The human Y chromosome is one of the smallest chromosomes, representing 2-3% of a haploid genome. It is the only chromosome that has no homologue at any state or sex, in contrast to the X chromosome that has a homologue in the female sex. The majority of the Y chromosome (95%), termed nonrecombining Y (NRY), does not undergo recombination during male meiosis; however, two regions, pseudoautosomal regions (PARI and PAR2), located at the distal portions of the telomeres, recombine with homologous counterparts on the X chromosome. From a functional viewpoint, the Y performs specialized roles that are crucial for males, and therefore for the whole population, such as sex determination and male fertility. The haploid status of the Y and its exclusive paternal transmission make it a very useful tool in different domains as follows: 1) the estimation of historical patterns of population movements and splitting;

2) forensic applications, such as identification of male DNA in cases with male/female stain mixtures; and

3) genealogical studies and paternity testing, especially for deficiency cases, where the alleged father is deceased and his male relatives need to be tested.


One unique feature of Y chromosome markers is that they are inherited as a single block in linkage. Therefore Y-linked variations are largely a result of accumulation of de novo mutations over time.[1] This feature is very useful in high-resolution discrimination of individuals. Large-scale sequencing efforts and the development of rapid mutation detection techniques have accelerated the discovery of Y-chromosome variation. Today, more than 200 biallelic polymorphisms and around 30 multiallelic markers are available,[2-5] most of which are suitable for polymerase chain reaction (PCR)-based genotyping techniques. Biallelic markers mainly include single base pair variants [single nucleotide polymorphism (SNPs)] and also a reduced number of small insertions/deletions (indels), whereas multiallelic markers mainly refer to microsatellites and minisatellites. The main difference between the two sets of markers is their mutation rate: biallelic markers present lower mutation rates (about 2 x 10~8 per base per generation) than microsatellite markers (2-3 x 10~3 per base per generation). Biallelic variants and insertion/deletion polymorphisms almost certainly represent unique molecular events and define stable and deep-rooted branches, known as haplogroups, that can be traced back in time over thousands of years. These haplogroups present either a wide geographic distribution or, in some cases, more regionally clus-tered.[3,4] The multiallelic markers define the internal diversity of these haplogroups, and the combination of the allelic states of different microsatellite loci are known as haplotypes. Microsatellite haplotypes are very useful for microevolutionary studies and to distinguish subtle genetic differences between populations and/or individuals.1-5-1 The high mutation rate of these markers, which enables a good discrimination between individuals, makes them the most suitable markers in forensic studies.[6] However, this high mutation rate has a disadvantage: the appearance of recurrent mutations. Thus, it is sometimes difficult to distinguish if two individuals are ''identical by state'' (share the same allele but not the same ancestry) or ''identical by descent'' (share the same allele and the same ancestor). This has important repercussions in population genetic studies because, at the population level, the use of these markers alone may lead to an underestimation of genetic distances among populations, thereby distorting genuine population relationships.


Y-chromosome studies have shown that Y-linked variation is nonrandomly distributed among human populations, showing lineage profiles that can be strikingly different among different worldwide populations.1-2-4-1 These observations have obviously important consequences in ascertaining the origin of an individual during forensic investigations. From a human evolution viewpoint, Y-chromosome studies have given a major contribution to a better understanding of human origins and population dynamics. Y-chromosome phylogenies support the African origin of our species around 150,000 years ago. The most divergent branches of the trees are restricted to African populations, and non-African populations find their roots in branches of African origin.[2-4] These observations support the scenario in which modern humans can be traced back to a single African ancestral population that lived in Africa (i.e., the so-called ''Out of Africa'' model), from where it dispersed throughout the other continents replacing preexisting human species. Substantial continental and local population structure has been revealed, and hypotheses of early human migrations at different times formulated, such as the mode and tempo of the peopling of Asia and subsequent colonization of the Americas and the colonization of the Pacific.[3]


Sex Assignment

The most obvious use of the Y chromosome in forensics is the sex assignment. The most commonly used test, the Amelogenin Sex Test (AMELY), takes advantage of the homology between the two pseudoautosomal regions of the sex chromosomes and amplifies a segment of the XY-homologous amelogenin gene pair.[7] Although this method avoids the ambiguous nature of a negative result as a result of the failure of the PCR reaction rather than to the absence of Y material, the reliability of the test depends on the assumption that the tested individuals present normal karyotypes and intact sex chromosomes. Nevertheless, individuals presenting a discordance between their sex phenotype and their karyotype (i.e., sex-reversed 46, XX males or 46, XY females) are present at appreciable frequencies in the population and can constitute a source of error in sex assignment tests based only in the AMELY test. It is suggested, therefore, to perform other sex tests in parallel, such as amplification of the SRY gene, which will give complementary information to the AMELY test.[8]

Identification and Discrimination of Male-Specific DNA

The analysis of Y-chromosome variation has been extensively used for forensic applications other than sex assignment. They can provide highly valuable information to resolve male-female DNA mixtures in, for example, sexual assault cases. In these cases, samples may present high amount of victims' cells, such as vaginal/anal washings, and sometimes no male autosomal profiles are identified. It has been shown that Y chromosome microsatellite analysis becomes a useful alternative because the use of specific Y-primers can improve the chances of detecting small amounts of the perpetrator's DNA in a background of heterologous female DNA.[9] Another obvious application of the Y chromosome is in paternity testing, especially for deficiency cases where the alleged father is deceased. In this case, the absence of the biological father can be resolved by the analysis of any relative sharing the same male line. However, when comparing the Y-chromosome profile in a paternity test or between a suspect and a sample, inclusion remains an important caveat. Although Y-linked microsatellites can be confidently used for exclusion purposes, nonexclusion can be problematic because 1) all the male relatives of a suspect/alleged father share presumably the same Y haplotype and 2) the Y chromosome of a suspect/alleged father may be present at high frequencies in the population under study, considerably reducing the reliability of the test. In any case, the high level of polymorphism of microsatellite markers offers a significant degree of discrimination between individuals. For example, a study of a German population using a 9-locus microsatellite haplotype, demonstrated a discriminatory capacity between Y-chromosome haplotypes of 97%.[10] However, this may not be the case in other populations with different genetic backgrounds and different population histories, where, for example, male-specific migration processes, founder effects, or genetic drift may have led to over-representation of specific haplotypes in the population.

Retracing Ethnic and Geographic Origins

Another possible information of interest for forensic investigators is that of ethnic origin. Although the highest genetic variation is observed between individuals and not between populations, Y-chromosome polymorphisms may provide the best resolution to ascertain the approximate geographic origin of a suspect.[11] Some haplogroups tend to be restricted to European populations, while others are restricted to sub-Saharan African or East Asian populations.1-2-4-1 Geographic clustering of Y-chromosome hap-logroups or haplotypes can be even more restricted. A recent Y-chromosome survey of the British Isles has shown that haplotype frequencies can differ considerably even over relatively short geographic distances.[12] Lineages of recent origin, such as haplogroup R-SRY2627, may exhibit a very limited distribution. This lineage has been observed only among Europeans and is almost restricted to Basque and Catalan populations.1-13-1 In this case, it can be highly informative to predict the origin of the population and for exclusion purposes. However, more populations need to be tested for additional markers in order to create highly discriminative databases that will increase the power of reliability when inferring the geographic origin of a sample.


The usefulness of Y chromosome data has been successfully used in some famous and controversial cases, such as U.S. President Thomas Jefferson's paternity of the children of one of his slaves. In 1802, he was accused of having fathered a child, Thomas Woodson, by Sally Hemmings. Also, Sally's last son, Eston Hemmings Jefferson, is thought to be the son of the President, although other scholars give more credence to the hypothesis that they were the sons of Jefferson's sister that fathered Eston. By analyzing several Y-polymor-phisms in 14 members of the different male lines involved in the controversy (e.g., those of Thomas Woodson, Eston Hemmings, President Jefferson, and his sister's sons, the Carr's line), the authors found that President Jefferson and Eston Hemmings share the same haplotype.[14] In contrast, this haplotype was absent in Thomas Woodson and the Carr's lines, and its frequency in the general population is very low (0.1%). The authors concluded that President Jefferson fathered his slave's last child, whereas he was not the father of Sally's first child. The possibility that any other President's male-line relative could have fathered Sally's last child cannot be excluded, highlighting therefore the difficulty of being conclusive in these studies, but no historical records support this hypothesis. This study nevertheless illustrates the usefulness of Y chromosome data to disentangle complex hypothesis of alleged paternities and genealogical relationships.

In the absence of male-line comparison, a suitable partner of the Y chromosome is the mitochondrial DNA (mtDNA). This molecule can be highly informative in genealogical studies because, as the Y, it does not recombine and is transmitted through the maternal line without any modification other than naturally occurring mutations. Moreover, analyses of mtDNA in forensics can be even more powerful than Y-chromosome analyses because mtDNA is present at a higher copy number in cells and is more likely to survive prolonged periods than nuclear DNA. The most notorious example of its use in genealogical and forensic studies is the identification of the remains of Tsar Nicholas II and his family. By analyzing the amelogenin gene and autosomal STR variation in nine skeletons found in a grave in Ekaterinburg (Russia), the authors could confirm the presence of a family group, composed of two parents and three daughters and four additional unrelated bodies. To ascertain if the five related individuals corresponded to the Romanov family, mtDNA was analyzed in all bodies and in a living maternal relative of the Tsarina, Prince Philip the Duke of Edinburgh. Indeed, the mtDNA sequence of the putative Tsarina and her three daughters matched exactly that of the Duke of Edinburgh, supporting the hypothesis that their remains correspond to the Romanov family.[15] As to the putative body of the Tsar, his mtDNA sequence presented a very rare sequence heteroplasmy (presence of two alleles at a particular nucleotide position). By analyzing the body of the Tsar's brother and two living maternal relatives, the presence of this rare heteroplasmy was confirmed in the Tsar lineage, providing a powerful evidence supporting the identification of Tsar Nicholas II and his family.[16]


In many societies, surnames are inherited patrilinearly, in the same manner as Y chromosomes. This parallel transmission can be used to tentatively associate surnames, or closely related human groups, and specific Y-chromosome haplotypes. For example, by using Y-chromosome microsatellites, it has been shown that half of the individuals with the English surname ''Sykes'' belong to a specific Y-chromosome haplotype, which is not present in non-Sykes samples and, in general, in other UK samples.[17] The presence of other haplotypes among the remaining Sykes samples has been attributed to historical accumulation of nonpaternity. However, further studies have shown that this lineage is present in Baltic States, although it is virtually absent in the British Isles, Scandinavia, and Iceland. This study, although preliminary, may have important forensic and genealogical applications. Increasing the number of microsatellites analyzed in individuals may eventually reach such a level of resolution that surname-specific haplotypes could be observed, with obvious important applications.

The use of Y-chromosome variation has also given insights into genealogies dealing with Jewish identity. According to Jewish tradition, males of the Levi tribe, of which Moses was a member, were assigned special religious responsibilities, and male descendants of Aaron, his brother, were selected to serve as Priests (Cohanim). Whereas in most cases Jewish identity is acquired by maternal descent, membership in the Cohen and Levi castes is determined by paternal descent. By studying a large group of Jewish individuals, which include Israelites, Cohanim, and Levites, it was shown that whereas Israelites and Levites exhibit a heterogeneous set of Y chromosomes, the Cohanim are mainly characterized by a unique haplotype that is present at high frequencies in both Ashkenazic and Sephardic Cohanim.[18] This haplotype, known as the Cohen Modal haplotype, is thought to be a potential signature of Judaic origin.

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