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There is growing evidence that several components of the mass neural activity contributing to the local field potential (LFP) can be partly separated by decomposing the LFP into nonoverlapping frequency bands. Although the blood oxygen level-dependent (BOLD) signal has been found to correlate preferentially with specific frequency bands of the LFP, it is still unclear whether the BOLD signal relates to the activity expressed by each LFP band independently of the others or if, instead, it also reflects specific relationships among different bands. We investigated these issues by recording, simultaneously and with high spatiotemporal resolution, BOLD signal and LFP during spontaneous activity in early visual cortices of anesthetized monkeys (Macaca mulatta). We used information theory to characterize the statistical dependency between BOLD and LFP. We found that the alpha (8-12 Hz), beta (18-30 Hz), and gamma (40-100 Hz) LFP bands were informative about the BOLD signal. In agreement with previous studies, gamma was the most informative band. Both increases and decreases in BOLD signal reliably followed increases and decreases in gamma power. However, both alpha and beta power signals carried information about BOLD that was largely complementary to that carried by gamma power. In particular, the relationship between alpha and gamma power was reflected in the amplitude of the BOLD signal, while the relationship between beta and gamma bands was reflected in the latency of BOLD with respect to significant changes in gamma power. These results lay the basis for identifying contributions of different neural pathways to cortical processing using fMRI.

The present study aims at investigating the association between common and rare variants of mitochondrial DNA (mtDNA), and increased risk of schizophrenia (SZ) and bipolar disorder (BPD) in a cohort of patients originating from the same Italian population. The distribution of the major European mtDNA haplogroups was determined in 89 patients and their frequencies did not significantly differ from those observed in the Italian population. Moreover, 27 patients with high probability of having inherited the disease from the maternal side were selected for whole mitochondrial genome sequencing to investigate the possible presence of causative point mutations. Overall, 213 known variants and 2 novel changes were identified, but none of them was predicted to have functional effects. Hence, none of the sequence changes we found in our sample could explain the maternal component of SZ and BPD predisposition.

Many statistical models of coupling between time changes of the band-limited power of neural signals and functional magnetic resonance imaging Blood Oxygenation Level Dependent (BOLD) signal time changes rely on linear convolution. The effect of nonlinear behaviors in single-trial relationships between neural signals and BOLD responses is rarely tested and included in models. Here we investigate whether using a static nonlinearity improves the prediction of single-trial BOLD responses from neural signals. A static nonlinearity is a nonlinear transformation of the convolution of neural responses which is implemented by the same nonlinear function for all time points. We evaluated this approach by applying it to simultaneous recordings of functional magnetic resonance imaging BOLD and band-limited neural signals (Local Field Potentials and Multi Unit Activity) from primary visual cortex of anaesthetized macaques. We found that using a simple polynomial static nonlinearity was sufficient to obtain highly significant improvements of the accuracy of single-trial BOLD prediction over the accuracy obtained with linear convolution. This suggests that static nonlinearities may be a useful tool for a compact and accurate statistical description of neurovascular coupling., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Aim: The aim of this paper was to analyze the relation between glomerular filtration rate (GFR) and albumin excretion rate (AER) in subjects with type 2 diabetes., Methods: Three hundred thirteen type 2 diabetic patients attending Diabetes Centre, Malta, were studied between 2008 and 2009. GFR was estimated using the Modified Diet Renal Disease (MDRD) formula while two spot measurements of urinary AER were used to determine albuminuria., Results: Forty-nine patients were hyperfiltrating, of whom 69% were normoalbuminuric, 24% microalbuminuric, and 6% macroalbuminuric; 229 subjects had normal eGFR; of these 67% were normoalbuminuric, 27% microalbuminuric and 6% macroalbuminuric; 35 subjects had eGFR<60mL/min/1.73 m2, of whom 43% were normoalbuminuric, 37% microalbuminuric and 20% macroalbuminuric. No association was found between eGFR and AER in subjects with hyperfiltration (P=0.39); however eGFR was strongly correlated with AER in subjects with eGFR <60ml/min/1.73 m2 (r= -0.376; P=0.026). In multinomial logistic regression analysis, eGFR was significantly associated with albuminuria in non-hyperfiltrating, but not in hyperfiltrating, subjects., Conclusion: Our data suggests that hyperfiltration and albuminuria occur independently of each other in the early stages of DN, but the decline in eGFR and albuminuria follow a parallel course in later stages of DN suggesting that they may share common pathophysiological mechanisms or they may be causally linked.

Recent studies have shown that the phase of low-frequency local field potentials (LFPs) in sensory cortices carries a significant amount of information about complex naturalistic stimuli, yet the laminar circuit mechanisms and the aspects of stimulus dynamics responsible for generating this phase information remain essentially unknown. Here we investigated these issues by means of an information theoretic analysis of LFPs and current source densities (CSDs) recorded with laminar multi-electrode arrays in the primary auditory area of anesthetized rats during complex acoustic stimulation (music and broadband 1/f stimuli). We found that most LFP phase information originated from discrete "CSD events" consisting of granular-superficial layer dipoles of short duration and large amplitude, which we hypothesize to be triggered by transient thalamocortical activation. These CSD events occurred at rates of 2-4 Hz during both stimulation with complex sounds and silence. During stimulation with complex sounds, these events reliably reset the LFP phases at specific times during the stimulation history. These facts suggest that the informativeness of LFP phase in rat auditory cortex is the result of transient, large-amplitude events, of the "evoked" or "driving" type, reflecting strong depolarization in thalamo-recipient layers of cortex. Finally, the CSD events were characterized by a small number of discrete types of infragranular activation. The extent to which infragranular regions were activated was stimulus dependent. These patterns of infragranular activations may reflect a categorical evaluation of stimulus episodes by the local circuit to determine whether to pass on stimulus information through the output layers.

To date, more than 100 cases with a deletion of chromosome 2q have been identified, although studies reporting small interstitial deletions involving the 2q24.2-q24.3 region are still rare. Here, we have described the genotype and the phenotype of a boy with a 5.3 Mb de novo deletion in this region, identified by SNP array analysis. The selected region included 20 genes, of which 4 are prominently expressed in the brain. Their combined haplo-insufficiency could explain the main clinical features of this patient which included mental retardation, severe hypotonia, joint laxity and mild dysmorphic traits., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Studies analyzing sensory cortical processing or trying to decode brain activity often rely on a combination of different electrophysiological signals, such as local field potentials (LFPs) and spiking activity. Understanding the relation between these signals and sensory stimuli and between different components of these signals is hence of great interest. We here provide an analysis of LFPs and spiking activity recorded from visual and auditory cortex during stimulation with natural stimuli. In particular, we focus on the time scales on which different components of these signals are informative about the stimulus, and on the dependencies between different components of these signals. Addressing the first question, we find that stimulus information in low frequency bands (<12 Hz) is high, regardless of whether their energy is computed at the scale of milliseconds or seconds. Stimulus information in higher bands (>50 Hz), in contrast, is scale dependent, and is larger when the energy is averaged over several hundreds of milliseconds. Indeed, combined analysis of signal reliability and information revealed that the energy of slow LFP fluctuations is well related to the stimulus even when considering individual or few cycles, while the energy of fast LFP oscillations carries information only when averaged over many cycles. Addressing the second question, we find that stimulus information in different LFP bands, and in different LFP bands and spiking activity, is largely independent regardless of time scale or sensory system. Taken together, these findings suggest that different LFP bands represent dynamic natural stimuli on distinct time scales and together provide a potentially rich source of information for sensory processing or decoding brain activity.

Genome-wide screenings for copy number variations (CNVs) in patients with schizophrenia have demonstrated the presence of several CNVs that increase the risk of developing the disease and a growing number of large rare CNVs; the contribution of these rare CNVs to schizophrenia remains unknown. Using Affymetrix 6.0 arrays, we undertook a systematic search for CNVs in 172 patients with schizophrenia and 160 healthy controls, all of Italian origin, with the aim of confirming previously identified loci and identifying novel schizophrenia susceptibility genes. We found five patients with a CNV occurring in one of the regions most convincingly implicated as risk factors for schizophrenia: NRXN1 and the 16p13.1 regions were found to be deleted in single patients and 15q11.2 in 2 patients, whereas the 15q13.3 region was duplicated in one patient. Furthermore, we found three distinct patients with CNVs in 2q12.2, 3q29 and 17p12 loci, respectively. These loci were previously reported to be deleted or duplicated in patients with schizophrenia but were never formally associated with the disease. We found 5 large CNVs (>900 kb) in 4q32, 5q14.3, 8q23.3, 11q25 and 17q12 in five different patients that could include some new candidate schizophrenia susceptibility genes. In conclusion, the identification of previously reported CNVs and of new, rare, large CNVs further supports a model of schizophrenia that includes the effect of multiple, rare, highly penetrant variants.

Objective: Synaptogyrin 1 (SYNGR1) is a transmembrane protein of neurotransmitter-containing vesicle. Recently, suggestive association between SYNGR1 intragenic polymorphisms and schizophrenia has been reported in the Indian population. Furthermore, some rare nucleotide changes with a potential pathogenic effect have been found in Indian and Chinese schizophrenia patients. In this study, we have performed an association study and a resequencing analysis in an Italian sample., Methods: Eight polymorphisms of the SYNGR1 gene were typed in a case-control sample consisting of 274 patients and 335 controls. In parallel, a mutational screening covering all SYNGR1 exons was conducted., Results: Evidence of association has been found for rs715505 (P = 0.028), a marker already reported to be associated with the disease. Resequencing analysis revealed two novel polymorphisms and several rare variants (13 of 16 as new variants), some of which might have relevance for gene expression and function., Conclusion: The results of our association study support a contribution of SYNGR1 to schizophrenia susceptibility. In addition, the resequencing analysis evidenced mutations with a potential functional role at the mRNA and/or protein level. Of particular interest is the p.isoc:S26G missense mutation identified in six patients (0.011) and three controls (0.004) which might be involved in the elimination of a potential protein kinase C phosphorylation site.

Background: The volume of data available on genetic variations has increased considerably with the recent development of high-density, single-nucleotide polymorphism (SNP) arrays. Several software programs have been developed to assist researchers in the analysis of this huge amount of data, but few can rely upon a whole genome variability visualisation system that could help data interpretation., Results: We have developed GenotypeColour as a rapid user-friendly tool able to upload, visualise and compare the huge amounts of data produced by Affymetrix Human Mapping GeneChips without losing the overall view of the data.Some features of GenotypeColour include visualising the entire genome variability in a single screenshot for one or more samples, the simultaneous display of the genotype and Copy Number state for thousands of SNPs, and the comparison of large amounts of samples by producing "consensus" images displaying regions of complete or partial identity. The software is also useful for genotype analysis of trios and to show regions of potential uniparental disomy (UPD). All information can then be exported in a tabular format for analysis with dedicated software. At present, the software can handle data from 10 K, 100 K, 250 K, 5.0 and 6.0 Affymetrix chips., Conclusion: We have created a software that offers a new way of displaying and comparing SNP and CNV genomic data. The software is available free at http://www.med.unibs.it/~barlati/GenotypeColour and is especially useful for the analysis of multiple samples.

Impairment of glutamatergic neurotransmission is one of the major hypotheses proposed to explain the neurobiology of schizophrenia. Therefore, the genes involved in the glutamate neurotransmitter system could be considered potential candidate genes for schizophrenia susceptibility. A systematic study on alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor genes has been carried out and the results obtained from the analysis on GRIA2, GRIA3 and GRIA4 are reported. No evidence of association with schizophrenia was found for the GRIA2 and GRIA4 genes; strong evidence of association with schizophrenia was found for GRIA3. This X-linked gene showed a different behavior in the two genders; a positive association with schizophrenia was observed among females but not in males. Female carriers of rs1034428 A allele were found to have a 2.19-fold higher risk of developing schizophrenia compared to non-carriers and 3.28-fold higher risk for developing a non-paranoid phenotype. The analysis at the haplotype level showed that susceptibility to schizophrenia was associated with the specific haplotype rs989638-rs1034428-rs2227098 CAC (P = 0.0008). We conclude that, of the three AMPA genes analyzed here, only GRIA3 seems to be involved in the pathogenesis of schizophrenia, but only in females., (2007 Wiley-Liss, Inc.)

Functional magnetic resonance imaging (fMRI) is a widely used method for studying the neural basis of cognition and of sensory function. A potential problem in the interpretation of fMRI data is that fMRI measures neural activity only indirectly, as a local change of deoxyhemoglobin concentration due to the metabolic demands of neural function. To build correct sensory and cognitive maps in the human brain, it is thus crucial to understand whether fMRI and neural activity convey the same type of information about external correlates. While a substantial experimental effort has been devoted to the simultaneous recordings of hemodynamic and neural signals, so far, the development of analysis methods that elucidate how neural and hemodynamic signals represent sensory information has received less attention. In this article, we critically review why the analytical framework of information theory, the mathematical theory of communication, is ideally suited to this purpose. We review the principles of information theory and explain how they could be applied to the analysis of fMRI and neural signals. We show that a critical advantage of information theory over more traditional analysis paradigms commonly used in the fMRI literature is that it can elucidate, within a single framework, whether an empirically observed correlation between neural and fMRI signals reflects either a similar stimulus tuning or a common source of variability unrelated to the external stimuli. In addition, information theory determines the extent to which these shared sources of stimulus signal and of variability lead fMRI and neural signals to convey similar information about external correlates. We then illustrate the formalism by applying it to the analysis of the information carried by different bands of the local field potential. We conclude by discussing the current methodological challenges that need to be addressed to make the information-theoretic approach more robustly applicable to the simultaneous recordings of neural and imaging data.

Local field potentials (LFPs) reflect subthreshold integrative processes that complement spike train measures. However, little is yet known about the differences between how LFPs and spikes encode rich naturalistic sensory stimuli. We addressed this question by recording LFPs and spikes from the primary visual cortex of anesthetized macaques while presenting a color movie. We then determined how the power of LFPs and spikes at different frequencies represents the visual features in the movie. We found that the most informative LFP frequency ranges were 1-8 and 60-100 Hz. LFPs in the range of 12-40 Hz carried little information about the stimulus, and may primarily reflect neuromodulatory inputs. Spike power was informative only at frequencies <12 Hz. We further quantified "signal correlations" (correlations in the trial-averaged power response to different stimuli) and "noise correlations" (trial-by-trial correlations in the fluctuations around the average) of LFPs and spikes recorded from the same electrode. We found positive signal correlation between high-gamma LFPs (60-100 Hz) and spikes, as well as strong positive signal correlation within high-gamma LFPs, suggesting that high-gamma LFPs and spikes are generated within the same network. LFPs <24 Hz shared strong positive noise correlations, indicating that they are influenced by a common source, such as a diffuse neuromodulatory input. LFPs <40 Hz showed very little signal and noise correlations with LFPs >40 Hz and with spikes, suggesting that low-frequency LFPs reflect neural processes that in natural conditions are fully decoupled from those giving rise to spikes and to high-gamma LFPs.

A number of studies support a possible link between mitochondrial dysfunction and schizophrenia. To test the hypothesis of a direct contribution of mitochondrial DNA (mt-DNA) in susceptibility to DSM-IV-TR-schizophrenia, we looked for differences in the frequency distribution of the major European haplogroups (hgs) in 142 patients and 190 controls both of Italian origin. A subgroup of patients (N = 37) and healthy counterparts (N = 41) was also analyzed for possible differences in the relative amount of mt-DNA versus nuclear-DNA in blood cells. Patients and controls were comparable for hg frequency distribution and the relative levels of mt-DNA even after stratification by gender and schizophrenia subtype. However, patients harboring the hg J-T showed an anticipated onset of the disorder. These results indicate that the J-T hg of mt-DNA may have a modulator effect on deeper determinants of schizophrenia., ((c) 2007 Wiley-Liss, Inc.)

Radar and optical observations reveal that the continuous increase in the spin rate of near-Earth asteroid (54509) 2000 PH5 can be attributed to the Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) effect, a torque due to sunlight. The change in spin rate is in reasonable agreement with theoretical predictions for the YORP acceleration of a body with the radar-determined size, shape, and spin state of 2000 PH5. The detection of asteroid spin-up supports the YORP effect as an explanation for the anomalous distribution of spin rates for asteroids under 10 kilometers in diameter and as a binary formation mechanism.

High-resolution radar images reveal near-Earth asteroid (66391) 1999 KW4 to be a binary system. The approximately 1.5-kilometer-diameter primary (Alpha) is an unconsolidated gravitational aggregate with a spin period approximately 2.8 hours, bulk density approximately 2 grams per cubic centimeter, porosity approximately 50%, and an oblate shape dominated by an equatorial ridge at the object's potential-energy minimum. The approximately 0.5-kilometer secondary (Beta) is elongated and probably is denser than Alpha. Its average orbit about Alpha is circular with a radius approximately 2.5 kilometers and period approximately 17.4 hours, and its average rotation is synchronous with the long axis pointed toward Alpha, but librational departures from that orientation are evident. Exotic physical and dynamical properties may be common among near-Earth binaries.

Glutamatergic dysfunction is one of the major hypotheses for the pathogenesis of schizophrenia. The GRIA1 gene encodes for one (GluR1) of the four (GluR1-4) ionotropic AMPA receptor subunits. GRIA1 is a good candidate gene for susceptibility to schizophrenia since it maps in 5q33, a region where the presence of susceptibility loci has been suggested by independent genome-wide scans and because its expression has been found to be decreased in the brain of some schizophrenia patients. We present data from a case-control association study on the Italian population with eight polymorphisms spanning the whole GRIA1 gene. Single-locus analysis revealed a significantly different allele distribution in cases and in controls of two SNPs (rs707176, 0.41 vs. 0.31, P = 0.009; rs2963944, 0.41 vs. 0.30, P = 0.007), and one microsatellite (rs10631988, allele 9: 0.40 vs. 0.29, P = 0.004). Haplotype analysis showed an increased frequency of a specific haplotype for these markers (C09CC, 0.39 vs. 0.28, P = 0.009). Therefore our data indicate that GRIA1 may be involved in susceptibility to DSM-IV-TR schizophrenia., (Copyright 2006 Wiley-Liss, Inc.)

The sequencing of entire human mitochondrial DNAs belonging to haplogroup U reveals that this clade arose shortly after the "out of Africa" exit and rapidly radiated into numerous regionally distinct subclades. Intriguingly, the Saami of Scandinavia and the Berbers of North Africa were found to share an extremely young branch, aged merely approximately 9,000 years. This unexpected finding not only confirms that the Franco-Cantabrian refuge area of southwestern Europe was the source of late-glacial expansions of hunter-gatherers that repopulated northern Europe after the Last Glacial Maximum but also reveals a direct maternal link between those European hunter-gatherer populations and the Berbers.

Complete sequencing of 62 mitochondrial DNAs (mtDNAs) belonging (or very closely related) to haplogroup H revealed that this mtDNA haplogroup--by far the most common in Europe--is subdivided into numerous subhaplogroups, with at least 15 of them (H1-H15) identifiable by characteristic mutations. All the haplogroup H mtDNAs found in 5,743 subjects from 43 populations were then screened for diagnostic markers of subhaplogroups H1 and H3. This survey showed that both subhaplogroups display frequency peaks, centered in Iberia and surrounding areas, with distributions declining toward the northeast and southeast--a pattern extremely similar to that previously reported for mtDNA haplogroup V. Furthermore, the coalescence ages of H1 and H3 (~11,000 years) are close to that previously reported for V. These findings have major implications for the origin of Europeans, since they attest that the Franco-Cantabrian refuge area was indeed the source of late-glacial expansions of hunter-gatherers that repopulated much of Central and Northern Europe from ~15,000 years ago. This has also some implications for disease studies. For instance, the high occurrence of H1 and H3 in Iberia led us to re-evaluate the haplogroup distribution in 50 Spanish families affected by nonsyndromic sensorineural deafness due to the A1555G mutation. The survey revealed that the previously reported excess of H among these families is caused entirely by H3 and is due to a major, probably nonrecent, founder event.

To investigate which aspects of contemporary human Y-chromosome variation in Europe are characteristic of primary colonization, late-glacial expansions from refuge areas, Neolithic dispersals, or more recent events of gene flow, we have analyzed, in detail, haplogroup I (Hg I), the only major clade of the Y phylogeny that is widespread over Europe but virtually absent elsewhere. The analysis of 1,104 Hg I Y chromosomes, which were identified in the survey of 7,574 males from 60 population samples, revealed several subclades with distinct geographic distributions. Subclade I1a accounts for most of Hg I in Scandinavia, with a rapidly decreasing frequency toward both the East European Plain and the Atlantic fringe, but microsatellite diversity reveals that France could be the source region of the early spread of both I1a and the less common I1c. Also, I1b*, which extends from the eastern Adriatic to eastern Europe and declines noticeably toward the southern Balkans and abruptly toward the periphery of northern Italy, probably diffused after the Last Glacial Maximum from a homeland in eastern Europe or the Balkans. In contrast, I1b2 most likely arose in southern France/Iberia. Similarly to the other subclades, it underwent a postglacial expansion and marked the human colonization of Sardinia approximately 9,000 years ago.

The phylogeography of Y-chromosome haplogroups E (Hg E) and J (Hg J) was investigated in >2400 subjects from 29 populations, mainly from Europe and the Mediterranean area but also from Africa and Asia. The observed 501 Hg E and 445 Hg J samples were subtyped using 36 binary markers and eight microsatellite loci. Spatial patterns reveal that (1). the two sister clades, J-M267 and J-M172, are distributed differentially within the Near East, North Africa, and Europe; (2). J-M267 was spread by two temporally distinct migratory episodes, the most recent one probably associated with the diffusion of Arab people; (3). E-M81 is typical of Berbers, and its presence in Iberia and Sicily is due to recent gene flow from North Africa; (4). J-M172(xM12) distribution is consistent with a Levantine/Anatolian dispersal route to southeastern Europe and may reflect the spread of Anatolian farmers; and (5). E-M78 (for which microsatellite data suggest an eastern African origin) and, to a lesser extent, J-M12(M102) lineages would trace the subsequent diffusion of people from the southern Balkans to the west. A 7%-22% contribution of Y chromosomes from Greece to southern Italy was estimated by admixture analysis.

A total of 202 Sardinian male subjects were examined for 13 biallelic stable markers, the complex 49a,f/TaqI system and three microsatellites of the Y chromosome in order to investigate, through surname analysis, on a possible territorial heterogeneity inside the island. The study of geographical distribution and linguistic derivation of Sardinian surnames allow us to discover their 'probable place of origin' and reconstruct ancient genetic isolates which borders are, today, no more recognizable. The molecular analysis revealed that about 90% of the Sardinian Y chromosomes fell into haplogroups E-M35, G-M201, I-M26, J-12f2 and R-M269. In contrast with the territorial homogeneity of these haplogroups, when the individuals were distributed according to their birthplace, a significant difference between the three historically and culturally distinct geographical areas into which Sardinia can be subdivided was observed when the individuals were distributed according to the ancestral location of surnames. In particular, the major contribution to this heterogeneity is due to the 'Sardinian-specific' haplogroup I-M26 (almost completely associated with the 49a,f-Ht12/12f2-10Kb/YCAIIa-21/YCAIIb-11 compound haplotype), which shows both a significantly higher incidence in the central-eastern (archaic) area and a significantly lower frequency in the northern area. The results of this study agree with the hypothesis that the ancestral homeland of this specific subset of haplogroup I is the mountainous central-eastern area of Sardinia, where the population underwent a long history of isolation since ancient times, and highlight the informative power of the surname analysis.

Thirty-five mitochondrial (mt) DNAs from Spain that harbor the mutation A3243G in association with either MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) syndrome or a wide array of disease phenotypes (ranging from diabetes and deafness to a mixture of chronic progressive external ophthalmoplegic symptoms and strokelike episodes) were studied by use of high-resolution restriction fragment length polymorphism analysis and control-region sequencing. A total of 34 different haplotypes were found, indicating that all instances of the A3243G mutation are probably due to independent mutational events. Haplotypes were distributed into 13 haplogroups whose frequencies were close to those of the general Spanish population. Moreover, there was no statistically significant difference in haplogroup distribution between patients with MELAS and those with disease phenotypes other than MELAS. Overall, these data indicate that the A3243G mutation harbors all the evolutionary features expected from a severely deleterious mtDNA mutation under strong negative selection, and they reveal that European mtDNA backgrounds do not play a substantial role in modulating the mutation's phenotypic expression.

Previous studies on human Y-chromosome polymorphisms in the European populations highlighted the high frequency of the 49a,f/TaqI haplotype 11 and of the Eu19 (M17) lineage in Eastern Europe. To better understand the origin and the evolution of the Eu19, and its relationship with 49a,f Ht11, this study surveyed 2,235 individuals (mainly from Europe and the Middle East) for the 49a,f Ht11 and for many biallelic markers defining the Eu19 lineage. As previously described, the highest frequency of Eu19 was found in Eastern Europe. All the Eu19 Y-chromosomes turned out to be 49a,f Ht11 or its derivatives, the distribution of which suggests that the Eu19/49a,f Ht11 emerged in Ukraine, probably in a Palaeolithic population. Thereafter, the spread of this lineage toward Europe, Asia, and India occurred at different waves over a few thousands years. At present this seems to indicate the influence of the Ukraine Palaeolithic groups in the gene pool of modern populations. For the first time it is possible to make inferences about the evolution of some haplotypes of the 49a,f system. In spite of its unknown molecular base, this is one of the first most informative polymorphisms of the Y chromosome.