823 research outputs found

    Lack of Association between Y-Chromosomal Haplogroups and Prostate Cancer in the Korean Population

    Get PDF
    The Y chromosome has recently been suggested to have an association with prostate cancer risk in human populations. Since this chromosome is haploid and lacks recombination over most of its length, haplotypes constructed from binary markers throughout the chromosome can be used for association studies. To assess the possible Y-chromosomal contribution to prostate cancer risk, we have therefore analyzed 14 Y-chromosomal binary markers in 106 prostate cancer cases and 110 controls from the Korean population. In contrast to previous findings in the Japanese population, no statistically significant difference in the distribution of Y-chromosomal haplogroup frequencies was observed between the case and control groups of Koreans. Thus, our data imply that the previously reported associations between Y-chromosomal lineages and a predisposition to, or protection against, prostate cancer might be explained by statistical fluctuations, or by genetic effects that are seen only in some environments

    Inferring human population sizes, divergence times and rates of gene flow from mitochondrial, X and Y chromosome resequencing data

    Get PDF
    We estimate parameters of a general isolation-with-migration model using resequence data from mitochondrial DNA (mtDNA), the Y chromosome, and two loci on the X chromosome in samples of 25-50 individuals from each of 10 human populations. Application of a coalescent-based Markov chain Monte Carlo technique allows simultaneous inference of divergence times, rates of gene flow, as well as changes in effective population size. Results from comparisons between sub-Saharan African and Eurasian populations estimate that 1500 individuals founded the ancestral Eurasian population similar to 40 thousand years ago (KYA). Furthermore, these small Eurasian founding populations appear to have grown much more dramatically than either African or Oceanian populations. Analyses of sub-Saharan African populations provide little evidence for a history, of population bottlenecks and suggest that die), began diverging from one another upward of 50 KYA. We surmise that ancestral African populations had already been geographically structured prior to the founding of ancestral Eurasian populations. African populations are shown to experience low levels of mitochondrial DNA gene flow, but high levels of Y chromosome gene flow. In particular, Y chromosome gene flow appears to be asymmetric, i.e., from the Bantu-speaking population into other African populations. Conversely, mitochondrial gene flow is more extensive between non-African populations, but appears to be absent between European and Asian Populations

    Logical Analysis of Data (LAD) model for the early diagnosis of acute ischemic stroke

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Strokes are a leading cause of morbidity and the first cause of adult disability in the United States. Currently, no biomarkers are being used clinically to diagnose acute ischemic stroke. A diagnostic test using a blood sample from a patient would potentially be beneficial in treating the disease.</p> <p>Results</p> <p>A classification approach is described for differentiating between proteomic samples of stroke patients and controls, and a second novel predictive model is developed for predicting the severity of stroke as measured by the National Institutes of Health Stroke Scale (NIHSS). The models were constructed by applying the Logical Analysis of Data (LAD) methodology to the mass peak profiles of 48 stroke patients and 32 controls. The classification model was shown to have an accuracy of 75% when tested on an independent validation set of 35 stroke patients and 25 controls, while the predictive model exhibited superior performance when compared to alternative algorithms. In spite of their high accuracy, both models are extremely simple and were developed using a common set consisting of only 3 peaks.</p> <p>Conclusion</p> <p>We have successfully identified 3 biomarkers that can detect ischemic stroke with an accuracy of 75%. The performance of the classification model on the validation set and on cross-validation does not deteriorate significantly when compared to that on the training set, indicating the robustness of the model. As in the case of the LAD classification model, the results of the predictive model validate the function constructed on our support-set for approximating the severity scores of stroke patients. The correlation and root mean absolute error of the LAD predictive model are consistently superior to those of the other algorithms used (Support vector machines, C4.5 decision trees, Logistic regression and Multilayer perceptron).</p

    Ancient Migratory Events in the Middle East: New Clues from the Y-Chromosome Variation of Modern Iranians

    Get PDF
    Knowledge of high resolution Y-chromosome haplogroup diversification within Iran provides important geographic context regarding the spread and compartmentalization of male lineages in the Middle East and southwestern Asia. At present, the Iranian population is characterized by an extraordinary mix of different ethnic groups speaking a variety of Indo-Iranian, Semitic and Turkic languages. Despite these features, only few studies have investigated the multiethnic components of the Iranian gene pool. In this survey 938 Iranian male DNAs belonging to 15 ethnic groups from 14 Iranian provinces were analyzed for 84 Y-chromosome biallelic markers and 10 STRs. The results show an autochthonous but non-homogeneous ancient background mainly composed by J2a sub-clades with different external contributions. The phylogeography of the main haplogroups allowed identifying post-glacial and Neolithic expansions toward western Eurasia but also recent movements towards the Iranian region from western Eurasia (R1b-L23), Central Asia (Q-M25), Asia Minor (J2a-M92) and southern Mesopotamia (J1-Page08). In spite of the presence of important geographic barriers (Zagros and Alborz mountain ranges, and the Dasht-e Kavir and Dash-e Lut deserts) which may have limited gene flow, AMOVA analysis revealed that language, in addition to geography, has played an important role in shaping the nowadays Iranian gene pool. Overall, this study provides a portrait of the Y-chromosomal variation in Iran, useful for depicting a more comprehensive history of the peoples of this area as well as for reconstructing ancient migration routes. In addition, our results evidence the important role of the Iranian plateau as source and recipient of gene flow between culturally and genetically distinct population

    The Influence of Different Stresses on Glomalin Levels in an Arbuscular Mycorrhizal Fungus—Salinity Increases Glomalin Content

    Get PDF
    Glomalin is a glycoprotein produced by arbuscular mycorrhizal (AM) fungi, and the soil fraction containing glomalin is correlated with soil aggregation. Thus, factors potentially influencing glomalin production could be of relevance for this ecosystem process and for understanding AM fungal physiology. Previous work indicated that glomalin production in AM fungi may be a stress response, or related to suboptimal mycelium growth. We show here that environmental stress can enhance glomalin production in the mycelium of the AM fungus Glomus intraradices. We applied NaCl and glycerol in different intensities to the medium in which the fungus was grown in vitro, causing salinity stress and osmotic stress, respectively. As a third stress type, we simulated grazing on the extraradical hyphae of the fungus by mechanically injuring the mycelium by clipping. NaCl caused a strong increase, while the clipping treatment led to a marginally significant increase in glomalin production. Even though salinity stress includes osmotic stress, we found substantially different responses in glomalin production due to the NaCl and the glycerol treatment, as glycerol addition did not cause any response. Thus, our results indicate that glomalin is involved in inducible stress responses in AM fungi for salinity, and possibly grazing stress

    Detailed Analysis of Japanese Population Substructure with a Focus on the Southwest Islands of Japan

    Get PDF
    Uncovering population structure is important for properly conducting association studies and for examining the demographic history of a population. Here, we examined the Japanese population substructure using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC), which covers all but the northern region of Japan. Using 222 autosomal loci from 4502 subjects, we investigated population substructure by estimating FST among populations, testing population differentiation, and performing principal component analysis (PCA) and correspondence analysis (CA). All analyses revealed a low but significant differentiation between the Amami Islanders and the mainland Japanese population. Furthermore, we examined the genetic differentiation between the mainland population, Amami Islanders and Okinawa Islanders using six loci included in both the Pan-Asian SNP (PASNP) consortium data and the J-MICC data. This analysis revealed that the Amami and Okinawa Islanders were differentiated from the mainland population. In conclusion, we revealed a low but significant level of genetic differentiation between the mainland population and populations in or to the south of the Amami Islands, although genetic variation between both populations might be clinal. Therefore, the possibility of population stratification must be considered when enrolling the islander population of this area, such as in the J-MICC study

    The Druze: A Population Genetic Refugium of the Near East

    Get PDF
    BACKGROUND: Phylogenetic mitochondrial DNA haplogroups are highly partitioned across global geographic regions. A unique exception is the X haplogroup, which has a widespread global distribution without major regions of distinct localization. PRINCIPAL FINDINGS: We have examined mitochondrial DNA sequence variation together with Y-chromosome-based haplogroup structure among the Druze, a religious minority with a unique socio-demographic history residing in the Near East. We observed a striking overall pattern of heterogeneous parental origins, consistent with Druze oral tradition, together with both a high frequency and a high diversity of the mitochondrial DNA (mtDNA) X haplogroup within a confined regional subpopulation. Furthermore demographic modeling indicated low migration rates with nearby populations. CONCLUSIONS: These findings were enabled through the use of a paternal kindred based sampling approach, and suggest that the Galilee Druze represent a population isolate, and that the combination of a high frequency and diversity of the mtDNA X haplogroup signifies a phylogenetic refugium, providing a sample snapshot of the genetic landscape of the Near East prior to the modern age

    Effect of a mixed reality-based intervention on arm, hand, and finger function on chronic stroke

    Get PDF
    [EN] Background: Virtual and mixed reality systems have been suggested to promote motor recovery after stroke. Basing on the existing evidence on motor learning, we have developed a portable and low-cost mixed reality tabletop system that transforms a conventional table in a virtual environment for upper limb rehabilitation. The system allows intensive and customized training of a wide range of arm, hand, and finger movements and enables interaction with tangible objects, while providing audiovisual feedback of the participants' performance in gamified tasks. This study evaluates the clinical effectiveness and the acceptance of an experimental intervention with the system in chronic stroke survivors. Methods: Thirty individuals with stroke were included in a reversal (A-B-A) study. Phase A consisted of 30 sessions of conventional physical therapy. Phase B consisted of 30 training sessions with the experimental system. Both interventions involved flexion and extension of the elbow, wrist, and fingers, and grasping of different objects. Sessions were 45-min long and were administered three to five days a week. The body structures (Modified Ashworth Scale), functions (Motricity Index, Fugl-Meyer Assessment Scale), activities (Manual Function Test, Wolf Motor Function Test, Box and Blocks Test, Nine Hole Peg Test), and participation (Motor Activity Log) were assessed before and after each phase. Acceptance of the system was also assessed after phase B (System Usability Scale, Intrinsic Motivation Inventory). Results: Significant improvement was detected after the intervention with the system in the activity, both in arm function measured by the Wolf Motor Function Test (p < 0.01) and finger dexterity measured by the Box and Blocks Test (p < 0.01) and the Nine Hole Peg Test (p < 0.01); and participation (p < 0.01), which was maintained to the end of the study. The experimental system was reported as highly usable, enjoyable, and motivating. Conclusions: Our results support the clinical effectiveness of mixed reality interventions that satisfy the motor learning principles for upper limb rehabilitation in chronic stroke survivors. This characteristic, together with the low cost of the system, its portability, and its acceptance could promote the integration of these systems in the clinical practice as an alternative to more expensive systems, such as robotic instruments.The authors wish to thank the staff and patients of the Servicio de Neurorrehabilitación y Daño Cerebral de los Hospitales NISA for their involvement in the study. The authors also wish to thank the staff of LabHuman for their support in this project, especially Francisco Toledo and José Roda for their assistance. This study was funded in part by the Project TEREHA (IDI-20110844) and Project NeuroVR (TIN2013-44741-R) of the Ministerio de Economia y Competitividad of Spain, the Project Consolider-C (SEJ2006-14301/PSIC) of the Ministerio de Educacion y Ciencia of Spain, the "CIBER of Physiopathology of Obesity and Nutrition, an initiative of ISCIII", and the Excellence Research Program PROMETEO of the Conselleria de Educacion of Generalitat Valenciana (2008-157).Colomer Font, C.; Llorens Rodríguez, R.; Noé Sebastián, E.; Alcañiz Raya, ML. (2016). Effect of a mixed reality-based intervention on arm, hand, and finger function on chronic stroke. Journal of NeuroEngineering and Rehabilitation. 13:1-10. https://doi.org/10.1186/s12984-016-0153-6S11013Fregni F, Pascual-Leone A. Hand motor recovery after stroke: tuning the orchestra to improve hand motor function. Cogn Behav Neurol. 2006;19(1):21–33.Patten C, Condliffe EG, Dairaghi CA, Lum PS. Concurrent neuromechanical and functional gains following upper-extremity power training post-stroke. J Neuroeng Rehabil. 2013;10:1.Turolla A, Dam M, Ventura L, Tonin P, Agostini M, Zucconi C, et al. Virtual reality for the rehabilitation of the upper limb motor function after stroke: a prospective controlled trial. J Neuroeng Rehabil. 2013;10:85.Dancause N, Nudo RJ. Shaping plasticity to enhance recovery after injury. Prog Brain Res. 2011;192:273–95.Kwakkel G, Kollen B, Lindeman E. Understanding the pattern of functional recovery after stroke: facts and theories. Restor Neurol Neurosci. 2004;22(3–5):281–99.Nielsen JB, Willerslev-Olsen M, Christiansen L, Lundbye-Jensen J, Lorentzen J. Science-based neurorehabilitation: recommendations for neurorehabilitation from basic science. J Mot Behav. 2015;47(1):7–17.Shaughnessy M, Resnick BM. Using theory to develop an exercise intervention for patients post stroke. Top Stroke Rehabil. 2009;16(2):140–6.Subramanian SK, Massie CL, Malcolm MP, Levin MF. Does provision of extrinsic feedback result in improved motor learning in the upper limb poststroke? A systematic review of the evidence. Neurorehabil Neural Repair. 2010;24(2):113–24.Arya KN, Verma R, Garg RK, Sharma VP, Agarwal M, Aggarwal GG. Meaningful task-specific training (MTST) for stroke rehabilitation: a randomized controlled trial. Top Stroke Rehabil. 2012;19(3):193–211.Levin MF, Weiss PL, Keshner EA. Emergence of Virtual Reality as a Tool for Upper Limb Rehabilitation: Incorporation of Motor Control and Motor Learning Principles. Phys Ther. 2015;95(3):415–25.Laver K, George S, Thomas S, Deutsch JE, Crotty M. Cochrane review: virtual reality for stroke rehabilitation. Eur J Phys Rehabil Med. 2012;48(3):523–30.Cameirao MS, Badia SB, Duarte E, Frisoli A, Verschure PF. The combined impact of virtual reality neurorehabilitation and its interfaces on upper extremity functional recovery in patients with chronic stroke. Stroke. 2012;43(10):2720–8.Saposnik G, Levin M, G. Outcome Research Canada Working. Virtual reality in stroke rehabilitation: a meta-analysis and implications for clinicians. Stroke. 2011;42(5):1380–6.Viau A, Feldman AG, McFadyen BJ, Levin MF. Reaching in reality and virtual reality: a comparison of movement kinematics in healthy subjects and in adults with hemiparesis. J Neuroeng Rehabil. 2004;1(1):11.Thornton M, Marshall S, McComas J, Finestone H, McCormick A, Sveistrup H. Benefits of activity and virtual reality based balance exercise programmes for adults with traumatic brain injury: perceptions of participants and their caregivers. Brain Inj. 2005;19(12):989–1000.Mazzoleni S, Puzzolante L, Zollo L, Dario P, Posteraro F. Mechanisms of motor recovery in chronic and subacute stroke patients following a robot-aided training. IEEE Trans Haptics. 2014;7(2):175–80.Duff M, Chen Y, Cheng L, Liu SM, Blake P, Wolf SL, et al. Adaptive mixed reality rehabilitation improves quality of reaching movements more than traditional reaching therapy following stroke. Neurorehabil Neural Repair. 2013;27(4):306–15.Mousavi Hondori, H., M. Khademi, L. Dodakian, A. McKenzie, C.V. Lopes, and S.C. Cramer, Choice of Human-Computer Interaction Mode in Stroke Rehabilitation. Neurorehabil Neural Repair, 2015.Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther. 1987;67(2):206–7.Paternostro-Sluga T, Grim-Stieger M, Posch M, Schuhfried O, Vacariu G, Mittermaier C, et al. Reliability and validity of the Medical Research Council (MRC) scale and a modified scale for testing muscle strength in patients with radial palsy. J Rehabil Med. 2008;40(8):665–71.Kopp B, Kunkel A, Flor H, Platz T, Rose U, Mauritz KH, et al. The Arm Motor Ability Test: reliability, validity, and sensitivity to change of an instrument for assessing disabilities in activities of daily living. Arch Phys Med Rehabil. 1997;78(6):615–20.Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.Romero M, Sanchez A, Marin C, Navarro MD, Ferri J, Noe E. Clinical usefulness of the Spanish version of the Mississippi Aphasia Screening Test (MASTsp): validation in stroke patients. Neurologia. 2012;27(4):216–24.Llorens R, Marín C, Ortega M, Alcaniz M, Colomer C, Navarro MD, et al. Upper limb tracking using depth information for rehabilitative tangible tabletop systems, in 9th International Conference on Disability, Virtual Reality & Associated Technologies. Laval, France: The University of Reading; 2012. p. 463–466.Alt Murphy M, Resteghini C, Feys P, Lamers I. An overview of systematic reviews on upper extremity outcome measures after stroke. BMC Neurol. 2015;15:29.Sloan RL, Sinclair E, Thompson J, Taylor S, Pentland B. Inter-rater reliability of the modified Ashworth Scale for spasticity in hemiplegic patients. Int J Rehabil Res. 1992;15(2):158–61.van der Ploeg RJ, Fidler V, Oosterhuis HJ. Hand-held myometry: reference values. J Neurol Neurosurg Psychiatry. 1991;54(3):244–7.Duncan PW, Propst M, Nelson SG. Reliability of the Fugl-Meyer assessment of sensorimotor recovery following cerebrovascular accident. Phys Ther. 1983;63(10):1606–10.Miyamoto S, Kondo T, Suzukamo Y, Michimata A, Izumi S. Reliability and validity of the Manual Function Test in patients with stroke. Am J Phys Med Rehabil. 2009;88(3):247–55.Woodbury M, Velozo CA, Thompson PA, Light K, Uswatte G, Taub E, et al. Measurement structure of the Wolf Motor Function Test: implications for motor control theory. Neurorehabil Neural Repair. 2010;24(9):791–801.Mathiowetz V, Volland G, Kashman N, Weber K. Adult norms for the Box and Block Test of manual dexterity. Am J Occup Ther. 1985;39(6):386–91.Oxford Grice K, Vogel KA, Le V, Mitchell A, Muniz S, Vollmer MA. Adult norms for a commercially available Nine Hole Peg Test for finger dexterity. Am J Occup Ther. 2003;57(5):570–3.Hammer AM, Lindmark B. Responsiveness and validity of the Motor Activity Log in patients during the subacute phase after stroke. Disabil Rehabil. 2010;32(14):1184–93.Bullinger HJ, F.-I.f.A.u. Organisation, and U.S.I.f.A.u. Technologiemanagement. Human Aspects in Computing: Design and use of interactive systems and work with terminals. Elsevier; 1991.McAuley E, Duncan T, Tammen VV. Psychometric properties of the Intrinsic Motivation Inventory in a competitive sport setting: a confirmatory factor analysis. Res Q Exerc Sport. 1989;60(1):48–58.Mazzoleni S, Sale P, Tiboni M, Franceschini M, Carrozza MC, Posteraro F. Upper limb robot-assisted therapy in chronic and subacute stroke patients: a kinematic analysis. Am J Phys Med Rehabil. 2013;92(10 Suppl 2):e26–37.Lin KC, Hsieh YW, Wu CY, Chen CL, Jang Y, Liu JS. Minimal detectable change and clinically important difference of the Wolf Motor Function Test in stroke patients. Neurorehabil Neural Repair. 2009;23(5):429–34.Fu TS, Wu CY, Lin KC, Hsieh CJ, Liu JS, Wang TN, et al. Psychometric comparison of the shortened Fugl-Meyer Assessment and the streamlined Wolf Motor Function Test in stroke rehabilitation. Clin Rehabil. 2012;26(11):1043–7.Hsieh YW, Wu CY, Lin KC, Chang YF, Chen CL, Liu JS. Responsiveness and validity of three outcome measures of motor function after stroke rehabilitation. Stroke. 2009;40(4):1386–91.van der Lee JH, Beckerman H, Lankhorst GJ, Bouter LM. The responsiveness of the Action Research Arm test and the Fugl-Meyer Assessment scale in chronic stroke patients. J Rehabil Med. 2001;33(3):110–3.Wolf SL, Catlin PA, Ellis M, Archer AL, Morgan B, Piacentino A. Assessing Wolf Motor Function Test as Outcome Measure for Research in Patients After Stroke. Stroke. 2001;32(7):1635–9.Reinkensmeyer DJ, Wolbrecht ET, Chan V, Chou C, Cramer SC, Bobrow JE. Comparison of three-dimensional, assist-as-needed robotic arm/hand movement training provided with Pneu-WREX to conventional tabletop therapy after chronic stroke. Am J Phys Med Rehabil. 2012;91(11 Suppl 3):S232–41.Takahashi CD, Der-Yeghiaian L, Le V, Motiwala RR, Cramer SC. Robot-based hand motor therapy after stroke. Brain. 2008;131(Pt 2):425–37.Sale P, Mazzoleni S, Lombardi V, Galafate D, Massimiani MP, Posteraro F, et al. Recovery of hand function with robot-assisted therapy in acute stroke patients: a randomized-controlled trial. Int J Rehabil Res. 2014;37(3):236–42.Hwang CH, Seong JW, Son DS. Individual finger synchronized robot-assisted hand rehabilitation in subacute to chronic stroke: a prospective randomized clinical trial of efficacy. Clin Rehabil. 2012;26(8):696–704.Timmermans AA, Seelen HA, Willmann RD, Kingma H. Technology-assisted training of arm-hand skills in stroke: concepts on reacquisition of motor control and therapist guidelines for rehabilitation technology design. J Neuroeng Rehabil. 2009;6:1.Levin MF, Kleim JA, Wolf SL. What do motor “recovery” and “compensation” mean in patients following stroke? Neurorehabil Neural Repair. 2009;23(4):313–9.Rosati G, Oscari F, Spagnol S, Avanzini F, Masiero S. Effect of task-related continuous auditory feedback during learning of tracking motion exercises. J Neuroeng Rehabil. 2012;9:79.Imam B, Jarus T. Virtual reality rehabilitation from social cognitive and motor learning theoretical perspectives in stroke population. Rehabil Res Pract. 2014;2014:594540.Schuster-Amft C, Henneke A, Hartog-Keisker B, Holper L, Siekierka E, Chevrier E, et al. Intensive virtual reality-based training for upper limb motor function in chronic stroke: a feasibility study using a single case experimental design and fMRI. Disabil Rehabil Assist Technol. 2015;10(5):385–92.Llorens R, Noe E, Colomer C, Alcaniz M. Effectiveness, usability, and cost-benefit of a virtual reality-based telerehabilitation program for balance recovery after stroke: a randomized controlled trial. Arch Phys Med Rehabil. 2015;96(3):418–25. e2.Llorens R, Gil-Gomez JA, Alcaniz M, Colomer C, Noe E. Improvement in balance using a virtual reality-based stepping exercise: a randomized controlled trial involving individuals with chronic stroke. Clin Rehabil. 2015;29(3):7

    Improved Resolution Haplogroup G Phylogeny in the Y Chromosome, Revealed by a Set of Newly Characterized SNPs

    Get PDF
    Background: Y-SNP haplogroup G (hgG), defined by Y-SNP marker M201, is relatively uncommon in the United States general population, with only 8 additional sub-markers characterized. Many of the previously described eight sub-markers are either very rare (2–4%) or do not distinguish between major populations within this hg. In fact, prior to the current study, only 2 % of our reference Caucasian population belonged to hgG and all of these individuals were in sub-haplogroup G2a, defined by P15. Additional Y-SNPs are needed in order to differentiate between individuals within this haplogroup. Principal Findings: In this work we have investigated whether we could differentiate between a population of 63 hgG individuals using previously uncharacterized Y-SNPs. We have designed assays to test these individuals using all known hgG SNPs (n = 9) and an additional 16 unreported/undefined Y-SNPS. Using a combination of DNA sequence and genetic genealogy databases, we have uncovered a total of 15 new hgG SNPs that had been previously reported but not phylogenetically characterized. Ten of the new Y-SNPs are phylogenetically equivalent to M201, one is equivalent to P15 and, interestingly, four create new, separate haplogroups. Three of the latter are more common than many of the previously defined Y-SNPs. Y-STR data from these individuals show that DYS385*12 is present in (70%) of G2a3b1-U13 individuals while only 4 % of non-G2a3b1-U13 individuals posses the DYS385*12 allele. Conclusions: This study uncovered several previously undefined Y-SNPs by using data from several database sources. Th

    Composite likelihood estimation of demographic parameters

    Get PDF
    which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Most existing likelihood-based methods for fitting historical demographic models to DNA sequence polymorphism data to do not scale feasibly up to the level of whole-genome data sets. Computational economies can be achieved by incorporating two forms of pseudo-likelihood: composite and approximate likelihood methods. Composite likelihood enables scaling up to large data sets because it takes the product of marginal likelihoods as an estimator of the likelihood of the complete data set. This approach is especially useful when a large number of genomic regions constitutes the data set. Additionally, approximate likelihood methods can reduce the dimensionality of the data by summarizing the information in the original data by either a sufficient statistic, or a set of statistics. Both composite and approximate likelihood methods hold promise for analyzing large data sets or for use in situations where the underlying demographic model is complex and has many parameters. This paper considers a simple demographic model of allopatric divergence between two populations, in which one of the population is hypothesized to have experienced a founder event, or population bottleneck. A large resequencing data set from human populations is summarized by the joint frequency spectrum, which is a matrix of the genomic frequency spectrum of derived base frequencies in two populations. A Bayesia
    corecore