recombination may be the reason why there are relatively few genes on the Y chromosome. If there is no chromosome crossing over, mutations within genes have little chance to be repaired or rectified and hence will be passed onto the next generation.

Y chromosome polymorphisms
The Y chromosome contains a large number of polymorphisms including variable number [41] and short tandem repeats (VNTRs and STRs), insertions, deletions and single nucleotide polymorphisms (SNPs). The first STR locus to be identified on the Y chromosome was DYS19 [42]. Since then hundreds of Y chromosome STR have been described. The development of Y STR typing has mirrored the development of the autosomal STRs, and multiplexes have been developed with increasing numbers of robust and highly discriminating Y STR multiplexes [43-46]. The growth in interest in Y STR loci has led to numerous


population studies to establish allele frequency databases. The ‘Y Chromosome Haplo- type Reference Database’ was established to collate STR haplotypes ( To ensure comparability between datasets, minimal and extended haplotypes were defined. Two commercial kits, the PowerPlex® Y (Promega Corporation) and the AmpFISTR® Yfiler® (Applied Biosystems) incorporate all of the extended haplotype loci (Table 13.2).

Forensic applications of Y chromosome polymorphisms

That the Y chromosome is only found in males makes it a valuable tool, in particular for the analysis of male and female mixtures after sexual assaults when differential DNA extraction is not possible; Y STR analysis has been successful with female:male ratios of up to 2000:1 [47]. The presence of male DNA has also been detected when vaginal swabs are analysed, even when no spermatozoa have been detected – either through the assailant being azoospermic (1-2% of rape cases) or through the deterioration of the spermatozoa [44,48]. The Y STRs can also be used to detect the presence of two male profiles – the interpretation of the mixtures depends on the presence of major and minor contributors [47].

In addition to using Ychromosome testing for the identification of evidential samples, it has also been used for paternity testing and is particularly valuable in deficient cases, where the alleged father is not available for testing. In these cases, any male relative who is paternally related to the alleged father can be used as a reference. An extreme example of where this has been used is the paternity analysis that linked the third US president, Thomas Jefferson to the child of one of his slaves, Sally Hemings [49]. Cases involving human identification have also used the Y chromosome as a tool to link remains to paternal family members, and as with deficient paternity cases the use of the Y chromosome is particularly advantageous when there are no parents or children to use as reference material; it also simplifies the sorting of the material following mass disasters [50]. The mutation rate in Y STR loci is similar to autosomal STRs, at approximately 2.8 × 10−3 [51, 52]. The Y chromosome will accumulate mutations as it is passed through the patrilineal line and direct comparison between males on the same lineage may result in a false exclusion if mutations are not considered. The non-random distribution of the Y chromosome among global populations, due largely to the widespread practice of patrilocality [53, 54] (where the female moves to the male’s birth place/residence after marriage), makes it a useful tool for inferring the geographical origins of biological material recovered from a crime scene and human remains [55]. In some cultures, where the male name is passed onto male children, there is also the potential of attributing surnames to Y profiles [56, 57].

Interpretation and evaluation of Y STR profiles
When the Y chromosome profiles from a reference and an unknown sample match, the significance of the match has to be assessed. The first step is to assess the frequencies of the Y STR haplotypes in the population of interest. The simplest method is to report the frequency of the Y STR haplotype in the population, known as the counting method. The figure quoted is entirely dependent upon the size of the database and is normally based on frequency databases that are constructed for the major ethnic groups represented within individual countries, although comparisons can also be made to the combined data in the yhrd databases with over 40000 haplotypes (representing at least the minimal haplotype). So, for example, a match can be reported as ‘the haplotype has been seen twice in 400 UK Caucasian individuals’. Difficulties arise in the interpretation of the Y chromosome. This is primarily caused by the patrilineal inheritance and clustering of male family members in relatively small geographic areas. This geographical clustering of male relatives coupled with the limited size of the haplotype frequency databases (many haplotypes are seen only once) makes the estimation of profile frequencies hazardous. An alternative method for assessing the significance of a match is to use a likelihood ratio and to incorporate population subdivisions with the increased potential for common co-ancestry [38]. Re- gardless of the method used to calculate the matching frequency, when presenting the results of Y chromosome analysis, as with mtDNA, there is a need clearly to state how the use of Y STR typing varies from that of autosomal markers and that there will be other males in the population with the same Y STR haplotype.

Further reading
Jobling, M., Hurles, M., and Tyler-Smith, C. (2004) Human Evolutionary Genetics: Origins, Peoples and Disease. Garland Science. Cavalli-Sforza, L.L., Menozzi, P., and Piazza, A. (1996) The History and Geography of Human Genes. Princeton University Press.

WWW resources
The Y Chromosome Haplotype Reference Database:
EMPOP – Mitochondrial DNA Control Region Database:

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