Differential Y-chromosome Anatolian influences on the Greek and Cretan Neolithic.

The earliest Neolithic sites of Europe are located in Crete and mainland Greece. A debate persists concerning whether these farmers originated in neighboring Anatolia and the role of maritime colonization. To address these issues 171 samples were collected from areas near three known early Neolithic settlements in Greece together with 193 samples from Crete. An analysis of Y-chromosome haplogroups determined that the samples from the Greek Neolithic sites showed strong affinity to Balkan data, while Crete shows affinity with central/Mediterranean Anatolia. Haplogroup J2b-M12 was frequent in Thessaly and Greek Macedonia while haplogroup J2a-M410 was scarce. Alternatively, Crete, like Anatolia showed a high frequency of J2a-M410 and a low frequency of J2b-M12. This dichotomy parallels archaeobotanical evidence, specifically that while bread wheat (Triticum aestivum) is known from Neolithic Anatolia, Crete and southern Italy; it is absent from earliest Neolithic Greece. The expansion time of YSTR variation for haplogroup E3b1a2-V13, in the Peloponnese was consistent with an indigenous Mesolithic presence. In turn, two distinctive haplogroups, J2a1h-M319 and J2a1b1-M92, have demographic properties consistent with Bronze Age expansions in Crete, arguably from NW/W Anatolia and Syro-Palestine, while a later mainland (Mycenaean) contribution to Crete is indicated by relative frequencies of V13.

Male amelogenin dropouts: phylogenetic context, origins and implications.

Several commercial PCR multiplex kits incorporate the amelogenin locus for the purpose of human gender identification. Consequently, erroneous results in the electropherogram profile of this locus can carry important forensic implications. In this study, dropout of the amelogenin Y allele was detected in 5 out of 77 phenotypically normal Kathmandu males using the AmpFlSTR Identifiler kit. A battery of male-specific markers including SNPs, STRs, STSs, and a minisatellite were amplified for the five amelogenin null samples in order to delineate the breakpoints of the deletions as well as assess the overall integrity of the Y-chromosome. This study represents the first to examine the haplogroup affiliation of the AMGY deletions. The analyses performed suggest a single origin for the five deletions as indicated by their allocation to a specific Y-haplogroup (J2b2-M241), related Y-STR haplotypes and identical regional localization of breakpoints. The age estimated from the microsatellite variation for the amelogenin deletions (if they are associated by descent) is approximately 6.5+/-3.3 ky, younger than the previously reported related age of the M241 haplogroup representatives (13-14 ky). Our data in combination with previous publications suggest a concentration of afflicted individuals in the Indian subcontinent, possibly as a result of common ancestry. The elevated incidence of the amelogenin dropout in these populations accentuates the need to utilize other loci for gender determination in order to obtain an accurate set of inclusion criteria in forensic casework.

Iran: tricontinental nexus for Y-chromosome driven migration.

Due to its pivotal geographic position, present day Iran likely served as a gateway of reciprocal human movements. However, the extent to which the deserts within the Iranian plateau and the mountain ranges surrounding Persia inhibited gene flow via this corridor remains uncertain. In order to assess the magnitude of this region's role as a nexus for Africa, Asia and Europe in human migrations, high-resolution Y-chromosome analyses were performed on 150 Iranian males. Haplogroup data were subsequently compared to regional populations characterized at similar phylogenetic levels. The Iranians display considerable haplogroup diversity consistent with patterns observed in populations of the Middle East overall, reinforcing the notion of Persia as a venue for human disseminations. Admixture analyses of geographically targeted, regional populations along the latitudinal corridor spanning from Anatolia to the Indus Valley demonstrated contributions to Persia from both the east and west. However, significant differences were uncovered upon stratification of the gene donors, including higher proportions from central east and southeast Turkey as compared to Pakistan. In addition to the modulating effects of geographic obstacles, culturally mediated amalgamations consistent with the diverse spectrum of a variety of historical empires may account for the distribution of haplogroups and lineages observed. Our study of high-resolution Y-chromosome genotyping allowed for an in-depth analysis unattained in previous studies of the area, revealing important migratory and demographic events that shaped the contemporary genetic landscape.

The Levant versus the Horn of Africa: evidence for bidirectional corridors of human migrations.

Paleoanthropological evidence indicates that both the Levantine corridor and the Horn of Africa served, repeatedly, as migratory corridors between Africa and Eurasia. We have begun investigating the roles of these passageways in bidirectional migrations of anatomically modern humans, by analyzing 45 informative biallelic markers as well as 10 microsatellite loci on the nonrecombining region of the Y chromosome (NRY) in 121 and 147 extant males from Oman and northern Egypt, respectively. The present study uncovers three important points concerning these demic movements: (1) The E3b1-M78 and E3b3-M123 lineages, as well as the R1*-M173 lineages, mark gene flow between Egypt and the Levant during the Upper Paleolithic and Mesolithic. (2) In contrast, the Horn of Africa appears to be of minor importance in the human migratory movements between Africa and Eurasia represented by these chromosomes, an observation based on the frequency distributions of E3b*-M35 (no known downstream mutations) and M173. (3) The areal diffusion patterns of G-M201, J-12f2, the derivative M173 haplogroups, and M2 suggest more recent genetic associations between the Middle East and Africa, involving the Levantine corridor and/or Arab slave routes. Affinities to African groups were also evaluated by determining the NRY haplogroup composition in 434 samples from seven sub-Saharan African populations. Oman and Egypt's NRY frequency distributions appear to be much more similar to those of the Middle East than to any sub-Saharan African population, suggesting a much larger Eurasian genetic component. Finally, the overall phylogeographic profile reveals several clinal patterns and genetic partitions that may indicate source, direction, and relative timing of different waves of dispersals and expansions involving these nine populations.

The TDI-FP assay in human Y chromosome SNP haplotyping.

One of the many commercial technologies for genotyping single nucleotide polymorphisms (SNPs) is template direct dye-terminator incorporation with fluorescence-polarization (TDI-FP assay). It is a single-base extension assay followed by reading the fluorescence polarization values in an appropriate instrument. We have evaluated the suitability of the TDI-FP technique to detect haploid uniparentally inherited DNA polymorphisms on the nonrecombining portion of the Y chromosome. A sample of 47 individuals has been genotyped for 8 Y chromosome biallelic markers. The SNP typing was blindly duplicated by the denaturing high-performance liquid chromatography (DHPLC) technique for comparison. In the cases under examination the TDI-FP assay was able to resolve an allelic state fully. Such a result showed 100% concordance indicating how efficiently the TDI assay can be used to genotype Y chromosome DNA SNPs. However, a percentage of indeterminate genotypes remained unresolved by simple visual inspection: it varied from 0% to 11% depending on the SNP locus and on the success of amplification. This is consistent with previous findings. A maximum likelihood classificatory analysis allowed some of the indeterminate genotypes to be assigned and some potentially misclassified samples to be identified. Their percentage remains relatively high despite retyping and therefore alternative techniques for these noncompliant situations are required.

Peopling of three Mediterranean islands (Corsica, Sardinia, and Sicily) inferred by Y-chromosome biallelic variability.

An informative set of biallelic polymorphisms was used to study the structure of Y-chromosome variability in a sample from the Mediterranean islands of Corsica and Sicily, and compared with data on Sardinia to gain insights into the ethnogenesis of these island populations. The results were interpreted in a broader Mediterranean context by including in the analysis neighboring populations previously studied with the same methodology. All samples studied were enclosed in the comparable spectrum of European Y-chromosome variability. Pronounced differences were observed between the islands as well as in the percentages of haplotypes previously shown to have distinctive patterns of continental phylogeography. Approximately 60% of the Sicilian haplotypes are also prevalent in Southern Italy and Greece. Conversely, the Corsican sample had elevated levels of alternative haplotypes common in Northern Italy. Sardinia showed a haplotype ratio similar to that observed in Corsica, but with a remarkable difference in the presence of a lineage defined by marker M26, which approaches 35% in Sardinia but seems absent in Corsica. Although geographically adjacent, the data suggest different colonization histories and a minimal amount of recent gene flow between them. Our results identify possible ancestral continental sources of the various island populations and underscore the influence of founder effect and genetic drift. The Y-chromosome data are consistent with comparable mtDNA data at the RFLP haplogroup level of resolution, as well as linguistic and historic knowledge.

The genetic heritage of the earliest settlers persists both in Indian tribal and caste populations.

Two tribal groups from southern India--the Chenchus and Koyas--were analyzed for variation in mitochondrial DNA (mtDNA), the Y chromosome, and one autosomal locus and were compared with six caste groups from different parts of India, as well as with western and central Asians. In mtDNA phylogenetic analyses, the Chenchus and Koyas coalesce at Indian-specific branches of haplogroups M and N that cover populations of different social rank from all over the subcontinent. Coalescence times suggest early late Pleistocene settlement of southern Asia and suggest that there has not been total replacement of these settlers by later migrations. H, L, and R2 are the major Indian Y-chromosomal haplogroups that occur both in castes and in tribal populations and are rarely found outside the subcontinent. Haplogroup R1a, previously associated with the putative Indo-Aryan invasion, was found at its highest frequency in Punjab but also at a relatively high frequency (26%) in the Chenchu tribe. This finding, together with the higher R1a-associated short tandem repeat diversity in India and Iran compared with Europe and central Asia, suggests that southern and western Asia might be the source of this haplogroup. Haplotype frequencies of the MX1 locus of chromosome 21 distinguish Koyas and Chenchus, along with Indian caste groups, from European and eastern Asian populations. Taken together, these results show that Indian tribal and caste populations derive largely from the same genetic heritage of Pleistocene southern and western Asians and have received limited gene flow from external regions since the Holocene. The phylogeography of the primal mtDNA and Y-chromosome founders suggests that these southern Asian Pleistocene coastal settlers from Africa would have provided the inocula for the subsequent differentiation of the distinctive eastern and western Eurasian gene pools.

Melting curve SNP (McSNP) genotyping: a useful approach for diallelic genotyping in forensic science.

The increasing availability of Single Nucleotide Polymorphisms (SNPs) and Deletion/Insertion Polymorphisms (DIPs), as well as the outstanding progress in SNP genotyping technologies, will impact forensics profoundly. We have developed a new method for genotyping SNPs and DIPs, which is based on the determination of melting curve profiles of amplified DNA in solution. We have termed this method Melting curve SNP (McSNP) genotyping. Melting curve profiles are composites of the particular melting temperatures (Tm) of the individual fragments that comprise the DNA sample. Simple mixtures of DNA can be resolved in a very robust and efficient fashion, since the samples can be scored in the plates in which they were amplified with no or very few post-PCR manipulations. As such, McSNP is one of the least expensive genotyping methods available and can and should be useful in forensic science.

Origins and divergence of the Roma (gypsies).

The identification of a growing number of novel Mendelian disorders and private mutations in the Roma (Gypsies) points to their unique genetic heritage. Linguistic evidence suggests that they are of diverse Indian origins. Their social structure within Europe resembles that of the jatis of India, where the endogamous group, often defined by profession, is the primary unit. Genetic studies have reported dramatic differences in the frequencies of mutations and neutral polymorphisms in different Romani populations. However, these studies have not resolved ambiguities regarding the origins and relatedness of Romani populations. In this study, we examine the genetic structure of 14 well-defined Romani populations. Y-chromosome and mtDNA markers of different mutability were analyzed in a total of 275 individuals. Asian Y-chromosome haplogroup VI-68, defined by a mutation at the M82 locus, was present in all 14 populations and accounted for 44.8% of Romani Y chromosomes. Asian mtDNA-haplogroup M was also identified in all Romani populations and accounted for 26.5% of female lineages in the sample. Limited diversity within these two haplogroups, measured by the variation at eight short-tandem-repeat loci for the Y chromosome, and sequencing of the HVS1 for the mtDNA are consistent with a small group of founders splitting from a single ethnic population in the Indian subcontinent. Principal-components analysis and analysis of molecular variance indicate that genetic structure in extant endogamous Romani populations has been shaped by genetic drift and differential admixture and correlates with the migrational history of the Roma in Europe. By contrast, social organization and professional group divisions appear to be the product of a more recent restitution of the caste system of India.

Y chromosome binary markers to study the high prevalence of males in Sardinian centenarians and the genetic structure of the Sardinian population.

We have analyzed a sample of 40 centenarians and 116 young controls from Sardinia, with a set of new Y chromosome binary markers, to evaluate if Y chromosome genes are involved in the high prevalence of males among centenarian Sardinians (1/2 vs. 1/4 in other populations studied). The results indicate that none of the seven lineages that account for >97% of the Y chromosome diversity in Sardinia provide an advantage with respect to the extreme longevity. However, our results, although based on the male-specific Y chromosome polymorphisms, give a clear profile of the pattern of genetic variability in Sardinia. Indeed they indicate that the Sardinian population had two main founder populations that have evolved in isolation for at least the last 5,000 years. These findings set the stage for future studies on longevity and other complex traits in Sardinia.

The Eurasian heartland: a continental perspective on Y-chromosome diversity.

The nonrecombining portion of the human Y chromosome has proven to be a valuable tool for the study of population history. The maintenance of extended haplotypes characteristic of particular geographic regions, despite extensive admixture, allows complex demographic events to be deconstructed. In this study we report the frequencies of 23 Y-chromosome biallelic polymorphism haplotypes in 1,935 men from 49 Eurasian populations, with a particular focus on Central Asia. These haplotypes reveal traces of historical migrations, and provide an insight into the earliest patterns of settlement of anatomically modern humans on the Eurasian continent. Central Asia is revealed to be an important reservoir of genetic diversity, and the source of at least three major waves of migration leading into Europe, the Americas, and India. The genetic results are interpreted in the context of Eurasian linguistic patterns.

The phylogeography of Y chromosome binary haplotypes and the origins of modern human populations.

Although molecular genetic evidence continues to accumulate that is consistent with a recent common African ancestry of modern humans, its ability to illuminate regional histories remains incomplete. A set of unique event polymorphisms associated with the non-recombining portion of the Y-chromosome (NRY) addresses this issue by providing evidence concerning successful migrations originating from Africa, which can be interpreted as subsequent colonizations, differentiations and migrations overlaid upon previous population ranges. A total of 205 markers identified by denaturing high performance liquid chromatography (DHPLC), together with 13 taken from the literature, were used to construct a parsimonious genealogy. Ancestral allelic states were deduced from orthologous great ape sequences. A total of 131 unique haplotypes were defined which trace the microevolutionary trajectory of global modern human genetic diversification. The genealogy provides a detailed phylogeographic portrait of contemporary global population structure that is emblematic of human origins, divergence and population history that is consistent with climatic, paleoanthropological and other genetic knowledge.

Maori origins, Y-chromosome haplotypes and implications for human history in the Pacific.

An assessment of 28 pertinent binary genetic markers on the non-recombining portion of the Y chromosome (NRY) in New Zealand Maori and other relevant populations has revealed a diverse genetic paternal heritage of extant Maori. A maximum parsimony phylogeny was constructed in which nine of the 25 possible binary haplotypes were observed. Although approximately 40% of the samples have haplotypes of unequivocal European origin, an equivalent number of samples have a single binary haplotype that is also observed in Indonesia and New Guinea, indicative of common indigenous Melanesian ancestry. The balance of the lineages has either typical East Asian signatures or alternative compositions consistent with their affinity to Melanesia or New Guinea. Molecular analysis of mtDNA variation confirms the presence of a single predominant characteristic Southeast Asian (9-bp deletion in the Region V) lineage. The Y-chromosome results support a pattern of complex interrelationships between Southeast Asia, Melanesia, and Polynesia, in contrast to mtDNA and linguistic data, which uphold a rapid and homogeneous Austronesian expansion. The Y-chromosome data highlight a distinctive gender-modulated pattern of differential gene flow in the history of Polynesia.

High-resolution analysis of human Y-chromosome variation shows a sharp discontinuity and limited gene flow between northwestern Africa and the Iberian Peninsula.

In the present study we have analyzed 44 Y-chromosome biallelic polymorphisms in population samples from northwestern (NW) Africa and the Iberian Peninsula, which allowed us to place each chromosome unequivocally in a phylogenetic tree based on >150 polymorphisms. The most striking results are that contemporary NW African and Iberian populations were found to have originated from distinctly different patrilineages and that the Strait of Gibraltar seems to have acted as a strong (although not complete) barrier to gene flow. In NW African populations, an Upper Paleolithic colonization that probably had its origin in eastern Africa contributed 75% of the current gene pool. In comparison, approximately 78% of contemporary Iberian Y chromosomes originated in an Upper Paleolithic expansion from western Asia, along the northern rim of the Mediterranean basin. Smaller contributions to these gene pools (constituting 13% of Y chromosomes in NW Africa and 10% of Y chromosomes in Iberia) came from the Middle East during the Neolithic and, during subsequent gene flow, from Sub-Saharan to NW Africa. Finally, bidirectional gene flow across the Strait of Gibraltar has been detected: the genetic contribution of European Y chromosomes to the NW African gene pool is estimated at 4%, and NW African populations may have contributed 7% of Iberian Y chromosomes. The Islamic rule of Spain, which began in a.d. 711 and lasted almost 8 centuries, left only a minor contribution to the current Iberian Y-chromosome pool. The high-resolution analysis of the Y chromosome allows us to separate successive migratory components and to precisely quantify each historical layer.

The Werner syndrome gene and global sequence variation.

We have identified a dense set of markers useful in association studies involving the Werner syndrome (WRN) gene. The homozygotic disruption of the WRN gene is the cause of Werner disease. In addition, this gene is likely to be involved in many complex traits, such as aging, or at least some of the traits and diseases related to age. To investigate the genetic variation associated with the WRN gene, a sample of 93 individuals representing all the continents was analyzed by denaturing high-performance liquid chromatography. A systematic survey of all 35 exons and flanking regions identified 58 single-nucleotide polymorphisms, 15 of which fall in the coding region and cause 11 missense mutations. The resulting global nucleotide diversity was 5.226 x 10(-4), with a slight difference between coding and noncoding regions.

Independent histories of human Y chromosomes from Melanesia and Australia.

To investigate the origins and relationships of Australian and Melanesian populations, 611 males from 18 populations from Australia, Melanesia, and eastern/southeastern Asia were typed for eight single-nucleotide polymorphism (SNP) loci and seven short tandem-repeat loci on the Y chromosome. A unique haplotype, DYS390.1del/RPS4Y711T, was found at a frequency of 53%-69% in Australian populations, whereas the major haplotypes found in Melanesian populations (M4G/M5T/M9G and DYS390.3del/RPS4Y711T) are absent from the Australian populations. The Y-chromosome data thus indicate independent histories for Australians and Melanesians, a finding that is in agreement with evidence from mtDNA but that contradicts some analyses of autosomal loci, which show a close relationship between Australian and Melanesian (specifically, highland Papua New Guinean) populations. Since the Australian and New Guinean landmasses were connected when first colonized by humans > or =50,000 years ago but separated some 8,000 years ago, a possible way to reconcile all the genetic data is to infer that the Y-chromosome and mtDNA results reflect the past 8,000 years of independent history for Australia and New Guinea, whereas the autosomal loci reflect the long preceding period of common origin and shared history. Two Y-chromosome haplotypes (M119C/M9G and M122C/M9G) that originated in eastern/southeastern Asia are present in coastal and island Melanesia but are rare or absent in both Australia and highland Papua New Guinea. This distribution, along with demographic analyses indicating that population expansions for both haplotypes began approximately 4,000-6,000 years ago, suggests that these haplotypes were brought to Melanesia by the Austronesian expansion. Most of the populations in this study were previously typed for mtDNA SNPs; population differentiation is greater for the Y chromosome than for mtDNA and is significantly correlated with geographic distance, a finding in agreement with results of similar analyses of European populations.

Melanesian origin of Polynesian Y chromosomes.

BACKGROUND: Two competing hypotheses for the origins of Polynesians are the 'express-train' model, which supposes a recent and rapid expansion of Polynesian ancestors from Asia/Taiwan via coastal and island Melanesia, and the 'entangled-bank' model, which supposes a long history of cultural and genetic interactions among Southeast Asians, Melanesians and Polynesians. Most genetic data, especially analyses of mitochondrial DNA (mtDNA) variation, support the express-train model, as does linguistic and archaeological evidence. Here, we used Y-chromosome polymorphisms to investigate the origins of Polynesians. RESULTS: We analysed eight single nucleotide polymorphisms (SNPs) and seven short tandem repeat (STR) loci on the Y chromosome in 28 Cook Islanders from Polynesia and 583 males from 17 Melanesian, Asian and Australian populations. We found that all Polynesians belong to just three Y-chromosome haplotypes, as defined by unique event polymorphisms. The major Y haplotype in Polynesians (82% frequency) was restricted to Melanesia and eastern Indonesia and most probably arose in Melanesia. Coalescence analysis of associated Y-STR haplotypes showed evidence of a population expansion in Polynesians, beginning about 2,200 years ago. The other two Polynesian Y haplotypes were widespread in Asia but were also found in Melanesia. CONCLUSIONS: All Polynesian Y chromosomes can be traced back to Melanesia, although some of these Y-chromosome types originated in Asia. Together with other genetic and cultural evidence, we propose a new model of Polynesian origins that we call the 'slow-boat' model: Polynesian ancestors did originate from Asia/Taiwan but did not move rapidly through Melanesia; rather, they interacted with and mixed extensively with Melanesians, leaving behind their genes and incorporating many Melanesian genes before colonising the Pacific.

The genetic legacy of Paleolithic Homo sapiens sapiens in extant Europeans: a Y chromosome perspective.

A genetic perspective of human history in Europe was derived from 22 binary markers of the nonrecombining Y chromosome (NRY). Ten lineages account for >95% of the 1007 European Y chromosomes studied. Geographic distribution and age estimates of alleles are compatible with two Paleolithic and one Neolithic migratory episode that have contributed to the modern European gene pool. A significant correlation between the NRY haplotype data and principal components based on 95 protein markers was observed, indicating the effectiveness of NRY binary polymorphisms in the characterization of human population composition and history.

Y chromosome sequence variation and the history of human populations.

Binary polymorphisms associated with the non-recombining region of the human Y chromosome (NRY) preserve the paternal genetic legacy of our species that has persisted to the present, permitting inference of human evolution, population affinity and demographic history. We used denaturing high-performance liquid chromatography (DHPLC; ref. 2) to identify 160 of the 166 bi-allelic and 1 tri-allelic site that formed a parsimonious genealogy of 116 haplotypes, several of which display distinct population affinities based on the analysis of 1062 globally representative individuals. A minority of contemporary East Africans and Khoisan represent the descendants of the most ancestral patrilineages of anatomically modern humans that left Africa between 35,000 and 89,000 years ago.